Skctiox TI.

Part II.

An

Intkodlhtion
To

NEMATOLOGY

J. R. CHRISTIE

Editor

nail'

ALBERT HASSALL

Born in Woolwich, Kent, England. M. R. C. V. S., Royal College of Veter-
inary Surgeons London, 1886. Inspector, 1887-1905; Assistant in Zoology, 1905-
1910; Assistant Zoologist, 1910-1922; Associate Zoologist, 1922-1924; Zoologist,
1924-1925; Senior Zoologist and Assistant Chief of Zoological Division, 1925-

1932; Collaborator, 1934- ; Bureau of Animal Industry, U. S. Department of

Agriculture.

Zoologist, biblographer, author of numerous papers in parasitology, compiler
of Index Catalogue of Medical and Veterinary Zoology published in collaboration
with Stiles. Nematologists' best friend and severest critic.

Section II.

Part II.

An

Introduction
To

NEMATOLOGY

J. R. CHRISTIE
Editor

y

ALBERT HASSALL

Born in Woolwich, Kent, England. M. R. C. V. S., Royal College of Veter-
inary Surgeons London, 1886. Inspector, 1887-1905; Assistant in Zoology, 1905-
1910; Assistant Zoologist, 1910-1922; Associate Zoologist, 1922-1924; Zoologist,
1924-1925; Senior Zoologist and Assistant Chief of Zoological Division, 1925-
1932; Collaborator, 1934- ; Bureau of Animal Industry, U. S. Department of

Agriculture.

Zoologist, biblographer, author of numerous papers in parasitology, compiler
of Index Catalogue of Medical and Veterinary Zoology published in collaboration
with Stiles. Nematologists' best friend and severest critic.

PREFACE

In IIk' preparation of Section 11, Parts II and
III, it lias been necessary to deviate from the
arrangement proposed in the original annomice-
ment. J)iiring the course of preparation it be-
came evident that the treatment of the subject,
as developed by the various authors, would re-
sult in more pages than can be saddle stitched
into one cover. It also became evident that it
^ would be impossible to complete some of the

chapters dealing with free-living and plant-
parasitic nematodes until long after most of
the others were ready for printing. Hence it
g r^ seemed advisable to so change the^rrangement

of the chapters as to permit the inunediate pub-
lication of completed manuscripts even though
it was necessary to modify what might seem the
most logical sequence.

The various authors are responsible for the
facts presented and the opinions expressed in
the parts accredited to them with the one ex-
ception of taxonomic nomenclature, for which
Dr. B. G. C'hitwood assumes responsibility.

To the contributors I wish to express my ap-
preciation and thanks for their sympathetic co-
operation as well as for the excellence of their
contributions and the care and thoroughness
with wliich these were prepared.

J. R. Christie.

i 1-^

CD

; a

i rn

a

o

CHAPTER IV
LIFE HISTORY. GENERAL DISCUSSION

B. G. CHITWOOD

The dovclopmoiit of iioiiiiitodos in its sim|)lost form is diroct,
or not marked liy a motamorpliosis siu'li as occurs in tlio in
sects. In Ronoral tlio newly hatched nematode rosenil)les tlie
adult in all gross morpholoRic characters with the exception of
the reproductive system and secondary sexual characters. The
various growth stages, except the adult stage, are teruiinated
liy molts (or ecdysesi, the nunil>er of nuilts lieing four, the uum
her of stages five. Internal changes do not occur to any marked
extent in the simplest form of life history. We should, there-
fore, speak of the stages previous to the adult as nynijihs, if a
terminology were used similar to that emi)loyed in the Arthro
poda, but usage has made larva, as applied to such stages, the
accepted term.

The number of uuilts occurring in the course of develojiment is
common for nearly all nematodes, and it ajipears to be the gen
eralized or primitive number for the class. I>evelopment may
be outlined as follows:

First stage (larva)

(molt)

Second stage (larva)

(molt)

Third stage (larva)

(molt)

Fourth stage (larva)

(molf)

Fifth stage (adult)
Correlated with mode of life, various adaptations or modifi-
cations h,ive taken place in the life history, these adaptations
having arisen through the need for food and a means of dis
semination. With free-living nematodes, living either upon
decaying matter or preying upon other microscopic organisms,
these factors seem to have played a smaller part than with
those living as parasites.

Probably need for dissemination was the earlier influence;
at any rate, it has caused the simplest modifications of life
history. The action of this factor on some free-living nema-
todes is evidenced by the occurrence of a persistent stage, the
cuticle of one of the larval molts being retained as a protec-
tive sheath or "cyst." It is not uncommon for such species to
have two types of larva, environmental conditions determining
whether or not larvae will be of the persistent type. The sig
nifieance of these persistent larvae is indicated by their nega-
tively geotropic tendencies, for tlie.v craw! to the highest sur-
face available and "standing" on their tails swing about,
catching upon any moving ob,iect. The climax of this type of
development is found in species where an encysted stage on
some arthropod (Rhabditis coarctata, see cover page, see. 1, part
1), or annelid is obligatory before the adult stage can be
reached.

The need for obtaining food plays a much more striking
role, being evidenced by all conceivable degrees of parasitism
both on and in plants and animals. In the group of "herbi-
vors" life c.vcles may be of numerous t.vpes, depending on
whether tlie nematodes are "grazers," passing from host to
host, or sedentary forms, entering the host and there under-
going all or most of the stages of development. Life histories
may be further modified by the factor of dissemination and
the growth habits of the host. Among the jiarasitcs of animals
the factors of dissemination and nourishment also play their
roles. We have forms that are parasitic only during a par
ticular larval stage, the third, which, incidentally, is usually
sheathed or "encysted." Certain parasites of annelids (i.e.,
Rhabditis pellio) pass the third stage in the nejihridia of their
host and can only develop to adults in the decomposing tissues
of their host. Other species (mermithids) enter their hosts
either as eggs or larvae and develop to ])readults (fourth stage)
within the body cavity, finally leaving their host before matur-
ing. In such instances the nourishment necessary for the entire
life cycle is obtained from the host and stored during the para-
sitic stages.

The type of life history in parasitic nematodes being entirely
correlated with the degree of parasitism, we find, with more
ndvanced parasitism, more complicated life cycles and more
morphologic changes taking place during the course of devel-
opment. Seurat (Ullfi; 1920), recognizing this, proposed a ter-
minology for the different types of life cycles based on the
mode of development.

Some forms have an alternation of generations, one genera-
tion being free living, the other parasitic. This type of life

cycle is termed hctnopenonx. In such forms we find free-living
adults giving rise to larvae which enter the host and develop
to i)arasitic adults. These larvae may or may not be ensheatlied
(third stage), i.e., the cuticle of one or more larval molts re-
tained though separated from the body. The stage ready to
enter the host is ti'rnied the infrclivc stage. Nematodes with
no alteration of generations are termed monogcnous. These
are by far the most common,

l'arasit<'s of animals may also be classified according to the
number of hosts necessary for completion of the life cycle.
Species in which there is a single host are termed monoxcnous,
those in which there are two or more hosts, hclcroxcnous.

Some nematodes have both free-living and parasitic stages,
the free-living st;iges being larvae, the parasitic stages late
larvae and adults. In these we find young larval stages (the
first and second) feeding U|)on bacteria and similar organic
matter, the third stage usually ensheathed or persistent, this
commonly being the infective stage. Upon entering the host
these species develop through the fourth stage to the sexually
mature adult.

A further development of parasitism is indicated by the ab-
sence of the free-living stages. Eggs of the parasite pass out
of the host and, outside, undergo only embryonic development
within the egg shell. In such instances the egg shell is often
covered by a protein layer (p. 178), and the embryo often con-
tains more yolk than forms in which the eggs hatch before en-
tering the host. With such a completely parasitic mode of
existence, the factor of dissemination again becomes manifest
and we find still other modifications in the life cycle.

Some nematode parasites of vertebrates pass through larval
stages in invertebrates, this course of development being either
obligatory or facultative; still others undergo larval develop-
ment in other vertebrates, such development usually being obli-
gatory, rarely facultative. The host in which such a parasite
develops to infeetivity is termed the intermediate or secondary
host while that in which it develops to sexual maturity is called
the terminal, definitive or primary host. Sometimes the inter-
mediate host is eaten by another animal (secondary interme-
diate host) in which the parasite can continue its existence but
cannot reach maturity. When this second animal is, in turn,
eaten by the primary host the life cycle is completed. If the
parasite neither feeds nor undergoes growth within an animal,
that host is termed a transport Itost. This type of intermediate
host serves chiefly as a means of dissemination and is faculta-
tive rather than obligatory.

We have attempted to extend Seurat 's outline to include all
nematodes. With the recent and extensive increase in informa-
tion on the life histories of vertebrate parasites it has become
very difficult to adjust Seurat 's classification to the many
variations in life cycles. For example it is hardly proper to
speak of a form as being heteroxenous when the use of an in-
termediate host is facultative {DictyocauUis filaria) yet other
nematodes in the same taxonomic group may be truly heteroxe-
nous requiring an intermediate host (Metastrone/i/his clonffa-
tus). In general one can say that the Spiruroidea, Filarioidea,
Camallanoidea, Draeunculoidca and Dioctophymatoidea are
heteroxenous. The Strongyloidea, Trichostrongyloidea and
Oxyuroidea are monoxenous while the Metastrongyloidea and
Ascaridoidea contain forms with both monoxcnous and heteroxe-
nous life cycles. Some e.xceptioiml forms do not fit into any
part of the classification. Ncoaplectana glaseri (Rhabditoidea)
and Probsimayria vivipara (Oxyuroidea) reproduce through
several consecutive generations within the host. Some strains
of a SIronpyloidcs species may reproduce without an alternation
of generations while other strains of the same species may be
predominantly heterogenctic. The diiBculty in fitting life his-
tories into a well defined classification appears to be due to the
adaptation of each species to its host which entails a means of
dissemination suitable to the host's environment and habits.

A large assembly of nematodes have been found in more or
less close association with vertebrates or invertebrates. Some
of these merely use the "host" as a means of transportation
{Ehabditis coarctata which may pass an encysted stage on the
surface of dung beetles). Such nematodes are not considered
parasitic unless the.v actually penetrate the host. Some well
known free-living nematodes have been reported also existing
under parasitic conditions. Thus Rhabditis strongyjoides has
been repeatedly taken, in the larval stage, from diseased skin
of dogs and Diploscapter coronata from the ahydrochloric acid
stomaches of human beings. Yet these forms are free-living

243

nematodes and it would not he proper to classify them other-
wise. If it happens that they are adaptable to unusual environ-
ments it is but an evidence of the nature of the group to which
they belong.

Because of the numerous difficulties and inconsistencies ap-
parent in any classification of nematode life histories, each of
the authors has followed the system which seemed most logical
to himself. Thus, the nematode parasites of invertebrates are
grouped according to the manner and site of parasitism, be-
ginning with the semiparasitic forms that mature at the death
of their host and feed upon the carcass, then taking up the in-
testinal parasites and finally the parasites of the body cavity.
Most of the invertebrate parasites belong to the Rhabditoidea
and Tylenchoidea in which groups parasitism has arisen so
many times and adaptations are so numerous that life cycles
have little in common with systematics. The vertebrate para-
sites are taken up according to their systematic position since
the large groups show some consistency within themselves and
distinct trends are apparent.

For those who desire an outline after the manner of Seurat,
we have revised his system to include groups with which he did
not deal. The classification is entirely artificial. Nematodes
are divided into the Vagantia or wanderers and the Parasitica.
The Vagantia includes members of the Rhabditoidea, Tylen-
choidea, Monhysteriua, Chromadorina, Enoplina and Dorylai-
moidea. Some representatives of most, if not all, of these
groups have been found in more or less close asspciation as
semiparasites or parasites of plants or animals but the groups
are basically free living. The only known modification in the
life history of such free living forms is the existence of n
persistent stage. Thus far, this stage is known only in ter-
restrial and semiterrestrial forms.

The Parasitica is subdivided into Phytoparasitica and Zoo-
parasitica. All the known nematode parasites of plants belong
to the Tylenchoidea though certain members of the Rhabditoidea
and Dorylaimoidea are commonly found in close association
with plants. In the Zooparasitica the heteroxenous group con-
sists exclusively of parasites of vertebrates including all mem-
bers of the order Spirurida, the suborder Dioctophymatina, and
representatives of the Triehuroidea, Ascaridoidea and Meta-
strongyloidea. Those monoxenous nematodes in which the adult
is wholly or partially free living belong to the Rhabditoidea,
Tylenchoidea and Mermithoidea and are all parasites of in-
vertebrates. The monoxenous nematodes in which the adult is
wholly parasitic include the Strongyloidea, Trichostrongyloidea,
Oxyuroidea and representatives of tlie Rhabditoidea, Meta-
strongyloidea, Ascaridoidea and Monhysteroidea. One com-
monly thinks of the groups with this type of life cycle as ver-
tebrate parasites yet NeoapJectana. and Ccphalobiiim viicvo-
bivorum are rhabditoid parasites of invertebrates, the Thelasto
matidae (Leidiincma, Psciidonymons), Rhigonematidae and
Ransomnematiiiae are oxyuroid parasites of invertebrates while
Longihncca, Rlmbdias, and Sfrontiyloidcs are rhabditoid para-
sites of vertebrates and Oiloiifobiii.i is the lone monhysterid
parasite of vertebrates.

CLASSIFRATIOX OF NEMATODES ACCORDIN'G TO LIFE HISTORY*

I. Vagantia (Free-living nematodes).

1. Without persistent stage.
Enoplidae

(1) Ejwplus commnnis (Marine)

2. With persistent stage.
Rhabditidae

(1) Eliabditis strongyloidcs (Soil, sometimes causing der-
matitis in dogs).

(2) Rhabditis coarctnta (Dung, encysting on dung
beetles).

II. Parasitica (Nematodes deriving nourishment from their
host).
1. Phytoparasitica (Nematode parasites of plants).

A. Vagrant parasites. More or less migratory, often feed
externally, do not permanently localize in part of plant.
Tylenehidae

(1) Criconemoides mutabile — Tagetes erecta (Exter-
nal, roots).

(2) Pratylenchus praicnsis — Cowpea (Internal, roots).

(3) Aphelenchoides ritzema-bosi — Chrysanthemums
(Leaf and bud).

(4) Ditylenchus dipsaci — Narcissus, onions, clover
(Stem, leaf, and bulb).

B. Semivagrant parasites. (Localize during definite pe-
riod of life history.)

Tylenehidae

(1) Angnina (ritici — wheat (Stem and seed).

*In this outline no attempt is made to supply all hosts or to include
all nematode life histories. Only examples are given.

C. Sedentary parasites. (Female does not migrate after
maturity.)
Tvlenchidae

(1)

-Tomatoes, potatoes, tobacco
Sugar beets, potatoes

(3)
(4)

b.

Uctcrodcra maiioiii-
(Roots and tubers).
(2) Heterodera schachtii
(Roots and tubers).

Tylenchulus scmipcnetrans — Citrus plants (Roots).
Botylencliulus reniformis — Cowpea (Roots).
2. ZooparasUica (Nematode parasites of animals).
A. Monoxenous (Only 1 animal host in life cycle).
AA. Adult stage wholly or partially free-living.

a. Only larval stages parasitic or semiparasitic.

aa. Feed in adult stage usually on carcass of host.
Rhabditidae

(1) Rhabditis pellio — Earthworms (Nephridia).
Diplogasteridae

(2) Piisiionchus aerivora — Termites (Head).

(3) Alloionema appendicidatum — Limax aler
(Foot, alternation of generations reported).

Steinernematidae

(4) Keoaplectana bibionis — flies (Intestine),
bb. Do not feed in adult stage.

Mermithidae

(1) Agamermis dccaudata — Grasshoppers (Body
cavity).

(2) Hermit subnigrescens — Grasshoppers (Body
cavity).

(3) AUomerinis myrmecophila — Lasius spp.
(Body cavity).

AUantonematidae

(4) Choiidronema passali — Popiliu.s interriipiiis
(Body cavity).

Tetradonematidae

(.1) Trtradoneiiia plicanx — Sciara coprophila

(Body cavity).
.\dult stage partially parasitic, partially free-living.
aa. Monogenetic (Without alternation of genera-
tions).
AUantonematidae

AUanlonema mirabilc — Hylobiiis abicliis

(Body cavity).

Tylenchinema oscindlae — Frit-iiy (Body

cavity).

Howardula bcnigna — Cucumber beetle (Body

cavity).
(4) Scatoncma wiillceri — Scatupsc ftiscipes (Body

cavity, sometimes reproduces several gen-
erations in host).
(.5) Aphelciichulus diplogaalcr — Ips typographiis

(Body cavity).

PdiaxiU/lrncliii.i ditipar — Ips typographiis

(Body cavity).

Sphacriilaria bombi — Bumbiis tcrrestris

(Body cavity).

Tripius gibbosus — Cecidomyia pini (Body

cavity),
bb. Heterogenetie (With alternation of genera-
tions).
AUantonematidae

(1) Fergusobia curriei — One generation in plant,
Eiicah/ptiis macrorrhynchia (Leaf and flow-
er) other in fly Feriisonina nicholsonia
(Body cavity).

(2) Heterotylenchus abberaiis — One generation
bisexual, other parthenogenetic, both in
body cavity Hylcmyia antiqiia.

BB. Adult stage wholly parasitic.

a. Heterogenetie (Free-living generation sometimes
suppressed).

Strongyloididae

(1) Strongyloides stercoralis — Man (Small in-
testine).

Rhabdiasidae

(2) Rhabdias biifonis — Biifo amrricanus (Luug).

b. Monogenetic.
aa. Reproduce in the host.

Atraetidae

(1) Probst mayria vivipara — Efjuines (Intestine).
Steinernematidae

(2) Neoaplectana glaseri — Japanese beetle (Body
cavity).

Cylindrogasteridae

(3) Longibucca lasiura — Lasiurus borealis
(Small intestine).

Diplogasteridae

(4) Cephalobium microbivorum — Grylhis assimi-

(1)
(2)
(3)

(7)
(8)

244

lis (Intestine).
Monliysteridae.
(.I) f>(/i)ii^ibi«,s- crti — Wliiilo (Baleen)-

(0) Monhi/stira cambari — Crawfish (Gills).

(7) Tripiilium carcinicoliim — OBcnrcinii.i lalntilis

(Gills).
Myenoliidac

(5) iljifiichiis 6o^■f/l(ll— l.eocliea (MiiscU- i!c con-
iioctivo tissue).

I'll, Ho not repioduoo in linst.

aaa. First tliree larval stages fror liviiiK.
.\iieylostoniatidae

(1) ".•lnc.i//(wft)Hi(i (luodcnale — M.ui ^Snlall intes-

tine).
Triehostrongylidae

(2) IIuimoncliKS cniitortiis — Sheep (Abomasum).

(3) Osiraltiocru:ia fitiformis — .\mplul)ians (In-
testine).

Syngamidae

(4) Si/tinaiiiiiK Irachra — Poult ly (Broiulii or
trachea) [Invertebrate, annelid, mollusc nr
insect transport host facultative].

(5) OUulanim tricuspid — Cats (Stomach),
fist moult in parent worm.]

Metastron^ylidae

(6) Dicli/ocdiilitu filaria — Sheep (Bronchi).
(.Vnnelid transport host facultative; 1st -
larval stages do not feed.]

Cosmocercidae

(7) Cosnwccrcoidr.i <hilui — .\m])hibians and
snails (Intestine).

l)bb. Eggs infective to host.
Thelastomatidae

(1) I.iidijtirma appendicutattim — Pfiiplaiicia
amcricana (Intestine).

(2) Psrniloni/mnus spirotheca — HtidrnphUiis pic-
ens (Intestine).

Oxyuridae

(3) Enierobiiis r^ermicularix — >ran (Appendix,
caecum).

(4) Oxyuris eqtii — Equines (Colon).
Heterakidae

(n) Hctcralis paUinae — Poultry (Intestine),
(fi) Ascaridia galli — Poultry (Intestine).
Ascarididae

(7) Ascaris himbricoidcs — Man (Intestine).
Trichuridae

(8) CapiUaria columbae — Pigeons (Small intes-
tine).

(9) Trichnris Irichiura — Man (Caecum).

B Heteroxenous (Two or more animal hosts in life cycle).
a. Eggs infective to intermediate host.
Metastrongylidae

(1) iletaxtronfjyhis clntigafiix — Earthworms —
Swine (Lung).

Heterakidae

(2) Subulura brumpti — Various insects — Poul-
try (Cecum).

Ascarididae

(3) Haphidnsrnri-a canadrnxis — Ernf/otr nymphs
— Minnows — Eunx liiciiin (Intestine). 2 in-
termediate hosts, mandatory.

Thelaziidae

(4) Gongi/Ionema pulclinim — Beetles, roaches —
Pig, sheep, deer (Esophagus and mouth).

(')) Spirocerca liipi — Dung beetles — Dog (Esoph-
agus).

(6) Ascarnps strongylina — Dung beetles — Swine
(Stomach).

(7) Physocrphalux srxnlatus — Dung beetles —
Swine (Stomach).

Spiruridae

(8) Tetramercs crami — Araphipods — Duck (Pro-
ventriculus).

Acuariidae

('.0 ChrUospnma hamulosa — Grasshoppers —
Poultry (Gizzard).

(10) Krhiniiria nncinala — Cladocera (Daphnia) —
Duck (Fore and mid-gut).

(11) Disphoiiinr .npiralis — Isopods — Poultry
( Esophagus iind crop).

(inathostomatidae

(12) Ilarlirlia (inUiiianim — Termites — Poultry
( Sni.'ill intestine).

Trichuridae

(13) CapiUaria annulala — .\nnelid transport host
obligatory — Chickens (Crop).

Cystoopsidae

(14) Ci/stoopsis- acipcnxeri — .\mphii)ods — Stur-
geons (Skin).

Eustrongylididae

(1.")) Jitistrotifnilides ignotu.i — .' Crustacean — Fun-
diilii.s diaplianus — Ardea herodiax (Gizzard).
Dioctophymatidae

(16) Dioctophyma renale — ? Crustacean — ? fish
— Man, dogs, mink (Kidney).
. Larvae infective to intermediate host,
aa. Enter final host per os.
Dracunculidae

(1) Dracunculiis medinensis — Cyclops — Man
(Under skin).

Philometridae

(2) Philnmclra nodulosa — Cyclops — Catostomus
cnmmrrsoilii (Lip).

(3) Philometra fujimotoi — Cyclops — Ophicepha-
hts argils (Fin).

Camallanidae

(4) CamaHaniis sxoeeti — Cyclops — Ophicephahis
gachiia (Intestine). Second intermediate
host, small fish? obligatory.

Pseudaliidae

(5) Murllrrius capillaris — Molluscs — Sheep and
goats (Lung).

Spiruridae

(6) Habronema mitscac — Munca domestica —
Equines (Stomach).

(7) Habronema microstoma — Stomoxys spp.
— Equines (Stomach).

(8) Draschia megastoma — 3[ii.ica domestica —
Equines (Stomach).

Gnathostomatidae

(9) Spiroxys contorta-
Turtles (Stomach),
host not mandatory.

(10) Gnathostoma spinigerum — Cyclops — Fish or
snakes — Felidae (Stomach). Second inter-
mediate host mandatory.

Ascarididae

(11) Conlracaecum spiculigerum — Minnows — Car-
nivorous fish — Cormorant (Proventriculus).
Second intermediate host mandatory.

(12) Eaphidascaris canadensis — Erogon nymphs —
Minnows — Esox iitciiis (Intestine). Second

intermediate host? mandatory.
Trichincllidae

(13) Trichinella spiralis — Eat, pig, man (Intes-
tine). Hosts serve both as intermediate
and final host.

bb. Enter final host through skin.
Dipetalonematidae

(1) Wuchercria bancrofti — Mosquitoes — Man
(Lymphatic system).

(2) Onchocerca volvnlus — Sinuilium damnosiim —
Man (Subcutaneous).

(3) Onchocerca ceriicalis — Ciilicoides nebcculo-
sis — Equines (Cervical ligament).

(4) Dirofilaria immitis — Mosquitoes — Dogs
(Heart).

Cyclops — Minnows —
Second intermediate

245

CHAPTER V

LIFE HISTORY (ZOOPARASITICA)

Parasites of Invertebrates

J. R. CHRISTIE, U. S. Horticultural Station, Beltsville, Md.

Introduction

There are many different types of association between nema-
todes and other invertebrates and it is difficult to draw a line
between what should and what should not be regarded as para-
sitism. Most of the nematodes that live within the bodies of
invertebrates are customarily referred to as parasites though
there is little evidence that some of them interfere materially
vpith the well-being of their "hosts." We know very little,
however, about the effects of these nematodes on the animals
that harbor them unless the manifestations are pronounced and
obvious. The only feasible procedure is to regard as eligible for
inclusion in this chapter all nematodes that regularly spend
part of the life cycle within the bodies of invertebrates regard-
less of the precise character of the association. Species for
which vertebrates serve as definitive hosts and invertebrates
only as intermediate hosts are dealt with in the following
chapter.

In general the parasites of invertebrates and those of verte-
brates are not found in the same phylogenetie groups and in
those cases where both belong to the same group the vertebrates
involved are almost always amphibians and reptiles. However,
the Thelastomatidae and the Oxyuridae have very close affini-
ties.

Arthropods, annelids and mollusks are the invertebrates most
commonly parasitized by nematodes though scattered cases have
been reported where other invertebrates, even nematodes them-
selves, serve as hosts. There are surprisingly few records of
marine invertebrates harboring nematodes and most of these
apparently deal with cases where the association is erratic or
accidental or where some vertebrate serves as definitive host.

Included among the nematodes harbored by invertebrates are
species where a parasitic mode of life is only now being ac-
quired and others where it is of great antiquity. There is great
diversity in the types of life cycles and to simplify discussion
and facilitate comparison the nematodes are divided into three
groups.

The first of these groups is made up of nematodes that are
more or less closely related to free-living species and in the life
cycles we often find a combination of saprophagous and "para-
sitic" habits. In one line of evolutionary development the
nematodes live and reproduce in the carcass of the "host," to
the death of which they may or may not have contributed. Life
cycles are simple, perhaps the most outstanding feature being
the frequent occurrence of dauer larvae,* a characteristic that
has been carried over from a free-living to a parasitic mode of
life. Another line of evolutionary development seems to have
culminated in a life cycle where the nematode may pass through
one or more free-living generations, then gain entrance to the
host and pass through one or more parasitic generations.

The second group comprises tliose nematodes, not included in
the first group, that inhabit the alimentary tract. Life cycles,
so far as known, are simple. With perhaps an occasional ex-
ception (i. g., Ccphalobium microbivoriim) , only the egg stage
occurs outside the host, a characteristic shared by verj' few
species in the otlier two groups.

The third group includes the body-cavity and tissue para-
sites. In contrast to the fir.st group, these nematodes are highly
specialized, obligate parasites and, in contrast to the second
group, they pass, at the most, only a transitory period in the
alimentary tract of the host. Five families are included in
this group. The Drilonematidae and Mycnchidae have received
little attention and our knowledge regarding life cycles is very
meager. The Tetradoneraatidac, Mermithidae and Allantone-
matidae have been somewhat more adequately studied. The
nematodes belonging to these three families have been parasites
for a very long time and many of them have complicated life
cycles that are highly adapted to individual requirements. Of

*'nie term dauer larva is used in tliis te-\t to designate a larva, in a
particular stage of development, that is especially adapted to withstand
adverse conditions and, when a dauer stage is not obligatory, that differs
from a larva of the same stage that develops when conditions are favor-
able and food is abundant. The term is not new, having been used by
Fuchs and others with approximately this same meaning and, while not
of classic origin, it is short, expressive, appropriate and useful. Dauer
larvae are of common occurrence in the Rhabditidae and Diplogasteridae
and are more characteristic of free-living than of parasitic species, hence
the term is not synonymous with "infective larva."

the various factors that have influenced these life cycles, two
stand out as being of great importance.

One of these factors is the necessity for the infective stage
to reach and gain entrance to the host. This, of course, is a
requisite in the life cycle of every parasite but for the allan-
tonematids and merraitliids there are certain restricting condi-
tions with which many of the others do not have to contend, at
least not to an equal extent. Some of the hosts are insects that
develop in seasonal cycles and where the total life span of the
individual may be only a few months. It is frequently neces-
sary that the parasite enter when the host is in a particular
stage and this stage may be available only at restricted times
of the year. As a result the life cycles of many of these para-
sites have become closely correlated with the life cycles of their
respective hosts.

The other factor is the ability of the nematode to take food
only during restricted periods. The fact that for many of these
parasites the free-living stage may be of considerable duration
and that during this period the nematodes take no food, but,
nevertheless, pass through important phases of the life cycle,
has had a profound effect on development. In many cases the
larval mermithid, during a comparatively short period of para-
sitic life, must make a phenomenal growth and store sufficient
nutrient materials to carry the adult through its relatively
long, free-living period of sexual activity and reproduction. The
larval allantonematid that develops to maturity outside the host
after only a very brief period of parasitic life, must exercise
the strictest economy in the utilization of its limited supply of
stored nutrients. Since, as a rule, only the female again be-
comes parasitic, the male must produce and mature its sperma-
tozoa though the production and maturation of the eggs by the
female is postponed. There can be little or no increase in
l)ody size during this free-living period, hence the adult, im-
pregnated female, after entering a new host, undergoes a pe-
riod of rapid growth. In the Sphaerulariinae a prolap.sus of
the uterus has resulted through the inability of the small, un-
derdeveloped bodj' of the young female to keep pace with the
rapidly growing reproductive organs.

Novitious Parasites and Semiparasites

Among these nematodes two lines of evolutionary develop-
ment seem to stand out more or less distinctly though it is ob-
viously improbable tliat they account for the origin of all the
different types of parasitism or semiparasitism encountered in
tills heterogeneous group.

One line of evolutionary development appears to have been
initiated when certain saprophagous nematodes utilized other
invertebrates, frequently saprophagous insects, as vehicles for
transportation. These "hitchhikers," first seeking protection
from desiccation in crevices on the external surface, eventually
entered the bodies of their "hosts." In the life histories of
species representing an intermediate step in this line of develop-
ment, larval nematodes, after gaining entrance to the body of
the "host" and becoming established therein, do not at once
grow to maturit3' and reproduce but remain in a more or less
quiescent condition. These larvae do not appear to interfere
materially with the life processes of the animal that harbors
them but when the animal dies from otlier causes the nematodes
immediately resume development and reproduce in the carcass.

In some cases, however, this type of relationship has evolved
to a point where it is no longer passive but where the nema-
todes are an important factor in bringing about the death of
the animal whose body they enter. Even though present in
small numbers, some species of NeoapJectana are said to kill
their insect hosts in a very short time.

The parasitic or semiparasitic relationship between these
nematodes and tlicir respective "hosts" is not always obliga-
tory. Johnson (101,3) concluded that entrance into the body
of an earthworm is not necessary in the life cycle of Rhahditis
maupasi but if larvae, during their sojourn in the soil, find suit-
able decaying organic matter they will develop and reproduce
therein. Neither is Pristionchus acrivora dependent on en-
trance into a termite or some other insect to complete its de-
velopment as it has been found reproducing in a number of dif-
ferent habitats including decaying plant tissues. Neoaplectana
fliaseri, on the other hand, appears to be an obligate parasite
that, in nature, develops only after entering the living body of
its insect host.

246

Most of llu'SO iioiiiatoilos :uo liisrwwil :iiul l'i'in;iU'.s inodiici'
fertile I'KKS only after eopulntioii. Males are usually somewhat
loss numerous than females, reaeh maturity a little quicker,
ami do not live quite so \o\\g. Aeeordiug to Johnson, females
of KhabdiU.i maiiimni usually, thouRh not always, reproduee
without males. In nmny speeies of this uroup a female may be
oviparous when young but toward the end of life sonio of the
last ecds produced may be retained and hatch in the uterus.
'Pile resultiiiR larvae may not escape thr(iii);h the vulva but un-
diTRo part of their development within the mother nematode,
eonsumiuf; her internal orjrans and convertint; her into a brood
sac. Incidentally, this same mode of reproduction is character
istic of many free-living species of Diplogastcr, Rhabdilix and
related genera.

The sec(uid line of evolutionary development referred to above
may have been initiated when, during periods of adversity, cer-
tain sai'rophagous nematodes, seeking refuge and succor, en-
tered and temporarily dwelt within the bodies of other inver-
tebrates. In the case of nematodes in this category parasitism
apparently does not ordinarily result in the death of the host
nor are the parasites able to live in a decaying carcass. Usually
these nematodes either inhabit the alimentary tract of the host
(e. g., Aiuiiostoma limacis) or arc associated with its reproduc-
tive organs (e. g., " Angiostoma" hclicis). For at least one
species (i. e., AUoioncma appcndiciiJaUi) an alternation of one
or more parasitic generations with one or more free-living gen-
erations has become a more or less regiilar procedure.

Rii.\BmTis M.\irpAsi Caullery and Seurat, 1919 (Syn. R. iiclUo
Butschli, 1S73; not Schneider, ISOG). Larvae of Shabtlitis
maiipasi are found in the nophridia and coelom of living earth-
worms. For Liimbricus terrcfitri.i L. the incidence of infection
is frequently very high and at least several and perhaps many
other species harbor these nematodes more or less frequently.

Larvae are found near the uephridiopore in the dilated, muscu-
lar termination or "bladder" of the neiihridial tube. Often
nearly every tube is inhabited, the number of worms in each
varying from 2 or 3 to 12 or more. Also larvae may occasion-
ally be found in the seminal vesicles. When in these above
mentioned locations larvae are in an active condition and not
ensheathed. Johnson concluded that these inhabitants of the
neiihridia are not necessarily confined to this location through
out the life of the earthworm but may move out into the soil
and later go back through the nepluidiopores into the same or a
different earthworm.

Larvae occur also in the coelom and these are usually en-
sheathed and inactive (Fig. 165C). Occasionally a larva may
be embedded in the muscles of the body wall or encysted on a
septum. Frequently several larvae are embedded in a brown,
oval body composed of cysts of the sporozoan. Monocystus, and
various earthworm tissues. Such bodies are most common at
the posterior end of the coelom.

There is no evidence that the presence of these larval nema-
todes is detrimental to the annelid. So long as the earthworm
is alive the nematodes remain in a larval stage but when the
earthworm dies they quickly grow to adults (Fig. 165 A & B)
and reproduce in the carcass. Otter (1933) concluded that a
female lives from 7 to 10 days after reaching maturity and lays
from 150 to 300 eggs. Males, in his opinion, live about a third
as long as females. No doubt several generations occur before
the food supply is exhausted though Johnson was uncertain on
this point. After the body of the earthworm is consumed large
numbers of larvae move out into the soil where they live await-
ing the opportunity to enter another earthworm. Larvae from
the soil are said to be in the same .stage as those from the
nephridia, but what this stage is has not been stated.

With regard to the method of entering the earthworm, John-
son writes: "Those that enter by the nephridiopores take up
their position in the terminal, bladder-like part of the nephridia.
Those that use the spermiducal apertures travel up the vasa
deferentia and occupy the seminal vesicles. Lastly, those that
pass in by the dorsal pores and the oviducal apertures find them-
selves in the coelom, where, being attacked by the amoebocytes,
they encyst. These encysted larvae coated with amoebocytes are
worked backward by the movement of the worm till they come
to rest in the tail end of the worm, where, together with other
foreign bodies, such as cysts of Monocjistix and discarded setae,
and with masses of dead brown-colored amoebocytes, they are
compressed and cemented into the brown bodies which are found
there."

According to Keilin (1925) the accumulation of foreign bod-
ies in the posterior segment of an earthworm may induce the
development of a stricture that will sever this distended ter-
minal i)ortion from the rest of the body. The detached portion
then decomj)oses and in this manner M. maupnsi and other
coelomic j)arasites of the earthworm may be liberated.

Males of E. maupasi are much fewer in number than females.
Although Johnson did not observe copulation, his rearing ex-

periments lead him tu ccincluiii' that most females are lier-
ma))hro(litic but that occasionally females occur that are able
to reproduce only after being fertilized by males. Otter, who
observed co]>ulaticin and agrees, in the main, with Johnson,
writes that li. maupa.ii "may thus be considered to be one of
those species of Rliabdilis in which hermaphroditism is in a
very early stage, and in which funetion.al males, females, and
hermaiihrodite females, exist side by side in fluctuating pro
jiortions. ' '

I'Eu.sTiONCiiu.s AKRIV0K.\ (Cobb, 1916), was first found by
Merrill and Ford in the heads of termites, /.rHro/criiif.s- /»ci/».r/».s'
Rossi,* collected ne.ar Manhattan, Kansas. Under natural con-
ditions the nematodes varied from 0 to about 75 per insect.
After experimental termites had been kept for 4 days in soil
heavily infested with P. acrivora, the average number of nema-
todes per insect was 46.0 while termites used as controls
averaged about 3 nematodes per insect. IIow the nematodes
enter or why, in living termites, they are found only in the
head are points that have not been determined. The parasites
do not reach nuiturity in living hosts but when the termites
are heavily infected they become sluggish and die, whereupon
the nematodes reproduce in the carcass. Hence, in this instance,
the relationship is not purely passive.

Merrill and Ford were able to rear this nematode in water
cultures with various substances supplied for food, preferably
the macerated bodies of insects. Eggs hatched in about 18
hours and the adult stage (Fig. 165 .T) was reached in about
2 days. The complete life cycle from egg to egg required about
4 to 5 days but after beginning to lay eggs an adult female
usually lived for 12 to 13 days. During a period of 13 days
one female, while under observation, copulated with 7 males and
deposited 317 fertile eggs and 14 infertile eggs. Males were
somewhat less numerous than females. They lived for about 19
days and one male, while under observation, copulated with 10
different females.

Toward the end of life a female becomes sluggish and eggs
are not extruded but hatch in the uterus. W'hile the resulting
larvae may sometimes escape through the vulva they usually
remain in the mother nematode, feeding on her internal organs.

Since Merrill and Ford's investigations nematodes identified
as P. aerivora have been reported from various other habitats.
They have been found in other termites, usually located in the
head while the insect is alive. They have been found in dead
pupae of the corn ear worm, Hcliotliis armigcra (Hiibn.), and
in dead pupae of the rose leaf beetle, Kodonota puncticoUia
(Say). They have been found in grasshopper egg masses where
they were reported to have been destroying the eggs. On sev-
eral occasions they have been found in decaying plant tissues.
However, the populations from these different habitats may
represent different strains or, perhaps, even different, though
closely related, speeies.

The peculiar habit of swallowing air, to which this nema-
tode owes its specific name, is shared by several species of Dip-
Jogastcr and Khabditis. When mounted in water on a micro-
scope slide, one of these nematodes may place its head against
the surface of an entrapped air bubble and air can be seen as
it passes down the esophagus to the anterior end of the intes-
tine where it is quickly absorbed. According to Cobb (1915)
some of these nematodes can ingest their own volume of air
in the course of an hour or two. The swallowing of air is ac-
complished by the usual rhythmic muscular movements of the
esophagus. During the first muscular movement a small bubble
of air passes quickly from the mouth to the median pseudobulb
where it stops. At the next muscular movement the bubble
passes on into the intestine while another simultaneously passes
from the mouth to the median pseudobulb. This may continue
uninterrupted for a considerable period of time.

Neo.\plectan"a bibionis Bovien, 1937, was studied by Bovien
(1937) who found it in Denmark associated with the dipterous
insects Bibio ferruginatns (L.), B. hortidaniis (L.) and Dilo-
phim rtdgari.i Meig.

An interesting and significant point in the life cycle of this
nematode is the occurrence of dauer larvae (Fig. 165 G). These,
according to Bovien, are in the third stage. A dauer stage is
not obligatory but occurs only when environmental conditions
arc unfavorable to enable the nematode to persist through pe-
riods of adversity. Dauer larvae are relatively sluggish and
are usually enclosed in a partly separated cuticle though this
may be lost before the end of the dauer stage. These larvae
are easily distinguished from third-stage larvae that develop
under favorable conditions being slenderer and differing in
other morphological details. Bovien found dauer larvae cling-
ing to the surface of adult flies and being transported by them.

The various host insects become infected by swallowing these
dauer larvae which, on reaching the alimentary tract, remain

*Regarded by Snyder, according to Van Zwaluwenburg (1928, p. 9),
as either Keliruliternie/t tibiaUjt Banks or R. claripennia Banks.

247

Fig. 165. NOVITIOrS PARASITES AND SEMIPARASITES

A-C — Rhabditw maupasi (A — Adult female; B — Adult male; C —
Larva escaping from *'cyst"). D-H — NeoapUctana bibinni.^ (D — Adult
male; E — Adult female; F — Larva that developed under favorable con-
ditions; G — Dauer larva of same stage as F; H — Pigmy female). I-J —
Pristioiu'hiis aerirora (1 — Newly hjitehed larva; J — Adult female). K —

Diptoffaster labiata, dauer larva. L & JI — AU-oionema appendicuUitum
( L — Adult female of parasitic generation ; M — Adult female of free-
living generation). A-C. after Johnson. 1913; D-H, after Bovien,
1937; I-K, after Merrill and Ford, 1916; L & M, after Claus, 1868.

;24«

iiiiclmiiKcd, :i|>))aii'iitly liaviiiK iio adverse effeot on the inswt.
WIu'ii rvt'iitnally the insect dies, presunmlily from otlier causes,
the larvae move into its tissues and jiroceed in development,
IiassiuK tlmiUKli several penerations and <|nickly IniildiiiK uji a
large iiopulation. When the carcass has lieeii consumed youug
nematodes move out into the soil and develop into dauer larvae.

Although Hies become infected while in the larval stage, if
the nenuitodes, on reaching the intestine, are wholly innocuous,
many of the insects must carry their infection on into the adult
stage. Rovien is not very lucid on this jioint Init he merifioTis
finding nematodes in living 1]\ i)upae, on one occasion in tlu'
tiody cavity.

Bovien concluded that development from egg to egg laying
female requires about 4 days. A young female is oviparous but
some of the last eggs laid by an old fcm.'ile liatch within the
uterus. Kach female usually produces somewhat in excess of
-"" eKRS.

It is not strictly necessary that N. bibioni.i enter living in-
sects as Rovien was able to rear several generations on dead
insects of different sjiecies if fresh cadavers were periodically
provided. Several generations could sometimes be reared on
egg albumen.

Gravid fenuiles (Fig. IG.') E") usually attain a length of up
to ■> mm. but Rovien reports finding mature, rci)roducing fe-
males that failed to reach a length of 1 mm. (Fig. IG.l H), per-
haps due to some nutritional deficiency. Between these dwarfs
and females of maximum stature numerous intermediate sizes
were found.

NEO.\PI,E(.-r.\NA GLASERI Steiner, lili!!1, was first fovind in dead
larvae of the .Japanese beetle, ropillid japonica Newni., col-
lected in New Jersey and is best known as a jiarasite of this
insect. However it has been demonstrated that this nematode
will infect larvae of the Enrojiean corn borer, Purausta nu-
bilalis (Hiibn.) and coleopterous larvae belonging to at least
nine genera including the white fringed beetle, Pnntomorus tcu-
colnma (Boh.).

The life historv of .V. glascri has been investigated by Glaser
(1932) and by Glaser, McCoy and Girth (l',t40). The following
account is based on their results that were secured, in part by
using Japanese beetle larvae as experimental hosts and in part
by rearing on culture media. It is lielieved that the behavior
of this nematode is not materially different whether growing on
culture media or in the various susceptible insect hosts.

Japanese beetle grubs acquire their infection by ingesting
third stage, infective larvae of the parasite. On reaching the
alimentary tract the larvae immediately develop to maturity
and copulate. A female will not produce offspring unless fer-
tilized by a male. The female is ovoviviparous, eggs hatching
within the uterus. Larvae may remain within the uterus and
move about for a considerable period but eventually pass out
through the vulva one at a time. If a female dies before all
larvae are l)orn those remaining may undergo partial develop-
ment within the dead body. Each normal-sized female produces
a total of aliout 1-" offspring and a generation under optimum
conditions requires about ■) to 7 days. By the time the first
generation of offspring liave matured the insect is usually
dead whereupon its entire body is invaded. The nematodes
usuall.v pass through two more generations consuming the car-
cass and leaving only a sac formed by the skin and head cap-
sule and filled with a thin fluid swarming with larval parasites.
In a few cases Glaser was able to infect newlj' killed beetle
grubs but he concluded that the nematodes do not enter and
multijily as readily in cadavers as in living insects.

With regard to the virulence of this parasite, Glaser, McCoy
and Girth (lit-tO) write that "occasionally an insect Iiost be-
comes parasitized very lightly, so that only one nematode be-
comes successfully established. This individual may be of either
sex, and while if frequently (if not always) causes the death
of the host, there is no reproduction."

McCoy, Girth and Glaser (19.38) report that exceptionally
large females of X. glaseri are occasionally found in beetle lar-
vae though never on cultures. Such individuals may develop
an enormous number of eggs, one giant female producing 1,420
larvae. When offsprings of a giant are reared to maturity on
cultures only normal sized females are obtained. >rcCoy, Girth
and Glaser concluded that fecundation at a late period in de-
velopment and abundant food are factors contriliuting to the
production of these giant females.

So long as conditions are favorable and abundant food is
availalile, the life cycle of N. glanni, according to Glaser, McCoy
and Girth (1940), is completed in three molts the third stage
being omitted. When conditions are unfavorable, as when the
carcass of the beetle larva has l)een consumed and food is ex-
hausted, the young parasites develop into third stage, dauer
larvae. At the end of the second stage growth ceases, the ali-
mentary tract is emptied, and, as a result of certain niorphologi
cal changes, the body becomes more slender. The second molted

(Utide is retained hcru'c the d.aui r Ijirva is ensheathed though
the sheath is not very tenaci(ni8 and may soon be lost. These
dauer larvae escape into the soil where they are able to persist,
in a more or less .'ictive condition, for at host S'i years.

• ■l.'L.si'r and his coworkers have reared this lU'inatode success-
fully on Petri dish jilates of veal infusion agar flooded with
living yeast, on jiofato culture medium, and on veal l>ulp
medium. These investigators found that "distiiu't cultural
characteristics occur in nematodes from different insect cada-
vers, . . . There is a slow decline in fecundity of the cultured
nematodes, some 'strains' dying out after .I or 6 transfers,
while others continue to yield good cultures after 20 or more
ti.-insfers. " If beetle larvae are infected with nematodes from
cultures that are dying out .and several generations are passed
in the natural host, the nematodes can again be reared success-
fully on cultures, the length of time before the cultures again
die out depending, to some extent, on the number of genera-
tions iiassed in beetle larvae.

Am.oionkma afpkndicui-atum Schneider, Is.'ill, has on sev-
eral occasions been found within the bodies of slugs. Schneider
found it originally in Arioii atrr (L.) and Clans (1890), who
investigated its life history, secured his material from the same
host. The life cycle of this nematode appears to represent a
somewhat different line of evolutionary development than the
life cycles already discussed. According to Claus (1890), one
or more free-living generations alternate with one or more
jiarasitic generations, both males and females (Fig. Ifi.'i L & M)
developing in each instance. Individuals of the parasitic gener-
ations leave the host .inst before reaching maturity by boring
their way out through the foot. On reaching the exterior they
nuifure, copulate and produce progeny that usually develop as
free-living individuals. Maupas (1899) found that larvae of
the free-living generation undergo the usual four molts and
reach maturity in about 3'4 days.

A regular alternation of a free-living with a parasitic gen-
eration does not necessarily follow, however, as there may be
several consecutive free-living or several consecutive parasitic
generations. There are usually consecutive free-living genera-
tions as long as conditions are favorable but when conditions
become unfavorable the nematodes "encyst" and these "en-
cysted" larvae will continue development only when taken into
the bod.v of a slug. According to Maupas, "encysted" larvae
that fail to gain entrance to a slug become exhausted and die
in about 4 months. Precisely how the nematodes enter the slugs
and wlietlier or not, in event of consecutive parasitic genera-
tions, females mature without leaving the host, are points that
seem to need further elucidation.

Claus found certain morphological differences between corre-
sponding stages of the two generations. Adults of the parasitic
generations are much larger than adults of the free-living gen-
erations and parasitic larvae, in the later stages of develop-
ment, are said to possess two long, ribbon-like, caudal append-
ages not present on free-living larvae of the corresponding
stage.

Other Species. Diplogaster labiala Cobb (in Merrill and
Ford, 1916) was found in the elm borer, Saperda tridciitala
Oliv., collected near Manhattan, Kansas. This nematode repro-
duces in the intestine of the living, adult liorer and may ac-
cumulate in sufficient numbers to rupture the gut and kill the
insect. Infected female beetles are usuall.v sterile. When reared
on cultures, Merrill and Ford (1916) found that eggs hatched
in from 30 to 32 hours and the nematodes matured in 7 to 10
days. Oviposition began from 2 to 4 hours after copulation and
lasted for about 2 days with an average output of^ seven eggs
per female. Only a few individuals were seen copulating a sec-
ond time. Apparently dauer larvae (Fig. lO."! K) develop when
conditions are unfavorable.

Xcoaplectana affinis, Bovien, 1937, was found in Denmark
where it infects larvae of the same insects that harbor Neoaplrc-
lann bibinni.s, i.e., Bibio fcrnif/iiiatii.s, B. hort iilanifs and VUo-
pitus vuli/aris. These two nematodes were differentiated mor-
phologically by Bovien (1937) only on the basis of males and
dauer larvae, the life cycles and behavior of the two being al-
most identical. Bovien made one observation, however, that de-
serves mention. When in the intestine of any of its three nat-
ural hosts mentioned above, .V. affinifi remained in the dauer
stage and was apparently innocuous so long as the insect re-
mained alive. When two larvae of a beetle, Tcirplwru.i sp.,
were experimcntall.v infected, they became moribund in a few
days and dissection revealed several adult and prcadult nema-
todes in the body cavity of each beetle. This observation sug-
gests that whether or not A', affinis remains passively in the
intestines depends on the insect involved.

A mode of life on the border line between saprophagous and
parasitic is characteristic of other nematodes, probably of a
considerable number. Other species of Neoapleclana are known
to exist but life cycles have not been investigated. Steincrncvxa

249

hravssei (Steiiier, 1923), found in the intestine of the wasp,
Cephalcia abictis (L.), is so closely related to the genua Neo-
aplectana that a similar mode of life is suggested but verify-
ing information is lacking.

Among the rather numerous and diverse nematodes that have
been reported from snails and slugs are representatives of the
Angiostomatidae and Cosmoeercidae, two families that include
also parasites of Amphibia. The four species mentioned below
will serve as examples but very little information is available
about life cycles. Angiostoma limacis belongs to the Angiosto-
matidae while the other three, according to Chitwood and Chit-
wood (1937), probably belong to the Cosmoeercidae.

Angiosioma limacis Dujardin, 184.5, has, on at least two oc-
casions, been found in the intestine of Arion ater (L.) (Syn.
Limax rufa) where, apparently, it reaches maturity. Chitwood
and Chitwood (1937) report finding a very closely related spe-
cies in the intestine of a salamander, Plctliodon cinerens.

Ascaroides limacis Barthelemy, 18.38, was found in eggs of
Deroceras agrestis var. cincracea Moq. Tand. (Syn. Limax
griseas), each infected egg containing one to four larval para-
sites. Barthelemy (18.">6) determined that the nematodes were
already present when the eggs were deposited. Apparently the
adult of this parasite has not j'et been studied.

"Angiostoma" helicis Conte and Bonnet, 1903, was secured
by its discoverers from the slug, Helix aspersa (Miill.), where
it occurred in the genital organs, especially the oviducts and
seminal vesicle, but not elsewhere in the body. Conte and Bon-
net (1903) concluded that the parasite is passed from host to
host during copulation.

Trionchonema riisticum Kreis, 1932, was secured from the
land snail, Folygyra espwola Bland. Presumably this parasite
is an inhabitant of the alimentary tract though the location
\\-ithin the host was not specified. Kreis (1932) refers to the
development of a "filariform" larva and suggests the possibil-
ity "that there is still another stage of development, perhaps
a rhabditiform larva, which could not be found and which may
perhaps be free-living. ' '

Parasites of the Alimentary Tract

All nematodes belonging to the families Thelastomatidae and
Rhigonematidae and to the subfamily Ransomnematinae are
parasites of the alimentary tract and one finds an occasional
species of the family Diplogasteridae that has acquired this
mode of life.

The thelastomatids are parasites of insects and myriapods and
scattered through the literature are descriptions of between 60
and 70 species but usually not much other information. How-
ever, studies by Galeb (1878), Dobrovolny and Ackert (1934),
and others indicate that most of these species probably have
about the same tj-pe of life cycle and that it is comparatively
simple. Eggs pass out of the host with the feces. Eggs do not
hatch in the intestine to reinfect the same host but must first
undergo some development on the outside to reach an infective
stage. The various arthropod hosts acquire their parasites by
swallowing these infective eggs.

In the genus Pseudonymous, the species of which are parasites
of aquatic beetles, the egg is provided with two entangling ap-
pendages, the so-called spiral filament (Fig. 13.") R, p. 176)
which, presumably, enables the egg to hang on aquatic vegeta-
tion thus increasing its chance of lieing ingested. From two to
four eggs of Biiicma biiirma and B. ornaia (Fig. 166G) are en-
closed in an outer capsule or case of loose texture formed, ap-
parently, by the entangling and anastomosing of polar fila-
ments. The purpose of this adaptation is obscure.

The Rhigonematidae and Ransomnematinae are small groups
with only a few species each. It seems proliable that life cycles
of these nematodes are not materially different from the type
of life cycle characteristic of many thelastomatids though, ad-
mittedly, such a statement is wholly conjectural.

Cephalobium microbivorum Cobb, 1920, a member of the
Diplogasteridae, inhabits the intestine of the black field cricket,
Gryllns assimilis (Fab.), Avliere it may occur in numbers up to
30 or more. Infected crickets have been collected in Virginia
and Kansas. In the region of Manhattan, Kansas, according
to Ackert and Wadley (1921), there are two races of this in-
sect each having one brood a year. One race matures during
April and May and overwinters in the nymph stage while the
other race matures during August and September and over-
winters in the egg stage. These investigators found that in
autumn over 85 per cent of the adults of the latter generation
were infected, the incidence being somewhat higher in female
(about 90 percent) than in male crickets (about 70 percent).

Eggs of C. microbivorum are usually deposited in a four-cell
stage and pass out of the host with the feces. Ackert and Wad-
ley concluded that probably eggs hatch after being voided and
that a cricket becomes infected by ingesting larval nematodes

perhaps after these have undergone a brief period of free-living
development. The two races of crickets provide the parasite
with suitable hosts throughout most of the year and, no doubt,
some of the nematodes pass the cold season in overwintering
nymphs. The presence of this nematode has no obvious effect
on the well-being of the cricket.

Leidynema appendiculatum (Leidy, 18.50) Chitwood, 1932.
— The life history of Leidynema appendiculatum, which was in-
vestigated by Dobrovolny and Ackert (1934), is probably more
or less typical of many thelastomatids and will serve as an
example of the family. This nematode is a parasite of the
cockroaches, Blatta orientalis (L.) and Feriplaneta americana
(L.). Out of 259 individuals of P. americana collected by
Dobrovolny and Ackert at Manhattan, Kansas, 90 harbored this
parasite in numbers of from 1 to 36 per host.

The egg, deposited in a one to a four-cell stage, passes out
of the insect with the feces. After extrusion it undergoes a
short period of development and a tadpole-like larva (Fig.
166 A) is formed. The larva is at first motile, wiggling and
squirming about, but becomes inactive as the infective stage
(Fig. 166 B) is reached. Dobrovolny and Ackert found that
at 37° C. eggs reach this infective stage in 3 to 7 days and

Fig. 166. PARASITES OF THE INTESTINE

A-F — Leidynema appendiculatum (A — -Egg with active embryo; B —
Egg with larva in resting stage; C — An early stage larva, presumably
second stage; D — Larval female showing intestinal diverticulum be-
ginning to form; E — Adult male; F — Adult female). G — Binema or-
naia, egg capsule. A-P, after Dobrovolny and Ackert, 1934.

250

that I'KK" iMiiitsiiiiinp motile laivm- :iro not infective. Alieala
(1!<34) found tliat tlio larva of IlUillirola bhiltar, a closely
rolatod llielastoniatid, molts in the okr before reaeliins the in
feetive since and while Dotirovolny and Aekort do not men-
tion the matter their liRnres indieate that L. (ipixniliciilalum
undergoes a similar molt. If kept moist at room temperatnre
and in sniidned lifrht infeetive vjxiix remain viable for a eonsid
erable time bnt are killed by jiroloiiK'ed exposnre to direct snn
light. Infective egRs are inRcsted by the insects and li.itih in
the posterior part of the midgnt.

Dobrovolny and .\ckert kept heavily infected cockroaches in
enptivity for more than a year and -saw no evidence that tlu'
insects were markedly affected by the parasites.

Body Cavity and Tissue Parasites

This (jroup imindes wh.it are, i)erluiiis, our oldest jiarasitic
nematodes in the sense that their ])riiKenitors w<'i'e t\w first to
assume a parasitic mode of life and throuKli the aRcs they have
become very highly adapted to this way of living. Some of the
allantonematids have become almost incrednlously si)eciali/.ed in
morplK)logy, liehavior and host parasite relationships and among
them are to be found some of the most unusual nematodes
known.

MVEXCIlin.VE

This is a small and comparatively little known group of nema-
todes that are parasites of amphibians and leeches. The sys-
tematic position of the family is somewhat questionable but
investigators who have studied the group regard it as probably
related to the Tylenchidae. Both se.xes arc characterized by a
medium sized stylet without basal swellings and by a peculiar,
sucker-like organ situated on the mid ventral surface about one-
fifth of the distance from head to tail, this latter presumably
marking the position of the excretory pore. Two species have
been reported from leeches.

MvENClirs BOTHRVOPHORUS Schuberg, 1004, was found in
iTcrnuiny ]>arasitizing the leech, KnipobthUit ortocuIaUt (L.)
(Syn. S'cpliclix viilgari.s (Miiller) iloi). Tand.). Different stages
of the nematode, including sexually mature individuals (Fig.
107 .-V & B), occurred in the connective tissues and larvae were
found within the muscle cells (Fig. 167 C). Adults were also
found in the cocoons of the leech. All the details of the life
cycle are not known with certainty but Schuberg and Schroder
(1904) concluded that larvae undergo the first part of their
development within the muscle cells, then leave this location
and enter the connective tissues where they continue develop-
ment to sexual maturity. From this point on the life cycle
is apparently continued outside the Iiost, presumably in the
cocoons. Schuberg and Schroder suggest that the nematodes
reach the cocoons either by penetrating into the gonads and
passing out with the reproduction products or b3' penetrating
directly through the body wall and entering the cocoon while
this structure still encompasses the body of the leech. The fact
that the i>arasites are frequently found in the connective tissues
immediately underlying the epidermis of the leech seems
to make the latter alternative all the more probable. Schuberg
and .Schriider concluded that the females lay their eggs within
the cocoons and that the resulting larvae infect the young
leeches. How the parasite enters the host has not been deter-
mined.

Myen-cius botelhoi Pereira, 1931, is a parasite of the leech,
Limnobdella bra.'iiUensi.s Pinto, and was found and studied in
Brasil. According to Pereira (1931), infected leeches harbored
the nematode in all stages of development. The epididymus was
a favored location but the parasite was found in other connec-
tive tissues tliimgh rarely in the muscles and never in the ali-
mentary tract. Apparently the worms occurred between but
not within the cells. The outstanding point of interest regard-
ing this nematode is the fact that Pereira found it regularly
within the sjiermatophores of the leech. It would appear, there-
fore, that the parasite enters the spermatophores at some time
during their formation or passage out of the leech and uses
them as a vehicle for transmission from host to host.

DRlLONEMATrD-IE

This is a small family of about a dozen genera that arc cither
monotypic or contain only a few species each. These nema-
todes are parasites of earthworms and occur in the coelomic
cavities, in or associated with the reproductive organs or em-
bedded in the muscles. Many of the species are characterized
by large, sometimes almost sucker-like, phasmids and some of
the species by large cephalic hooks. Very little is known about
life cycles.

DiCELis FiLARi.\ Dujardin, 184.i. — Of the specimens of Liim-
bricus rubelluit Hoff., collected by Wiilker (1926) in Germany
near Frankfort a. M., about 2.^ percent harbored this parasite

(Fig. 1(17 10 \- F) but other species of earthworms collected in
the .s.ime region were not infected. The usual number of nema-
todes per host was 6 to H with a maximum of 22, females gen
erally outnumbering nmles. The parasites occurred in the body
cavity of the host in the region of the reproductive organs but
not in the nephridi.-i.

The covering of the egg (Pig. ]()7 D) is thick with a rough
outer surface indicating that the shell proper is probably cov-
ered by an external coat and suggesting that the egg is
e(iuipped to resist adverse conditions and jiersist in the soil for
.1 considerable period. lOggs are laid in the body cavity of the
host but do not continue development in this location. Wiilker
did nut (iinl larv;il stages either in earthworms or in surround
ing soil and was unable to follow the life cycle. It is not
known how eggs are expelled from the host, or in what stage,
the p;irasites enter. Wiilker demonstrated that if the earth
worm dies these nematodes are unalile to reproduce in the car-
cass but perish with the host.

■1 l-:TKM)ONKM.\Tin.\E .\XD MKR.MITHIDAE

To the family Tetradonematidae there have, as yet, been as-
signed only two sjiecies, Tetradoncma pUcan.i and Aproctonema
rntomophaiinm. These, essentially, are primitive mermithids
and must be included in any general consideration of life
cycles in this group.

Fig. 107. .MYENCHIDAE AND DRILOXEMATIDAE

A-C — Miienchuit bothryophorus (A — Adult female; B — Adult male;
C — Larva in muscle cell). D-F — Dicelis filaria (D — Eggs; E — Adult
male; F — Adult female). A-C, after Schuberg and Schroder, 1904:
D-F, after Wiilker, 1926.

251

The mermithids are preeminentl.v insect parasites although
crustaceans, spiders, snails, and some other invertebrates are
included among their hosts. Most of our knowledge regarding
life cycles and habits has beeu derived from a study of species
that infect insects and the following discussion has, of necessity,
been written with these hosts in mind.

Eggs may hatch outside the host and larvae reach the body
cavity of the young insect by penetrating its body wall or eggs
may be ingested and larvae reach the body cavity by penetrat
ing the wall of the gut. In the former type of life cycle there
is a tendency for larvae to enter while their hosts are young
and for each host to harbor a small number of parasites. In
the latter type of life cycle the chances of the host becoming
infected are likely to increase with its age and food consump-
tion and the number of parasites per host is likely to be greater.
Tetradonema plicans, after reaching the body cavity of its
dipterous host, develops to maturity, copulates and lays its eggs
as an internal parasite. This is a simpler and probably a more
primitive life cycle than that known for any mermithid. Most
mermithids, after completing growth, force their way out of the
host and are free living during the adult stage. For Ae/amer-
mis decaiulata, Mcrmis subnigrcsccns, and probably some other
species, the free living period is of two years' duration and
during it the worms undergo their last molt, copulate, and fe-
males lay their eggs. Aproctotiema entomophagum develops to
maturity and copulates within its host but females emerge to
lay eggs, while Paramermis contorta undergoes its final molt
within the host but emerges before copulation. For both these
species the free-living stage is of very short duration and these
life cycles seem to represent intermediate steps between the
life cycle of Tetradonema pUean.i and that of such species as
Agamermis decaudata.

If a species enters its host by penetrating the body wall the
posterior portion of the larva is often modified to serve as a
propelling organ. In some cases, as for example species of
Agamermis, this modified posterior portion, which may consti-
tute as much as four-fifths of the total body length, is de-
tached during the act of penetration and remains on the out-
side. In other species this modified portion is relatively shorter
and persists to form a horn-like appendage at the posterior ter-
minus of the fully grown larva.

In most mermithids, especially those having an adult, free-
living stage of considerable duration, the intestine grows rap-
idly during parasitic development until it fills nearly all the
space in the body not occupied by other organs. This modified
intestine, filled with reserve nutrient materials and frequently
referred to as the "fat body," is largely responsible for the
opaqueness of the fully grown larva. The adult becomes in-
creasingly transparent as these stored nutrients are consumed
and life ends when they are exhausted.

Most mermithids are represented by both sexes but the sex
ratio is subject to a good deal of variation, not only as between
different species but in the same species. Males of Amphimer-
mis suimiislii and of Agamermis deeandata considerably out-
number females while males of Mermis vigrescens and M. sub-
riigrescens are rarely found. The sex ratio of some species is
influenced by environmental conditions during parasitic develop-
ment. One or a few parasites per host results in a prepon-
derance of the larvae developing into females while a large
number of parasites per host results in all, or nearly all, devel-
oping into males. Convincing data demonstrating this environ-
mental influence on sex ratios have been presented by Caullery
and Comas (1928) for Parainermis contorta, by Christie (1929")
for Mermis subnigreseens, and by Kaburaki and Ij'atomi (1933)
for Amphimermis zuimusM. There is evidence suggesting that
some other species behave in a similar manner.

Functional females that possess such male characters as cau-
dal papillae, male copulatory muscles, and even rudimentary
spicules have been reported from numerous species. It seems
probable that there is some correlation, as yet not understood,
between the influence of environment on sex and the occurrence
of these so-called "intersexes."

Females of Hexamermis sp. (parasite of the ant, Fheidoie
pallidula) and of Agamermis decaudata lay eggs only after
copulation. Females of AUomermis myrmecophilia and of Mer-
mis subnigreseens produce viable eggs in the absence of males
though individuals of the latter species have been observed in
copula.

The presence of mermithid parasites affects insects in various
ways; development of the gonads, especially the ovaries, is
usually suppressed resulting in sterility; wing muscles are some-
times weakly developed reducing ability to fly ; internal fat de-
posits are largely consumed; development of the body as a
whole may be retarded and metamorphosis delayed ; and infected
individuals may be .sluggish or, in the case of ants, have a
voracious appetite. As a rule external morphological characters
are not appreciably modified but there are exceptions, that of

ants being the most outstanding. The emergence of the para-
site usually results in the death of the host.

Numerous species of ants are rather commonly infected with
mermithids. Males, females, workers and soldiers have been
reported as harboring these parasites and there is wide varia-
tion in the effects of the mermithids on the external anatomy
of the hosts. In some instances infected ants show little recog-
nizable difference from normal individuals of the same sex or
caste, except, perhaps, a somewhat more distended gaster and
slight variations in color. This seems frequently to be the
case with infected males but sometimes, according to Gosswald
(1930) and Vandel (1934), infected females, workers or sol-
diers are not materially modified. In some instances, on the
other hand, the external anatomy is greatly modified (Fig. 169
C-G) and infected ants are not identical to any normal caste
but show female, worker and soldier characters in varying de-
grees. Such individuals are called intercastes.

In the genus Lasius infected females resemble normal females
but are easily recognized, at least in many instances, by a
smaller head, shorter wings, and a somewhat more distended
gaster. Intercastes of this type have been designated mer-
mithogj/nes.

In the genus Pheidole, Wheeler (192S) found a variety of
different intercastes with mixtures of soldier, worker and female
characters. He recognized five more or less distinct types
lias'.'d on thn degree of resemblance to one or another of these
three normal castes. In all these types the resemblance was
more especially to woikers and soldiers and for these intercastes
Wheeler proposed the term mermithergates.

To Vandel (1930), working with Pheidole pallidula, the sit-
uation was somewhat simpler as he was able to recognize only
two types of intercastes. One type showed no very pronounced
difference from normal workers except a somewhat more dis-
tended gaster. The other type he believed to be modified sol-
diers and for these he proposed the term mermithostratiotes re-
serving the term mermithergates for those intercastes where
resemblance to workers predominates.

Gosswald (1930) found young mermithid larvae in ants at
various times of the year and concluded that there may be con-
siderable variation in the time when these insects acquire their
parasites. Although mermithids have been found in larval ants,
only a few such cases have been reported, and Vandel concluded
that the infection is usually acquired during or just prior to
the pupal stage. Based on the size and development of larval
mermithids from young ants, Gosswald concluded that the para-
sites may be acquired when the immature insects are in differ-
ent stages of development and that the stage when the parasites
nre acquired determines, in a large measure, the degree to which
the adult host will be modified.

How ants acquire these parasites is a question that has
aroused considerable interest but stimulated little actual inves-
tigation. Gosswald (1930) conducted infection experiments
with Lnsius alienus and used eggs of what was, presumably,
AUomermis myrmecophilia. His results indicate that the ant
acquires this parasite by Ingesting the eggs. As ant-infecting
mermithids belong to several genera (Agamermis, He.ramermis,
Allomerinis, etc.) life cycles and behavior undoubtedly differ
and all may not necessarily enter the host at the same time or
in the same manner. It would be surprising if an ant became
infected with a species of Agamermis by ingesting its eggs.

Tetradonema plicans Cobb, 1919, is a parasite of the dip-
terous insect, Sciara coprophila Lint. It has been found in only
one collection of these insects made by Hungerford (1919) at
Manhattan, Kansas, in which every individual was infected. It
occurred in larval, pupal, and adult flies each insect harboring
from 2 to 20 parasites with an average of about 10, the number
of males slightly exceeding the number of females. T. plicans
passes its adult stage and lays eggs within its host, differing in
this respect from any mermithid of which the life history is
known.

How the insects acquire their infection has not been deter-
mined. Eggs (Fig. 108 G) secured by Hungerford from around
females dissected out of fly maggots hatched in a few hours
when placed in water and the larvae that emerged seemed to be
identical with the youngest larvae found within the insects.
These larvae were of two types, a slender type about 12.')M long
with a curved caudal end and a plumper type about 90/^ long.
This difference, presumably, is sexual dimorphism. Hungerford
found eggs of the parasite in the digestive tract of small Sciara
larvae and concluded that eggs are probably swallowed and
nematode larvae, after hatching, penetrate through the wall of
the gut into the body cavity. He noted, however, that "the
older maggots are much less susceptible to infestation than the
younger ones" and he figures the tail of the adult parasite with
a horn-like projection whicli suggests that the larva has a cau-
dal propelling organ, two characteristics that one is inclined

2.52

Fig. 168. TETRADOXEMATIDAE AXD MERMITHIDAE

A-F — Api ortonemn fntotiiofihagxim (A — Fertilized ese: B — Egg con-
t»ining ovic larva: C — Very young larval female; D — Older larval fe-
male; E — Larvnl male; F — Spermati^ed female). G & H^ — Tftrndonpiun
plirnnn ( G — Egg ; H — Egg-laying female with male* attached } . I —
AUomermiit mermifOphyUi, egg. J-M — Apamfrmiit dpratidatn (J — Xewly
deposited egg; K — Egg containing ovit- larva; L — Infective, preparasitic

larva; M — Grasshopper nymph containing one fully grown para*<itic
female). N — Mermis suhnigrescens, females depositing eggs on vege-
tation. (All eggs. A. B. G. I, .7. & K, drawn to snme scale). .\-F,
after Keilin and Robinson. 19^3 (C-F, drawn from compressed speci-
mens) ; G & H. after Hungerford, 1919; I. after Crawley and Baylis.
1921: J, K & M. after Christie, 19^6; L, after Christie. 1929; N. after
Christie, 1937.

253

to associate with a species that enters its host by penetrating
the body wall.

After arriving in the body cavity of the host the larval nema-
todes grow rapidly and development is usually so timed that
females copulate and deposit eggs before the fly pupates.
Adult flies were found that contained egg-laying female nema-
todes and also small larvae that approximated the size usually
reached after a few daj-s of parasitic life. Hungerford believed
these small individuals had been arrested in development by
the growth and maturity of the other worms.

Eggs pass through the vulva and are retained within the
separated but unshed cuticle of the final molt which, near the
middle region of the body, becomes distended to form a more
or less spindle-shaped egg capsule (Fig. 1(58 H). Eggs are not
normally discharged from this capsule prior to the death of the
female. This final molt of the female is the only one men-
tioned by Hungerford. How the males circumvent this encom-
passing cuticle and effect coition is not explained. The host
insect is eventually killed and the body disintegrates to set free
a residual mass of nematode eggs.

Hungerford found that the internal fat deposits of infected
fly larvae were largelj' consumed leaving the body much more
transparent than that of a normal individual. Most infected
fly larvae died before pupating but where the infection was
acquired late or the parasites were few in number the fly might
endeavor to pupate. Many such pupae died being little more
than nematode-filled shells but some succeeded in casting off
the larval skins. The emerging, infected adults were able to
fly and differed very little in appearance from normal indi-
viduals but they lacked functional reproductive organs.

Aproctonema entomophagum Keilin, 1917, was found in
England where it is a parasite of the dipterous insect, Sciara
pulhda Winn., the larval stages of which inhabit decaying wood.
The morphology and life history of the nematode are discussed
in a paper by Keilin and Robinson (1933) upon which the fol-
lowing account is based. It will be noted that the host of this
parasite belongs to the same genus as the host of Tctradonema
plicans and the two nematodes have many points in common.

Each infected larval fly usually harbors several females of A.
entomophagum (Fig. 168 F) and a varying number of smaller
males (Fig. 168 E). Mention is made of one larval fly that
contained 2 females and 10 males. The parasites reach ma-
turity in the body cavity of the host and copulate whereupon
the males die and the females emerge forcing their way out of
the host in the manner of most mermithids. Egg laying begins
almost immediately after emergence. Each female deposits
somewhat over 200 eggs and when egg laying is completed the
female dies. Hence only the female has a free-living, post-
parasitic stage and it is of very short duration.

The egg (Fig. 168 A) is laid before cleavage but develops
rapidly and in a few days contains a coiled larva (Fig. 168B)
that molts before hatching. There seems little reason to doubt
that the larval mermithids enter the young fly larvae by pene-
trating the body wall though actual penetration was not ob-
served.

If infection occurs late in the development of the fly larva
the parasites may be carried through the pupal stage and in-
fected adult female flies were found though not infected adult
males. The parasites delay the metamorphosis of the insects
and infected adult female flies lack functional reproductive
organs.

Paramermis contorta (Linstow, 1889) Kohn, 1913, is one
of the aquatic mermithids of which there are a considerable
number. It is a parasite of Chironomus larvae and was dis-
covered and studied in Europe. Each host usually harbors one
parasite but sometimes two to three or more. The sex ratio,
as reported by different investigators, varies a great deal but
in most cases females have considerably outnumbered males.

According to Kohn (190.5), P. contorta molts before leaving
its host. This, undoubtedly, is the last molt and the uteri are
already filled with eggs. The parasite may issue through the
anus or force its way directly through the body wall, the ma
.iority emerging just before their insect hosts would normally
pupate. The worms settle into the mud at the bottom of the
pool and copulation soon takes place tg be followed immediately
by egg laying. According to Comas (1927), the uteri are emp-
tied and egg laying completed in 4 or 5 days whereupon the
female dies.

Eggs are laid before cleavage but develop immediately and
hatch in the course of a few weeks. The mermithid larvae swim
in the water and seek young Chironomus larvae which they en-
ter by penetrating the body wall. Comas states that these
mermithid larvae do not appear capable of living long in
water and, if unable to find and enter a host, will die in a few
hours. Comas recounts that if a mermithid larva attempts to
penetrate between the more posterior abdominal segments of
its prospective host, the Chironomus larva may reach back and

with its mandibles pull the nematode away or bite it in two.
If penetration is attempted nearer the middle of the body the
insect will be unable to reach the nematode and penetration is
more likely to take place.

Allomermis myrmecophilia (Crawley and Baylis, 1921)
Steiner, 1924, was named and described by Baylis and its life
history was studied by Crawley (Crawley and Baylis, 1921).
The specimens were from two species of ants collected in Eng-
land, Lasius alienus (Fijrst), and L. flavus (F.) and a third
ant, L. niger (L.), was reported as a host. Observations on a
mermithid identified as this species and secured from the same
ants were made in Germany by Gosswald (1929; 1930).

After completing its parasitic development this mermithid;
according to Craw-ley, emerges from the ant, sometimes through
the anus and sometimes between two of the ventral plates of
the gaster, whereupon it enters the soil. As with many other
mermithids, emergence apparently occurs over a considerable
period during summer and autumn ; Baylis mentions specimens
that emerged during July. Crawley first saw eggs in the uteri
of experimentally reared females on December .5. Egg laying
begins before completion of the final molt and many eggs are
retained within the separated but uncast cuticle after the man-
ner of Tetradoncma plicans. As mention is made of four ex-
perimental females that had molted by November 20, one might
infer that two molts take place after emergence but Crawley
and Baylis are not explicit on this point. Some of Gosswald 's
(1930) ant-infecting mermithids molted twice after emergence
Init presumably these were not A. myrmecophilia. Bj' actual
count Crawley found that one cast cuticle contained 6,560 eggs
and another 5,900 eggs. Oviposition continues after the cuticle
is cast off and probably at least as many more eggs are laid
making a total egg output of 12,000 or more. Eggs (Fig.
16S I) are embedded in a "gelatinous" matrix that causes
them to collect in masses around the vulva or sometimes to be
extruded in tlie form of a ribbon. Crawley and Baylis failed
to find males of this mermithid and Gosswald demonstrated that
females develop and lay viable eggs without copulation.

Crawley believed that ants become infected while in the larval
stage and Gosswald 's infection experiments seem to indicate
that eggs of the parasite are ingested. Crawley and Baylis re-
ported finding only mermithogynes which, when present in a
colony, rarely exceeded the normal females in number and usual-
l.y were much fewer. One series of colonies showed an average
proportion of about 1 to 12. Gosswald found infected males
and workers of Lasius alienus and L. flavus and one infected
male of L. niger. Each infected ant usually harbors one mer-
mithid though sometimes as many as three.

Infected males and workers, according to Gosswald, show, at
the most, only very slight external differences from normal ants.
The ovaries and wing muscles of mermithogj-nes fail to de-
velop normally, according to Crawley and Baylis, but, except
for a marked reduction in the size of the wings and a more
distended gaster, the external characters show no pronounced
dift'erence from those of normal females (Fig. 169 C & D).

Hbxamermis sp. This unidentified species of the genus
Hexamermis is a parasite of the ant, Pheidole pallidula (Nyl.),
and its life history was studied in France by Vandel (1934).
Most individuals complete parasitic development by late summer
or autumn and emerge from the ant by forcing their way out
through the anus. They do not remain in the ant galleries but
penetrate a short distance into surrounding soil where they oc-
cupy small cavities. The final molt occurs about a month after
emergence and is followed, within the next month, by copula-
tion and egg laying. One of Vandel 's experimental females had
begun to lay eggs by December 23 and was still laying eggs on
March 15. Females exhaust their reserve nutrient materials,
stop laying eggs, and die by the end of March or soon there-
after. Hence there is one generation each season with no post-
parasitic individuals in the soil during late spring and early
summer.

The infected individuals of this ant are mermithergates and
mermithostratiotes and, with at most very few exceptions, each
harbors one parasite. It is not known how the parasite enters
the host. Vandel concluded that the infection is acquired either
immediately prior to, or during the pupal stage. The location
where eggs are laid, the small number of parasites per host, and
the vestigeal caudal appendage of the adult is circumstantial
evidence suggesting that the larva penetrates the body wall of
the young ant.

Copulation is necessary in the reproduction of this mermithid.
Experimental females reared in the absence of males by Van-
del failed to lay eggs. These females lost their opaque appear-
ance very slowly and some lived for from 22 to 33 months after
emergence whereas females that were allowed to copulate and
that layed eggs lost their opaque appearance much more quickly
and lived for only about 5 months after emergence.

Agamermis dbcadbata Cobb, Steiner and Christie, 1923, oc-

254

curs ill the north i-oiitrnl and northoastorii Uiiitod States wiicrc
it is a common parasite of grasshoppers inoUidinR both Acridi-
dae and TotliKouiidae. It sometinioa iiifeets crickets (drylli-
dae) and has been found, occasionally, in leaf hoppers and
beetles. The life history of this merinithid was studied by
Christie (I'.KiG) upon whose work tlie following account is based
and which applies to the soil and climatic conditions of north-
eastern Virginia.

The free living stages of this nematode occnjiy small cavities
in the soil usually from ."> to 15 cm. below the surface (proliably
deeper in sandy or loose soil). When inhabited by .'idults each
cavity, almost without exception, contains one female aiul sov
eral males, generally two or three, sometimes as many as eight,
coiled and intertwined to form a "knot." Copulation is neces-
sary and females reared in the absence of males fail to lay
eggs. Egg laying begins about the first of July, continues until
interrupted by the advent of cold weather, and eggs (Fig.
108 ,1 & K) accumulate over the surface of the soil cavities and
over the parent nematodes. For the most part eggs laid during
a given summer do not hatch until the following spring. Cleav
ago and embryonic development take place after deposition and
the first molt occurs within the egg shell.

At the time of hatching the second stage larva is immediately
infective. The body, which shows a high degree of organiza-
tion and development, is divided into two parts by the node
(Fig. 1()8 LV In the anterior part, which constitutes about
one fifth of the total length, one finds most of the organs com-
mon to nematodes including esophagus and esophageal glands,
intestine, nerve ring, and excretory pore. The posterior part
of the body serves as a propelling and food storage organ and
contains a row of cylindrical cells, probably modified intestinal
cells. An anus is apparently lacking.

During late fall and winter a female is surrounded by her
total egg output of the season. Egg counts on six females
made during the winter showed the total number of eggs present
to vary from L!,(>2."i to 6,.530. As will be noted later, a female
lays eggs during two summers hence these figures represent
roughl.v about half the total egg output.

Although some larvae may begin to emerge from the eggs
fairly early in spring, a greater part of them hatch during a
short period at about the middle to the latter part of June. The
species of grasshoppers that mo.st commonly serve as hosts
(Mclanoplus fcmurrtibrum and Conoccphalns brcvipennis (Scud-
der) in northeastern Virginia) also hatch at about this time.
The larval nematodes migrate to the surface of the soil and
climb grass and other low vegetation when it is wet with dew
or rain. They seek newly hatched grasshopper nymphs and
enter their body cavity by penetrating the body wall. Pene-
tration takes place under the edges of the pronotum, between
the abdominal segments, or at other places where the chitinous
covering is thin. Penetration is effected by the use of the
stylet probably aided by the dissolving action of a chitin sol-
vent secreted by one or more of the most anterior esophageal
glands.

After the anterior end is inserted into the host the body of
the larva breaks at the node and the postnodal portion is left
on the outside. If the body fails to break, as occasionally hap-
pens, the postnodal part undergoes no development in the host
but remains as a vestigeal appendage that eventually sloughs
off. The nodal scar (Fig. 93, p. 89) persists throughout the
parasitic stage as convincing evidence that no molt takes place
during this period. The number of parasites per host is
usually one (Fig. 168 M), sometimes two, rarely three or more.

Ouee inside the body cavity of the host the parasite under-
goes a period of phenomenal growth accompanied by pro-
nounced morphological changes. The stychocytes (see p. 92)
arc a conspicuous anatomical feature of larvae that have been
in the host from 4 to 10 days (Fig. 93, p. 89). As the body
increases rapidly in length it becomes filled by the intestine,
in fact intestinal tissue eventually fills all available space not
occupied by other organs even growing past the base of the
esophagus and extending into the neck region. Apparently
this modified intestine performs no digestive function but serves
as a reservoir for nutrient materials. Males remain in the
host for from 1 to 1V> months and females from 2 to 3
months. The mermithids emerge head foremost forcing their
way through the body wall between the segments, fall to the
surface of the ground, and enter the soil.

During the first winter in the soil males and females remain
isolated each individual forming a separate "knot." The final
molt takes place the following spring about the latter part of
June and at this time males seek the females. It will be noted
that only two molts have been observed. Egg laying begins
soon after the final molt, usually about the first of .Tuly, and
continues until interrupted by cold weather. The following
spring a year-old female begins laying eggs slightly earlier
than one that has just molted. By the end of the second sum-

mer of egg laying the reserve food has become exhausted and
the transparency of the body is in sharp contrast to its
opaqueness at the time of emergence from the host. Most fe-
males probably fail to survive a third winter in the soil. In-
formation regarding the longevity of males is not very satis-
factory but it seems probable that they live for about the same
length of time as females.

.1. ilccaudala causes no noticeable change in the external
anatiiMiy of grasshoppers. Infected individuals sometimes have
distended abdonu'us and are likely to apjicar sluggish, adults
being incapable of suslaimnl flight. The most pronounced ef-
fect of this parasite is on the gonads of the host (Fig. 109 A
& B). It is doubtful if infected female grasshoppers are capa-
ble of laying eggs as the ovaries are always greatly reduced in
size. The effect on the testes is less pronounced and infected
male grasshoppers have been observed in copula. The cme>-g-
gence of the parasite invariably results in the death of the host.

Mekmis siJHNiORKSCf;NS Cobb, 1930, appears to be strictly a
grasshopper parasite. It occurs in the United States over about
the same range as Affajnermis drcaudala where it has been
found infecting nine different species of grasshoppers including
both Acrididae and Teltigoniidae. Several other species have

H -~- ^^^-x^ ^— G

Fig. 169. EFFECTS OF MERMITHIDS ON THEIR HOSTS

A & B — Dissections of adult female grasshoppers, Melanoplus femur-
rub rum, showing reproductive organs (A — Normal grasshopper; B —
Grasshopper parasitized by Agamennis decaudata) . gas cne, gastric
caeca ; int, intestine ; o i% ovary ; ovd, oviduct ; spthc, spermatheca. 0
& D — Females of the ant. Lasius alienus (C — Normal female: D — Fe-
male parasitized by Allomermis mermicophyla, i.e., a mermithogyne).
E-G — The ant, Pheidole absurda (E — Individual parasitized by a mer-
mithid, i.e., a mermithergate; F — Normal worker; G — Normal soldier).
H — The ant, Pheidole f/auldi, a mermithergate. A & B, after Christie,
1936; C & D. after Crawley and Baylis. 1921; E-G, from Wheeler,
1928, after Emery; H^ after Wheeler. 1928.

2.15

Au^usr September

Fig. 170a. LIFE CYCLE OF AGAilERillfi DECAUDATA

Diagram illustrating 12-month period, August to July, inclusive. ".
"knot" composed of one female and several males that emerged froni
hosts 2 years previous to beginning of period represented, b. "knot"
composed of one female and several males that emerged from hosts 1
year previous to period represented. Mermithids that would emerge
during September and October of period represented are omitted for
simplicity. Female in "knot" a has, by October, completed its second
summer "of egg laying and dies during ensuing winter but the accumu-
lated eggs, deposited during previous summer, hatch May to June. Fe-
male in "knot" ii has, by October, completed its first summer of egg
laying and the accumulated eggs hatch May to June while the second
summer of egg laying is begun during May.

been experimentally infected. Attempts to infect other insects
including crickets (Gryllidae), mole crickets (Gryllotalpinae),
and larvae of several species of Lepidoptera have been unsuc-
cessful. The following account of the life history is based on
investigations by Christie (1937) conducted, for the most part,
in Massachusetts.

Grasshoppers become infected with .1/. siibnigrescens by swal-
lowing the eggs. In order to bring this about the egg-laying
habits of this nematode are radically different from those of
Againer7nis decaudata, otherwise the two life cycles are some-
what similar. Eggs of .V. siibnigrescens are never laid in the
soil. Gravid females climb low vegetation on which they lay
their eggs (Fig. 168 N) and to which the eggs cling l)y means
of the entangling appendages or bissi.

The egg, when deposited, contains a fully developed infec-
tive larva (Fig. 140 B, p. ISl). The shell proper is protected
by an outer covering that is divided into two cup-like halves
by a groove at the equator (Fig. 14(1 A, p. ISl). At each pole
there is a raised or thickened area formed by the attachment
of the entangling appendages (Fig. 139, p. 181). The outer
covering breaks apart along the groove at the equator and the
two cup-like halves are easily removed. In the shell proper
there are two opposite areas at the equator where the color is
lighter than elsewhere and these areas are partly dissolved by
the digestive action of the host thus facilitating the escape of
the larva. Botli the outer covering and the shell proper con-
tain brown pigment, presumably to protect the larva from the
action of sunlight. Eggs deposited on foliage remain viable
throughout the summer. When eggs were kept experimentally
in a moist chamber sonic remained viable for a year.

When an egg reaches the alimentary tract of its host the
outer covering has usually been rubbed off. The two opposite
areas of the shell at the equator gradually become clearer and
begin to protrude until they appear as colorless hemispherical
projections (Fig. 140 C, p. 181) that finally rupture and pro-
vide openings for the escape of the larva. The larva itself does
not appear to aid in its own liberation. Wlien first freed it is
rather sluggish but soon becomes active, penetrates the wall of
the gut and enters the body cavity. Penetration through the
intestinal wall is aided by the stylet which is rhythmically pro-
truded.

From 1 to 5 parasites per host is the number most frequently
encountered but there is great variation and grasshoppers har-
boring 100 or more parasites of widely different ages are not
uncommon in some localities. As a nymph grows older and its
food consumption increases, its chance of becoming infected
is correspondingly greater. The sex ratio of M. siibnigrescens
is intluenced by the number of parasites per host. When a
grasshopper harbors a large number, all develop into males but
when a grasshopper harbors only 1 or 2 these usually develop
into females (Christie, 1929).

The parasitic development of M. siibiiignscens is essentially
the same as that of Agamcrmis decaudata. There is the same
rapid increase in size and the same extensive proliferation of
intestinal tissue. Males remain in the host from 4 to 6 weeks
and females from 8 to 10 weeks. At the end of this time the
parasites force their way through the body wall of the host
and enter the soil. When a grasshopper harbors parasites of
different ages, all that are too immature to escape and survive
in the soil perish with the host when the older ones emerge.

June

Postparasitic individuals of M. siibnigrescens are found in the
soil down to about 60 cm., the majority occurring from 15 to 4.1
cm. below the surface. They usually remain isolated and one
larely finds a "knot'' composed of a female and one or more
males as is characteristic of Againerniis decaudata. Most in-
dividuals emerge from the host during summer and autumn
and molt the following April. This is the final molt and the
only one that has been observed. Copulation may take place
and has been seen on several occasions but copulation is not
necessary as females reared in the absence of males produce
viable eggs. By July females begin to exhibit a brownish color
due to accumulating eggs and by September they are nearly
Iilack except for a short region at each extremity of the body.
At this time most of the eggs are viable but they are not laid
until the following spring. Before ovipositing, a gravid female
8") mm. long contains about 14,000 eggs.

Egg laying usually begins in May and may continue through-
out July or even into August, depending on weather condi-
tions. Eggs are laid during rain and should the early summer
months be dry egg laying will be delayed. Gravid females
climb grass and other low vegetation over which they con-
stantly move while eggs are being laid. If rain continues egg
deposition goes on throughout the day but if the rain stops
and the foliage becomes dry females coil up, fall to the sur-
face of the ground and enter the soil, presumalily to resume egg
laying during the next rain.

It is not known how long females live after the uteri are
emptied of eggs but by this time their stored food is nearly
exhausted and it seems highly improbable that the.v are able to
survive a third winter or to develop more eggs. However, if
prevented from coming to the surface to deposit eggs they are
able to survive a third winter and to lay eggs the following
spring. Females that normally would have deposited eggs in
1932 were buried in containers and prevented from coming to
the surface (Christie, 1937). When examined during May,
1933, many of these females were alive, in good condition, and
filled with eggs. There was no evidence tliat eggs had Ijeen
deposited, although these females promptly began laying eggs
when brought to the surface and placed in the light.

Apparently eggs are not laid at night. Egg laying is con-
trolled, at least in part, by light stimuli. When an ovipositing
female is placed in the dark, egg laying promptly stops, but is
resumed just as promptly when the female is again placed in
the light. The head of the adult female is colored with areas
of reddish brown pigment which, presumably, is an organ for
light perception. The male, which never comes to the surface,
lacks this pigment.

Merniis siibnigrescens has about the same effects on its host
as does Agamcrmis decaudata. These effects are suppression
of the gonads, especially the ovaries, and death of the host
when the parasite emerges. With If. subnigresccns the effect
on the gonads of the host is much more variable than with A.
decaudata due to variations in the nnmlier of parasites per host
and the time the parasites are acquired.

.-VLLANTONEMATIDAE

The Allantonematidae is a group of insect parasites that are
closely related to the preeminently plant-infecting Tylenchidae.
The species that have been studied and named jnobably con-
stitute but a small part of the number that exist but in nearly
every instance where the life cycle is known it follows the same
genera! plan and differs from that found in any other group of
nematodes.

Adult gravid females occupy the body cavity (haemocoel) of
the insect, frequently in small numbers, often one per host.
Here larvae accumulate and develop to a certain stage, molting
at least once (probably twice in most species) ; then they escape
from the host either by entering the alimentary tract and pass-
ing out through the anus or by entering the female reproductive
system and passing out thi'ough the genital aperture. Most
species infect both males and females of their host insect. In
some eases the only known way by which larvae are able to

Aug list

September

Octtbrr

huv. -Alir

Hay

Ju n e

July

Fig. 170b. I.IKK rYCl.E OF AGAilKltMlS DECAVDiTi — Continued

Disgram ilhislraling fnsuiiig rj-nionth piTioii. August to July, in-
clusive, c, nierniilhids einerKtiig from hosts SejiteinlxT to October. Fe-
nmle and miiies remain in separnte cavities until latter iiart of May
when males seek female, copulation takes place, and. ilurins; .luiie, the
(emnle begins it-s first summer of egg laying. Female in "knot" h has.
by October, completed its second summer of egg laying and dies during
the ensuing winter but the accumulated eggs hatch May to .June. (While
the above diagram is essentially correct for a nia.iority of individuals
where grasshoppers serve as hosts, the various life-cycle changes are
actually spread out over somewhat greater periods of time than the
diagram indicates. A few eggs hatch before May and June. A few
prcparasitic larvae enter hosts as early as .\pril and as late a.s August
and the time of emergence is correspondingly affected. A few individuals.
especially males, emerge from hosts at least as early as July.)

leave the host is via the female reprtiduetive system ami the
fate of Uirvae that iiilialiit the beily cavity of male insects is
not yet fully understood.

A free living stiige is passed wheievor the liost in.scct umlef-
goes its early development and during tliis period the nema-
todes molt at least once (as a rule prohalily twice) and Ijccome
adults. In the adult male the stylet is usually either ahseiit or
weakly developed and the esophageal glands are ineonspicuous
ami apparently lacking. In the preparasitie adult female the
stylet is usually well developed and at least one of the esopha-
geal glands is large and conspicuous. E.xeeptions to these mor-
phological differences between the sexe.s are usually correlated
with deviations from the more typical life cycle. The apparent
absence of esophageal glands and the somewhat more rapid de-
velopment of the genital primordiuni in the male usually make
it possible to distinguish sex at an early stage sometimes while
a larva is still within the egg.

The ovary of the adult preparasitie female is small and com-
posed of only a few cells the extent of its development differ-
ing somewhat with different species. When copulation takes
place the uterus is packed with small, more or less spherical
spermatozoa. After copulation males usually die and impreg-
nated females enter their respective hosts, usually by penetrat-
ing the body wall while the insect is still in the larval stage.
The fact that in most species only the female possesses an effec-
tive stylet and at least one well-developed esophageal gland has
been regarded as evidence that these structures function in
connection with penetration into the host. There is little reason
to doubt that the stylet is employed for this purpose. It has
been suggested that penetration is further facilitated by a
secretion of the esojihageal glands which may serve as a cliitin
solvent. The validity of this suggestion does not rest entirely
on morphological evidence for Bovien (1S)32) demonstrated that
ScntDtirma wiill'cri does, in fact, exude a rather copious secre-
tion through the stylet at the time of penetration.

The free-living stage is usually of short duration. There is
no evidence that the nematodes feed during this period (with
the exception of Fergusobia citrrici) and larvae, at the time
they leave the host, are at least nearly as large as young
adults. However, after entering a new host, the female under-
goes a very great increase in size. The fully grown gravid fe-
male of most species is curved ventrad ;ind assumes a form
usually referred to as "sausage-shaped." There are exceptions,
however, and, for example, AUantonrma miriiblr is oval while
in many species of A ph clench id us the body is bent dorsad with
the vulva on the outside of the curve.

Some species deposit eggs in the body cavity of the host but
in many species eggs hatch before deposition and the uterus be
comes distended with developing eggs and larvae that gradually
fill the greater part of the body and push the ovary into the
anterior end. As a rule larvae eventually pass through the
vulva into the body cavity of the host. There is a tendency for
the other internal organs of the female to degenerate, the ex-
tent of this degeneration differing in different species.

In most species the rapid increase in the size of the female
after becoming parasitic provides space for the rei)roductive or-
gans. In one group, the Sphaerulariinae, adequate s|iace for the
developing reproductive organs is not provided by a corre-

sponding increase in body size. The uterus of Si>li(ini(laria
hombi is everted through the vulva and the entire reproductive
system develops outside the body jiroper. This prolapsed uterus
increases enormously in size and the body proper remains at-
tached to otu^ end :is a vestigial and apparently fiinctionless
structure. 'I'ripiu.i i/ibbusut! (Syn. Alractoncma iiibbumim) rep-
resents an intermediate stage in the evolutionary developnuMit
of this peculiar adaptation and the size of the body and of the
jMolapsed uterus is le.ss disproportionate. In both these species
the life c.vele, so far as known, is essentially the same as that
of most allantonematids.

There are, nevertheless, several deviations from this typical
life cycle. Young adult males, as well as young adult females,
of Par(i.iiti/lciicliii.s di.ipar typograpki enter the body cavity of
their host insect where they are found in large numbers, while
neither adult males nor adult females of Chondronema passali
become parasitic, only larval stages being found in the host
insect. Chnndronevia pansali enters its host, not as young
adults, but as young larvae, probably by being ingested.

Two species of this family have heterogeneous life cycles.
There is interpolated into the life cycle of Heteroli/lcncliiis aber-
rans a parasitic, parthenogenetic generation and into the life
cycle of Fergusobia ciirriei several, consecutive, "free-living,"
parthenogenetic generations. The parthenogenetic females of
Fergusobia currici occur, associated with their "host" insect, in
plant galls where they feed on plant cells and are, in fact,
plant parasites. In each of these heterogeneous species, how-
ever, the gamogenetic generation still follows the typical allan-
tonematid plan of development.

Tylenchinbma oscinellab Goodey, 1030, is a body-cavity
parasite of the frit-fly, Oscinclla frit. (L.). The life history of
this nematode was studied in England by Goodey (1930, 1931).

The frit-fly has three generations a year. Eggs are laid on
small oat plants generally during May and fly larvae penetrate
the shoots, destroying the central tissues. This is the first or
stem generation. Adult flies appear by mid-July and deposit
eggs on the panicles of oats where the larvae attack the tissues
of the inflorescence. This is the second or panicle generation.
Adult flies again appear during August or early September and
lay eggs on various species of wild grasses. This is the third
or grass generation; also it is the overwintering generation and
winter is passed in the larval stage. The life cycle of the nema-
tode is, of necessity, closely correlated with that of the frit-
fly and like it, undergoes three generations a year (Fig. 17.5).

Infected flies hariior usually one, sometimes two or three,
more rarely four to eight, adult female nematodes that give
birth to living young. Eggs pass into the uterus of the mother
nematode where they undergo development. As more and more
eggs are produced the uterus becomes distended, pushing the
ovary into the anterior end and finally occupying most of the
space within the body. Larvae (Fig. 171 A & C), escaping
from the egg membranes, pack the posterior etui of the uterus
and finally pass through the vulva into the body cavity of the
host. Here they accumulate and continue development. Goodey
observed one molt that takes place when a larva is about 4G0/i
long and which he believed to be the second suspecting that the
first molt takes place while the larva is still within the uterus of
the mother. The gonads undergo considerable development and
show differences that make it possible to distinguish sex. The
wall of the intestine becomes well stocked with reserve food
globules.

After attaining a size nearly as large as free-living adults,
the larvae escape from the host. To accomplish this they pene-
trate the food reservoir of the fly's digestive system from which
they migrate through the intestine to the rectum and are e.iected
through the anus. With regard to this escape of larvae, Goodey
writes as follows: "Parasitized flies of both sexes, having
failed to develop their sex cells, fly about and instead of taking
part in the normal process of reproduction are able only to
deposit larvae of the nematode parasite. Normal females go to
oat panicles and there lay eggs; similarly, the parasitized fliea
responding to the same urge of the life-cycle rhythm also fly

2o7

to oat panicles, but, instead of eggs, deposit larvae of the nema-
tode parasite. These find their way, possibly in response to
some ehemotactic stimulus, into the plant tissues surrounding
the fly larvae." In this environment the nematode larvae con-
tinue development and two final molts take place, the last
cuticle separating while the larva is still within the cuticle of
the preceding molt.

Larvae that Goodey removed fi'om the gut of infected flies
and kept in tap water completed their final molt in about 41
hours. Males remained alive for about 14 days and females for
about 29 days but copulation did not take place while the worms
remained in water. In nature copulation follows the final molt
and the uterus of the female is distended with spermatozoa.
The preparasitic female (Pig. 171 F & G) has a well devel-
oped stylet with basal swellings and a large dorsal esophageal
gland. These structures are inconspicuous or lacking in the
male. (Fig. 171 E).

Tlie male does not again beconu- parasitic but the impreg-
nated, precocious female enters the body cavity of a frit-fly
larva. Goodey did not actually observe the entrance but as-
sumed, no doubt correctly, that it is accomplished by penetrat-
ing the body wall. The incidence of infection is about the
same for male and female flies except possibly in the grass or

overwintering generation, where Goodey found that about two-
thirds of the infected flies were females.

After becoming parasitic the female nematode increases very
greatly in size and is about fully grown when the host emerges
from its pupal ease. Tlie body has assumed the characteristic
"sausage shape" and the ovary has completed its development
(Fig. 11.') J, p. 136). The stylet is retained and Goodey be-
lieves that probably the parasite continues to take food via the
alimentary canal.

Tylenchhicma oscincUae produces no noticeable effect on the
external characters of its host but it prevents the normal de-
velopment of the gonads and both male and female flies are
sterilized. Occasionally, however, parasitized flies of both sexes
develop normal sex organs and when this happens the parasite
fails to undergo normal development. In regard to this Goodey
(1931) writes: "In the great majority of cases the worm man-
ages to get the upper liand and grows to sexual maturity within
the host, but occasionally the fly, during its final metamorpho-
sis, is able, by some means, to Imild up its gonads in the nor-
mal manner. When this happens the worm fails to grow, re-
mains non-functional and becomes degenerate. . . . These rela-
tionships may possibly be explained on the supposition that the
worm secretes or excretes something, perhaps from the intesti-

rig. 171. ALLANTONEMATIDAE

A-G — Tylenchinema oscinellne (A — Very young male larva and, B,
genital primordium of same; C — Very young female and, D, genital
primordium and esophageal gland of same; E — Adult male; F — Adult,
preparasitic female and, G, anterior end of same. For fully grown.

adult, parasitic female, see Fig, 115 J, p. 136). H-J — Allantonema
mil-able (H — Adult male; I — Adult, preparasitic female after copula-
tion ; J — Fully grown, adult, parasitic female. For stage intermediate
between I and J, see Fig. 115 I, p. 136). A-G, after Goodey, 1930;
H-J, after Wulker, 1923.

il58

FiK. 172. ALLANTONEMATIDAE

Al — yScatonemn wulkeri. (A — Newly hatched female larva; B — New-
ly hatched male larva; C — Partly grown male larva; D — Female just
before final molt; E — Adult preparasitic female after copulation; F —
Male just before final molt; G — Adult male; H — Adult parasitic female
a few days after entering host; I — Fully grown gravid female). J-0 —
BelerotyUnehuH aberrans (J — Egg laid by female of gamogenetic gen-
eration; K — Egg laid by female of parthenogenetic generation; Lr — New-
ly hatched larva of gamogenetic generation; M — Adult preparasitic

female of gamogenetic generation; () — Fully jjruwii female of par-
thenogenetic generation). P — Aphplenrhnhm tliplopajtter, adult para-
sitic female. Q-S — FerguHohiu curriei Hi & R — Adult male and adult
female, respectively, of "free-living" generation, i.e., from EttcalyptiiH
galls; S — Gravid female of "parasitic" generation, i.e., from body cavity
of gall fly). T & U — Parasitylenrliux dinpar ti/pographi, adult parasitic
male and adult parasitic female, respectivelv. A-I. after Bovien, 1932;
J-0, after Bovien, 1937; P, T & U. after Fnchs. 1915; Q-S, after Car-
rie, 1937.

259

Fig. 173

Diagram illustrating life cycle of Scatotienui iriilkeri. The adult para-
sitic female (a) produces offspring (b) that eventually enter the female
fly s reproductive organs and are extruded with the eggs (c). Outside
the host these larvae develop into adults (rf) and copulate whereupon
males die and impregnated females (e) enter flv larvae. These females
then undergo a period of growth (/) and mav begin producing off-
spring (n«) while the fly is still in the larval stage or females mav be
only partly grown (though adult) (p) when the flv pupates and begin
flaying eggs (a) when the fly becomes adult. After Bovien, 1937.

Fig. 174. CnONDROXEMA PASSALI

A — Oldest larva found within body cavity of host: B — Youngest larva
found within body cavity of host: C-E — Portions of body of adult fe-
male filled with eggs or larvae and serving as brood sac; P — Eggs.
All figures after Christie and Chitwood. 1931.

nal [esophageal] gland, nliieli prevents tlie normal growth of
the host's sex-eells. At the same time it. is quite likel.v that the
same may be true of the host; if once its reproductive organs
become sufficiently developed, then it is able to pour out some
substance which definitely inhibits the growth of the worm."
Allantonema mirable Leuckart, 1884, is a bodv cavitv
parasite of the pine weevil, Eylohius ahirtis (L.) and occurs
in Europe but has not been found elsewhere. This nematode
differs from TylencMnema oscinellae, not so much in its life
cycle, which is essentially the same, as in the form and degen-
eration of the gravid female. Unlike most allantoiiematids, the
fully grown female (Fig. 171 J) is oval, some L.T to 2 mm.
in length and about half as wide as long. Its bodv is virtually
a sac largely filled by the uterus as it becomes di.stended witii
eggs and larvae. The other internal organs degenerate to such
an extent that if vestiges persist their identitv has not liecn
recognized.

Eggs hatch in the uterus where they begin to accumulate
during late summer and where they remain during the winter
undergoing little development. In "the spring larvae begin to
pass through the vulva into the body cavity of the weevil
where they undergo two molts. Larvae finally leave the host by
penetrating its alimentary tract and passing out thiougli tlie
anus.

The adult female of Hylnbins abiFfix eats small holes in the
bark on the trunk and roots of fir and certain other coniferous
trees. In this cavity eggs are laid and hatch, the young weevils
tuiineling into adjacent tissues. In order to pass their free-
living stages in the immediate vicinity of newly hatched weevils,
the larval nematodes must escape when and where female
weevils are laying eggs, albeit not through the genital aperture
of the insect. Wiilker (1923) observed only one molt during
free-living development which took place after 8 to 10 days.
Bovien (1937) found that larvae, taken from the rectum of
adult weevils and placed in hanging drops of water, became

adult in 5 to 6 da3'S. The final molt is followed very soon by
copulation after which males die and impregnated females enter
the body cavity of weevil larvae that, in the meantime, have
hatched.

The adult preparasitic female of A. mirable (Fig. 171 I) has
a well developed stylet and Bovien (1937) figures two esopha-
geal glands, one opening into the esophagus on the dorsal side
near the base of the stylet and the other on the ventral side
farther back. In the adult male (Fig. 171 H) a stylet is pres-
ent though somewhat more weakly developed than in the female
but the esophageal glands are inconspicuous or lacking.

By about July, when the weevils are pupating, the parasitic
female nematode is producing ova. Fuchs (1915) states that
ni/lohiiif: abii'tis lives for at least 31 months and, finding fe-
males of A. mirable in 2-yearold weevils, he concludes that the
nematode lives for at least 2 years.

SrATOXEM.4. wuLKERi Bovien, 1932, is a liody cavity parasite
of the dipterous insect, Scatopse fiiscipes Meig., the immature
stages of which develop in manure and other putrescent mate-
rial. Eggs of this nematode hatch in the uterus where larvae
(Fig. 172 A & B) undergo early development, the extent of
this development varying considerably. In some cases, which
Bovien (1932) regards as exceptional, an individual, while still
within the uterus, ma.y reach maturity and, in turn, develop
larvae within its uterus, thus creating three generations, one
within another. Most of the progeny, however, pass through
the vulva into the body cavity of the host as partly grown
larvae. These larvae enter the reproductive system of the in-
sect and pass out with the eggs. When an infected fly dies
not all the harbored parasites necessarily perish but some
larvae may complete development, molt, and copulate after
which impregnated females escape from the dead body. As
male flies die soon after copulation Bovien concludes that, in
moist surroundings, part of the nematodes may be able to

260

^V-J

Fig. 173. TTLEXCHINEilA OSCINELLAE

Schematic drawing illustrating life history of frit-fl.v in its three
^easonal generations, and the approximate time occupied by each, linked
with that of its parasite. Tylenchinema oscin^llae. The various stages
of the rty and worm are greatly enlarged whilst the outs and gr.Tss are
smaller than natural size. Although the female fly only is shown it is
to be understood that the male also carries the parasite. The dotted
circles contain stages of the parasite related to the corresponding stage
of the host. The circles cut into the pupa and imago hut not into the
fly larva in each case, thus showing that the parasite is within the pupa
and fly hut not within the larvae, c I, ensheathed larvae; / r, food
reservoir of fly with larvae passing in: g f, growing female worms; 7» /.
mature female worms, .^fter Goodey, 1931. explanation quoted verbatim.

escape from the decaying insects. Otherwise tlie fate of larvae
harbored by male fiies is unknown.

Bovien observed only one molt, the last, which may occur
liefore, but usually not until after, emergence from the host.
As this molt takes place not later than 24 hours after emer-
gence and is followed immediately b.v copulation, the free living
stage is of short duration. In the adult, preparasitic female
(Fig. 172 F) the stylet and esophageal glands (Bovien figures
two) are well developed while in the adult male (Fig, 172 G)
these structures arc inconspicuous or absent. By the less well-
developed genital primordium and the presence of esophageal
glands one can distinguish female larvae while they are still
within the egg.

Regarding penetration of preparasitic females into the body
cavity of a fly larva Bovien (1932) writes as follows: "In
many cases I found the nematodes in the act of entering the
body of the larva. In a few cases I saw dead nematodes, which
had not succeeded in penetrating the body wall, held fast by it.
Tlie jienetration may take place through all parts of the surface
of the larva and no preference seems to be given to any ])ar
ticular region. The very beginning of this act, however, was
not observed. I placed female worms in hanging drops
together with Scatopse-\aT\ae, the presence of which had an
unmistakably attractive influence on the nemas. The
nematodes slung themselves around the body of the larva,
pressing their mouths against the skin without being able to
puncture it, I suppose this failure may be :iscril)ed to the lack
of supporting surfaces. On the third day the worms were dead.
,\n oblong, somewhat spiral-wound, coagulated ma.ss of secre-
tion had been ejected from the aperture of the buccal stylet,
and the salivary [esophageal] glands apjieared to be empty.''
The jjrcscnce of the parasite does not result in sterility of thi'
host.

Chondronema PASSALi (Lcidy, 18.')2) Christie and Chitwood,
Ifl.Sl, is a body cavity parasite of the beetle PopiliiiK ivlrrr\ip-

Fig. 176. HETEROTYLENCHUS ABERRANS

Diagram illustrating life cycle of Heterotylenchua aberran.t. The
adult parasitic female of the gamogenetic generation («) lays eggs (6)
that develop into females of the parthenogenetic generation (c). These
females lay eggs (rf) and the resulting larvae (e) enter the reproductive
organs of the female fly and pass out through the genital aperture.
Outside the host these larvae develop into adults of the gamogenetic
generation (/) and copulate whereupon males die and impregnated fe-
males (ff) enter fly larvae. While the fly matures and pupates the fe-
male grows (/i) to reach full stature (a) and lav eggs (b) . After Bo-
vien. 1937.

tits (L.) (Syn. Pasxalus cnrnutns Fab.). This beetle occupies
galleries in decaying stumps and logs where eggs are laid and
where larvae develop and pupate. Leidy (18.52) found 90 per-
cent of the adult beetles infected and Christie and Chitwood
(1931) estimated that each beetle usually harbors from .")00
to 1,000 parasites. In the body cavity of the insect one finds
larvae in all stages of development from young, newly hatched
individuals (Fig. 174 B) to those that are fully grown (Fig.
174 A) but never adults.

Larval nematodes of both sexes taken from the body cavity
of a beetle have a minute stylet, a moderately large esophageal
gland (presumably the dorsal), and exceptionally large and
conspicuous phasmids. Sex can be distinguished at a rather
early stage partl.y through differences in the genital primordia
but more especially through differences in the general appear-
ance of the body, females being more opaque than males. Move-
ment is sluggish.

The mode of exit from the host has not been determined.
Once the nematodes have escaped neither males nor females
again become parasitic but remain in the beetle galleries
throughout the remainder of their lives. The mouth, anus, and
vulva of the female become vestigeal. If the vulva functions
it is only during copulation. Eggs (Fig. 174 F) are retained
within the body where they accumulate and hatch pushing aside
the internal organs and converting the female into a brood
sac (Fig. 174 C-E).

C. passali enters its host as a very young larva but it is not
known how this is accomplished. Larvae of all sizes may be
found in old beetles at any time of the year when the insects
can be collected. The incidence of infection seems to be very
much lower in larval beetles and pupae than in adults. These
circumstances, together with the exceedingly large number of
parasites usually harbored by a beetle, caused Christie and
Chitwood (1931) to suggest that the larval nematodes enter
per 0.1, possibly the gravid female and her entire progeny being
swallowed.

261

Heterotylenchus aberrans Bovien, 1937, is a body eavity
parasite of the onion fly, Hylemya antiqiia (Moig.), and its
life history was studied by Bovien (1937) at Lyngby, Den-
mark. Tlie onion fly hibernates in the pupal stage and emerges
in May to lay eggs on onion plants or in nearby cracks in the
soil. The young fly larvae move down the plant usually inside
the sheath and finally burrow into the bulb. Pupation takes
place in the soil or occasionally in the bulb. There are two or
perhaps, occasionally, three broods a year with considerable
overlapping.

In the body cavity of infected flies one finds from one to
four large, adult females of B. aberrans (Fig. 172 N) and a
greater number of smaller, adult females (Fig. 172 O). The
larger individuals are females of the gamogenetic generation
and the smaller ones are females of the parthenogenetic gener-
ation. The reproductive organs of a gamogenetic female, as
compared with these structures in most allantoneraatids, are

exceptionally small. Much of the space within the body is
occupied by the intestine which, according to Bovien, is with-
out a lumen. A small stylet is present and the three esophageal
glands, empty and reduced in size, are grouped around the base
of the esophagus. Eggs (Fig. 172 J) are deposited in the body
cavity of the host where they hatch and whore the larvae de-
velop into parthenogenetic females.

The outstretched reproductive organs of a parthenogenetic
female are relatively much larger than those of a gamogenetic
female. The esophagus and esophageal glands have almost com-
pletely degenerated but a small stylet is present and, according
to Bovien, the intestine is represented by a single row of
large, binuclear cells. Eggs (Fig. 172 K), which are smaller
than those of the preceding generation, are deposited in the
body cavity of the host and from them develop larvae of both
sexes. These larvae remain in the host until they are ready to
undergo their final molt when they penetrate the fly's ovaries.

Fig. 177. SPH.VEKULARIINAE

. A-D — Sphaerularia bombi (A — Fully grown lavva; B-D — Adult para-
sitic females showing progressive stages in prolapsus of uterus. For

fully grown adult parasitic female, see Fig. 115 A, p. 136). E-I

Tripius gibbosus (E — Newly born larva; F — Young but sexually mature
fomale; Ci — Sexually mature male; H — Adult parasitic female' showing

early stage in prolapsus of uterus; I — Adult parasitic female showing
late stage in prolapsus of uterus. For stage intermediate between H
and I. see Fig. 115 K, p. 136). J — "Ti/lerwlius sulphureus piceae."
adult parasitic female. A-I. after Leuckart. 1887; J, after Fuchs. 1929

262

mi(irnto to ami assiiiiMr in llu' dvidiuls and osiaiu' tl[i(in;;h tlif
gonititl aiH'itiiro.

Both miilo ami foiiialf tliis an' iiarasiti/.i'd. liovicn t'uniul no
cvidoiico that male tlios arc romliTod sterile lint the ovaries
of iiifeeted females fail to develop and heeause of this the
nematode larvae ean seareely he transferred to onion )dants
with the OKKs of their host. However, Rovien noted that in
feeted female tlies "strelehed ont the ovipositor, as if thev
wanted to lav eRRS-" As in tlie life eyele of Ttilt iirliiiit ma ii.i
ciiiilhK. infeeted female Hies prol>;ilily .•leccnnpaiiy normal fe
males to the plaee where eRgs are laid Imt deposit there, not
ogRS, bat larval nematodes. Hovien fouiul no evidenee that the
genitalia of male tlies are invaded ami he eonelnded tlial larvae
■liave no way of eseaping from male tlies.

The free living stages of the nematode arc passed in elose
assoeiation with the larval insects, cither in the onion i)lant or
in nearby soil. The nematodes reach maturity, copulate and the
males die. Impregnated females (Fig. 171! M) enter larval
Hies presumably by penetrating the body wall though the act
of penetration was not observed. The adult male has a stylet
with basal swellings comparable to that of the female but
somewhat more slender. .\11 tlirei' esophageal glands are well
developed in the preparasitic female but inconspicuous or lack
ing in the male. After entering the host a female develops into
the large, parasitic individual of the gamogenetic generation.

The life cycle of //. abirrans (Kig. I7(iK therefore, consi.sts
of a parthenogenetic generation, passed entirely within the host,
alternating with a gamogenetic generation that has both para
sitic and free-living stages. If the parthenogenetic generation
was omitted the life cycle would be es.sentially the same as
that of most other members of this family.

Ferousobi.v cfRRlEl (Currie, IH.'fT) n. comb. [Synonyms:
Anguilhilina (Fcrflii.sobia) tiimifacii nx Carrie, 1937; Anguilhi'
Una (Fcrijiixobia) curriei (Currie, l!t37) Johnston, 103S; not
AnpuilluUna Uimtfacirns (Cobb, l!i.'!2) |.

Fcrfjusobia curriri occurs in Australia where, in association
with flies of the genus Fergtisonhm, it produces galls on Eiica
lyptus trees. This association was discovered by Morgan (lii;^3)
and later investigated by Currie (1937), the following ae
count being based on the hitter's observations. There are many
species of Ffrgiisoiiiiia that attack Fiirnliiptiix trees in Aus-
tralia and, according to Currie, all are probabl.y associated
with a nematode. Several species of Eiirah/ptiif: are attacked
and galls may be formed on leaf buds, axil buds, stem tips,
and flower buds, depending on the species involved. The fol
lowing account of the life history of FcriivKnbia curriei is based
on a study of flower galls on Euciiliiptii.i tnacrorrhynchia and
of the associated fly, Frrffusoyiiiia iiirholxonia. Currie regards
the stages of the nematode found in the galls as true plant
para.sites but is inclined to regard the relationship with the gall
flies as symbiosis rather than parasitism.

Each female fly harbors two gravid female nematodes (Fig.
172 S). These nematodes deposit eggs and the resulting larvae,
on reaching the proper stage, leave the body cavity and enter
the reproductive system of the "host." Adult flics emerge
during summer and females, after mating, lay eggs in young
flower buds, depositing with each egg from 1 to ."lO nematode
larvae. The same fly or different flics may lay numerous eggs
in a single bud as many as 74 eggs and 227 nematode larvae
having been found. The larval nematodes immediately start to
feed on the anther primordial cells that form a ring around
the inner wall of the bud cavity and under this stimulus the tis
sue proliferates rapidly forming masses of large, thin-walled
parenchymatous cells full of mucilagious cell sap. The fly eggs
hatch in about 6 weeks and by this time masses of gall tissue
are already i)resent in the bud. On hatching a fly larva moves
in between two of these cell masses and tears out a small crypt
in which to lie. The larval nematodes migrate into this crypt
and quickly develop into adults all of which are parthenogenetic
females (Fig. 172 R). Apparently the nematode passes through
several parthenogenetic generations feeding on surrounding
plant cells and in no way injuring the insect. During its first
two instars the fly larva feeds on the viscous cell sap which
oozes from surrounding cells that have been punctured by nem
atode stylets. During its last larval instar the fly larva tears
down the walls of the cavity and feeds on the ruptured cells.
In autumn both male (Fig. 172 Q) and female nematodes
appear that become the adults of the gamogenetic generation.
This "preparasitic" female does not differ materially from the
female of the preceding parthenogenetic generations (Fig. 172
R). Both the adult male and the adult "preparasitic" female
have a stylet and three well developed esophageal glands. As in
most other allantonematids, the male does not become parasitic.
Jnst before pupating, if the fly larva is a female two adult, for
tilized female nematodes enter its body cavity, presumably by
penetrating the body wall. Male flies are never infected, female
flies invariably so. Once in the body cavity of the "host" the

feniah' ui'malodes iiruceed in their di'VelopmeMl and, li\ tlie
time the fly has emerged as an adult, they :ire dipositing eggs.
The life cycle of Fcrriusohia curriri, therefore, consists of
several i);irthenogi'nelic gener.ations passed entirely outsid<' the
"host" alternating with a gamog<Mietic geru'ration that has
lioth a "freeliving" and a "parasitic" stage. If the parthe
migenetic generations were omitted the life I'ycle would be es-
sentially the sanu' as that of uu)st allantonematids.

In the case of Frriiiixoliia curriri associated with FerfjusoiiiiKi
iiicliDl.ioiiia in galls of Fiicnlnptiis macrorrlninchia, only two
gr.ivid "parasites" are normally found in each female fly but
in souu' other species of Frrnu.soiiiua, usually those of larger
size, a female fly may harbor a gre.-iter number. As Currie sug
gests, further work may demonstrate that the nematodes asso
ciated with difTcrent species of flies are themselves specifically
distinct.

Tripius (Jinnosus (Lcuckart, 1886) Chitwood, 1!135 |Syno
iium, Atr<icl<i)\<ma (jibhoxum (Leuckart, ]8S())1 is a parasite of
the dipterous insect Cccidomjiia pini (Degeer). Since the in-
vestigations by l-enckart (18S7'), following its original discov
cry in (jermauy, this nematode has not been reported else
where or received further study. Each infected larva of C.
pini usually harbors a dozen or more, sometimes as many as
.'lO, adult female parasites showing diffi'rent degrees of de
velopment.

Eggs are laid in the body cavity of the host where they
hatch and where larvae (Fig. 177 E) accumulate in great num
bers. Leuckart could never find larvae in the alimentary tract
or secure other evidence that they pass out through the anus
and he was inclined to believe that they are liberated by the
death and decomposition of the insect. The extrusion of larvae
along with the eggs of the host when adult flies are ovipositing
seems to be an uninvestigated possibility.

The free living period, passed in the soil, is of short duration
and in a few days after leaving the host the larval nematodes
have developed to adult males and females (Fig. 177 F & G).
Ijcuckart mentions one molt, apparently the last, but noted
that sometimes the cuticle shed by the male is double. After
copulation males die and females enter new hosts. Leuckart
did not determine how the young females reach the body cav
ity of larval flies but suggests entrance through the mouth or
anus as a possibility. In the light of our present knowledge of
this group, penetration directly through the body wall seems
more proliable. Fly larvae are su.sceptible to infection from
the time they hatch until they go into the pupal stage.

During parasitic development of the female the uterus is
gradually everted through the vulva (Fig. 177 H) and develops
on the outside eventually forming an oval structure, somewhat
exceeding in size, but always firmly attached to, the body
proper that, in the meantime, has become greatly foreshortened.
The remainder of the reproductive system and part of the
modified intestine occupy this prolapsed uterus (Fig. 177 I).

The effect on the host is not pronounced and when the nem-
atodes are present in moderate numbers fly larvae are able to
pupate and become adults. However. Leuckart concluded that
this parasite is not harmless and that heavily infected flies
frequently die in the pupal stage.

Spn.*.ERUL.VRl.\ BOMBi Dufour, 1S37. This remarkable nema-
tode is a parasite of queen bumble bees. It has been reported
from several species of Bomhiis, each host usually harboring on(>
or, at the most, only a few adult female parasites though
Leuckart (1887) found 32 in one bee. Vespa rufa and V. viil-
f/arix have also been reported as hosts. This parasite has been
found in several localities in Europe and North America and is
apparently widesjiread.

S. bombi, in so far as information is available, has the typi-
cal allantonematid life cycle. Eggs are laid and hatch in the
body cavity of the host and larvae, after a period of parasitic
development, pass out by way of the anus and enter the soil.
Here the nematodes reach maturity and cojiulate whereupon the
males die and the impregnated females enter their new hosts.
The free-living period, according to Leuckart, is of several
months' duration.

Queen bees hibernate in the soil and Leuckart found that
under coniferous trees where the soil is moist and covered with
humus and moss is a favored place. Leuckart concluded that
the bees become infected in autumn when they are penetrating
the soil preparatory to hibernation and that this explains why
only queens are parasitized. Infected queens, due to retarded
development of the ovaries, are either unable to produce eggs
or produce only a few and both Schneider (188.")) and Leuckart
were convinced that such queens never found colonies.

The interesting and unusual feature about this nematode is
not its life cycle but the morphological development of the
parasitic female. After entrance into the new host the body
of the young female undergoes little or no increase in size.
Instead "the uterus is everted through the vulva, carries within

263

it tlic other reproductive organs as well as the modified intes-
tine or "fat body," and develops outside the body proper (Fig.
177 BD). This prolapsed uterus increases enormously in size
while the body proper remains a relatively minute, functionless
structure that may sometimes become detached (Fig. 11. "i A, p.
13G).

Other Species. In addition to the species already discussed,
the number of allantonematids that have as yet been named
and described is not great and for most of these information
about life cycles, especially regarding free-living stages, is
meager or lacking. A few exceptions, however, may be noted
briefly.

Bradynema rigldnm (v. Siebold, 1836) zur Strassen, LS92, is a
parasite of the dung beetle, Aphodiiis fimetarius (L.) and
Bradynema strasseni Wiilker, 1921, is a parasite of the wood-
boring beetle, Spondylis biiprcsloidcs (L.). These two nema
todes have been rather extensively investigated in Europe (zur
Strassen, 1892; Wulker, 1923) though the free-living stages of
B. rigldnm are still imperfectly known. Both have the typical
allentonematid life cycle, larvae passing out of the hosts by
way of the anus.

Souardula benifftia Cobb, 1921, is a parasite of the cucumber
beetle, Diahrotica vittata (Fab.) and, less commonly, of the
related beetles, D. trivittata (Mann) and D. di(odcciinpuncta1a
(Fab.). This nematode has the typical allantoiiematid life cy-
cle, larvae passing out with the eggs of the host (Fig. 178).
Beetles of both sexes are infected and the fate of larvae that
find themselves in male beetles is not known. Cobb (1928) was
of the opinion that these larvae may be transferred to female
beetles during copulation. He found considerable numbers of
larvae in the proximal end of the male genitalia but was un-
able to demonstrate experimentally that such larvae are ac-
tually transferred to female beetles.

In the genus Aphclenchuliis the adult, parasitic female is
usually characterized by being curved dorsad with the vulva
on the outside of the curve. A. diplogaster (Linstow, 1890),
Filipjev, 1934 (Fig. 172 P) is a parasite of the bark beetle,
Ips typographus (L.) and A. tomici Bovien, 1937, is a parasite
of the bark beetle, Pityogenes bidenlalus (Hbst.) (Syn. Tomi-
ciis bidens (F.)). These two nematodes are very closely related
and both have the typical allantonematid life cycle, larvae pass-
ing out of the host by way of the anus (Fuchs, 1915; Bovien,
1937) to undergo free-living development in the frass of the
beetle galleries.

■' Tylenchus" aptini Sharga, 1932, was found in Scotland,
where it is a parasite of the thrips, Aptinothrips rufiis (Gme-
lin). Eggs of this parasite are deposited in the body cavity
of the host and larvae leave by way of the anus. Males remain
in the host until bursa, spicules and gubernaculum arc formed
and Sharga (1932), finding no evidence that males enter the
gut or pass out through the anus, suggests that copulation
takes place before the parasites leave the host. Furtliermore,
Sharga states that "after several ecdyses the mature female
stage is reached" and his discussion and drawings seem to in-
dicate that one or more of these ecdyses take place after the
female has passed through the free-living stage and entered a
new host. If copulation takes place before this parasite leaves
the first host and the female molts after entering the second
host, the life cycle is, indeed, a departure from that known for
any other allantonematid.

Parasitylenchtis dif:par (Fuchs, 191:1) Mieoletzky, 1922, sub-
species, typographi (Fuchs, 1915) is a parasite "of the bark
beetle, Ips 1 ypographiis (L.). In general this nematode has the
typical allantonematid life cycle. The adult, parasitic female
gives birth to larvae, large numbers of which accumulate in
the body cavity of the host to eventually enter the gut and
pass out through the anus. In one respect, however, the life
cycle differs from that of most allantonematids. After com
pleting free-living development young adults of both sexes enter
the new host. One finds in the body cavity of infected beetles
200 to 300 adult parasitic females (Fig. i72 U) and an even
greater number of adult jiarasitic males (Fig. 172 T).

Fuchs (1915) did not observe copulation or determine
whether it takes place before or after entering the new host.
However, he was able to rear to maturity larvae taken from
the rectum of a beetle, the adult stage being reached in 7 to
10 days. The experimentally reared females did not lay eggs
and it seems probable that eggs are not laid until after en-
trance into a new host. If this is true we have, not a free-
living generation, as Fuehs called it, but a free-living stage.

Ostensibly, Tripiii.\ gibbositf: and Sphaenilaria hombi are the
only members of the Sphaerulariinae that have as yet been re-
ported. It may be noted, however, that Fuchs (1929) has de-
scribed two very unusual nematodes from bark beetles, viz.,
"Tylenchus sulplnirriis picear" and "Tylenchus siilphiireiis
pini." Fuchs maintained that in the case of these two nema-
todes the gravid female is not a prolapsed uterus basing his

contention, in part, on a failure to find any vestige of the body
proper or transitional stages showing the uterus in the process
of prolapsus. But in (he case of Sphaenilaria bombi, as Leuck-
art points out, the body proper is sometimes detached and one
wonders if Fuehs' material included a sufficiently complete
series of developmental stages. If the gravid female of ' ' Ty-
lenchus siiiphnreiis picear" (Fig. 177 J) is not a prolapsed
uterus its resemblance to the gravid female of Sphaerularia
hiinibi is, to say the least, very renuirkable.

Fig. 178. EOWARDVLA BESHI.\S

Showing relative size of beetle. Diabrotvja vittattt, and of its par.i-
?'ites (line XY indicates actual length of beetle) : also egg of beetle and
larval nematodes deposited with it. After Cobb, 1921.

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2Go

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266

CHAPTER VI

LIFE HISTORY (ZOOPARASITICA)

II I'AKASI'I'KS OK VKirrKI'.KATKS

ASA C. CHANDLER. Rico Institute, Houston, Texas; J. E. ALICATA, University of Hawaii,
Honolulu, T. H.; and M. B. CHITWOOD. Babylon, N. Y.

In:roductIon

The life cycles of tlie nematodes piiriisitic in veitelii:itis
differ in no essential from those of free livinj; nematodes, hnt
are subject to a numl)er of modifications which enable the
parasites to train access to new hosts with more facility and
greater certainty. With a few exceptions these nematodes
have tive stages of development separated by four moults as
do most free living nematodes, but in a few forms (e.g.. Con
tracacciim and Trivhiiullo) the number of molts is said to be
increased, and in some forms one or more of them is sujipressed
to the extent of being passed through rapidly in the egg,
or in hatched larvae with no intervening period of growth.

The outstanding feature in the life cycle of parasitic nema
todes is a cessation of develoi)ment of the young worms aftei
reaching an infective stage, while they await an opjiortunity
to gain access to a new delinitive host. In most eases the or
ganisms pass through this jieriod of w.'iiting outside the body
of the original host, either (1) as embryos inside the egg
shells (oxyurjds, ascaridids, trichurids) ; (2) as free living but
nonfeeding third stage larvae, often enclosed in the .shed
cuticle of stage two (Stroii(iijlui<l< s, many strong.vlins) ; or
(3) as third stage larvae, usually encysted, in the bod.y of an
intermediate host, which in some cases is obligatory (e.g.,
spiruroids, eamallanins, some metastrongylids) but in other
cases is optional (e.g., CapUlaria aiiiiiilain, Si/iinamiix Iraclira).
In many cases such larvae are capable of re-encystment, some-
times over and over again, in other hosts — transport hosts —
in which development to maturity does not occur. In a few
cases such secondary intermediate hosts have become neces-
sary parts of the life cycle (e.g., Gnalhostoma spinigeriim).
In the filariae and a few other nematodes (e.g., Hahronima)
the infective larvae do not become encysted, and habitually
emerge through a break in the labium of the vector as a re
suit of their own activities. A striking exception to the usual
waiting period outside the body of the host occurs in the case
of TrichiniUa spiralis, which passes its waiting period en
cysted in the flesh of the parental host.

In considering the life cycles of parasitic nematodes from
an evolutionary standpoint it is necessary to consider possible
ways in which the nematodes may have developed into para
sites of vertebrates. One method was presumably the re
suit of ingestion by the host, followed by adaptation to the
environment encountered inside the alimentary canal. It
seems probable that the Oxyuridae, for instance, became para
sitic in this manner. Such nematodes might lie expected to
have the simplest possible type of life cycle, reproducing
generation after generation in the lumen of some part of the
alimentary canal, with enough eggs or larvae escaping witli
the feces to allow for spread to other hosts through the me
dium of contaminated food or water. It seems remarkable
that only a single instance (Probst mayria viripara) is known
of a parasite which has unequivocally adapted itself to this
type of life. The nearest approach, with the exception of
Probstmayria, is the facultative parasitism of a number of
species whose congeners are saprozoic free-living forms, e.g.,
a species of Longibucca in the stomach of a snake (Chitwood,
1933), and another species of Longibucca in the stomach and
intestines of a bat (Mcintosh and Chitwood, 1934) ; Diplo
scapter coronata in ahydrochloric human stomachs (Chandler.
1!>38) ; and Ccphalobiis parasiticus in the stomachs and in
testines of monkeys (Sandgronnd, 1'.I39). In addition to these
cases, it is claimed by a number of writers (Koch, 1925;
Penso, 193:;) that Evlcrobius vrntiicufaris. Passalunis atn-
biguus and other oxyurids are callable of reproducing, gen
eration after generation, in the lumen aiul walls of the intcs
tine. This is denied by others (Zowadowsky and Schalimov,
1929; Lentze, 193.5) because of the demonstrated need of
oxygen by the embryos before they can complete their de
velopment. Even if the larvae can occasionally develop to
maturity in the gut walls, such an occurrence can certainly
be considered the exception rather than the rule. One other in
stance of repeated generations in a single host has been
claimed for Strongyluidcs stcrcoralis (Nishigori, 1928; Faust,
1931) but this is a case of short circuited rather than con
tinuous development, and occurs only under exceptional con
ditions. The offspring of wonns in the intestine do not
grow to maturity directly in the intestinal lumen, but migrate

through the body as they wouhl if Ihcy h.-iii infected from
outside.

With the few exceptions mentioned above, the simplest type
of life cycle in the case of obligatory parasites is that ex-
hibited by most species of oxyurids, in which the eggs fail
to develoi) beyond a certain point (morula stage in some,
"tadpole" in others) until exposure to oxygen outside the
body of the host, followed by reentrance of the embryonated
eggs or hatched larvae into the same or another host with
food or water contaminated by them. In many cases, jiossibly
in all. this simple cycle is modified further by a stage in
with the larvae attach themselves to the mucous membnuie,
liury their heads in it, or actually burrow into the walls of
the gut before they take up their residence in the lumen as
adults.

Few parasites other than the Oxyuroidea have as simjile a
life cycle as that described in the last paragraph. Most of
them have an instinct for burrowing at some time during the
course of their development and exercise it either (1) by bur-
rowing through the skin and going on a tour of the body
via the circulatory system, lungs and throat before reaching
the intestine; (2) by burrowing into the mucous membranes
of the alimentary canal, either being content to live buried
in the gut wall for a few days, or entering the circulatory
system and going on a tour of the body similar to that of the
skin penetrators or, in some eases, burrowing directly through
into the body cavity or through mesenteries, parenteral tis
sues, etc.; or (3) by burrowing into the body cavity or tissues
of an intermediate host, either through the surface or through
the walls of the gut after being ingested.

Two possible origins of this burrowing habit suggest them-
selves. One possible origin is as a useful instinct on the part
of gut parasites to serve either one or both of two purposes,
(1) to protect the young worms from being swept out of the
intestine with the feces, and (2) to provide a better type of
nourishment for the period of rapid growth and development.
There can be little doubt but that the burying of the head of
fourth-stage larvae of Dermatoxys vcligera (Wetzel, 1931)
and the use of the "corpus" of the esophagus of Oxyuris eqiii
as a mouth capsule (Wetzel, 1930) are steps in this direction.
One could then visualize as further developments complete
burrowing into the gut wall, penetration into the circulatory
system, and the circuit through the body that would neces-
sarily be entailed.

Tlie alternative explanation is that the worms which mi-
grate through the body originally became vertebrate parasites
by burrowing through the skin. An initial step in this direc-
tion can be observed today in the occasional invasion of the
skin of dogs and sometimes of other animals by Ehabditis
strongyloides, the adults of which live in soiled straw bed
ding. Successful development of adult parasitism by this
method would necessitate an ultimate location in the body
whence the eggs or embryos could escape in order to reach
new hosts. This condition would be fulfilled in the case of
those parasites which, after penetration of the skin, reach
the circulatory system and eventually arrive in the lungs,
where, still imbued with an instinct for burrowing, they
would escape into the air spaces. Here they could successfully
reach maturity and reproduce (e.g., Metastrongylidae) or
they could be carried passively, via trachea and throat, to the
alimentary canal. Successful parasitism would, of course, be
dependent upon loss of the burrowing instinct after the third
moult, which actually occurs.

The temporary burrowing into the intestinal mucosa of the
larvae of such worms as Ascaridia, Hacmonchus and Oesopha-
gostomum might, then, be construed either as a step in the
direction of a more extended migration, as practiced by re-
lated worms, or as a step in the direction of the simple
oxyurid type of life cycle, with abandonment of a primitive
but no longer necessary migration from skin to intestine. In
those species which usually perform the entire migration, the
failure of some individuals to do so (e.g., Ascaris. hookworms)
could be either atavistic or progressive. The fact that the
curtailed migration is more likely to occur in the normal than
in abnormal hosts is of little help in the matter, for it could
be argued either that the reason for the failure of migra-
tion in normal hosts is due to less restlessness in such hosts
and a consequent slipping back to ancestral ways, or that it is

267

duo to more perfect adaptatio.i and therefore more advanced
evolution.

It is, as a matter of fact, probable that the migration is
primitive for some worms and secondarily acquired for others.
Worms which may be assumed normally to develop directly in
the intestine are at least occasionally able to reach the in
testine even if injected under the skin. This was demon-
strated by Harwood (1930) in tlie case Cosiiioccrcoidcs diikac,
for although he found the larvae of this worm to be incapable
of skin penetration, he succeeded in recovering a few worms
from lungs and intestine after subcutaneous injection. There
is some reason to believe that the Strongyloididae and Rhab-
diasidae, the latter of which never establish themselves in the
intestine at all, may be primitively skin penetrators, whereas
it is very unlikely that the ascarids are. Whether parenteral
migration is primitive or secondary among the Strongylina is
not so easy to guess.

An interesting derivative of the migratory type of life cycle
is the course of develoi)ment of TricliinclUi. Th? unique life
cycle of this worm has apparently resulted from a precocious
development and hatching of the eggs in the uterus of the
mother, accompanied by early acquisition of the burrowing
instinct, the result being the invasion of the parental host in-
stead of a new host. The Strongylokles life cycle is another
derivative in which the parasitic worms have become partheno-
genetic and a free-living sexually-reproducing generation may
be interpolated in the course of a cycle of development whicli
is otherwise similar to that of hookworms.

In the case of nematodes whose larvae hatch outside the
body and have an instinct for burrowing it is easy to conceive
of the accidental or, in time, routine invasion of intermediate
or transport hosts. This might come about by invasion from
the outside (e.g., Protostrongylinae), or by penetration through
the gut wall after being swallowed (e.g., Anisakinae). Such
penetration of hosts other than the definitive one, and subse-
quent encapsulation in parenteral tissues, is an extremely com-
mon phenomenon, and occurs in all the major groups of para-
sitic nematodes. In some instances it is a more or less ex-
ceptional phenomenon, e.g., the encystment of Tojcocuia larvae
in mice (Fiilleborn, IH21) ; in others it constitutes an im-
portant but not absolutely essential factor in the epidemiology,
e.g., Syngamun trachea; and in still others it has become ob-
ligatory, the invaded hosts then becoming true intermediate
hosts rather than transport hosts, e.g., spiruroids.

The frequent encapsulation of some nematodes in transport
hosts and its non -occurrence in others is i)robably dependent
upon the behavior of the larvae in the hosts concerned. Larvae
that keep on the move do not become encapsulated. It is
for this reason that most spiruroids are encapsulated, whereas
Habioncma and filariae are not. No encapsulation of hook-
worm or Ascaris liimbricoides larvae occurs when these enter
rodents since the larvae complete the migration to the intes-
tine, and are then evacuated because the environment is un-
suitable for growth to maturity. On the other hand, since
Toxocara is encapsulated in mice, it must be assumed that this
worm loses its burrowing instinct before it has regained the
alimentary canal, and then becomes quiet enough to be en-
capsulated by the host.

In the Metastrongylidae alone all gradations can be found
from more or less accidental and unnecessary penetration of
an intermediate host (e.g., Dictyocaulus filaria) to obligatory
development in specific invertebrates (e.g., Aleta.stroiipyhiK.
Protostrongylus and Muellerius). Similar obligatory depend-
ence upon specific intermediate hosts has become the lot of
the entire group of spiruroids, the C'amallanina, the Diocto-
phymatina, and apparently at least one ascaridoid, SiibiiUira
hrumpti (Alieata, 1939).

A clue to the origin of the iilarioid type of life cycle, in
which the microfilariae are withdrawn from blood or skin
by blood sucking arthropods, and are eventually given an
opportunity for reinvasion of the skin by these same arthro-
pods, after development within them, is afforded by the
habronemas (see p. 286). In these the larvae show a definite
step towards the filarial type in that they fail to become
encapsulated in the intermediate host, there to await passive
transfer to the definite host, but instead remain free and
active, and leave the intermediate host, under suitable con-
ditions, of their own volition. The further steps to a filarial
life cycle are merely (1) substitution of a parenteral for a
gastrointestinal habitat for the adult worms, and consequent
liberation of the embryos into the blood or tissues whence
blood-sucking insects can withdraw them; and (2) successful
penetration of the skin by the infective larvae to reach their
deiinitive location.

It will be seen that in no case is there reason to believe
that intermediate hosts of nematodes are ancestral hosts, as is
the case with intermediate hosts of flukes.

The same modifications in life cycle have a tendency to re-
appear over and over again in the various groups of para-

sitic nematodes, and sometimes several of the principal types
may occur within a group of closely related genera. In the
genus Habroncma, for instance, the species parasitic in the
stomachs of horses are deposited by the intermediate hosts
on the lips or skin and they reach their destination by way
of the mouth, either by direct migration into it or by being
licked from the skin. In the habronemas parasitic in insec-
tivorous birds, on the other hand, there can be little doubt
but that they reach their destination in the orthodox spiruroid
fashion, by the intermediate hosts harboring them being
swallowed. In the species found in raptorial birds, however,
a secondary transport host is usually if not always involved.
Because of this lack of uniformity within even nearly related
forms, and because of the endless number of minor varia-
tions by which one type of life cycle grades into another,
we believe that a clearer picture of the life cycles of parasitic
nematodes can be given by discussing the outstanding types
and principal variations in each natural group, than by dis-
cussing types of life cycles irrespective of the natural groups
in which they occur. By way of summary, however, we sug-
gest the following classification of the principal life cycle
types :

A. Monoxenous or Direct (no intermediate host required).

1. Continuous reproduction within host, generation after
generation ; various stages of worms occasionally carried
out of bod.v and infect other hosts through contaminated
food. Ex., Probstmayiia ; facultative rhabditoid para-
sites.

2. Discontinuous, eggs or embryos escaping habitat of
adults, and usuall.v leaving parental host.

(1) Without free-living phase.

a. Simple. Eggs leave body of host, usually l)Ccoming
embryonated outside, reenter via the mouth usually
before hatching, and grow to maturity in the ali-
mentary canal. Ex., Enterobius, Trichiirin.

h. With temporary burrowing into mucosa. Ex.,
A scar id ia.

c. With parenteral migration via blood system to heart
and lungs, returning to intestine via throat. Ex.,
Ascaris laiiibricoidcs.

d. With parenteral migration via blood system to
definitive locations elsewhere in body. Ex., Capil-
laria hepatica.

(2) With free-living phase. Eggs usually hatch out-
side body of host into first-stage larvae which grow to
third (infective) stage while free, but in some forms
may develop to third stage before hatching.

a. With skin ])enctration and migration to intestinal
tract via heart and lungs.

(a) Free-living forms larvae only. Ex., Necator.

(b) With possilile development of an alternative
generation of free-living adult males and fe-
males. Ex., Strongyloides.

b. Without skin penetration; infection by mouth.

(a) With temporary burrowing of larvae into
mucosa. Ex., Ilaeinonchiis.

(b) With more extended burrowing and forma-
tion of nodules in intestinal wall. Ex.,
Oesophagoslomii III.

(c) Migration through intestinal wall and for-
mation of nodules in parenteral locations.
Ex., Strongyhis.

c. With optional use of transport host. Infective
larvae when ingested by various invertebrates be-
come enc.vsted and reach final host when trans-
port host is eaten. Ex., Syngamus ; Dictyocaulus.

B. Heteroxenous or Indirect (development occurs only in

an intermediate host)

1. Passive Indirect. Embryonated eggs or larvae enter
an intermediate host and become infective upon reach-
ing third stage. Pinal host reached when intermediate
host is eaten. Migration in definitive host, if any, via
tissues or natural passages, not via blood system.

(1) Eggs cr larvae leave host with feces.

a. Embryonated eggs or larvae are swallowed by
intermediate host. Ex., MetasiroiigyUis, spiruroids.

b. Larvae superficially penetrate foot of molluscs. Ex.,
Protostrongylinae.

(2) Larvae leave host through skin or by other paren-
teral routes. Develop after being swallowed by in
termediate host. Ex., Dracunculoidea.

2. Active Indirect. Larvae actively leave intermediate host
to reach skin of definitive host.

(1) Larvae reach intermediate host by eggs being eaten.
Ex., Habroncma.

(2) Larvae reach intermediate host by being sucked
from blood or skin. Ex., Filariae.

3. Double Indirect. Larvae utilize two or more succes-
sive intermediate hosts.

268

(1) Swoiul niiil siilisf(nicnl iiiti'iiiu'ilinli' liosis <i|ilii)ii:il,
I'ossililo Yai'iatioii in nmiiy siilnlivisions aliovo.

(2) Two snccfssivo inlormodiali' hosts (ililiRatorv : deli-
iiitivi' host roHchoil t)V ciitiiiK <•' second inti'inu"-
diiito host. Kx., (liiutlio.itoma.

RHABDITOIDEA

As noted on p. 2li7, thi'io iiro a consideialilo nnnilur iif mnui
todes IirlonKini; fo this pi-oiip whieh are faenltative parasites
of verteliiates, but only the Klialidiasidae and StioiiKyloididae
have heeonie obliflator;/ parasites of vertelrrates. In Imtli oC
these families there is a tendeney for an alternation between
f ree liviiiB and parasitic Renerations, and in both, e.xeept in
Olio species, I'ara.i't ronni/loitlts itiiichesi, there is a sn|)pre.ssion
of males in the parasitic H''">''''''io"- The larvae of most sjie
cies pellet r;ite the skin or mucous membranes and iiiinrate to
the luntis before trrowiiin to maturity. The Rliabdiasidae nia
ture in the luiiKs. and this is probably the mure ]iiimitive
condition; the StrouKyb'ididae only exceptionally mature in
the luiiKs, ordinarily returiiiiiK to the intestine before ma-
turinj;.

Stronuvi,oidii).\k

The life cycle of Stronmiloidis stercoral iv of man. the main
features of which were first elucidated by Grassi (1S78) and
I>euckart (1S.S:;), has been studied by a large number of
proniiiient parasitologists, yet even today there is no unanimi
ty of opinion about some jihases of it. Grassi observed di
roct development into filariform* larvae; Leuckait discov
ered that an alternation of gener.-itioiis might occur; van
Dunne (ISH):;) first demonstrated that infection resulted from
skin iH-netration ; and Looss (liH)")) showed that the migrntimi
of the larvae after penetration paralleled that of Ancylo.iloiixi.
Important additional details or interpretations w^itli resjiect
to this or related species have been added by Leiclitensteni
(lS9i>. 190.-)), Fiilleborn (1!>14), Sandground (lltiii). Xislii-
gori (1!»2S), Kreis (1>»32), Faust dilHS"), Liicker (l!t.S4),
Graham (1!).'?6-I03i1), Beach. T. 1)., n!l3.5 193(i) and Chitwood
and Graham (liHO).

The parasitic females live more or less deeply imbedded in
the mucous membrane of the small intestine where they pro
duce embryonated eggs which in this species hatch promptly
within the host. The embryos are rhabditiform, and resemble
those of hookworms except for the very sliort stoma. They nor
mally pass out of the body with the feces of the host, and
then begin to feed and grow. From this point on they may
follow either o le of two courses of development, known re
spectively as the direct or liomogonie type, and the indirect
or heterogoiiic type.

In the homogonic type of development the rhabditiform
larvae grow and transform into filariform larvae, sometimes
in 24 hours or less. Looss reported two molts in the course of
the develoiunent of rhabditiform to filariform larvae in the
human and other species, and Lucker (1934) observed two
molts in the larvae of S. ranxoiiii of pigs, but other observers
have not mentioned more than one molt. The -second stage
larva, according to Lucker. does not at first differ in any
morphological characters from the first stage larva, but transi-
tion to the filariform type of larva begins soon afterwards.
The first molt occurs 12 to 18 hours after hatching, the sec-
ond within 48 hours, at room temperatures. The filariform
larvae are unsheathed and constitute the infective stage. They
creep up on points of vantage in the soil or culture, often
clustering together in brush like groups to await an opportu-
nity to burrow through the skin of a host.

In the heterogoiiic type of ilevelo])meiit the rhabditiform
larvae, instead of developing into filariform larvae, change
into adult free living males and females. With the exceptimi
of Lucker (1934), no observer has mentioned or suggested more
than a single molt in the course of this development, but
Lucker has been able to trace the usual four molts and five
stages. The only morphological changes are in size and in
growth of the genital primordiiim until the fourth stage is
reached, when the structure of the head simulates that of the
adult, and the male and female characters are gradually as
sunied. At the time of the final molt the ovaries of the females
and spicules of the males are fully formed. Adults may be
found after 36 to 48 hours at room temperature.

The impregnated females produce eggs soon after they
reach maturity, and these hatch soon after being deposited.
These first-stage rhabditiform larvae are morphologically simi
lar to those hatching from eggs deposited by the iiarasitic fe
males, although a few small differences have been mentioned

*The term "filariform** is used here to denote the third stage larva of
Stronffyloitles to distinguiKh it from the third stage larva of strongyliiis
which is called "slrongyliform** larva. Its use in no way signifies a
similarity to any slage of tilariids. Actually, the esophagus is very
similar to that of an infective strongyl larva. — B. O. C.

by Kreis (1932). AIIIi.mikIi Kieis. like all ollicis lirfure him,
fails to niention luore than a single molt, l.ucker was able to
trace the orthodox two molts before the infective filariform
larva was iirodnced, .just as in the case of filariform larvae of
direct devi'lopmeiit. No dilTercnce between the two types of
infective larvae has been noted.

Heacli (193r) 193(i) showed that under particularly favorable
conditions there may be several generations of free living
bisexual forms. Kouri, Hasnuevo and .Xrenas (1930) reported
that .S*. sicrciirnli.s, after numerous free living generations, be-
comes entirely free living; the females become iiarthenogenetic
and there are no males, but the fecundity of the females gradu-
ally decreases until the cultures become sterile.

.Nishigori ( 1928) first demonstrated the opposite extreme in the
life cycle of .S*. sti-rroriiliK — internal auto infection (called hyper-
infection by Faust), with complete eliinination of a free liv-
ing stage. Nishigori also suggested circumstances under which
this might occur. Faust (1931) and Faust and Kagy (1933)
continued Nishigori 's observations, but the evidence was in-
conclusive for many until Faust and detiroat (1940) made ob-
servations at autoiisy of a case which left no room for doubt
but that under exceptional conditions in human beings auto-
infection by filariform larvae of S. nlircoralis through the walls
of the colon can occur. There is no certainty, however, that
it occurs in other siiecies or hosts.

The filariform larvae of S. .stfrc(ir<ili« and most other sjiecies
normally jienetrate the skin. If swallowed they burrow through
the mucous niembranes of mouth, esojihagns or stomach. Miiii-
nig (1930), however, states that sheep are usually infected
with S. papilloxiiK by mouth, this species being a poor skin-penc-
trator, and that larvae administered by month do not migrate
to the lungs. Lucker 's (1934) experiments with .S. ransiimi
suggest that in this species also migration to the lungs may
not take place after oral infection.

The larvae of .S*. xhrcorallx, after penetrating skin or mu-
cous membranes, enter the circulatory system and are carried
to the lungs. Faust (1933) states that they reach the lungs
unchanged; they are sometimes recovered as earl.v as the third
day, and sometimes as late as the thirtieth day. Although no
molts are mentioned, Faust distinguishes iiost-filariform, pre-
adolescent, adolescent, aid mature female mid male forms. The
post-filariform type of larvae is found most commonly in the
lungs about the fifth day; if carried to the digestive tract
they seem unable to establish themselves. These larvae are
slenderer than infective larvae, with longer esophagus, and
are more plastic. The preadolescent forms also occur princi-
pally ill the lung tissue and bronchioles, and are believed to be
too immature to establish themselves in the intestine. At this
stage, according to Faust, sexual differences are observable
for the first time, the female being still more slender than the
post filariform type and with a longer esophagus, whereas the
male shows decided resemblances to the rhabditiform larva.
The adolescent forms are migratory, and are commonly found
not only ill the lungs but also in the upper parts of the respira-
tory ti-ee, e.sophagus and intestines. Both mature females
and males were reported from lung tissue and bronchioles, but
only mature females from the intestine, where they burrow
into the walls. Lucker (1934), studying S. ransomi, ob.servcd
only a single molt after entering the body of an animal, this
occurring in the intestine about 6 days after infection ; Looss
(1911) also reported only a single molt, but Fiilleborn (1914)
apparently considers that two molts occur. By analogy with
other nematodes, and with the development of the free living
adults of atrongyloidcs itself, it would seem more probable that
two molts do occur in the course of the development in the
host.

There has been much difference of opinion on several points
in connection with the life cycle of Strimt/yloides, particularly
(1) the factors determining whether the development is homo-
gonic or heterogoiiic; (2) the reproduction status of the jjara-
sitie females, and (3), since the work of Kreis (1932) and
Faust (1933), the occurrence and function of parasitic males.

Sandground (1926) gave a brief but valuable summary of
views up to the time of his writing on the factors determining
direct or indirect development. Environmental factors were
first thought to be the cause, but Braun (1S99) and others
showed that such was not the case; Sandground felt that there
remained no substantial rea.soii for questioning the gener-
ally accepted idea that the direction of development was fixed
before the larvae entered their period of free life. Leichten-
stern (190.-|) advanced the view that there were two genetically
different varieties of the human species, differing in their life
cycles, the indirectly developing variety being confined to the
tropics, the directly developing one being especially character-
istic of the temperate zone. Leichtenstern considered the
heterogonic type to be the more primitive and gave a very
jilausilile explanation for the evolution of the homogonic type.
Darling (1911) suggested as a cause environmental effects on
the rhabditifonn larvae jirior to leaving the host, and Brumpt

269

Fig. 179. DEVELOPMENT Ob' STJi'OMiY LOI UKS AND h'HAJilJJAS

A-L — Strongyloides ransomi (A-B — Direct cycle, A — First stage larva.
newly hatched; B — Larva in first molt; C-J — Indirect cycle: C —
First stage larva, newly hatched ; D — Larva in first molt ; E — Larva
in second molt ; F — Larva in third molt ; G — Larval female in fourth
molt, H — Fiist stage larva from free-living female, newly hatched; I —
Second stage larva, immediately after first molt; J — "Filariform" larva
undergoing second molt; K-Lr — Parasitic generation, K — Larva from
suiall intestine of pig about 4 days after percutaneous infection; L —
Larva fi om pig, showing early final molt) . M-0 — Rhabdios fulleborjii
(M — Free-living female with larva, the genital organs already destroyed:
N — Cuticular hull of female with only one filariform larva, 115 hr. old
culture; O — Filariform larva (Same as N) from which ruticle of fe-

male has been carefully removed) . P-Q — Rhnhdia^ fuscovenosa (P —
Infective rhabditiform larva 72 hours after hatching from egg of para-
sitic generation; Q — Filariform larva (infective larva) from free-living
generation) . R — Parastrongyloides winckesi male, S-W — Rkabdias fua-
corenosa, direct development {S— Rhabditiform larva ; T — Ensheathed
infective larva; U — Anterior end ; V — Anterior end during third and
fourth molts; \V — Posterior end of same). A-L, after Lucker, J, T..
1934, U. S. D. A. Bull. no. 437. M-0. after Travassos, L., 1926.
Arch. Schiffs. u. Tropen-Hyg. v. 30. P-Q. after Chu. T. C. 1936, J.
Parasit. v. 22 (2). R, after Morgan, D. O.. 1928, J. Helm. (6).
S-W, after Goodey. T., 1924, J. Helm. 2.

270

<I!I21> piishfd till' i.ott'niiinatioii ;i:ifK still r'lirtliii', l» ilu- dc
velopiiift OKRS. Siiiidttrouinl (lil'JO), wlio ro|ioitiMl tlio nndliiR
of sperins in frmali' worms jinil romUiili'd that the worms
wore liermapliroditic, sii(;K>'sti'd that tlio diri'ition of drvrlop
mont is dotormiiiod Ivv tlio cliioinosoiiial constitiilioii of tlio
ORRS siibsi>(iU(Mit to firtilizatioii. Kaust (l!i:!3), liaviiiK found
what he inti'rprotod as parasitic niaU's. suntri'stcd that fntilizi'il
*'BBS givo risi" to hotoioKoiiic and iitifi'rtili/.ed orks to lionio
gonic progeny. Snlisecpiontly Beacli (, 1!I,'!.">1 ".).'!(>'), working in
Faust's laboratory, showed conelusively that the course of
development can l>e iiitluenccd by nutritional conditions; as
these become less favorable more and more of the rhabditi
form larvae undergo direct development to filariform larvae
instead of becominu males and females. The evidence indi
catcd that the potential females are intluenced in this way
more readily than the potential males.

Meanwhile Graham (ISKUi l'.)3il) started two pure lines of .S.
rata of rats from original single larva infections of the homo
gonic and heterogonic type, respectively, and found marked
inherent dilTerenees between them. In each line over 85 per-
cent of the total progeny were of its own type, with an ex-
treme difference in the number of males produced. Graham
also observed that there was .-i falling off in heterogonic larvae
in winter as comjiared with summer, brought about b.v climatic
effects on the host, not on the develojiing larvai'. Tlie conclu
sion seems warranted, therefore, that the course of develop
ment is dependent upon nutrition or other cnvirontuental con
ditious and not upon genetic constitution, but that there are
genetic differences in the e.\tent to which different strains
are influenced towards homogony by a given degree of unfavor
ableness in the environment.

The reproductive status of the parasitic females was brought
into question by Sandground (lilifi^ ; prior to that time it
had been generally accejited that they were partheuogenetic,
although Leuckart ai>parently suspected that they were hernia
phroditie, by analogy with the condition in the parasitic genera-
tion of Rhabdia.i. Satulground believed them to be protandrous
hermaphrodites; he described what he interpreted as sperms
and observed what seemed to be fertilization in specimens of
S. ratti. Faust (1933), having found male worms in the lungs,
concluded that the sperms observed by Sandground luobably
were the result of copulation. He considered the worms to
be bisexual early in life, later becoming parthenogenetic. Chit-
wood and Graham (1940) concluded that -S. ratti was parthe-
nogenetic since they were unable to find sperms and also un-
able to find fertilization membranes. The weight of evidence
is therefore in favor of parthenogenesis.

The occurrence of parasitic males described by Kreis (1932)
and Faust (1933) has not been confirmed by others. In an
unpublished observation, one of us (J. E. A.) has noted adult
rhabditiform males in the fresh feces from a ease of human
strongyloidiasis but it was unknown whether these were para-
sitic males or males developing from eggs of parasitic females.
The fact that the supposed parasitic males of Kreis and of
Faust were rhabditiform and practically identical with free-
living males is sufficient cause for doubt that they are really
males of the parasitic generation, for in the one other mem-
ber of the Strongyloididae in which males have been found —
Parastronffyloidcs uinchcsi, Morgan 1928 — the parasitic males
are filariform like the females. We suggest that, since Faust
not only observed eggs and rhabditiform larvae, but also
filariform larvae which he interpreted as the progeny of
the parasitic worms, in the lungs and bronchioles of infected
hosts, the males observed were free living males produced
precociously in the lungs. The observations of Beach (1. c.)
that males will develop more readily than females under subop-
timal conditions would account for the failure to find free-
living females. Graham's work with single-larva infections
has shown clearly that males are at least unnecessary in S. ratti,
though no conclusions can be drawn from this, for it is, of
course, possible that there might be differences between spe-
cies in this respect. For the present the occurrence of rhab-
ditiform parasitic males in members of the genus Strongy-
loides must certainly be considered sub jtidice.

Fig. 180. DEVELOPMENT OF STRONGTLOIDKS

A-G — StTontryloiileg stercorals (A — Parasitic female; B — Free living
male; C — Free living female; D — Filariform larva (human strain A),
from lung tissue of experimental dog three days after skin inoculation;
E — Post-filariform larva from same: F — I'readolescent female from lung
of experimental dog 11 days after skin inoculation, note developing
genital primordium; G — Adult male from lung tissue of experimental
dog 57 days after skin inoculation). H-M — Strongyloitle/t sp. from dog.
free living generation (H — First stage larva; I — Infective larva: J —
Tail of infective larva; K — Head, adult female; L — Adult female; M —
Tail, male). A-C. after Faust. E. C, Human Helminthology. 1939.
D-G. after Faust. E. (',. 1933. Am. J. Hyg. v. 18 (1). Remainder
original drawings by M. B. C.

271

Ehabdiasidae

The niembers uf tlio genera EJiabdian and Entoinclat:, now
separated into a separate family from Strunyyloides, resemble
Strongyloididae in having an alternation of generations, at
least in some species. This double life cycle was tirst demon-
strated by Meczuikov (18G.j) in the case of M. btifonis. Unlike
StrongyluidcK, the parasitic generation, at least of some species
of Sliabdias, consists of hermaphroditic females, possessing a
well developed seminal receptacle. Seurat (1920a), however,
thinks that the parasitic forms of Entumdas dujardini and
E. entomclux from Anguis fragilis are parthenogenetic rather
than protandrous hermaphrodites, since he was unable to find
seminal receptacles or to detect sperms.

As in Strongyloides, l)oth homogonic and lieterogonic types of
development may occur in the free-living phase of the life cycle
of Sliabdia.i. In most of the species one type or the otiier
strongly predominates or may even occur exclusively, though
in some of the forms in which one type of development was
long thought to occur exclusively, the alternative type has
more recently been observed. Travassos (i;i2()) called atten-
tion to the fact that the species found in Amphibia and La-
certilia have indirect development, while those found iji snakes
liave direct development. Chu (iy3(i), however, reported some
unpublished observations of Chitwood 's, and also some of his
own, in which both types of development were found in sev-
eral amphibian and reptilian species, (ranac, eustreiitus, fulle-
borni, and fuscovenosa var. caUtiicnfiin). In the last-named spe-
cies Chu observed only homogonic development except wlien
an especially favorable culture medium was used, whereupon
a small percentage of free-living adults, predominantly males,
were usually found. The oflspring of these adults failed, how-
ever, to infect snakes. It seems evident from this data that the
course of development of Bluibdia!< is determined by factors
similar to those operating in the case of Utroiigijloidcs.

Whereas in SI niiigiituidc s both direct and indirect infective
larvae are filariform, in the Rhabdiasidae the direct huvae are
rhabditiform while the indirect ones are filariform (cf. Figs.
17ii, P-Q). The free-living adults of different species vary con-
siderably in their mode of reproduction. Travassos describes the
free-living female of S. fiiUcborni of frogs as producing only
one or two larvae, which may become fully developed within the
mother, destroying her tissues, whereas Chu (lit.^G) describes
K. fuscovenona var. cataiiciiin as having a few eggs in each horn
of the uterus, which are usually laid when little or no develop-
ment has occurred.

According to Goodey (,l!t24) the homogonic larvae of S.
fuscovenosa undergo two ecdyses outside the body of the host,
the second shed cuticle being retained as a tight-fitting sheath
for the infective larvae. The sheath is shed' upon gaining
entry to the host. The larvae molt twice more during de-
velopment in the host's parenteral tissues, but both shed
cuticles are retained as sheaths. Although the infective larvae
of S. bufoiiis were reported by FuUeborn (1920) to penetrate
the skin, and by the same writer (1928) to migrate to the
lungs via the circulatory system, Goodey (1924) failed to
get the infective larvae of R. fuscovenosa to penetrate skin,
although their behavior outside the body was like that of
skin-penetrating larvae, and he also thought it probable, from
their distribution in the body, that they migrated to the lungs,
after penetrating the gut wall, by direct migration through
the mesentery and not via the blood stream. Fiilleborn (192S)
called attention to the fact that larvae of E. bufoiiis would
also penetrate snails and possibly other invertebrates, where
they rcmaiu unchanged for weeks, capable of infecting a frog
when the snail is eaten. Similarly the larvae may sometimes
became encapsulated parenterally in frogs which may then
act as "transport hosts" for infection of larger frogs which
eat them. Fulleborn suggests that since the skin of snakes is
hard to penetrate transport hosts may constitute the principal
method of infection for these hosts.

STRONGYLINA
I. STRONGYLOIDEA AND TRICHOSTRONGYLOIDEA

Three geneial types of life cycles, which more or less merge
into each other, occur in the superfamilies Strongyloidca and
Triehostrongyloidea of the suborder Strongyliua. One of these,
characteristic of the Ancylostomatidae and a few other forms
in the Strongyloidca and Triehostrongyloidea, is essentially
the same as the homogonic cycle of Ehahdias, except that the
parasitic worms are bisexual. It involves development to the
third (infective) stage outside the body of the host, skin pene
tration, and parenteral migration via the circulatory system
after infection. The second, characteristic of most of the

Triehostrongyloidea and many of the Strongyloidca, differs
in that there is no skin penetration, and no migration in the
host beyond the walls of the alimentary canal. The third,
characteristic of the Syngamidae in the Strongyloidca, in-
volves development and molting within the egg, w^ithout feed-
ing or growth, with at least optional establishment in an in-
vertebrate transport host, and a parenteral migration which
leads to the respiratory system but not lieyond. We think it
probable that both types 2 and 3 were derived from type 1,
although it is also possible that type 2 is the most primi-
tive, and that types 1 and ?> were both derived from this.

1. Ancylostoma spp.
The genus Ancylostoma will serve as a typical example of the
first type, involving skin penetration and parenteral migration.
The eggs of these worms are deposited by the adult females
in the lumen of the small intestine, whence they make their
exit with the feces; at the time of leaving the body of the
host they are nearly always in the four-celled stage of devel-
opment, normally being unable to progress beyond this point
without free oxygen. Under optimum conditions of oxygen,
moisture and warmth (7.1° to 8.')° F.) the eggs proceed with

Fig. 181. DEVELOPMENT OF HOOKWORMS

Ani-ylostonui dtindenale. A — First stage larva ; B — Second stage; C —
'I'liird stage. D-H — Development of primitive and definitive capsules;
( 1) — Bladder-like structures forming around the larval oral cavity, with
heginning of formation of the primitive larval teeth; E — Nearly com-
pleted primitive capsule, with triangular teeth at base, and old larval
oral cavity still running through center of primitive capsule; F — Fully
developed primitive capsule with beginning of formation of bladders at
its base; G — Later stage in development of dorsal and ventral bladders
which will eventually form the definitive capsule; H — Later stage in
development of definitive capsule, with primitive capsule still connected
with esophagus by a strand of tissue; I — Female larva with definitive
capsule formed but primitive capsule still attached ; J — -Male after final
moult but last cuticle still enclosing it; K — Male larva with primitive-
capsule. After Looss. Chandler. A. C. 1929, Hookworm Disease.

272

thoir (U'voli)|)niiMif laiiidly, :iii<l :i rliiiliilitifi)iiii liirvji iiiav
liatih witliin :;4 lunirs. This larva is aliout •_'."!() ^ loiiR, with nii
iMonuali'il liiiccal cavity ami a typical rhahilitiform csophaKiis
IKisscssiiiK csoiihaiioal valves. Tlu'so larvae were shown l>y Mc
Coy (IJIJill to (icvclop normally with oTily pnrc cultures of cer
tain species of living bacteria as food. Tniler favorable con
(litions the larvae underKo the first ecdysis or molt within 4S
li.niis atter liatchinj;, bnl second sta(;e larvae show very slight
niorpholoKical difTeronccs from first sta^e larvae, although they
arc about 400 to 4:U) A" long, .\ftor a niiniuiuni of about 2 more
d.-iys the larvae cease fecdiuK. undergo a second ecdysis, and
enter the third or infective staRO. The cuticle shod at this
molt is normally retaiiu'd as a protective sheath, though it may
occasionally be lost. The most important inori)holo^rical changes
in the infective larva are noted in the shape of the tail and the
structure of the esophaRUs. The tail is shorter and more stumi)y
than that of the prccediuK stages. The esojihaKus is "lilari
form," or preferably "strouByliform," i.e., it is more uni
form ill width with tapering anterior portion, and the esoplia
seal valves are lacking. The anterior portion of the lumen of
the stoma is closed and the reuuiining posterior portion remains
open in a characteristic shape. According to .\licata (l!>.'i."))
the various third stage larvae of strongylid nematodes para
sitic m swine can be differentiated, among other ways, by the
form of the stoma; there is a jiossibility that this character
istic may hold true for other members of the Strongylina.

The infective larvae climb up on ob.jects as high as a film of
moisture extends, and show positive thermotropism and thig-
motropism. They retire from excessive warmth in direct sun-
light. They migrate vertically if buried in soil, but migrate
laterally to a very slight extent (Chandler, 1925).

.Mthough Leuckart (ISOO showed that .(. caiiiiiiim of dogs
could 1)0 transmitted per n.i, and Leicliteustern (ISS(i) proved
the same thing for .1. iltuHlciiali' of man, the usual mode of in-
fection is by iienetration of the skin; this method of infection
was first demonstrated by Looss (ISiiS). In subser|uent work
Looss (190.")) established the course which the larvae follow
in the body to reach the intestine. Skin penetration is accom
plishcd in a few minutes when the larvae are able to obtain
leverage, as in mud, to help them in their burrowing, but they
are nimble to penetrate when submerged iu water. Within 3.")
to 40 minutes the larvae, having left their sheaths behind them.
have reached the dermis and within a few hours are in the sub
cutaneous tissue. Many find their way into superficial lym
phatic capillaries, and a few directly enter blood vessels. Some
larvae are slow in entering the circulation, and may be en-
capsulated in the .skin, especially in hosts sensitized by previous
exposure. Certain "foreign" species of hookworms, e.g.
Aiicnlo.'ttoma braziUense and Uncinaria' stowccplmla in man,
commonly fail to enter the circulation at all but wander aim-
lessly in the skin, causing "creeping eruption." Although the
larvae may remain in the skin for considerable periods no de-
velopment takes place there (Fiilleborn, 1927).

When larvae enter the lymphatics they are carried first to
the regional lymph glands, and then to the main lymph chan-
nels leading to the thoracic duct, through which they enter the
circulation. Such larvae, as well as those which entered the
blood system directly, eventually reach the right heart, whence
they are pumped out to the lungs. Here the ma.iority burrow
into the air spaces (Fiilleborn, 192.')), and are then mechani-
cally carried in mucus, helped by epithelial cilia, to the trachea
and throat. If .swallowed they now pass to the alimentary
canal, and grow to maturity in the intestine.

Although .skin penetration is undoubtedly the usual mode of
infection, infection by mouth can also occur. There has been
considerable controversy as to whether swallowed larvae had
of necessity to penetrate the mucosa and migrate to the lungs
before growing to maturity, or whether they could develop to
maturity without such migration. Yokogawa (192(5) investi-
gated the matter and found that when A. canhnim larvae are
fed to puppies a few penetrate the walls of the alimentary
oanal and enter the circulation, but the great ma.iority of those
which develop at all do so directly, without migration. In ab-
normal hosts, however, such as rodents, most of them perform
the usual migration via the circulatory s.vstem, and a few mi-
grate through the tissues to the body cavity whence they enter
the liver, or go through the diaphragm to the ])leural cavity,
whence thev enter the lungs. This work was confirmed In-
Scott (1928). Fiilleborn (1926-1927) showed that the larvae
of Uncinaria strnociphala of dogs also develop directly after
oral infection, few migrating even in abnormal hosts. Several
Japanese workers, however, (Myiagawa, 191fi; Myiagawa and
Okada, liiSO, 19H1; Okada ig.'Sl) have persisted in the belief
that lung migration is a biological necessity for hookworms.
Foster and Cross (1934) carried through some further cxjjeri-
ments which conclusively confirm the earlier work, showing that
the lung .journey is not a biological necessity for these worms
(though it apparently is for Strongyloidex sfrrcoraUn.) Swal
lowed larvae rarely migrate in su.sceptible normal hosts, but

coniinonly do so in abriormal hosts and in resistant normal ones.
I.oo.ss (1911) and S'okogawa (192(i) observed that sw;illowed
hookworm larvae remain in the stomach at least 2 days, and
I'illleborn (1927) found tin'y could remain there at least ")
(l.iys, partly in the lumen, jiartly deep in the mucous glaruls.
Ill' demonstrated that the larvae have an initial tendency to
burrow into the glands, later to return to the lumen, as is the
case with Asroriiiia. lie thinks that something in the secretion
of the mucous glands causes the larvae to lose their mobility;
possibly the .same mech.'inism is responsible for the loss of the
burrowing instinct in the l;irvae reaching the intestine from the
Inngs after skin penetration (see below).

The minimum time rc(|uired for the larvae to reach the
trachea after skin penetration is usually about 3 days, but the
ma.iority re(|uire 4 or ."i days, and some still longer. By the
time the larvae appear in the bronchioles and tr;ichea they have
grown slightly in length, have developed a provisional mouth
capsule, and are ready for the third molt, although there is no
evidence tli:it the.v ever complete it before reaching the diges-
tive tract. The formation of the provisional, and subsefiuently
of the definitive, month capsules is accomplished by the devel-
opment of dorsal and ventral bladder like structures posterior
to the already existing mouth. These spread around tin' sides
and finally unite (Looss, 1905) (Figs. 181).

Up to the time of the third molt the larvae grow very little
in length, but increase from about 20 m to 30 M in diameter.
The molt usually occurs very soon after the larvae reach the
intestine, and the larvae at this time lose their tendency to
burrow, so remain in the intestine. There is no evidence that
they temporarily burrow into the glands of the stomach as do
larvae that are directly swallowed. The young worms now
grow very rapidly. They may reach a length of 2.5 to 3 mm
within a few days. Sexual differentiation now begins, and in
from 4 to 6 days after the third molt the definitive mouth cap
sule is developed. By the time the worms have reached a
length of from 3 to 5 mm. the fourth molt takes place. There-
after the worms grow to maturity, copulate, and begin egg pro-
duction. In the case of Aitcylostoma dnodeiiale in man the
eggs first appear in the feces 5 to 6 weeks after infection,
whereas in A caiiiinim of dogs, eggs may appear as early as 15
d;iys (Herrick, 192S).

2. IIaemonchus contortus

The life cycle of this worm as worked out by Ran.soni (1906),
Veglia (1916) and others is essentially the same as that of the
ancylostomas in its free-living phase. The infective, ensheathed
third stage larvae, however, are not skin-penetrators, but have
a tendency to climb up on vegetation or other ob.iects where
they are in a favorable position to be ingested by their herbiv-
orous definitive hosts. Here they curl up, and are remarkably
resistant to cold and to moderate desiccation. Upon being in-
gested by the final host the larvae bury themselves in the mu-
cous glands and crypts of the abomasum, where they undergo
the third and fourth molts; the sdult stage is reached after
about the 9th to 11th days, and the worms emerge to live in the
lumen of the organ, beginning egg production about 3 weeks
after infection. Although there is no evidence that the worms
perform a parenteral migration in sheep, Ransom (1920)
showed that they do migrate to the lungs in guinea pigs.

3. Syngamus trachea

The life cycle of this worm was first experimentally worked
out by Ortlepp (1923). The eggs of the worm are laid in the
bronchi or trachea of the host in an advanced stage of seg-
mentation. Under favorable conditions the first-stage larva is
developed in about 3 days, but the egg does not become infec-
tive until after 1 to 2 weeks, whereupon they may or may not
hatch. Ortlepp observed only a single molt during the course
of development and interpreted the infective larva as a second-
stage larva but Wehr (1937) demonstrated that the develop-
ing larva undergoes two molts within the egg. Buckley (1934),
studying 5. ierci of cats, also observed the usual two molts.
Yokogawa (1922) also missed the first molt in the case of
Xippostrongylus muris, and in spite of the large amount of
experimental work done with that worm the missed molt was
not discovered until 1936, when Lucker demonstrated it. The
first cuticle in both these worms is extremely thin, and the
second ecdysis may be in progress before it is coinpletely shed.

Infective larvae, whether hatched or .still in the eggs, are
infective when directly swallowed by susceptible hosts, but
very often they are swallowed by various invertebrates; when
this happens they penetrate the gut wall and become encap-
sulated in the body cavity. Walker (1.SS6) and Waite (1920)
both called attention, on epidemiological grounds, to the impor-
tance of earthworms in the dissemination of this parasite, but
Clapham (1934) first experimentally worked out the role played
by these annelids. Subsequently Taylor (1935) showed that

273

Fig. 182. DEVELOPMENT OF THE STRONGYLINA

A-C — Syngamus tracheaii^. (A — Ensheathed second stage larva; B —
Third stage larval female; C — Ensheathed young fourth stage larval
male). D-F — Syngamus ierei (D — Third stage larva; E — .\nterior end
of third stage larva; F — Tail of third stage larva). G — Haemonchus
contortus on blade of grass. H-N — OUulanus ti'icuspis (H — First stage
larva; I — Second stage larva; J — Tail between first and second stage:
K — Third stage (infective) larva; L — Fourth stage female; M — Fourth

stage male; N — Gravid female). 0-U — Dictyocaulus arnfieldi (0-^Egg
from the feces; P-Q — First stage; R — Second stage; S — Third stage; T
— Fourth stage male; U — Fourth stage female). A-C, after Ortlepp.
1923, J. Helm. v. 11. D-F, after Buckley, 1934, J. Helm. v. 72. G,
after Ransom, 1906, U. S. Bur. An. Ind. Circ. 93. H-N, after Cameron,
1927, J. Helm. v. f>. O-II. after Wetzel and Enigk, 1938, Arch. Wiss.
u. prakt. Tierheilk. 73(2).

274

siiiiils iiiul sliiRS wuiild also si'ivo as transport liosts, ami later
found that tlio pneystod larvae would remain viable in these
niolUises for several years. More reeeiitly Clnpham (l!>Sila,
l!).!i>h"l showed that niaRBots. erane tiy larvae, spring tails ami
eentipedes would serve in a similar eapaeity, and that the
worms were alile to survive metamorphosis in the tissues of
tlies.

When iiiKesteil liy these hosts the infeetive larvae lialih fnini
the eRKS if they have luit already done so, penetrate the gut
wall, and enter the body eavity, where they are eventually en
eapsulated by the host tissues, t'lapliani has shown that the life
eycle is eompleted somewhat nuire readily with the aid of a
vector than without, and was able to infect chickens readily
with a starlint; strain when an earthworm vector was used,
whereas Taylor ( 1!>11S^ had had difficulty in doinjr so by direct
infection. I'lapham calls attention to the fact that Siiii'li'miix
trachea is evidently nndergoinK evolution in its life cycle; at
present it can still develop without an intermediate host, and
iuis not as yet adapted its requirements to any imiliciilar inter
mediate host, Init can use almost any that happens to swallow
it. She makes the reasonable suggestion, however, that in time
difTerent strains may adapt themselves to different intermedi
ate hosts, as determined by the food habits of the final hosts.
and thus i>erhaps give rise to new species. At present, however,
the effect of living in a transport host seems to be to rliiiiiiiair
physiological differences; for example, in the case of starling
strains developing in chickens. Tt is ]>ossible that some species
of StjiiDamiis may already have reached the stage of reciiiirixn
an intermediate host, since Buckley (1S134) was unable to ii\
feet cats with eggs containing third stage larvae of S. irrci.

After infection by swallowing eggs, free larvae, or larvae
contained in invertebrate transport hosts, .S". trachra appar
ently reaches the lungs via the circulatory .system. Orflepp
(1923) found the larvae in the lung tissues within 24 hours
and Wehr as early as 17 hours after infection. Welir found
fourth stage larvae after 3 days and immature adults after 7
days; some of the latter were already in cDpiila even before
entering the trachea.

Variatioks in the Life Cycle in Other Stroncyi-oide.v

AND TrICHOSTRONGYLOIDEA

The preparasitic stages of nearly all the members of the
Strongyloidea and Trichostrongyloidea, except the Syngamidae,
are remarkably similar, involving two free living rhabditiform
stages separated liy a molt, and a strongyliform third stage, in
which the shed cuticle is usually retained as a sheath. The
time intervals between the molts and the total time required to
reach maturity vary considerably; in some species, e.g. Ornitlio-
strongi/lus quaflrirndiatiis, the infective third stage may lie
reached within 3 days. The infective larvae are distinguish
able by characters of the mouth, buccal cavity, esophagus,
shape of tail, length of sheath, etc., and also, as Lucker has
shown in a series of papers (e.g., I^ucker, 1938) by the num
ber and arrangement of cells in the intestine.

The only important variation from this formula is the molt-
ing of some species within the egg, thus eliminating a period
of feeding and growth outside the host ; this, as already noted,
occurs in Synfiamim and it also occurs in XcmatoiUnis spp.
(Ransom, 1911; Maupas and Seurat, 1913) and in OsuaUlo
cruzia fijiformis (Slrongyhis auriciilari.t, Zeder) (Maupas and
Seurat, 1913 >. According to the latter authors, Ostcrtagio
marshalli hatches as a second stage larva and undergoes its
second molt 2 or 3 days later without feeding. This is not
true, however, of 0. circumcincia. When botli molts occur
inside the egg the infective embryos may or may not hatch
prior to being swallowed by a host, eggs containing infeetive
third-stage larvae being infective as well as the free larvae.

Strong ylacantha glycirrhi^a, according to Seurat (1920b),
hatches at the end of 48 hours but the larvae fail to feed, and
at the end of a month hare molted twice and are ensheathed
in both shed cuticles, .just as in the case of Dictyncaiiliis (see
below).

A striking exception to the usual course of events occurs in
the case of Olliilaniis iricuspis, according to Cameron (1927).
This parasite of the stomach of eats is viviparous. The eggs
hatch in the uterus of the mother, and the larva undergoes its
first molt before it is born, acquiring the typical tri cuspid
tail. Third stage larvae are found free in the stomach of the
cat, but it is not certain whether the second molt occurs before
or after birth. This form is believed by Cameron to leave the
stomach with the vomitus of the eat. When eaten by another
cat with the vomitus the larvae change to fourth-stage larvae
and finally adults. Some part of this development is believed
to take place in the depths of the mucous membrane. No other
method of exit from the cat has yet been found ; no larvae were
ever seen in the intestine, nor were mice infected when fed on
cat stomach or infected vomitus. Continuous auto infection is
believed possitde but improbable; Cameron suggests the pos-

sible production of a substance inhibiting complete larval de-
velojiment, as postulate<i by Fiilleborn in tin' case of UhitlxUas
hiifonis in the lungs of frogs.

The mode of access of the infective l:nvae to the final host
varies in different species, even, sonietinu's, within the same
genus. There arc three possibilities: (1) pcTwtration of the
skin; (2) ingestion with food or water; (3; ingestion with a
transport host. Skin penetration is characteristic of most of
the hookworms (l*'amily Aucylostomatidae) — Avrylontoma,
Xecalor, i'ncinaria iind (laigerin — but Iliiiioslomiiiii seems to
be an exception in that, althinigh the larvae, at least of B.
Irigonncrplialiim, seem to be capable of penetrating under cer-
tain conditions (Ortlepp, 1937, p. 2(17), they do not clo so as
re.idily as other hookworm larvae (Cameron, 1923; Schwartz,
192.'>), and normally infect by mouth. Although most of the
hookworms ;ire able to infect the host by mouth as well as
through the skin, and may even be able to dispense with the
parenteral migration (see above), Ortlepp (1937) was unable
to cause infection in sheep by the oral route with larvae of
Caigeria pacliy.scrli.i. Most other members of the Strongy-
loidea and Trichostrongyloidea fail to i)enetrate the skin al-
though a few {Slcphaiiiiriis deniattis, Nippostrongylux miirix,
Langixlriata mii.seiili, Trichostrongyliin caJcaralus) are able to
do so. Other species of Trirhostrongylux apparently do not
penetrate the skin. Xippo.ilroiigyhix miirix is almost wholly
dependent upon skin penetration ( Vokogawa, 1922), whereas
for Langiatriaia miisciili oral infection is probably more impor-
tant in nature (Schwartz and Alicata, 1936).

The great majority of the worms belonging to the groups we
are considering normally enter the host by mouth, with con-
taminated water or food. In most cases the larvae climb up on
living vegetation and are more or less resistant to desiccation.
This is true of all the Strongylidae so far as known (except
Stephaniinix), and all of the Trichostrongyloidea with the ex-
ception of the few mentioned in the preceding paragraph, and
OUiiIanus.

The development within the host involves varying degrees
and types of migiation. Skin-penetrating larvae usually follow
the route described above for ancylostoraes, but Schwartz and
Alicata (1936) showed that the larvae of Longislriata muscnU
do not normally do so; they appear in the stomach within a
few hours after skin penetration, and in the intestine soon after
that, but they were not found in the liver, lungs or stomach
walls. Their actual route was not determined. In the case of
this worm, whether infection is by skin or mouth, the entire
development takes |)lace in the intestine, contrary to what
happens in other skin-penetrating £orms, even in the nearly
related Xippo.itrongyliis.

Nematodes infecting by mouth may or may not migrate via
the blood stream. Most of the Trichostrongyloidea (e.g.
Cooperia, OrnithoxtroiigyJiis, Ostcrtagia, Obeliscoidcs, Graphid-
iiiin. Eacmonchu.^, Hyoxtrougyliis, most species of Trichostrong-
his, Xematodinis) perform no migration at all beyond a more
or less temporary invasion of the glands or crypts of the
stomach or duodenum. Some forms, e.g., Ornilhostrongybis
qiiadriradiatiia, may reach the adult stage of development as
carlv as the third" or fourth day after infection (Curillier,
1937).

The Strongylidae show various gradations from invasion
of the circulatory system and transportation with the blood, to
mere temporary invasion of the glands. Of the three common
species of Strongylus in horses each shows characteristic fea-
tures in its migration, the larvae of S. vulgaris being found in
aneurisms in the anterior mesenteric vein, those of S. ideniatus
under the peritoneal walls of the abdominal cavity, and those
of S. equinus in liver and pancreas. According to the usually
accepted view (see, for example, Xeveu-Lemaire, 19.36) .S. vtil
garis penetrates the walls of the jntestine and migrates through
the body via the circulatory system, passing through the capil-
laries of both liver and lungs to be distributed all over the body
by the systemic arterial circulation. Ninety percent stop in the
anterior' mesenteric artery, to the walls of which they adhere
by using the mouth as a sucker. The resulting irritation leads
to the formation of an aneurysm and thromboses. Here they
remain for .") months, meanwhile growing and passing through
two molts; one at a length of 3 to 4 mm, the other at a length
of 7 to 10 mm. Having jiassed the final molt they release their
holds and are carried by the blood stream to the walls of the
cecum or colon. They remain imbedded in the walls in little
nodules under the mucosa for about a month, and finally make
their exit into the lumen. Olt (1932) thinks that the normal
migration is via the lungs and trachea as in the case of hook-
worms, but that some larvae burrow through the intestinal
walls and l)etween the laminae of the mesenteries until they
reach a large bloodvessel. If this is a large, heavy-walled
vessel the slow jiassage through it leads to inflammation and
the characteristic aneurysms. Wetzel and Enigk (1938a), on
the other hand, believe they have convincing evidence that no

Fig. 18,!. STROiVOTLUS TULGARIt:

Verminous aneuvvstns jiffecting the anterior mesentei'ic
Foster & Clark, 1937. .\i>i. J. Tniii. Med. v. 17 (1).

artery. After

Strongj/lus larvae migrate via the hiiigs and trachea, but under-
go tlieir whole dfveloptueut within tlic abdominal cavity.

S. edentatus larvae penetrate the walls of the intestine and
the majority come to rest under the peritoneum, though the
route followed in reaching this location has not been traced.
Some, probably carried by the blood stream, reach the liver
and lungs. After about 3 months, during which they grow
much larger, the larvae migrate to the roots of the mesenteries
and travel between the laminae to the walls of the cecum and
colon. Here they become lodged for about a month in large
subserous liemorrliagic nodules wliich eventually open into the
lumen of the intestine.

S. equiniis larvae penetrate the walls of the intestine and
make their way to the liver and pancreas. It has generally
been assumed that they arrive in these places via the blood
stream, but Wetzel's observations (I.e.) throw doubt on this.
After development to the fourth larval stage they return to the
walls of colon and cecum, again by an undetermined route, and
continue their growth in nodules in the walls of these organs.
After reaching the final stage of development by a fourtli molt
they pass into the lumen.

The Trichoneminae of horses are believed not to migrate out
of the intestine at all. Many of them, jierliaps all, penetrate
into the walls of the mucosa where they develop in nodules. They
undergo the tliird molt when about 1 mm long, becoming what
Ihle and Ocirdt (1923) call "Triehonema" larvae, provided
witli a provisional moutli capsule. Tlie final molt occurs in the
lumen of the intestine.

Trioilontopliorus tcnuicolUs- is believed by Ortlepp (102.T) to
develop directly in the lumen of the cecum and colon, without
even temporarily burying itself in the mucosa. He was never
able to find larvae of this species in nodules. However, only
fourtli stage larvae were found, and there is nothing in Ort-
lepp's observations to preclude a hookworm-like migration via
lungs and trachea on the part of the third-stage larvae.

The Oesoidiagostomiuae have a life cycle in the host essen-
tially the same as that of the Trichoneminae, the young worms
tending to Ijuvy themselves in the mucosa, where tliey cause the
formation of cysts or nodules. Here thej- undergo their devel-
opment to the final stage, emerging into the lumen of the intes-
tine at about the time of the final molt, or in some cases even
later, when they have grown to a length of 4 or 5 mm.

According to Spindler (1933), Oexophagostomnm quadrix-
plmilatum (= loiigicaudiim) of pigs produces inflamed liipiefy
ing cysts within 4.S hours after infection, and the larvae begin
escaping into the Inmen after aliout 17 days. Similar inflamed
cysts are produced by most other species of oesophagostomes,
but Goodey (1924) failed to observe tlieiu in experimental in
feetions with 0. dcntatiim and Schwartz (1931) saw onl}' small
noninflamcd nodules at the site of attachment of adult worms
of this species in contrast to the inflamed lesions caused by
quadrispiniilatum. Chabcrtia oviniis, though nearly related to
Oesophagostotniim, also fails to develop in submucous nodules.

Stephaiturus diniatiis, (see Schwartz and Price, 1932; Ross
and Kauzal, 1932) whether entering by skin or mouth, migrates

Fig. 184. OESOPHAGOSTOMVU BIFVKCUM AND
METASTRONaTLUS S'ALMI

A — Nodules of Oesophagoatomum. bifurcum in the large intestine of
an African (after Brunipt). B-E — Metnstrongylns salvii (B — Egg with
fully developed embryo; C — Newly hatched first stage larva; D — First
stage larva undergoing first molt; E — Second stage larva undergoing
second molt while still enclosed within the cuticle of first molt). A. after
Chandler. 1940 (fig. 146) Int. to Parasit. B-E, after Alicata, 1!):!5,
U.S.D.A. Tech. Bull. 489.

to the liver via the blood stream. The third molt occurs about
70 hours after infection, and the larvae have a provisional
mouth capsule. Normally such larvae escape from the capil-
laries in the liver and wander in the hepatic parenchyma until
they reach the surface capsule. They wander under this for a
time but eventually, 3 months or more after infection, break
free into the body cavity and make their way to the perirenal
fat tissue, perforating the walls of the ureters to establish con-
nection with the outside world. They tliemselves become en-
closed in capsules of host tissue.

II. METASTRONGYLOIDEA

In this supeifamily of the Strongylina the early development
follows somewhat different patterns from that of the other
members of the suborder, except in a few instances (e.g.,
Strongijlacaniha resembles Dictyocaidus in hatching and then
reaching the infective stage without feeding or growing, and
the Sj'ugamidae also resemble Dicti/ocaulus in having optiiuial
transport hosts).

Three principal types of development occur among the Mcta-
strongyloidea : (1) the Dicfi/ocaidus type, in which the larvae
go through two molts and reach the infective stage, surrounded
by one or both shed cuticles, without feeding or growing; (2)
the Metastrongylus type, in which the first-stage larvae con-
tinue their development after ingestion by earthworms, and
(3) the Prutostrongylus type, in which the first stage larvae,
attracted by the mucus of snails or slugs, continue their devel-
opment after entering the slime glands in the foot of these
molluscs, and becoming encapsulated in the muscular connec-
tive tissue under the epithelium.

I. Du-i'YOrwi.is si'P,

Tho ogRS of /'. filiiriii iiiiil l>. rni/xin/.v Iwitcli in tlie Inoiulii.
or at least in tlic iiitostino, as tlii'v aro loaviiiR the body of tin'
dotiiiitivo liost, Imt tliosi- of />. nrnfiilili, aiTiiidiiiu to Wi't/.il ,inii
Kiiigk (IS'.'tS) fail to liatoli in ttio UinRS, anil iisually do mil
liati-li nntil a few lionrs after leavinR tlie body. The first nioll
nsiially takes plaee at room temperature in from 1 to ;; days,
anil the seeond in from 3 days (in />. anifii'lili) to aliimt I'J
days (P. filaria) later, t'snally both sheaths are present in
early third stage larvae, but the lirst eutiele is eventually lusl.
These infeetive larvae live a long time in moist soil or water,
and .-ire able to survive in earthworms if eaten by them, al
though they do not depend upon the earthworm as an inter
mediate host. The use of earthworms as transport hosts seems
to be of less importnnee in the e.iso of Dictiincaidiis than in the
oa.se of Si/nflamux (see aboveK However, there is no evidenee
as yet that DirlnoftDiliix ean use as large a variety of transiiorl
hosts as ean Siinonmiis.

'2. Mbri'ASTKON'CVI.US

Mi'taslroiiffjiiu.i ilontiatiui (= apri), M. .salmi, and Chornt
.ilrotiffiilii.t pudcndotictii.i. The eggs of these worms eontain
fully developed embryos when deposited. .\lthinigh usn.-illy
stated to liateh in the bronchi or intestinal tract during passage
out of the definitive host, Alieata (10.S.">) found that they are
usually passed in the feces unhatched, and remain unhntehed
until taken into the bod.v of a susceptible intermediate host.
The eggs or embryos nia.v, however, remain viable for '.i months
in moist soil.

When ingested by earthworms (species of Jlrloilriliis ,iiul
I.iimbricus) the larvae burrow into the walls of the esophagus
and proventriculus of these hosts. Alieata has found them there
K! hours after exposure to infection. They also enter the
circulatory system and may be found in the hearts, but
Schwartz and Alieata (1!)2!0 showed that migration via the
blood stream was not an essential part of the life cycle of this
worm in its intermediate host. In the earthworm the first molt
occurs about 8 to 10 days or more after infection, and the
second one a few days later, this molt beginning before the
first cuticle has been shed. The seeond cuticle is retained by
the third .stage larvae, which are now infective. The larvae do
not si)ontaneou.sly leave the host, and an earthworm may re
main infective over winter, and probably at times for several
years. Upon death of the earthworms the larvae are able to
survive for 2 weeks in moist soil. Pigs become infected by
eating infected earthworms or liberated infective larvae. After
ingestion, according to Hobmaier and Hobmaier (li)29), they
migrate via the lymphatics or blood stream, und rgoing the third
molt in mesenteric lymph glands, and then proceed via the
lymjihatic and blood .systems to the lungs, where they become
mature after a fourth .■ind final molt.

?,. Pkotostrongvi.inak

.Ml the members of the family Protostrongylinae resemble
one another in requiring molluscs as intermediate hosts. In
all cases the embryonated eggs hatch before leaving the body,
or soon after, and the first stage larvae may live in soil or
water for several weeks, but without further development. The
larvae are attracted by the slime of molluscs, and upon coming
in contact with a mollusc they creep into furrows in the foot,
whence they penetrate into mucous glands, burying themselves
in the muscular connective tissue under the e])itheluni. Here
they coil up and soon become enclosed in a tubercle resulting
from encapsulation by the host. The fir.st molt usually takes
place after a week to 10 days at room temperature, the larvae
having grown comparatively little in length, but having become
thicker. The second molt usually takes place in from 10 or
12 days (Aelurostrongylux, MiicUcriti.s, Crenosoma) to 4 or .t
weeks (Elaphostrongylus), after which the larvae are infective
when molluscs containing them are eaten. In most cases little
specificity is shown with respect to the species of molluscs
utilized as intermediate hosts, although, possibly because of
the habits of the snails, certain species seem to be of prime
imjiortance. I'mtdstroiij/i/liis riifisccns develops primarily in
Ilelicella (Hobmaier and Hobmaier, 1930) ; Miiellfriiis capil-
larix can utilize a great variety of snails and slugs, :ilthuug]i
Pavlov (1937) found only Ilelicella obxia to be important in

Fig:. IH.-, DEVELOPMENT OV l'R( ITOSTKdXi; Yl.I X AE IN
MOLLU.S(.'S

Larvjte of MueUerUi^ capiUnris in AgrUtlimtix aurfittiH. X — Larvae in
furrow of foot of mollusk a few hours after infection; B — On first
day of infection (sagittal section); C — Coiled larva in foot on second
day of infection (horizontal section) ; D — I^arvae in sole of foot on 16th
(liiv of infection. .After Hobmaier, 1934, Ztschr. f. Parasitenk, v. 6 (5).

.Jugoslavia; Aelumstrongyliis abstriistis, reported by Cameron
(1927) to utilize mice as intermediate hosts, apparently er-
roneously, according to Hobmaier and Hobmaier (1935) devel-
ops in a variety of snails and slugs, but Epiphragviophora
proved most suitable. Other forms in which a variety of mol-
luscs have been shown to serve as hosts are Aelurostrongi/liis
fatcifonnis (Wetzel, 1938), Crcnonoma viilpis (Wetzel and
Miiller, 1935), and Elaphostrongylus odocoilei (Hobmaier and
Hobmaier, 1934).

Hobmaier (1934) believes that the utilization of molluscs as
intermediate hosts by the Protostrongylinae grew out of the
habit of the larvae of seeking protection from desiccation in
the slime of the molluscs. This predilection for slime extends
to the period of passage through the colon of the definitive
host, for the larvae are commonly found burying themselves
in the intestinal mucus and thus becoming located on the sur-
face of fecal pellets instead of iuside. In this position those
larvae which were not protected from desiccation by the mucus,
and subsequently the ti.ssues, of snails would fail to survive.
The larvae, as Hobmaier points out, differ widely in their
habitat in the snail from the parthenitae of flukes, which prob-
ably develop in snails because these were ancestral hosts.
Whereas fluke parthenitae are true internal parasites of mol-
luscs, lungworm larvae are scarcel.v more than external para-
sites. Larvae ingested by snails usually pass all the way
through the alimentary canal and fail to develop.

277

ASCARIDINA
OXYUROIDEA

1. Enterobius vermicularis

111 spite of the fact that the oxyurid type of life cycle is
the simplest and probably the most primitive of any found
among nematodes parasitic in vertebrates, a search of the
literature has failed to reveal a single instance in Avhich a de-
tailed molt by molt account of the life cycle has been descrilied.
The life C3'cle of Entcrobiuf: vennicidaris, so far as it is knoivn,
will serve as an example of its type.

The adult female worms, with the uteri filled with develop-
ing eggs, live in the lower part of the large intestine and par-
ticularlj' in the rectum. They do not ordinarily deposit their
eggs in the lumen of the intestine, but crawl out of the anus
and deposit them in the perianal region, leaving trails of eggs
as the}' creep about. Contact with air is apparently a stimulus
to oviposition (Philpot, 1!>24). Although they frequently re-
main outside the anus and release the eggs in showers when the
body ruptures, MacArthur (1930) and others state that they
commonly retreat into the rectum, to repeat their egg-laying
expeditions out of the anus over and over again, particularly
at night.

The eggs when deposited by the females, or contained in the
uterus of females which have voluntarily migrated out of the
intestine, are fairly uniformly in the "tadpole" stage of de-
velopment, apparently being unable to progress beyond this
point without free oxygen. Within 6 hours after leaving the
body they develop a coiled larva (ring and-a-half embryo)
which is infective. According to Brumiit (1922) the larva
undergoes no molt before hatching nor, according to Philpot
(1924), as a free larva in water. However, Alicata (1934) sug-
gested that a molt within the egg shell might be general for
the Asearidina, and Entcrohin.i might well be reexamined.
Chitwood (personal communication) believes he has seen a
molt in the egg, and thinks there may be two.

Development of the larva in the egg will occur in oxygenated
water, and in this medium the larvae commonly emerge in
from 9 to 24 hours at 37° C, but they only live for a few days,
so it is evident that water cannot be an important vehicle of
infection. Exposed to air a considerable proportion of the
eggs survive for at least 6 days at humidities above 62 percent
(Jones and Jacobs, 1939).

When ingested the eggs hatch in the stomach or intestine,
and the worms live during the early part of their development
in the lower part of the small intestine, cecum and upper por-
tions of the colon, not infrequently invading the appendix.
Heller (1903) states that there definitely are two molts in the
small intestine, and probably three. Chitwood, (personal com
munication) reports having seen a molt in the epithelium of the
appendix. By analogy with other nematodes there is probably
a total of four molts.

Although the worms have repeatedly lieen reported as bur-
rowing into the mucous membranes, especially of the appendix
(Penso, 1932), it seems probable that this is a habit only of the
fourth-stage larvae. Chitwood (personal communication) re-
ports having found the fourth-stage larvae in sections of the
appendix. He has observed a definite period 6 to 9 days after
infection when symptoms of invasion appeared, followed 4 to 7
days later by migration of the worms from the anus. Exposure
to air after operation would account for the deposits of eggs
which Penso reports and figures deep in the walls of the ap
pendix.

There has been a large amount of discussion as to whether
internal autoinfeetion by the worms can occur. The fact that
infections persist even for many years in spite of the most care-
ful efforts to prevent reinfection from the anus via the hands
has lent support to this idea. However, the demonstration by
Lentze (193.5), and Nolan and Reardon (1939) of the ease
with which airborne infectious can occur seems sufficient to
account for the persistence of infections. On the other hand,
Zawadowsky and Schalimov (1929), Lentze (193.5) and others
have called attention to the failure of development and infec
tion of eggs or embryos left under conditions such as exist in
the lumen of the large intestine. It would be difficult to say
that internal auto-infection could never occur, but the evidence
is all in favor of the view that if it does occur it is an abnormal
and exceptional condition.

Copulation of the young adult worms usually takes place in
the upper parts of the colon or in the cecum, where the males
live for some time. The females do not migrate to the rectum
until they contain developing eggs. Eipe females begin to ap-
pear about 15 days after infection.

2. Other Oxvuroide.v

The life cycles of other Oxyuridae are the same in essential
features, but differ in details. Oxyuris eqiii differs in that the
fourth-stage larva has a special structural development of the
anterior portion or "corpus" of the esophagus which
enables the larva to use it as a highly developed buccal
capsule for adhering to the mucosa (Wetzel, 1931). The ripe
females of this species creej) out of the anus as do those of
fJntcrobiua. but this is probably not true of forms parasitic in
rodents. The fourth stage larva of Dfnnatoxys vcUgera is also
provided with a special structure for adhering to the mucosa,
but in this case the end is accomplished by the development of
four conspicuous hooks on the head (Fig. 156, X, Y) (Dikmans,
1931), which is buried in the mucosa (Wetzel, 1932). These
specializations for maintaining a position in the colon are of
interest as indicative of a need for some sort of protection
against expulsion from the body before maturity is reached, a
need which may perhaps, as has already been suggested, have
led to a deeper burrowing into the mucosa and ultimately to a
parenteral migration.

According to Philpot (1924), Aspiculuris ictraptcra has a
life cycle strikingly like that of Eiitrrobitix, differing only in
the earlier stage at which the eggs cease development before
expulsion, and their failure to hatch outside the body. Sypliacia
obvelata differs in that the eggs have developed embryos when
they leave the host. All stages of development from the young-
est larva to adult can be found in the cecum of naturally in-
fected mice, and are strikingly similar to those described and
figured for Aspiculuris. Tachygnnctria loju/icoUis and T. ilcn-
laia definitely undergo a molt before hatching from the egg.
PassaJunis cimbiniius, according to Penso (1932), is capable of
internal auto-infection; the gravid females burrow into the
mucosa to deposit their eggs, and the larvae subsequently
emerge to continue their development. Penso, however, postu-
lates a similar behavior on the part of Entcrobitis vermicularis,
and thinks that Wetzel's observations on Dcrmatoxys vcUycra
were in error, the larvae with buried heads being emerging
from, not entering, the mucosa, .\lthough Piissalurus ambigiins
may sometimes deposit its eggs in the mucosa, Penso 's observa-
tions need to be extended before this can be accepted as a
normal or usual procedure.

Probstmayria rivipara (Atractidae) is, so far as known at
present, unique among nematodes that arc known to be obliga-
tory parasites of vertebrates in reproducing continuously gen-
eration after generation in a single host. It is among the.
nematodes what the Pupipara are among the Diptera, or Tiiiiga
among fleas. Its larvae hatch in the uterus and grow almost
to the size of the parents before being born (vide Ransom,
1907). They resemble the parents except for lack of develop-
ment of the genital organs. No stage of development is known
outside the body of the host. Transfer to new hosts is believed
by Jerke (1902) to be accomplished by contamination of food
or water by worms jiassed in the feces; such worms, he says,
remain alive in feces for several days.

ASCARIDOIDEA

In the Asearidoidca there are ahvays one or more molts be-
fore the embryos leave the eggs and, with few if any excep-
tions, there is a phase of burrowing into the mucosa, and in
many cases more extensive migration from the lumen of the in-
testine to the body cavity, liver, lungs or other tissues of the
definitive or of an alternating host.

Heter.\kidae

The members of this family bridge the gap between the typi-
cal oxyurid life cycle and that of the ascaridids. At least one
sjiecies, Subulura brumpti (see below), has become dependent
upon an intermediate host.

The life cycle of Hetcrakis gallinac, according to Clapham
(1933), is of the typical oxyurid type except that the females
do not migrate out of the anus to deposit eggs, but oviposit in
the ceca. Earlier writers have reported burrowing and encyst-
nieiit in the cecal walls, or penetration into cecal glands, but
Clapham was unable to find any evidence of migration or bur-
rowing, the larvae passing directly to the ceca within 48 hours
and maturing in the lumen. The first molt occurs in the egg
(Alicata, 1934), the third not until 10 days after infection.

Other species of Heterahis {isolonche, beramporia) burrow
into the intestinal mucosa at some time during development
and reach maturity in tumors which form around them. This
possibly is the first step in the direction of the Ascaris type of
life cycle.

DEVELOPMENT OF THE ASCARIDIXA

A — PuJtsaiuruK nmbiguuit. B — "0.ri/uri»" brer-icnudn showing emer-
gence area and embryo in outline after inculmtinn for 64 hours at 22°
C. C-il — Aitpictiluris tetraptera (C — EgK incubated in water 24 hours;
D — 43 hours; E — 08 hours; F — Larva from intestine 4 hours after feed-
ing; G— Larva from cecum 4 hours after feeding; H — After 18 hours;
I — After 44 hours; J-K — 10 days after feeding; J, male. K. female;
L-M — 18 day*; after feeding. L. female. M. male). N-Q — Supfiarin
obvelata (N — Uterine egg containing mature emt>ryo ; O — Hatched em-
brj"o; P — Youngest larva found in cecum ; Q — Male measuring .8 1
mm.). R — EnierohiuM vermiculariM, larva three days after hatdiing in
Ringer's solution. S-T — Derma toxi/s vpUgern (S — Head. T- — ^Head.
fourth stage). U — Probstmayria riripara, lateral view of female am-
taining a well developed embr>'o. a second less developed and two eggs.
V-Y — Aficaridia gaUi ( V — cephalic extremity of second stage larva
showing oral prominence; W — Second stage, newly hatched; X — Tail of
third stage female showing preanal swelling; Y — Tail of fourth stage

male). Z-CC — Ancurin himbrwoides (Z — Second stage (newly

hatched); AA — Third stage; BB — Fourth stage (21 days); CC — Fifth
stage (29 days old). I)I>-EE — Cosmocercoides dukae (DD — Newly
hatched larva;' EE — Infective larva). FF-II — Contracaecum aduncuni
(FF-GG — Hatched larvae; HH — Anterior end of larva armed with
boring tooth; I1-— Larva from body cavity of Ascartui bifilonu). JJ —
Subulura brt/wpti, encysted infective larva recovered from body cavity
of the beetle Alphitobtufi diaperinus. KK — Hetarakis guUinae, infec
tive larva found newlv hatched in the small intestine. A-R. after Phil-
pot. J. Helminth., v. 2 (5), pp. 239-252. S-T. after Dikmans. 1931.
Trans. Amer. ilic. Soc. v. 50 (4). U, after Ransom, 1907, Trans.
Amer. Mic. Soc. v. 27. V-Y, after Roberts. 19^7. Bull. 2 An. H. Sta.
Queensland. Z-CC. after Roberts. 1934, Bull. 1. An. H. Sta. Queens-
land. DD-EE. after Harwood. 1930, J. Parasit. 17. FF-II, after
Markowski, 1937, Hull. Acad. Polon. Ser. B. J.7. after Alicata, 1939.
J. Parasit. 25. KK, after Ctapham, 1933, J. Helminth, v. 11 (2).

279

V-^^r^: :■"

Dermtttoxys veliffern, Phofnmicrograph of fourth stage larva pene-
trating mucous membrane. After Wetzel. li>31. J. Para.sit. v. 18.

Asrnriilia finjli.
erts. 1H:i7. Bull.

Fig. 188.

Section nf small intestine showing larva. After Rob-
.\'fi. 2. Animal Health Sta. Yeerongpilly. Queensland.

The life cycle of Ascaridia galli ma.v well be a second step
towards that of Ascaris. As elucidated bj- Ackert (1931),
Alieata (1934) and Roberts (1937) this worm undergoes one
molt in the egg and then normally remains enclosed in the egg
until infection. There are three molts in the host, the tirst of
these (second molt) occurring about (3 days after infection and
the others at about 6-day intervals thereafter. After reaching
the third stage, on about the ninth or tenth days, the larvae
Inirrow down between the villi and penetrate into the glands of
Lieberkuhn, the posterior ends of the bodies remaining free in
the lumen. Itagaki (1927) observed that at certain seasons in
Japan (midsummer and midwinter) the larvae habitually pene-
trated into the mucosa, about as described by Ackert and by
Roberts, causing fibrous nodules, but that in spring and autumn
they remain in the lumen. Roberts reported less tendency for
the larvae to burrow into the mucosa in April and May than
in November. Although on rare occasions the larvae penetrate
too deeply and enter the peritoneal cavity, mesenteries, liver.
or even the lungs (Ackert, 1923; Guberlet, 1924), it is clear
that this is purely accidental.

Svbuhira iriimpti. according to Alieata (1939), has depart-
ed from the usual heterakid life cycle pattern in requiring an
intermediate host. This is the only member of the subfamily
Subulurinae in which the life cycle has been investigated, and
it is possible that the use of an intermediate host has become
general in this group as it has in the Anisakinac.

Alieata was unable to infect chickens by feeding embryonated
eggs, either just recovered from the uteri of gravid females, or
incubated in \vater at about 24° C. for 1 week, but succeeded
in producing infection by feeding naturally infected arthro-
pods harboring the cysts in the body cavity. The cysts contain
coiled nematodes having bulbed esophagi and conspicuous
esophageal valves as in the adults (Fig. 1S6, JJ). High inci-
dences of natural infection were found in the following arthro-
pods collected on poultry farms in Hawaii: (Coleoptera) Der-
mestes vulpinus, Gojioccphalus scriatum, Ammoplwnis insiilaris,
Alphit oh hits diapcriniis ; and (.Dermaptera) EiibonlJia ainin-

lipes. Encysted larvae were also found in grasshoppers (Con-
ocephalns aallalor) l.'i days after experimental infection.

CoSJIOt'ERCIDAE

At least some of the members of this family resemble the
typical Ascarididae in that the larvae, burrowing into the
mucosa, enter the circulatory system and reach the lungs, where
they escape into the air spaces and eventually make their way
back to the intestine via trachea and esophagus. They differ,
however, in having a free living phase outside the body. Cos-
mocerca trispinosa (= Nematoxys longicaiida) has long been
known to occur in the lungs of salamanders in an immature
form, and in the intestine as an adult. Von Linstow considers
its growth in the lungs as analogous to the growth of Ani-
sakinae in an intermediate host. Harwood (1930) found that
Cosmocercoides dukac (his Oxi/somatium variabilis) undergoes
a molt after 5 days of free life outside the bod.v and, although
his observations on development after infection are inconclu-
sive, that the larvae are found in the lungs not only after sub-
cutaneous inoculation, but also after infection by mouth. They
do not, however, penetrate the skin.

Ascarididae

The ma.)ority of the Ascarididae have a migratory phase lie-
fore becoming adult in the intestine. The larvae, burrowing
into the mucosa, enter the circulatory system and are cariiod
via liver or lymphatic system to the heart, thence to the lungs
where they become free in the air spaces, and thence via trachea
and throat back to the alimentary canal. Toxascaris leonina,
according to Wright (1935), does not perform this migration;
the life cycle is similar to that of Ascaridia except that the sec-
ond-stage larvae burrow into the mucous membranes almost
immediately after hatching, and return to the lumen of tlie
intestine after the third molt, on the 9th or 10th day. As
shown by Fiilleborn (1922) and others, some larvae penetrate
all the way through into the liody cavity and enter viscera by

280

tie. ixa.

Aitcnris tttitnn. Liirva in sfctinn of iiinu.-t' lung 1 VM-t'k iiflt'i" iiifei'tiori.
AftiT ISansoiii. 1!)20, U.S. 11. A. Yeailiook.

this louto, :iiiil souu' aio luolmlil.v ]pii-kc'il \ii> :ni(l cniicd h.v
the circulatoiv system.

Axcarus Iinnbricoide.s. Long: tlimij^lit Ui liave a liireet devel-
opment in the intestine, Ascari.s Iiiiiibricoidi's was fiist shown to
undergo a preliniiiiaiy migration tluough the body by Stewart
(1914) ; Stewart found that eggs fed to rats migrated to the
lung.s, and erroneously concluded that rats served as intcrmedi
ate hosts. Shortly thereafter Ran.som and Poster (1917) and
Chandler (1918) called attention to the probability that the
migration through the body was a part of the normal develop-
ment in the definitive host; experimental proof, with details
of the development, was supplied by Hansom and Foster in
llliO. Details of the course of the migration were worked out
and reported by Ransom and Cram in I'.l'Jl, and further details
were supplied by Roberts (lil34).

The first-stage larva appears in the egg on about the eighth
day at the optimum temperature of HO to 33° C, and the first
molt occurs in the egg on about the ISth day. Ransom and
Foster (lifJO) fir.st observed that the embryo underwent a molt
in the egg. Later Alicata (1934) reported that the egg is not
infective until after this molt; he also pointed out that the
embryos of A-'scaridia lineata, Parascaris cqiionnn, Toxocara
canis, Toxa.scuris leonina, Heleral'is gaUinae and the roach
oxyurid Blatticola blattac also underwent a molt, a feature
which may be common in the Ascaridina and which determines
when the egg has reached the infective stage.

Normally the eggs of Ascarii Inmbricoidcs hatch in the small
intestine after lieing swallowed, but they will sometimes hatch
when implanted subcutaneously or intraperitoneally (Ransom
and Foster, lfl20; Yoshida and Toyoda, 1038) or in artificial
media containing glucose or various nitrogenous substances
(Voshida and Toyoda, I.e.).

The second-stage larva has a small, sclerotized, knob-like
structure at the anterior end, called the "boring tooth." The
larvae bore into the intestinal wall, mainly in the duodenum
and upper part of the .je.iunum, after hatching; the ma.jorit.v
have disappeared within 2 hours. The ma.iorit3' enter the blood
stream after some hours and are found in the liver in from IS
hours to several days after infection. A few apparently enter
lymphatics since they are sometimes found in mesenteric lymph
glands, but from here they seem to go via mesenteric venules
to the liver rather than directly to the lungs. Within .t or 6
days all have left the liver and have gone to the lungs via the
blood stream; some appear in the lungs within 18 hours, and
they may continue to be found there for 10 or 12 days, al-
though most numerous on about the third to fifth days. Dur-
ing the first 2 days of this migration the larvae grow consider-
ably. About the fifth or si.^th day the larvae in the lungs,
measuring about 0.8 to 1 mm in length, undergo the second
molt. The third stage larva has three lips with papillae, l:icks
the boring tooth, has a highly developed muscular esojihagus,
has the intestiiuil cells packed with granules, has a distinct
nerve ring and oval genital primordium, and a conical tail
turned dorsad at the tip.

On the tenth to twelttli days llie llni<l It occins, also in

till' lungs. In the <ipinion of Roberts, althotigli second and
Ihiril stage larvae m.'iy be found in the intestine prior to the
tenth day (Ransom recovered larvae from the trachea as
early ;is the third day), these larvae have not completed their
development in the bmgs an<l probably fail to I'slablisli them-
selves in the intestine The suggesticui is made that the oc-
currence of such l;irvae in the intestine may indicate unfavor-
able conditions in the lungs resulting from excessive infections.
Roberts found some hundreds of fourth stage larvae in the in-
testine on the 14lh aiul 21st days, but no molting third-stage
larvae were fcnmd between the 11th and 14tli days. Fourth
stage larvae are 1.4 mm or more in length. The cuticle begins
to show striations, fin like lateral alae are present, the lips
resemble those of the adult, the esoyihagus is less bulbous, and
the sexes can be diflCrentiated by a difference in U'ngth of tail.
Rudimentary geiiilal tubules are present in the body cavity.

.\fter arri\al in the intestine the larva grows enormously,
reaching a length of l(i to 2.") mm 2!) days after infection. Lar-
vae undergoing the fourth nudt measure 17.3 to 22.5 mm (Rob-
erts). The lateral alae have become inconspicuous, the genital
tubules and body wall muscles are comparatively well devel-
oped, and the cliaracteristic features of the tail of the two
sexes are present, (irowth to maturity and beginning of reju-o-
duction takes several weeks.

It is obvious that the only striking difference between this
life cycle and that of the heterakids is the entrance into the
circulatory system when burrowing into the intestinal wall, the
consequence of which is the migration through the body via
liver, heart .and lungs. The determining factor seems to be the
age at which the larvae do their burrowing. Eiitcrobiiis and
Dermatoxys, as we saw, burrow as fourth-stage larvae, and
some species of Ilclnakis do likewise and live as adults in the
burrows; Ascaridia burrows while in the third stage; but As-
cari.i burrows immediatel.v after hatching as a second-stage
larva. The burrowing heterakid larvae are too large to enter
or be sucked into blood vessels, whereas the Asearis larvae can
easily do so. The failure of T()xa!icari.<i larvae to enter the
circulatory system except rarely ma.v be found to be due to a
difference in size, particularly in the diameter of the larvae.

Toxocara canis has essentially the same life cycle as Ascaris
himbriroidrs, and the same is true of Neoascaris vitulorum
{vide Schwartz, 1922), of Parascaris equorum (vide Baylis,
1923), of A.'icaris coliimnaris (vide Goodey and Cameron, 1923),
and probably of all other A.scaridinae. According to Fiilleborn
(1921), Toxocara canis is frequently encapsulated in the tis-
sues of mice or other abnormal hosts, which thereby become
transport hosts.

Anisakin.\e

It has long been known that various members of this sub-
family occur as immature worms in the body cavity, mesen-
teries and other organs of various vertebrates, and sometimes
invertebrates, whereas the adults occur in vertebrates which
prey upon these hosts. Although morphological characters
often suggested affinities between larvae and adults there
was little experimental evidence in support of them. More-
over the various larval forms were not clearly differentiated
from each other. Baylis (1916) for instance, showed that a
number of larval forms were confused under the iianu' "Ascaris
capsnlaria," which he believed on moriihological and distri-
butional evidence to be the larval form of "Ascaris dccipicns"
(now Porrocaeciim tircipiens). The same confusion probably
holds for other species.

Thomas (1937a, 1937b) experimentally worked out the life
cycle of Coiitracaccum spiciiligcriim. Eggs obtained from the
proventriculus of a cormorant contained active molted larvae
with a boring tooth after being incubated in water for 5
days, and on the sixth day they molted a second time and then
hatched. Many attached themselves by the anterior end of the
sheaths, which seemed adhesive, but the.v swam freely when
detached. On the thirfi-eiith day a third molt was in progress,
with a cuticular tooth still present. When swallowed b.v tad-
poles or guppies (.Lahislis rctici(hilits) the larvae shed their
sheaths and were found free in the intestine or in the body
cavity. About 3 months later larvae were found encysted in
the mesenteries; they had grown to 1.3 mm in length (from
less than 400 m). In cysts developed by the host tissues they
continue to grow until nearly adult size is reached. Unlike
most nematodes the number of molts is not limited to four;
as many as eight molted cuticles have lieen removed from en-
cj'sted worms from a natural infection.

There is evidence that when ;in infected fish is eaten by
another fish the larv.-ie penetrate the intestinal wall and re

281

encyst in the mesentery. This was observed to occur when
a parasitized guppy was fed to a black bass. In all cases
the worms retain the cuticular "lioring tooth" until the defin-
itive host is reached, although three lips can be seen under
the cuticles in older larvae. Natural infections with similar
worms were found in several species of fish in Illinois. Sexual
maturity is reached only in birds. Fledgling cormorants be-
come infected when fed on infected guppies. The larvae at
first penetrate into the glands of Lieberkuhn, and when
fish are present in the ventriculus the.y leave the glands and
l)enetrate into the food during its digestion.

Kahl, 1936, investigated the life cycle of Contracaecum
clavatum and concluded that it can undergo partial develop-
ment in a great variety of intermediate hosts, including Sagitta,
Calanidae, amphipods and medusae among invertebrates, and
in Ammodytcs and Mcrangiis among fishes. Wiilker, 1!)29,
thought there was a succession of three hosts, — plankton, plank-
ton-eating fish, and piscivorous fish, but Kahl thinks that all
three hosts are not necessary; development to the stage in-
fective for the definitive hosts can take place directly in such
fish as Merlangux merlangus. Merlangiis can also serve as a
definitive host, if infective larvae are swallowed Avith the
flesh of smaller intermediate hosts.

Markowski (1937), influenced by Wiilker's work, found
that certain species of eopepods served as first intermediate
hosts for C. adinicum, and presented evidence for the view that
a variety of plankton-eating or carnivorous fish might serve
as second intermediate hosts, although he expressed doubt
that the larvae developing in the parenteral organs of a fish
would develop to maturity in the intestine of tlie same fish,
even if it were a suitable host. Markowski did not con-
sider the possibility of a plankton host being unnecessary. Ac-
cording to Kahl the larvae undergo their early development
in the intestine of the intermediate hosts, and then, when
about 5 mm long, acquire a boring tooth and penetrate into the
body cavity where they molt again, but retain the sheath
with tooth and posterior spine until eaten by the final host.
Essentially then, the life cycle of this species is similar to that
of C. spicidigeriim, although according to Kahl the eggs de-
velop embryos only after being swallowed by a host. For a
species living in marine hosts this might be necessary. It is
probable that all the species of Contracaecum conform very
closely to the same pattern.

Thomas (1937c) worked out the life cycle of Ehaphidascaris
canadensis. The eggs of the species may become embryonated
after 8 hours outside the host and are infective within 24
hours, after one molt within the egg. When eaten by nymphs
of dragonflies, these eggs hatch, the first cuticle is shed, and
the larvae penetrate into the body cavity. Infected nymphs
caused infection in guppies, which in turn caused infection
in fingerling muskelunge. In Douglas Lake the livers of all
yearling Perca ftavesccns are full of Bhaphidaxcaris cysts,
whereas the plankton-feeding fingerlings are free of infection.
Guppies can be infected directly by the embryonated eggs,
the intervention of an invertebrate host apparently being
unnecessary, as in the ease of Contracaecum adiincnm. In
small bottom-feeding or nymph-eating fish, then, they become
encapsulated in the mesenteries and liver and continue growth
until eaten by species of Esox, in which the cycle is completed.
R. acus of Europe presumably has a similar cycle, since the
larvae are found in the inner organs of various cyprinoid,
salmonid and pereid fishes, whereas the adults are found in
Esox, Perca, Alosa and AnguiUa.

The observation of Baylis on the probable relation between
Porrocaecum decipiens of seals and walruses and encapsulated
larvae in various fishes have already been mentioned. A num-
ber of European writers have reported encysted larvae of
Porrocaecum in insectivores (moles, shrews, desman) and
Schwartz (1925) has reported them from under the skin of
moles and shrews in the United States; he, and also Solonit-
zine, who has found the larvae of a Porrocaecum on the serous
surface of the stomach of a desman (Dcsmana moschata),
tliink the adult stage is probably reached in a bird of prey.

Walton (1936a) found evidence for a similar life cycle for
Multicaecnm tenuicolle. Encysted larvae were found in spe-
cies of Sana and in Siren; 3 weeks after being fed to a young
alligator, presumably parasite-free, several immature males
and females were found. A similar cycle was found by Wal-
ton (1936b) for Ophidascaris labialopapUIosa; the larvae were
encysted in mesenteries and muscles of Sana spp., the adults
developing in Natrix spp. Similar larvae encysted in mus-
cles of Amphiuma, however, failed to develop in Natrix. Ort-
lepp (1922) failed to get larvae of O. filaria to penetrate the
mucous membranes when the ripe eggs were fed to a mouse,
although those of Polijdelphis anoura migrated to liver and
lungs like typical Ascaridinae.

SPIRURINA

Spiruroidea

The members of this snperfamily, with a few exceptions,
show a striking degree of uniformity in the general features
of their life cycles. Although many species tend to live in
tlie walls of the alimentary canal or in more distant locations
in the body, the eggs, usuallj- embryonated, escape with the
feces, and usually hatch only after being eaten by an inter-
mediate host. The embryos of Habronema, however, hatch be-
fore escaping from the body. In most cases there is some
degree of specificity with respect to the intermediate host,
but usually it is not very close. After ingestion by the inter-
mediate host the first-stage larvae emerge from the egg, pene-
trate into the bodj' cavity or tissues, undergo two molts, and
become encapsulated as third-stage larvae. These larvae are
usually not sheathed, as are the larvae of metastrongyles;
the second cuticle is not needed as a protection, since this is
provided by a capsule produced by the host, so is completely
shed.

Infection of the definitive host is nearly always by ingestion
of the infected intermediate host, although an alternative
method occurs in the ease of Habronema (see below). Not in-
frequently transport hosts may intervene between the true
intermediate host and the definitive host, and it is possible
that this can occur in all spiruroids. When the larvae are
eaten by a host in which the worm is unable to reach ma-
turity they burrow through the walls of the alimentary canal
and become reencysted. In most cases this seems to be an
optional course of development which is frequently favorable
to ultimate access to a definitive host (e.g., Spirocerca, Habro-
nema mansioni) but in the case of at least one species, Gnatho-
stoma spinigerum, a second intermediate host has apparently
become indispensable in the life cycle. After reaching the final
host the worms undergo two more molts before reaching
maturity. Being too large to enter blood vessels in the in-
testinal wall, they usually reach their destination, if this
is outside the alimentary canal, by direct migration through
tissues or along natural passageways.

Gongylonema pulctirum will serve as an example of a typical
spiruroid life cycle. Gnatliostoma spinigerum and Draschia
megastoma will serve to exemplify two important variations.

GONGYLONEM.\ PULCHRUM

The adult worms live imbedded in the mucous membranes
of the esophagus, tongue and oral cavity. The eggs escape
into the lumen and leave the body with the feces in a fully
embryonated condition. No further development takes place
until the eggs are ingested by a suitable intermediate host.
This may be anj' of a large number of beetles, particularly
scarabaeids, or cockroaches. Twenty-four hours after inges-
tion by Btatrlla germanica, according to Alicata (193.5), empty
egg shells are found in the crop and intestine. The absence
of larvae in the lumen or wall of the intestine and the pres-
ence of a few still adhering to the wall of the crop, apparently
ready to invade the body cavity, suggests that hatching takes
place in the crop, and that the larvae find their way into
the body cavity by piercing the wall cf the crop. Forty-eight
hours after ingestion of eggs, first-stage larvae are found
in the body cavity, especially in the thoracic region.

The newly hatched first-stage larva is cylindrical with a
spine and a small hook near the anterior end on the ventral
side, behind which about 20 rings of minute spines encircle
the anterior end of the body (Fig 190B) ; the tip of the blunt
tail is encircled by 8 to 10 small refringent points, a character
which is diagnostic of the first-stage lai'va. The filariform
esophagus and intestine are about equal in length. l)oth trans-
parent. The larvae wander about in the body cavity and grow
to double their original length in about 2 weeks, and at this
time are preparing for the first molt (Ransom and Hall,
1916; Alicata, 1935). The actual molt, according to Alicata,
does not occur until about the 19th day.

The second-stage larvae lose the cuticular armature at the
anterior and posterior ends, which are bluntly rounded. The
slender esophagus occupies about one-half the body length,
and in older larvae becomes differentiated into an anterior
muscular portion and a posterior glandular portion. These
larvae increase in size to a length of 1.5 to 2 mm by the
end of the fourth week, when they liegin the second molt.
At about this time they usually penetrate the muscles of the
body wall, and sometimes, in heavy infections, other muscles,
and they may become partially encysted prior to the second
molt.

Third stage larvae are found encysted at the end of about
a month. This stage is distinguished by a raised lateral bor-

282

Fig. 190.

Develoimient of Ctonmilonpin/i putchrum. A — Egg with fully devel-
oped embryo; B — Fir.st stuKe larva, anterior end; C — First stage larva
from intermediate host, four days ;iftcr experimental infection; D — Tail,
lateral view; E — First stage 1jiiv;i undergoing first molt; F — Second
stage larva; G — Third stage larva encysted in niuseulature of roach
[BUttella gerrnanirit) , H — Third stage, hiteial view; I — Posterior end

showing four digltiform prncesKes ; J — Posterior end of male undergoing
third molt; K — Posterior end of female undergoing third molt, h—
Fourth stage larva, anterior end; M — Posterior part of male in fourth
molt; N — ^Region of vulva of larva undergoing fourtli molt. After
Alicata. 19^5. D.S.D.A. Tech. Bull. 489.

283

(liT of the mouth and by four, occiisioiuilly only two, small
fligitiform processes on the tail. The larvae are found imbedded
within the sarcoplasm suriounding a niusfle fiber. As the
cysts become well formed they are sometimes pushed out into
the body cavity, remaining attached to the muscle by a thin
strand, or eventually falling free. Baylis (192(i) found that
the larvae would eseajie from disintegrating cockroaches into
water, and could be kejit alive for a number of days, Imt
since the larvae settle to the bottom he concluded that drinking
water was not an important means of infection. Freed larvae
were found to be incapable of skin penetration. The possibility
exists, of course, that larvae, either in or out of their inter-
mediate hosts, might reencyst in some transport host; Alicata
(I.e.) cites the finding of third stage larvae in the stomach
wall of a mole.

Upon ingestion by a definitive host (Alicata used guinea
pigs for experimental infections) the larvae are liberated
in the stomach and may invade the esophagus within one-half
hour after feeding, entering through the tissue at the gastro-
esophageal junction. They migrate ujiward througli the epithe-
lium of the esophagus and may roach the tongue as early
as the third day. Larvae begin the third molt on the ninth
day after ingestion, and many fourth-stage larvae are pres-
ent by the twelfth day. These larvae are characterized by
development of the reproductive organs, gradual develop-
ment of the characteristic cuticular bosses at the anterior
end, and loss of the caudal appendages. The final molt oc-
curs about a month after infection ; the minimum time re-
quired for growth to maturity seems not to have been de-
termined definitely, but Ransom and Hall (I.e.) report the
finding of egg-bearing females in a sheep about 3 months
after infection, and Alicata (lilS-'i) obtained an adult male
70 days after infection.

Gnathostoma spiniuekum

The adult worms live in tumors in the wall of the stomach
of Felidae, or of the esophagus of mink, the eggs escaping
into the alimentary canal through ojienings which eventually
develop from the tumors into the lumen. The eggs escape
from the body in an early stage of development (one to two-
celled stage according to Pronimas and IJaengsvang, 1933;
one to many-celled according to Refuerzo and Garcia (1938).
In aerated water they become embryonated in a minimum
of about 4 or o days, and in 2 days or more thereafter the
embryos emerge from the egg in an onsheathed condition,
being, therefore, in the second stage. These larvae have
smooth cuticles devoid of spines or striations, and are armed
with a spine at the anterior end.

The larvae usually live for only a few days in tapwater
(Prommas and Doengsvang, 1933) although sometimes they
may live for a month or more (Yoshida, 1934). Further de-
velopment is known to occur only when the larvae are ingested
by Cyclops. Attempts to infect mammals, fish, frogs, fleas
and Cladocera have all been negative. The development of the
larvae in Cyclops was independently discovered by Prommas
and Daengsvang (I.e.) in Siam and by Yoshida (1934) in
Japan. These workers showed that sheathless motile larvae
were found in the stomachs of Cyclops soon after experimental
exposure, and that by the following day they could be found
in the body cavity. According to Refuerzo and Garcia (1938),
the larvae in the liody cavity 1 day after infection lose the
sclerotized oral spine, and a tieshy enlargement representing
the future lips develops at the anterior end. Three days later
the cuticle becomes striated, its armature of spines develops,
and a head bulb armed with four rows of spines, and con-
nected with cervical sacs, is also present. The larvae seem
to have completed their development to the infective stage
by the sixth day.

Attempts to infect cats by feeding them infected Cyclops
have been uniformly negative (Yoshida, 1934; Prommas and
Daengsvang, 1936) but Prommas and Daengsvang succeeded
in infecting a catfish, Clarias batrachus. The larvae were
found in the muscles of the stomach or intestine of the fish
2 to 6 days after infection and after 6 days or more they
were found, some free and some encysted, in body muscles.
Chandler (1925a) had reported the presence of numerous
gnathostome cysts in the mesenteries of Indian snakes, which
he found to undergo further development in cats (1925a)
until the adult morphology of Gnathostoma spinigerum was
reached (1925b) ; Chandler also called attention to reports
of probably identical larvae in pelicans and eagles. Subsequent
to the work of Prommas and Daengsvang many other interme-
diate hosts, natural and experimental, have been added, in-
cluding a considerable variety of fresh-water fishes, frogs,
and snakes. In all of these the larva undergoes considerable
growth, but does not develop more than 4 rows of spines on
the head bulbs, in contrast to the 8 to 11 found in the adults

of Gnathostoma sphif/rnim. It is probable that the larvae al-
w^ays become encysted ultimately.

Chandler (1925a) showed that when gnathostome cysts in
snakes are fed to cats they penetrate through the alimentary
canal and can be found parenterally within 2 days after in-
fection. Some are found free in the abdominal cavity, under
the parietal peritoneum, or in the capsules of the kidneys,
but the majority, and nearly all later in the infection, are
found burrowing in the liver. A single larva was also found
in the liver of an experimentally infected guinea pig. The
larvae in the livers of cats grow somewhat, and a vulva
and rudimentary genital tubes develop within (3 days. No
further development was observed in cats infected for as long
as 4 weeks, although in the meantime there was extensive
damage done to the liver. Subsequently (1925b) Chandler
found, in naturally infected cats, all stages of development
from (presumably) fourth-stage larvae burrowing in tine
liver, exactly like those obtained from exjierimental infectious,
to forms, still sexually immature, which had undergone the
final transformation to the adult morphology, and had 8 to
11 rows of hooks on tlie liead bulb, arid comiilcx spines on the
liody. Some of the worms which had undergone the final molt
were found still in the liver, but others were evidently migrat-
ing out of the liver; a few were found in the mesentery or
in the diaphragm, and several were in the stomach wall;
one was free in the .stomach. The worms in the stomach wall
were not yet enclosed in hard-walled tumors, Imt occurred
in submucous purulent cavities. It was evident from these
observations that the worms, upon gaining access to a defini-
tive host, migrate through the walls of the stomach or in-
testiiu> to the abdominal cavity and enter the liver, where
they burrow and feed actively for several weeks. They finally
enter the wall of the stomach from the peritoneal side, and
grow to maturitj'.

Africa et al (193(ia) fed rats with encysted larvae and
found the larvae in the liver and body muscles 8 to 25 days
later. Infection of cats fed on gnathostome cysts from
cold-blooded hosts has been confirmed by Prommas and Daeng-
svang (1937), the prepatent period being 28 to 32 weeks,
and l)y Africa et al (193()b), who found semi mature worms
in tlie diaphragm and in nodules in the stomach wall nearly
4 months after infection. It is clear that the formation
of a tumor about the worms in the wall of stomach or esopha-
gus, which finally opens into the lumen, is a late stage of
development. It also seems evident from observations made
by the writer (1925b) that these tumors, when in the stomach
of cats, frequently become perforated into the peritoneum
and are then fatal. Yoshida 's observation that in luink the
tumors form on the esophagus in the lower part of the
thoracic cavity suggests that this may be the normal host and
habitat, and that in these circumstances there is less danger
of fatal parenteral perforation.

Draschia meqastoma

The life cycle of this worm is of particular interest since
it represents an intermediate evolutionarj- step from that
of the typical spiruroids to the filariae. It was first worked
out in detail by Eoubaud and Descazeanx (1921).

The female deposits embryonated eggs in the alimentary
canal which, according to Roubaud and Descazeaux, hatch be-
fore leaving the body of the host. The first-stage larvae
possess a hooklike structure similar to the hook of Gongy-
loiiema, but the larvae are in a very immature state, the con-
tents of the body being granular in appearance, with no dif-
ferentiation. These larvae are ingested by young nuiggots of
flies, and there seems to be a fairly high degree of specificity.
Draschia megastoma and Habronema miiscae have been found
to be capable of development in a number of species of
Musca and also in Miisciim stabiilaiis and in Fannia, but ac-
tual transmission has been observed only in Musca domestica,
and was definitely found by Eoubaud and Descazeaux to fail
in the case of Muscina stabulans because of inability of the
larvae to escape from the proboscis of that species. H. micro-
stoma, on the other hand, develops primarily in Stomoxys,
but has been reijorted as developing in Sarcophaga, Lyperosia
and }[tisca as well, though Roubaud and Descazeaux (1922b)
state that it does not reach the infective stage in Musca
flomcstica. Development of Eabroncma larvae has also been
reported from Drosophila.

The ingested larvae bore through the walls of the ali-
mentary canal of the maggots and enter the body cavity.
They live free in the body cavity for only a brief time,
and about the third day they penetrate into the Malpighian
tubules. Here they become quiet, and undergo the first molt
on the third or fourth day after ingestion. They lose the
oral hook, become immobile, and grow very thick and aausage-

284

Fig. 191. DEVELOPMENT OF SPIRUKOlOKA

AJ — ~0 nathostoma spinifferum (A — Larva emerging from egg through
opercular t^nd ; B — Newly hatched larva with loose enveloping sheath,
anterior spine : C — Anterior end of larva dissected from oy clops on
first day of infection, no anterior spine but large fleshy lip. two pairs
of contractile cervical sats; D— Larva from Cyclops on fourth day of
infection, cephalic bulb with four rows of miuut€ spines, lip smaller ;
F — Larva in body cavity of ryclops; E — Same larva; O — ^Larva from
cyst in mesentery of cobra; H- — -Head, bulb and lips of larva from liver
of artificially infected cat; I — Gnathostoiue from liver of artificially in-
fected cat; J — Section of liver of cat showing riddling of tissue by
burrowing gnathostomes) . K-M — Stages in the development of Habro-
nema mimcae. (K — Egg with embryo; L — Second stage larva; M—
Third stage larva before the molt). N-O — Sections pointing out the
histological reaction of the fat cells parasitized by Uabronema inunca^-
(N — Fat cells at the beginning of the infection showing peripherial
Uiickening and hypertrophy of parasitized cell in relation to normal;
O — Section of a fat sac enclosing many parasites). P — Fragment of

fat tissue of larva of Slu^ca dom-fstica showing aciculate larva of H.
muHcae in hypertrophied and transformed fat cell. Q-S — Development
of H. microatomurn in Stomoicys. (Q — Group of adipose cells of the larva
of Stomoxyti of which three are infested with a young larva of H.
tnicrostamum ; R — Sausage shaped larva; S — Older second stage larva).
T-CC — Draachia nie{jastoiua. (T — Embryonated egg; U — Aciculate larva
emerging from egg shell; V — Aciculate larva in intestine of fly; W —
Second stage larva immediately after molt in malpigbian tubules of fly
larva; X-Y — Second stage larvae recovered from larva (X) and pupa
(Y) of fly; Z — Full grown second stage larva; AA — Second stage larva
about to molt; BB — Second stage larva, full grown and about to molt,
removed from malpigbian cyst; CC — Posterior end of same). A-D,
after Refuerzo & Garcia. 1938. Philip. J. An. Ind. (5 (4)). E F,
after Prommas and Daengsvang, 1933, J. Parasit. G-J, after Chandler,
1925, Parasit. v. 17. KCC. after Roubaud and Descazeaux, Bull. Soc.
Path.' Exot., V. 14, 15.

285

like. An outline of the stoma appears at the head end, and a
conspicuous caudal vesicle and outline of the pyriform rec-
tum at the posterior end, but throughout the rest of the body
the nuclei are still scattered without definite order. Gradually
during the next few days the worm elongates, and the alimen-
tary canal, nerve ring, and rectum become well developed.
Meanwhile the tissue of the wall of the Malpighian tubule
surrounding the larva degenerates and is finally reduced to a
mere membrane, which serves as a sheath. On the eighth
day, at about the time of emergence of the adult fly, the
larvae begin to break loose into the abdominal cavity, still
enclosed in the membrane, but they now molt a second time
and their movements become very active, resulting in their
soon freeing themselves.

These third-stage larvae, the infective forms, may appear
as early as the ninth day. They migrate forward to the
head of the fly, and collect in the interior of the labium.
Attracted by warmth and moisture they move down into the
labellum, and escape through the delicate membrane between
the lobes of this structure when the fly is resting on a warm
wet surface, e.g., the lips, nostrils or wounds of an animal.
If on the lips, the larvae have an opportunity to reach the
stomach via the mouth, and grow to maturity in a normal
manner, but from the nostrils they reach the lungs, and from
the skin the subcutaneous tissues, and in either case fail to
grow to maturity. There is no doubt but that animals
could also be infected by swallowing flies harboring infective
larvae, but in the case of habronemiasis of horses this would
probably not be a common method in nature. On the other
hand it would probably be the principal if not the exclusive
method in the case of habronemiasis of insectivorous birds.
Still another possibility — ingestion by a transport host — is
suggested in the case of habronemiasis in birds of prey ;
this is supported by the finding of abundant larvae of H.
mansioni encysted in the stomach walls of toads by Hsii and
Chow (1938). Tliis species had previously been recorded
from the bearded vulture, Gypaeiii.'i barbatiis, but several spe-
cies of falcons were experimentally infected by feeding them
larvae from toads.

Habroneina muscac and H. micrn.ttomiim have similar life
cycles {vide Roubaud and Descazeaux, lB22a), but different
in details. These two species, instead of undergoing devel-
opment in the Malpighian tubes, develop in cells of the fat
body, the thickened walls of the cells serving ns temporary
"cyst" walls. H. micro.stomum. which develops in the blood-
sucking Stomoxys, might be expected to be introduced into the
tissues when the insect pierces the skin, and be forced to
find its way to the stomach by some roundabout parenteral
route, but Roubaud and Descazeaux (1922b) point out an in-
teresting biological adjustment which makes this unnecessary.
They point out that, as a result of interference by the worms
in its proboscis, the fly is unable to rasp a hole in the skin
to suck blood, and is forced to revert to the habits of its an-
cestors and non-blood-sucking relatives, and obtain moisture
and nourishment from the lips or other exposed moist sur-
faces.

The failure of the larvae of Habroneina to become encysted
in the intermediate host, there to remain until eaten by a
definitive host, and the substitution of a voluntary exit from
this host in response to warmth and moisture, are definite
steps in the direction of a filarial life cycle. As remarked
by Roubaud and Descazeaux (1922b), however, the habrone-
mas are imperfectly adapted for parenteral parasitic life. Their
larvae, in spite of the fact that they leave the body of the
intermediate host on the surface of the body of the definitive
host, are unable to penetrate the tissues, and are unable to
reach maturity outside the alimentary canal. With (1) de-
velopment of a parenteral adult habitat (already attempted
by many spiruroids but always hampered by the necessity for
the eggs to reach the alimentary canal), and (2) develop-
ment of ability to enter the skin on the part of the infecting
larvae, the only important change necessary to bring about
a filarial life cycle is the substitution of the blood or skin for
the alimentary canal as a means of exit for the larvae. Such
a development could hardly fail to occur in the case of a
parenteral parasite with a blood-sucking intermediate host.

Other, Spiruroidea

The life cycle of the ma,iority of the Spiruroidea in which
it has been determined conforms in general pattern to that of
Gongylonema, except for the intermediate hosts involved. In
some cases there seems to be far less specificity with respect
to intermediate hosts than in others, but some instances of
apparent specificity are probably due to incomplete data.
Thus Cheilospirura hamulosa was not known to develop in any-
thing but grasshoppers until Alieata (1937) showed that an
amphipod and 10 species of beetles belonging to 7 different

families, as well as several grasshoppers, could b? utilized as
intermediate hosts by this worm. On the other hand, Cram
(1931) got negative results from feeding eggs of C. spinosa
to cockroaches, ground beetles, sowbugs and crickets, but ob-
tained development in two species of grasshoppers. Again,
whereas Telramercs fissispina is reported as capable of devel-
opment in grasshoppers, roaches, Daphnia, Gainmariis and earth-
worms. Swales (1936) found that the eggs of T. crami failed
to hatch in various species of Cladocera, but developed read-
ily in two species of amphipods. Members of the genera
Ascarops, Physocepltaliis and Spirocerca seem to develop pri-
marily in dung beetles ; Spirura, Protospirura and Gongy-
lonema in beetles or roaches; Oxyspirura in roaches; Seurocyr-
nea in roaches and grasshopper nymphs; Acnaria in grass-
hoppers; Tetrameres in various Orthoptera and Entomostraca ;
Eartertia in termites (workers); Echinuria in Cladocera,
Dispharynx and Hedrnris in isopods ; Cystidicola in amphipods,
and Spiroxys in eopepods. Spiruroid larvae, possibly Protos-
pirura, have been found in fleas also. Under experimental con-
ditions Physaloptera iurgida, according to Alieata (1938), is
able to develop in cockroaches, but there is a possibility that
other arthropods are utilized under natural conditions.

Spiroxys contorta, as reported by Hedrick (193.5), differs
from the majority of the Spiruroidea but resembles Gnatho-
stoma in that the eggs become embryonated in water after
leaving the body of the host. It differs from Gnathostoma,
however, in that the definitive host can be infected directly
by the third-stage larvae in Cyclops, without requiring a
second intermediate host. In nature, however, transport hosts
— fish, tadpoles, frogs, newts and dragonfly nymphs, and fre-
quently turtles as well — are commonly made use of. The
lar%-ae of this worm are further peculiar in that they continue
to grow after they reach the infective stage, both in Cyclops
and in the various transport hosts. The development of a
"sausage" form by the late first-stage larva of Oxyspirura
mansoni, as figured by Kobayashi, is highly suggestive of
Habroncma or the filariae.

As far as known at present Giialkostoma spiiiigenim is the
only spiruroid which requires a second intermediate host, but
it is quite possible that this will be found to be true of other
Gnathostomatidae as well, and perhaps of still other spiruroids.
The larvae of Echiiiocepliahis (family Gnathostomatidae) have
been found encysted in the tissues of a bivalve, Margaritifera
vulgaris, which is presumably the first intermediate host. Simi-
lar larvae have been found in a sea urchin. Since the adults
occur in oyster-eating fishes no second intermediate host may
be necessary.

The course of migration in the definitive host is usually,
as noted above, by burrowing directly through tissues or
natural cavities, or by migration along natural passageways.
The path of Oxyspirura mansoni to the eye, according to
Fielding (1926), is by way of esophagus, mouth and lachrymal
duct, the larvae sometimes arriving in the eye 20 minutes after
infected roaches are fed to chicks.

The migration route of Spirocerca hipi (—sanguinolenta)
is not so clearly known. Faust (1927) thought that the larvae,
after ingestion with the flesh of a transport host (hedgehog),
reach the aorta via the portal system and lungs, but does not

Fig. 192.

Development of Ascaropsiniie larvae. A-E — Ascarops strons^ylina
(A — First st.age larva, anterior end, lateral view; B — Larva recovered
from an intermediate ho.st three days after e.xperiinental infection; C —
Larva undergoing first molt: D — Third stage larva, lateral view; E —
Encysted larva, third stage). F-K — Fhysocephtilus sexakttus (F — An-
terior end. lateral view; G — Larva from intermediate host 2 days after
experimental infection; H — Larva from intermediate host 12 days after
experimental infection; I — Larva undergoing first molt; J — Encysted
third stage larva (from Hobmaier, 1925); K — Third stage, tail). After
Alieata, 1935, U.S.D.A., Tech. Bull. 489.

Fig. 193.

A-G & G — Spiroirtjs contortus; (A — Free-living larva with sheath;
B — Five-day old larva from cyclops; C — Ci/clops leucknrti with three
larval nematodes: G — Fully developed larva from body cavity of cyclops.
showing genital primordium). O-E — Disphnrtni.r spiriilis (D — Head;
E — Tail). F — Tetrampres atuerirana, tail of third stage larva. H-I —
Tetrameres crami <H — Third stage larva from Oammarus fa-scintus 32
days after infection: I — Diagrammatic illustration of papillae ^on
tail of third stage larva). J — Larval spirurid larva from cat flea. K-M
— Protospirura. muricnla (K — Lateral view of anterior extremity of in-
fective larva; L — Lateral view of tail of 3.5 mm. specimen; M — Free-
had sketch of rosette of papillae on tail of same). N-P — Oxyspirura
mansoni (N — Larva just after hatching; O — Larva at end of first lar-
val stage; P — Mature larva). Q — Habronema mansioni, larva. A-C, &
G, after Hedrick. L. A., 1935, Tr. Am. Mic, Soc. v. 54(4). D-F, after
Cram, E. B., 1931, U.S.D.A. Tech. Bull. 227 H, I, after Swales, 1936,
Canad. J. Ees. D. 14. J, after Alieata, J. E., 1935, J. Parasit. v. 21
(3). K-M, after Foster, A. 0., and Johnson, C. M.. 1939, Am. J.
Trop Med. v. 19 (3). N-P, after Kobayashi, H., 1928, Taiwan Igakk.
Zasshi Formosa, No. 280. Q. after Hsu, H. P., and Chow. C. Y., 1938,
China Med. J. Suppl. II.

286

Fig. 192. DEVELOPMENT OF ASCAROPSINAE LARVAE

Kig. 19.3. DEVELOPMENT OP Sl'IRUROIDEA

287

make it clear how a worm l.iO M in diameter is able to pass
througli capillaries, or why the worms appear iu the ab-
dominal aorta before the thoracic, and never cause lesions
in vessels anterior to the aortic arch. It seems far more likely
that the larvae follow^ the route indicated by Hu and Hoeppli
(1936) ; after penetrating the gastric wall they proceed to the
coronary, gastroepiploic and coeliac arteries, and via these
to the upper abdominal and lower thoracic portions of the
aorta, eventually reaching the upjier thoracic aorta from below.
In the aorta the worms attach themselves to the wall and
cause the formation of characteristic nodules. Some worms
remain iu this position but many migrate outward through
the aortic wall and through the intervening tissue until they
reach the esophageal wall, iii which they find a favorable habi-
tat in which to reach maturity and reproduce. The eggs reach
the lumen of the esophagus through a secondary opening
from the tumor in its wall.

FILARIOIDEA

The Filarioidea are unique among nematodes, so far as is
known at present, in having perfected a mechanism by which
bott exit from and entrance to a host takes place through the
skin. The larvae of Dracuueuloidea escape through the skin,
though by a different mechanism, and the habronemas suc-
ceed in infecting a host when deposited on certain areas
of skin (the lips) but in neither case is both exit and entrance
accomplished by way of the skin. As noted under the discus-
sion of Spiruroidea, the evolutionary process by which the life
cycle of iilariae developed is clearly foreshadowed by the
course of events in the case of Eabronema.

WUCHEMailA BANCBOFTI

Hanson's (1878) discovery of the ingestion of filarial em-
bryos by mosquitoes and their development in these insects set
a landmark in the history of medical entomology, since it was
the first instance of a human blood infection being transmit-
ted by an insect. Low (1900) first demonstrated the mechanism
by which the larvae were returned from mosquitoes to man,
and Annett, Dutton and Elliott (1901), Lebredo (1905),
and Bahr (1912) added further details.

The adult worms live iu the lymphatic system and liberate
their larvae, known as microfilariae, into this system, whence
they eventually, unless blocked, make their way into the blood
stream. Their presence in the peripheral blood is periodic in
most parts of the world, being present at night, but not in
the daytime. Similar periodicity, though often less complete,
is observed in many other filarial infections; in some spe-
cies, however, e.g., Loa loa, there is a diurnal periodicity, and
in others, e.g., Dipetaloncma perstans, no periodicity has been
observed. Two principal theories have been proposed to ac-
count for the periodicity: one, originally advanced by Man
son, is that the larvae retire to internal organs during the
day and enter the peripheral circulation only at night ; the
other, advanced by Lane (1929), is that the worms have cycli-
cal parturition, producing their entire day's output of larvae
at the same time each day, and that these worms are all
destroyed in the host within 12 hours after they appear in
the blood stream. Some support is given to this theory by
O'Connor's (1931) observation at autopsies that at certain
hours all the adult female filariae have their uteri crowded
with embryos, while at other hours they are uniformly spent.
On the other hand, the persistence for a year or more of mi-
crofilariae transferred to an uninfected host (Underwood and
Harwood, 1939) is against this theory, though the fate of
microfilariae in infected and nou-iufected hosts may not be at
all comparable. As yet there is no unanimity of opinion as
to the reason for microfilarial periodicity.

The microfilariae of Wuchereria bancrofti as seen iu blood
smears are covered by a sheath which has very generally been
thought to be not a shed cuticle but a delicate, stretched vitel-
line membrane. Augustine (1937) questioned this, since he
observed that developing microfilariae in the uterus of Vagri-
filaria columbigallinae clearly show the vitelline membrane sur-
rounding eggs containing coiled larvae, but none of the micro-
filariae from the vaginal region show any evidence of a sheath,
and accumulations of crumpled hyaliue ob.iccts interpreted as
the remains of discarded vitelline membranes were found at a
higher level in the uterus, .lugustine was able to see no evi-
dence of a sheath on the microfilariae of this species while they
were in capillaries but was able to follow its formation on dry-
ing slides. He concludes, therefore, that the sheath is, as in
other sheathed nematode larvae, the loosened but unshed cuti-
cle from an incomplete ecdysis. This conclusion seems to us,
however, to be very doubtful, since no other nematode larvae
are known to molt at such an early stage in development, and

since two other molts have been observed during the course of
development of the larvae in their mosquito hosts; this would
bring them to the third stage, which is usual for infective lar-
vae in intermediate hosts (see p. 237). Some species of
filariae are not provided with sheaths.

The larvae are in a very immature state of development.
They are covered by a layer of sub cuticular cells, and within
the body have a column of nuclei which subsequently develop
into the esophagus and intestine.

This column of cells is broken at certain definite spots rep-
resenting the future position of the nerve ring, the excretory
pore and cell, and the anus. There are also a few large cells:
an excretory cell just posterior to the excretory pore, a genital
cell well behind the middle of the body, and a group of three
cells previously reported as genital cells 2 to 4, but which
Feng (1936) says give rise to the anus and rectum, and which
Abe (1937) says belong to the sphincter between intestine and
rectum, and are ultimately lost. There is a difference of opin-
ion as to the existence of a stylet at the anterior end of the
worm. The structure so called appears to be a rudimentary
mouth cavity.

Upon ingestion by suitable species of mosquitoes the larvae
become unsheathed iu the stomach and penetrate into the body
cavity, whence the majority migrate at once to the thoracic
muscles, where development to the infective stage takes place.
The factors which determine the suitability of particular mos-
quitoes have not been elucidated. Development takes place
readily in mosquitoes of a variety of genera, including Ano-
pheles, Culex and Aedes, but sometimes nearly related species
within these genera differ widely in their ability to serve as
nurses. For example, Culex quitiquefasciatus and C. pipiens
are good hosts, whereas C. vexans is not ; and Aedes variegatns
is a very good host whereas A. aepi/pti and A. albopictus are
not. As yet nobody has succeeded in obtaining development
in any arthropods other than mosquitoes.

Upon arrival in the thoracic muscles the larvae become qui-
escent, lying parallel with the muscle cells. Here in the course
of 2 or 3 days they become considerably foreshortened, often to
approximately half their original length, and at the same
time grow considerably in girth, assuming what is known as
the "sausage" stage. Only the caudal tip of the body fails to
thicken, and is retained as an attenuated tail-like structure.
Meanwhile a large excretory bladder develops and subsequently
a large rectal cavity, and the outlines of the esophagus and
intestine become defined. On the fifth day, according to Abe
(1937), the larva undergoes its first molt, the cuticle develop-
ing an annular break near the anterior end. After this molt
the larva reaches its maximum shortness and thickness and then,
as the alimentary canal becomes well developed, begins to
lengthen. As it approaches its maximum length it becomes
active again and, according to Abe (I.e.), undergoes a second
molt about the time it is ready to leave the thoracic muscles
(In his experiments on the 13th day). The loosened cuticle
breaks near the middle of the body and is shed. The larvae
now become active and migrate out of the thorax. The ma-
jority go through the neck and head and move down into the
interior of the labium, but a few get lost and can be fouud in
the abdomen, legs, palpi, etc. Infective larvae commonly reach
the labium about 2 weeks after infection in warm weather, but
have been known to complete their development in 9% days.
In the labium they are stimulated by warmth, and when the
mosquito is biting, escape through the delicate membrane where
the labella join the shaft of the labium. The larvae do not,
of course, interfere with skin-piercing as do the larvae of
Habroncma in the labium of Stomoxys, since in mosquitoes
the labium itself is not a piercing or sucking organ. After
leaving the proboscis and becoming free on the skin the larvae
were believed by Fiilleborn (1908), on the basis of experiments
with Dirofilaria imniitis, to penetrate into pores and enter
through unbroken skin, but Yokogawa (1938) carried out a
series of experiments which indicate that they can only enter
broken skin, and presumably in nature use the wound made
by the mosquito.

Nothing is known about the development of the larvae after
they enter a human host until they reach maturity iu the lym-
phatic system. Dirofilaria immitis requires about 9 months to
reach maturity, and it is improbable that IViichrrcria bancrofti
takes any longer, if as long.

Other Fll.iriae

The life cycles of comparatively few species of filariae are
known, but among those that are known there is comparatively
little variation. As already noted, some microfilariae are
sheathed and some are not, but there is no evidence that the
presence of a sheath has a "muzzling" effect in keeping the
microfilariae from passing in or out of the capillaries, as Man-
son had thought. This was shown by O'Connor (1931) in the

288

Fig. 194. DEVELOPMKXT OF FIl.AK I (H DKA

A — -Mouth parts of Simutium dnmno»um, fixed in alcohol, cleared in
warm clove oil, showing position of larvae of Oiu^hocerca volvulus
emerging and in situ, B-E — O. rohttlus (B — Early thoracic form, sec-
ond day; C — Thoracic form, seventh day; D--.SliKhtly later thoracic
form; E — Proboscis form, ninth day). F — Mature larva of Wurhererui
hancrofti escaping from proboscis of Citlex iaiiucnu. G — Larvae of
Dirofiiaria repens in AnophfUs (11 days). H — Wyrhfirpria hancrofti
larvae two days after entering Aed^a variegatuji. I-Mature larvae of
W. hancrofti in thoracic muscle.s and proboscis of itio>^(iuito. J — Em-
bryonic development of Loa Ion. K — Detailed drawing r)f Witrhf^rprin
hancrofti larva, L — Microfilaria in deeper layers of mnjunctiva in

rase with disturbance of vision, keratiti.s, and iritis, M — Second larval
stage of Onchocerca in the thoracic muscles of Simulum metallicum.
uppro.^imately 4H hours after fe.'ding upon infested patient. N — Third
larval stage or so-called "sausage form" of Onchorerca on edge of
thoracic niusdes of S. or hi arrum several days after feeding upon in-
fested case. A-E. after Blacklock. O. B.. 1926. Ann. Trop. Med. v.
20 (2). F. after Francis. E., 1919. Hyg. Lab. Bull. 117. G. H, & J.
after Fuelleborn. F. Handb. path. Mikr. Jena v. 6. I & K. after
Chandler. A. C, 1940 (Figs. Ifiri and IfiO). L-N. after Strong, et al..
19:^4. Contrib. Dept. Trop. Med.. Harvard. VI.

289

case of Wuchereria bancrofti and by Harwood (1932) in the
ease of Litomosoides carinii.

The microfilariae of Onchocerca, which are unsheathed, differ
from those of other filariae in that they live in the skin, and
do not enter eitlier the lymphatic or blood systems. The adult
worms, living in subcutaneous tissues, are encapsulated by the
host in hard nodules, through which the larvae are able to
burrow and escape. The salivary secretion of the intermediate
hosts (Simulium) seems to exert a definite chemotactic effect
on the microfilariae, since they may be many times more nu-
merous in the stomach of a fed fly than in a comparable quan-
tity of tissue.

The intermediate hosts are usually Diptera. Fleas were
stated by Brein! (1921) to serve as intermediate hosts for
Dirofilaria immitis and Summers (1940) corroborated this,
showing that development would occur in several species of
fleas, and in a shorter time than in mosquitoes. Noe (1908)
followed the development of Dipetalonema (jrassH in a tick,
Shipicephalus sanguineus; the microfilariae of this species are
said to be too large to enter the blood circulation and are found
m the lymph, which the ticks suck more than they do blood at
the beginning of a meal. This work has not been confirmed
and is open to suspicion in view of the fact that the embryos
of related species {Dirofilaria reconditum, Dipetalonema per-
stans) live in the blood and develop in mosquitoes. Savani
(1933) has also reported filariae in dog ticks in areas where
Dirofilaria immitis is common. The intermediate hosts of
Wuchereria and Foleyella are various mosquitoes; of Dipeta-
lonema perstans and Mansonella ozzardi, Culicoides; of Loa loa.
Chrysops; of Onchocerca spp., Simnlium or Culicoides; and of
Dirofilaria, fleas and mosquitoes.

There is some variation with respect to the site of develop-
ment in the intermediate hosts. The majority of the species
studied — Tfuchereria bancrofti, Microfilaria malayi (adult per-
haps unknown), Dipetalonema, Mansonella, Dirofilaria recon-
ditum, and Onchocerca spp. — develop in the thoracic muscles
of their dipteran hosts, but Loa loa develops principally in
the muscles or fatty connective tissue of the abdomen of Chry-
sops (Connal and Connal, 1922), and Dirofilaria immitis devel-
ops in the haemocoele of fleas and in the Malpighian tubules of
mosquitoes. These sites of development are of great interest
in view of the similar sites utilized by Draschia and Habronema
in museoid files.

Fig. 195.

Development of Wtichererm bancrofti, 1 — Larva 10 hours after in
fection. 2-4 — Larva 2-3 days after infection. 6-6 — Larva four days
and tliree hours after infection. 7-8 — Larva 5V2 days after infection.
1' Larva 5 M* days after infection, just before first molt. 2'-3' — Larva
7^ days after infection. 4' — Larva 9V2 days after infection of
posterior end of esopliagus. 5'-6' — Larva 11 days and 10 hours after
infertioa.

290

CAMALI.ANINA

Tlio iiii'inlicrs of Imlli sii|»"rfiiiiiilics iif tliis siiIkikIit. I'mih.iI
liinoiilc;! ami Orin'iiiu'iiloidoa, so far as known utilize coin'iioiis
as intorniodiato hosts. Tlu'io can ho no doutit, from a oonsid
oration of tlio habitat ami life cycU-, that tho Caniallanoidoa,
ihvi'llinK as adnlts in the alimentary canal of aquatii' liosts, arc
the more primitive, and that the tissue dwcllinR Draciincnloidca,
sometimes occurring in land animals, are a later evolutionary
development. The relation of these two groups is conip;iratilc,
in a broad way, with the relation of the Si)irnroidea and the
Kilarioidea. In the case of the Filarioidca a habitat in the
tissues is accompanied by evolution of a new method of exit and
rtiitrance of embryos via the skin, whereas in the Dracuuculoidea
it is accompanied by a new — but difTerent — method of exit via
the skin, suitable for an aquatic animal, but with retention of
the primitive oral path of entry.

C.\M.VT,I..\NUS SWEETI

The life cycle of this worm was worked out by Moorthy
(1038). The adult worms live in the intestine of a freshwater
fish (Ophiciplialus flachiin) and produce free larvae which es-
cape with the feces of the host. The embryos have a tinely
striated cuticle, a single dorsal denticle or boring cuticular
tooth, and fairly well differentiated internal organs. On reach-
ing water the larvae are swallowed by suitable species of
Cjirlops and reach the body cavity 2 or .S hours after infection.
These larvae undergo the first molt '2i to 36 hours later, and
the second one after -■) to 7 days, in hot weather. The third-
stage larvae are provided with ridged jaws suggestive of those
of the adult, and have three unequal mucrones at the tip of
the tail. No mention is made of these larvae becoming en-
cysted in Cyclops. When infected Cyclops are eaten by small
fish the larvae are activated by fish bile, escape from their
copcpod hosts and undergo further development, including pos-
sibly the third molt, in the intestines of these fish. The infec-
tion of the final host is thought to result from feeding on the
second intermediate host, and the larvae undergo their fourth
and final molt in the intestines of this host, acquiring the adult
type of mouth. Whether the intervention of a second inter-
mediate host is optional or obligatory was not determined, but
in nature it would probabl.v be the usual thing, since the final
liost does not ordinarily feed on Cyclops directly.

A-B — CamaUanuB gtreeti (A — Head, fourth stage; B — Tail, same).
C — Procamailanus fulvidraconin, mature embryo. D — Uninfected Cy-
clops. K — Cyclops infected with Dra4'uncutu« medinfnsU. F-G — Dra-
cuneulus medinensis (F — Cephalic region undergoing second molt; G —
Tail, same. A-B, after Moorthy, 19:i8, J. Parasit. v. 24 (4). C. after
Li, 1935. J. Parasit.. v. 21 (2). D. F,, after Fuelleborn. 1913. Filario-
•en des Mensch. F. G. after Moorthy. 1938, Am. J. Hyg. v. 27 (2).

.No encysted forms of ('. siicti were fouiul in fish hosts, nor
was any evidence found of their penetrating the walla of the
intestine, but caniallaniil larvae of another type were found
encysted in the body cavity, loosely attached to the intestines.
These were observed to exeyst when eaten by Opliiciphaliis
(jachua, but failed to undeugo further develoimient in that host.

An essentially .similar develoi)nu'nt in Cyclops has been dem-
on.strated for I'rocamallanus fill roil raconis by Li (l!t3.">), except
that only one molt was observed. It seems i)robal>le that the
first one was overlooked, since Li's figure of a (i-day old larva
corresponds with Moorthy 's second stage larva of Camallaniix,
and his second stage larva with Moorthy 's third stage. How-
ever, Fereira vl al (Ifi.Sfi) state that P. cearetisis develops only
to the second stage in Ditiptomiis, the third and fourth stages
being |)a.sscd in the intestines of the fiy of a fish other than
the definitive host. Although they speak of this host as a
"waiting host" (i.e., transport host) it would appear to be a
true second intermediate host if their observation is correct
that development to the third stage does not occur in Cyclops,

It will be seen that the canuillanid life cycle is e-ssentially
the same as that of Hpiroxys or of Gnatlwstoma except for the
l)roducti"n of free embryos instead of eggs by the parent
worms.

DrACUNCULUS ilEDlNEXSIS

The adult female guinea worm, nraciinculiis medinensis,
when preparing for parturition, appears in the subcutaneous
tissues of her host and jiroduces a small ulcer on the surface of
the skin. Upon stimulation by chilling of the skin, which hap-
pens in nature when the skin is plunged into water, she con-
tracts violently in such a manner that a portion of the larva-
filled uterus is prolai)sed through a rupture in the cuticle, and
the prolapsed portion of the uterus, bursting, liberates a small
cloud of larvae. These larvae are unusually large (about OOO
/;» long), have a striated cuticle, a cuticular boring tooth or
denticle, well-developed esophagus and intestine with dilated
lumen, and a long filiform tail.

These larvae swim about in water and undergo further devel-
opment only after being swallowed by certain species of cope-
pods. The details of their development was worked out by
Moorthy (1938). They reach the body cavity a few hours
after being swallowed. They undergo two molts in the body
cavity, the first one on the .5th to 7th day after infection, the
second on the 8th to 12th day in hot weather. They start under-
going the second molt before casting off the exuviae of the
first. The larvae grow very little in size, and actually de-
crease in length due to the loss of most of the filamentous tail.
The third stage larvae increase slightly in size for about a
week after the second molt, but after that undergo no further
development; they are infective for the definitive host 4 to 8
days after the exuviae of the second molt are shed. They have
a long esophagus of the adult type, and four mucrones at the
tip of the tail. They remain active in the body cavity of the
Cyclops for 4 or o weeks, but subsequently coil up and become
quiet, but are not encysted. In addition to the usual type of
larvae Moorthy also found a small proportion (1: 900) of
"abnormal" larvae in which the tail is malformed. Moorthy
suggested timt these may have been males, but it is more likely
that they should be regarded as abnormal individuals.

The early development of the larvae in the definitive host has
not been followed. Sexually mature females 12 to 24 mm in
length were found by Moorthy and Sweet (1938) in deep con-
nective tissues of experimentally infected dogs 67 days after
infection, and Moorthy believed that at this time fertilization
had already taken place. Migration of the worms to the
subcutaneous tissue and the formation of an ulcer for the
egress of larvae occurs about a year after Infection in man.

An essentially similar life cycle occurs in the case of D.
ophithnsis of garter snakes (Brackett, 1938). Cyclops infected
with this species may be eaten by tadpoles and possibly other
transijort hosts; in tadpoles the larvae were found to remain
free and viable in the body cavity for at least 2 weeks, but no
further growth or development was observed.

The Philometridae, which have been found in a great variety
of parenteral locations in aquatic hosts, have a life cycle es-
sentially similar to that of Dracunculits. Thomas (1929) found
that the first-stage larvae of Fhilometra nodtilosa are devoured
by Cyclops and invade its body cavity. Attempts at infection

291

Fig. 197. DEVEIAU'lIENT OF C.'i.MALI.ANlXA

A-TI — Cnmtitlnnus sivreti (A — First stage larva; B — Anterior end >in-
dergoing second molt; C — Posterior end undergoing second molt. D —
Head, third stage). E-J — DracuiiaiUis medineiixix (E — First stage,
anterior end; F — Same, posterior end; G — Anterior end moulting larva;
H — Posterior end; I — Posterior end of normal larva undergoing first
molt; J — Normal third stage larva), K-L — Procamnllnnus iulvidriicrinis
(K — Larva. 6 days old; L — Larva, 14 days old). M — Cross-section o£

guinea worm showing uterus filled with enihryos. -X about 30 {after
Leuckart). N -Diagram of guinea worm iti the skin at the time of
blister formation. A-D, after Moorthy, 1938, J. Parasit. v. ?4 (4).
E-J, after Moorthy. 1938, Am. J. Hyg., v. 27 (2). K-L, after Li. 1935.
J. Parasit. V. 21 (2). M, N, after Chandler, 1940, Introduction to
Parasit.

■M2

•<>r nsli from Citclopx a wcok aftrr iiifrctiim failod, pii'sumalily
hwaiisi' of iiia(lo<niatc timi" for tlio larvar lo ri'aili llio iiifi'ctivc
staRC. Fiiruyama ( I!i:f4l suci'ccilcii in cimipU'liiiK llio life
cycU", ill till' case of /'. ftijimoloi. Iiv foi'diiiif oxpi'riini'iitally
infoctod Cui'lops to thi" liotiiiilivo liost. Voiins iiialc ami finialc
worms won' found in tlu" liody cavity, from wluMici' tin' finialrs
siilisoiiut'iitly mittrati'd to their final liahitat in tlio tins. In
I'liilonu'tridao tlio motliod of ivscapo of the larvae is not as sp<>
eializod as in the ease of hrarunviiliis : the larvae of some spe
eies escape via the oviducts of the fish, while in the case of
I', fiijininloi the ripe viviparous females leave the fins of their
host, rupture, and liberate their larvae into the water. It is
easy to .see how the ffuine.-i worm life cycle could h;ivc evulvnl
from the camallanoid type liy the substitution of escape i)f
eiuliryos IhroUKh the skin for escape via the anus, which would
be very simple ia the case of parasites which reproduced in
parenteral habitats in acpiatic hosts.

TRICHUROIDEA

The membors of this superfamil.v, with the exccjition of
Trirhiiiilhi and CjixtDopxis (see below 1, have a simjile life cycle
eharactorizod by embryoiiation of eggn outside the body of the
host; access to a new host by swallowing of crks coutainiuK
first stage larvae provided with an oral spear; au<l direct mi
gration. via the blood stream if outside the alimentary canal, to
the site of developmi'nt. without jireliminary development el.se-
where in the body. The life cycle of CapiUaria col it m hii r , re-
cently worked out in detail by Wehr (IPH!)), will serve as an
example of the t.vpical Trichuroidea.

C'APII.I..\RI.V COHMB.VF,

The adults living in the small intestine are more or less im
bedded in the mucosa, but the eggs make their way into the
lumen and escape with the feces in an unsegniented state.
I'nder favorable conditions of temperature, moisture, and oxy-
gen segmentation occurs slowly, the first cleavage occurring in
about 48 hours, the morula stage in about .'•! days, and the in-
fective first-stage larva in t> to 8 days. No molting was ob-
served to occur in the egg. and hatching does not normally
take place before the egg is swallowed by a host. The entire
development from newly hatched larvae to adult worms takes
place in the small intestine of the definitive host.

The first-stage larva, like all other trichuroid larvae, has an
oral spear. It has a long slender esophagus which posteriorly
lies superficial to and only partly imljcdded in the stichosome,
which consist of two rows of opposing cells. The intestine is
much shorter than the esophagus (ratio 1:3..")) and is termi-
nated by a short rectum. The anus is subterminal.

The first molt occurs between 7 and 14 days after infection.
The second-stage larvae are slenderer, and appear to have no
oral spear; the stichosome consists of only a single row of cells,
and the intestine is relatively longer. The second molt occurs
about 14 days after infection. The third stage larvae are still
slenderer, with relatively longer intestine, and the genital iirim-
ordium is long. The third molt occurs between 14 and Til days
after infection. The fourth-stage larvae are very slender, and
sexually differentiated. The time of the final molt was not
determined, but some sexually mature adults with eggs were
found by the liHh day.

Other TRicnrRiDAE

The available evidence indicates that the life cycle of Tri-
chiirtK is essentially the same as that of CupiUaria ciilnmlxii ,
and it is probalile that it is also the same for other species
of CapiUaria which inhabit the intestines of their hosts. The
aliility of CapiUaria larvae to use transport hosts was shown
by Wehr's (19.'!6 i demonstration that earthworms can serve as
vectors for C. annulata, the crop-worm of chickens. Fiilleborn's
(l!l23b) figures of Trichuris trichiura larvae are strikingly
similar to Wehr's figures of the first stage larva of CapiUaria.
.Mthough Neshi (IBIS, quoted by Yokogawa, l!l:20) reported the
finding of four larvae of Trichiiris vtilpix in the lungs of a dog
■Jl hours after experimental infection, such migration on the
l>art of Trichuris has not been observed by other workers
either in normal or abnormal hosts (see Fiilleborn, ]!l23a).

.As Vogel (li)30) pointed out, the entire group of Trichuroi-
dea show a remarkable tendency to localization during their
larval development in paiticular organs or tissues — what Vogcl
called "organotropism." In all cases except Trifliiiirlla this
organotropism continues throughout the adult life of the worms.
Different species of Trichuridae are known to develop and live
as adults in the esophagus, stomach, small intestine, cecum,
colon, respiratory tree, liver, spleen, urinary bladder, and
epithelium. The available evidence indicates that the newly
hatched larvae of those species which do not grow to maturit.v
in the intestine itself reach their destination by burrowing into

the inlestiii.'il wall, entering the circulatory system, .'ind escap-
ing from the capillaries in the organ in which tlu'.v are to de
veloii (iood evidence for this li;is been obtained in the c'lsc of
CapiUaria iKpalira of the liver of rals. Vogel (lit.'iO) showe<l
that if young larvae of C. Inpat ira, recovered frinu the liver a
few <l;iys ;iftei' infection, were planted in the si)leen, lungs, or
under the skin, a few would succeed in reaching the liver.
Normall.v this worm penetrates the cecum, sometimes as early
as (i hours after infection (Lnttcrmoser, l!!38b), and is carried
directly to the liver via the hejjatic |)ortal system (Fiilleborn,
l'.>;;4; .Nishigori, lil:;.")), only an exceiitional few peru't rating
into the abdominal cavity, or being carried beycnid the liver
to the lungs :uid systemic cii'cnlation. In the cise of Tri-
(■liiisi>n\oi<l( s crassifaiula of the nr-in:u'y bt.-idder of i-ats, ^'oko-
gawa (UfJl) fed embryonatcd eggs to rats and 1 to 4 days
later fouini a few larvae in the abdominal and pleural cavities
and the lungs; these he thought were Trirlmsomoidrs larvae
from his fei'ding. but their size makes it evident that they
were not.

.\n unusual situation with resjiect to transfer of infection to
new hosts exists in the case of CapiUaria hi'patica, which is sug-
gestive of a inissible step in the evolution of the TrichineUa life
cycle. The eggs of this worm are deposited in the liver tissues
of rats or mice, and reni;iiii there in an early stage of devel-
opment (one to four cells), viable for at least 7 or 8 months
(Luttermoser, l!t.'i8a). Only exceptionally do any of the eggs
escape from the liver to be voided with the feces, and eating of
an infected liver by a susceptible animal cannot result in infec-
tion because the nonembryonated eggs are not infective.
Momma (1!I30) suggested tlies as a factor in disseminating the
eggs from decaying carcasses, and also showed that eggs in
the feces of cats that have fed on infected rats .-ire viable.
Troisier and Di'schiens (19311) and Shorb (1931) independently
suggested that the usual method of transmission in n:ituie is
by ingestioii of eggs that have become embryonatcd after being
freed from the liver of an infected animal, either by decompo-
sition or by being eaten Ity another animal, usually the latter.

Trichinell.\ spir.\i,is

The life c.vcle of this worm is unique among parasitic nema-
todes in that the period of waiting for a new host is pas.sed in
the pniental host instead of in the open or in an intermediate
host. The life cycle of CapiUaria hepatica, described above, is
a ste|i in this direction, since in this case there are two periods
of waiting, one in the liver tissue of the parental ho.st, the
other (the usual one) after embryonation in the o])eu. In the
case of TrichineUa this double period is reduced to one by the
complete elimination of the usual period of waiting outside the
host, resulting from (1) precocious development to a burrow-
ing larval stage in the uterus of the mother, and (2) consequent
ability to infect the tissues of the parental host and to sub-
stitute development in this for the usual development in the
open or in an alternate host.

The life cycle of this worm was one of the first to be worked
out in its essential features, contributions having been made by
Herbst, Kiicheumeister, Leuckart, and Virchow from 184S to
ISliO. The first entirely cojrect account of it was given by
Leuckart (IS(iO). The adult worms live in the small intestine.
The females produce no egg shells, and the ova, unlike those
of other Trichuroidea, develop precociously in the uterus, being
born as active burrowing larvae, though in a very early stage
of development, suggestive of microfilariae. There is an oral
spear as in other members of the group, but the alimentary
canal is rudimentary. This very immature larva enters the
circulation, passing capillaries in lioth liver and lungs, and is
distributed over the entire body. Presumably as the result of
a special organotropism as suggested by Vogel (1930), the
attraction in this particular case being the striated voluntary
muscles, the larvae leave the caiiillaries and immediately pene-
trate through the sarcolemma into the interior of muscle cells,
Iiossibly by means of extra-corporeal digestion. As to whether
the larvae actually penetrated into the muscle cells has long
been a matter of dispute, but seems finally to have been set-
tled by Jensen and Roth (1938). Immediately after penetra-
tion, accomplished b.v a boring movement of tlie spear-bearing
head end, the larva is seen lying lengthwise .iust under the
.sarcolemma, or between the sarcolemma and adjacent muscle
cells, .leusen and Koth think it likely that a histolytic enzyme
is also involved in the i)enetration of the muscle cells and in
dissolving the fibrillae inside.

Once inside the cells the larvae come to rest and begin their
growth and differentiation, the muscle substance meanwhile
undergoing degenerative changes. By the 17th day, according
to .Jensen and Roth, the larva has grown from 100 to 400 or
.jOO m in length and has its esophagus and intestine clearly dif-
ferentiated. According to Stiiubli, however, it ma.v have in-
creased its length 10 times, to 800 to 1,000 M, in from 10 to 14
da.vs. After 11 days it begins to roll up spirally in a spindle-

293

Fig. 198. DEVELOPMENT OF TRICHUROIDEA

of victim uf trichiniasis. F-J—CripinniU, cohtmbne (F— Anteiior end of
unhatched first stage larva; G— Late first stage larva from intestine of
pigeon 7 days after infection; H— Embryo or unhatched first stage
larva; I— Second stage larva; J— Third stage larva_ in _molt._ A-E, after
Chandler. 1940. introduction to Parasitology.

A-C — Stages in calcification of TrichineUa (A — Ends calcified; B —
Thin layer of calcareous material over whole cyst; worm beginning to
degenerate. C — Complete calcification). D — Larvae of TrichineUa spv-
rails encysted in striped muscle fibers in pork. Camera lucida draw-
ing of cysts in infected sausage. E — Larvae of trichina worms burrow- „ „ ,^ , a, , n i, r
ing in huniar, fiesh before encystment, from preparation from diaphragm U.S.U.A. tech hsull. b

F-J. after Wehr, 1939,

294

Fig. 199. TRICHURon)K.\ -VND ])I OCTOPHYMATOIDEA

A-D — Cijatnnpxiii ncipenneri (A — Embrj'o; B — Head, male; C — Adult
female; D — Conneclion of esojihageal region and body proper of fe-
male.) E — CnntonpKitt larvii enc.vsted in appendage of Gnnniiantu jjhttth
cheir. Fl — TrichineUa npimlui (F. Molt at fourth hour; G — Molt after
14 hours; H — Third molt of female after 48 hours; I — Molt after 70
hours). J-K — Trichuris friyliiiirn (J — From the (.-eeum of a guinea pig:
K — Larva pressed from egg). 1,-R — Tiirliinella spiralis ( L — .Section of

intestine showing female in lunii-a propria; M — Young larva entering
muscle; N — Young larvae; ()-R — Stages in encystment and calcifica-
tion). S-T — Eiislrongi/lides (S — Head: T — Tail). A-D. and E, after
Janicki, ('., and Rasin. F.. 19:10. Ztschr. Wise. Zool. v. 136. F-I,
after Kreis. H. A., 1937, Zentralbl. f. Bakt. v. 138. J-K, after Fuelle-
born, F.. 1923, Arch. Schiffs--u. Tropen. v. 27. L-R, after Staubli, in
Handb. path. Mikroorg. v. 8. Remainder original.

295

shaped enlargement of the muscle fiber, and after 4 to 6 weeks
becomes encapsulated. If not ingested by a host suitable for
their future development, the larvae ultimately die and there
is fatty degeneration and finally calcification of the cysts.
Trichinae are said to remain alive and infective for as long as
11 years in the muscles of swine, and to have lived for 12 to 24
years in man, according to Baylis. Prenatal infection with
trichinae has been demonstrated in guinea pigs by Roth
(1936); Mauss got negative results in rats, rabbits and
hamsters. In spite of the fact that the larva undergoes so
much growth and differentiation Staubli was unable to detect
any evidences of molts, and the writer has seen no reports of
any being seen by later observers. By analogy with other
nematodes, however, it seems probable that the infective larvae
have undergone at least two molts. Infection has not been ob-
tained with larvae less than 19 days old and only after 21 days
can one obtain a high percentage of infections. This seems to
indicate that the larvae undergo a change, such as a molt,
prior to that time.

When the larva has undergone its full development, whether
encapsulated or not, it is infective when eaten by another ani-
mal. Development in the intestine is extremely rapid, sexual
maturity being reached and copulation occurring on the third
dav, and embryo production beginning on the fifth day. Ac-
cording to Kreis (1937) there are four molts in this brief
period, at about 4, 12, 48 and 70 hours after ingestion. How-
ever, his evidence is not very convincing. According to recent
investigations one molt was obtained after ingestion and the
cuticle of the resultant nema passed uninterrupted over the
vulva, indicating that at least one more molt would be neces-
sary before maturity.

It is evident from this account that Tiichinella spiralis is not
only unique among nematodes in utilizing the parental host as
a sole resting place while awaiting an opportunity to gain ac-
cess to another host by cannibalism (insofar as it passes from
individual to individual of one species) but it is also unique
among the Triehuroidea in having different "organotropisms"
for the larval development and for the adult development, the
former being the striated voluntary muscles, particularly the
most active ones (pectoral and tongue), the latter the mucous
membrane of the small intestine.

Cystoopsis acipensem

This is an aberrant worm with respect to both its morphology
and its life cycle. The females with their large spherical
bodies and the small cylindrical males live in pairs in cyst-like
cavities just under the skin of young sturgeons. According to
Janicki and Rasin (1930), a well-developed vulva and muscular
vagina are present, but they seem to be used only for the en-
trance of sperms and not for the exit of eggs. The spherical
body is filled with numerous coils of the uterus filled with
embryonated eggs. These, according to the authors quoted,
escape only by a bursting of the thin wall of the cyst and
rupture of the parasite.

Experimentally the embryonated eggs are eaten by certain
species of amphipods, and the larvae, liberated in the stomach,
penetrate into the body cavity. The young larvae possess a
mouth spear like other Triehuroidea, and are in a very early
stage of development. At the end of about 2 weeks they have
reached their full size, and then migrate into the appendages
or into muscle layers. Here they coil up after the manner of
Trichinella larvae and soon become encapsulated. The capsule
thickens with time, and by the end of 3 months cannot be
broken under a coverglass. No experiments have been per-
formed to prove the infectiousness of the larvae encysted in
Gammarus, but there seems to be no reasonable doubt but that
• young sturgeons are infected by eating amphipods, and that the
young worms migrate through the tissues of the host to their
location in the skin as do some species of Trichuridae.

DIOCTOPHYMATINA

The life cycles of members of this group are very imper-
fectly known. The available information concerning the genus
Enstrongylides has been summarized by Cram (1927). Larvae
described by Rudolphi as Filaria cystica from under the peri-
toneum and in the abdominal muscles of certain Brazilian fish
were regarded by Jagerskibld as belonging to this genus.
Ciurea (1924) found similar larvae in other fish from the
Danube, and he also regarded them as belonging to Eustrongi/-
tides. Larvae found in Brazilian fishes by Schneider and by
Leuckart are stated by Jiigerskiold to resemble E. ignotus of
water birds.

Chapin (1926) found the preadult stage of this species in
Fiindulus diaphanus at Washington, D. C. From one to three
specimens were found in each fish, and adult characters could

be seen beneath the last cuticle, corresponding exactly to those
of adult worms found by him in Ardea herodias from the same
locality.

More recently Mueller (1934) reported similar larvae from
Fttnduhis, in cysts attached to the mesenteries. They were 100
mm long by 0.685 mm in diameter, blood red in color, and the
head was provided with 12 papillae, in 2 circles of 6 each, char-
acteristic of the genus. Von Brand (1938) found a high per-
centage of Finulidus from Chesapeake Bay parasitized with
this same larval form; individual fish harbored from 1 to 8
worms. Von Brand states that the encapsulated nematodes did
not harm the host, but that after the host died they left their
capsules and endeavored to escape from the dead host by bur-
rowing through the tissues, eventually emerging through the
gill region or body wall. He Avas able to keep the worms alive
on sterile nutrient media for as long as 2 months, but there
was no growth or development.

The larvae found by Ciurea are large, 28 to 70 mm long by
264 to 539 /^ wide, and are rose-red or brown-red in color. On
each side of the body near the anterior end is a row of small
lateral papillae. The mouth aperture has the form of a cleft
and has three small pointed papillae on each side of it, and
three larger papillae just outside of these. The larvae have tails
of two types, one enlarged near the end and regarded as that of
the male, and the other rounded off without enlargement and
regarded as that of the female. Whether the fish are first or
second intermediate hosts is unknown. The thick-shelled eggs
are undeveloped when they leave the body of the host.

Even less is known about the life cycle of Dioclophiiwn
reiiale. The adults are usually found in the pelvis of the kid-
neys, partieularlv the right one, where they eventually destroy
the entire pareiichvma. Worms, often immature, are frequently
found in other locations, particularly in the peritoneal cavity.
The eggs, in an unsegmented condition, normally escape from
the body' with the urine. They develop slowly in water, re-
quiring from 1 to 7 months for embryonation, according to
the temperature, and then remain viable for at least 2 years,
although they do not hatch. Beyond this point nothing is
definitely known about the life cycle, but the frequency of in
fection in fish-eating animals makes its highly probable that
fish serve as vectors for this worm as well as for Eustrongyhdes.
Ciurea (1921) found a specimen 63 cm long in the peritoneal
cavity of a dog fed, between 3 and 4 months previously, on 14
specimens of a cvprinid fish ildiis idiis) from the Danube, Init
it is doubtful whether the worm was actually acquired from
this feeding. Ciurea also found an active larva in the muscles
of Idus which he thought might be that of Dioclophyma. but
his figure and discription are more suggestive of an ascarid
larva. Swales (1933) reported D. reiialc as a very common and
important parasite of mink in Canada, and stated that on mink
farms the infection was definitely associated with the feeding
of fish to these animals.

It has generallv been assumed that Dioctophi/ma. after enter-
ing the alimentaiv canal of a definitive host, is carried via the
blood stream to the kidneys as a young larva, there to undergo
its growth to maturity. Its occurrence in the peritoneal cavity
was thought to be accidental and rare, and due to rupture of
the cvst-like remnant of the kidneys after the complete atrophy
of its parenchvina. As a matter of fact, however, the worms
are very frequently found in the abdominal cavity of dogs, in
the majority of cases without evidence of damage to the kid-
neys. Wislocki (1919) found them in that location in every one
of" 12 dogs which he examined, and in only two cases could a
portal of entry through a partially destroyed kidney be sur-
mised. Brown, Sheldon and Taylor (1940) found 13 of 20
■ infected dogs in North Carolina with worms in the body cavity
onlv 6 had worms in the right kidney as well, and 1 had them
only' in the right kidney. Lukasiak (1930) called attention to
the" fact that in spite of numerous searches, especially in the
kidneys, larvae have never been found, and relatively young
forms" have been found not in the kidneys but in the alidominal
cavity, by preference between the lobes of the liver. Stefanski
and Stra'nkowski (1936) found a case in which a worm in the
abdominal cavity was clearly in process of entering the right
kidney; its anterior end was lodged in the tissue of the right
kidiie"y, the substance of which had not been destroyed. From
this and similar cases which they quote from the literature,
and from the other evidence cited above, these authors conclude
that the larvae of the worm, travelling via the blood stream,
stop in the liver, grow, and finally continue their development
in the abdominal cavitv, probably penetrating the kidney only
after the final molt, and hollowing out a canal in the substance
of this organ. Since the larvae are probably too large to enter
capillaries, it seems to us more probable that the worms reach
the body cavity by directly burrowing into it, as do Gnath-
ostoma "larvae;" we know of no evidence that the liver is in-
volved at all.

296

Fig. 200.
Diartofihftma rfnule feinnlc. anterior extrprnily of the j)ar;isite coiled
in the pelvis of the right kidney. .After Stefanski and Strankowski,
1936. An. de rarasit. Hninaine et Conip. v. 14 (1).

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297

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1931. — Developmental stages of some nematodes of
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1931. — Human strongvloidiasis in Panama. Am. J.
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1933. — Experimental studies on human and primate
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1914. — Untersuchungen ueber den Infektionsweg Viei
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lS20a. — Perkutaue lufektion bei Angiostomiim nigro-
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1920b. — Ueber die Anpassung der Nematoden an den
Parasitismus und den Infektionsweg bei Askaris und and-
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1921a. — Askarisinfeckion durch Verzehren eingekap-
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1921b. — Ueber die Wanderung von Askaris und and-
eren Nematoden-larven in Korper und intrauterine As-
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1923a. — Ueber die Entwicklung von Trichozejihalus ini
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1923b. — Ueber den " Mundstachel" der Trichotraeli-
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1924. — Ueber den Infektionsweg bei Bepalicola he-
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1925. — Ueber die Durchlassigkeit der Blutcapillaren
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1927. — Ueber das Verhalten der Larven in Korper des
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1924b. — The anatomy and life history of the nema-
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1938. — Idem. II. Homogonic and lieterogonic prog-
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1932. — A note on the tissue-penetrating abilities of
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.9 613.

Rec. Egypt, (iovt. Sch. Med., v. 4:

Low, <i. ('. 1900. — A recent observation on Filaria noclurna
ill Ciilix, probable mode of infection in man. Brit. Med. J.,
v. 1: 14.56 1457.

LUCKEH, J. T. l934a.^Devclopiiunt of the swine nematode
Slront/iiloUtcs raiisomi and tin' behavior of its infective
larvaJ.' l'. S. Dept. Agric. Tech. Bull. No. 437, 30 pp.

1934b. — The morphology and development of the prc-
parasitic larvae of I'<i>tl( riostomiim rat:ii. J. Wash. Acad.
Sc, V. 24: 3(12 310.

193(i.- -Preparasitic molts in Xippostroiigyliis miiris,
with rennirks on the structure of the cuticnla of Tricho-
strongyles. Piirasit., v. 28 (2): 161-171.

193H. — Description and differentiation of infective
huvae of three species of horse strongyles. Proc. Helm.
Soc. Wash., V. 5 (1): 1-5.

l.rKA.siAK. .1. 1!);S0. — Anatomische und entwicklungsgesehicht-
liihe rntersuchungen an Dioclophyme renale (Goeze,
1782). Arch. Nauk. Biol. Towarzv.st. Nauk. Warszawsk.,
( 1929), V. 3 (3) : 100 pp., figs. l-O", pis. 1-6.

LfTTERMOSEK, G. W. 1938a. — Factors influencing the develop-
ment and viability of the eggs of Capillaria hepatica. Am.
J. llyg., V. 27 (2) : 275-289.

193Sb. — An e.\perinH'iital study of Capillaria hepatica
ill tlie lat and the mouse. Ibid., v. 27 (2) : 321-340.

Mac.\rthuk, W. P. 1930. — Threadworms and pruritis ani. .T.
Ro.v. Army Med. Corps, v. 55: 214 216.

JIcCoY, G. R. 1929. — The growth of hookworm larvae on pure
cultures of bacteria. Science, v. 69 (1777): 74-75.

McIntosii, a. and CiimvooD, B. G. 1934. — A new nematode
Longibticca lasiiira, n. sp. (Rhabditoidea, Cyliudrogastri-
dae) from a bat. Parasit., v. 26: 138-140.

Manson, p. 1878. — Gn the development of Filaria sanguinis
hominis, and on the mosquito considered as a nurse. J.
Linn. Soc. Lond., Zoo!., (75), v. 14: 304-311.

MAKKOW'sKr, S. 1937. — Ueber die pjntwickluiigsgeschichte und
Biologic des Nematoden Contracarrtim adancum (Rudolphi,
1802). Bull. Internatl. Acad. Polon. Sc. e Lett., Ser. B,
Sc. Nat. (II), pp. 227-242, 2 pis.

M.AUP.^.s, E. and Seurat, L. G. 1913. — La Mue et I'enkystement
cliez les .Strongles du tube digestif. Compt. Rend. Soc.
Biol., Paris, v. 74: 34-48.

JIecinzkow, E. 1865. — Ueber die Entwickelung von Ascaris
nigrorcnosa. Arch. Anat., Phvsiol. & Wiss. Med., Leipz.,
pp. 409-420, pi. 10, figs. 1-11.

MlYAGAW.*., Y. 1916. — Ueber den Wanderungsweg der Ankylos-
toina duodenale innerhalb des Wirtes bei Oralinfektion
und iiber ihren Hauptinfektionsmodus. Mitt. Med. Fakult.
K. Univ., Tokyo., v. 15: 411-452.

MiYAGAWA, Y. and Okada, R. 1930. — Biological significance of
the lung journey of Anchylostoma larvae in the normal
host. First Report. Jap. J. E.xper. Med., v. 8: 2S5-308.
1931.— Idem, Second Report. Ibid., v. 9: 151-207.

Momma, K. 1930. — Notes on modes of rat infestation with
Hepaticola hepatica. .4nn. Trop. Med. & Parasit., v 24
(1): 109-113.

MoNNiG, H. 0. 1930. — Studies on the bionomics of the free-
living stages of Trichostrongylu.'i spp. and other parasitic
nematodes. Union So. Africa Dept. Agric, 16th Rpt. Dir.
Yet. Service, pp. 175-198.

MOORTUY, Y. N. 1938. — Observations on the de%'elopment of
Dracuiiculus niedinciisis larvae in Cvclops. Am. J. Hvg ,
V. 27 (2): 437-460.

1938b. — Observations on the life history of Camallanus
sueeti. J. Parasit., v. 24 (4) : 323-342.

MOORTHY, Y. N. and Sweet, W. C. 1938.— Further notes on
the experimental infection of dogs with draeontiasis. Am
J. Hyg., V. 27 (2) : 301-310.

MoRo.iN, D. C. 1928. — Parastrongyloides winchesi gen. et sp.
nov. A remarkable new nematode parasite of the mole and
the shrew. J. Helm., v. 6: 79 86, 4 figs.

Mueller, J. F. 1934. — Additional studies on parasites of Onei-
da Lake fishes including descriptions of new species. Bull.
N .Y. State Coll. Forestry, v. 7: 335-373.

299

Neshi, G. 1918. — Ueber die Entwickluiig des TrichocephaUia
inuerhalb des Wirtes. (Japanese). Tokyo. Med. Woclieu-
schr., No. 2080.

Nevbu-Lemaire, M. l!>3t).— Traite d'lielmiiitliologie medieal et
veterinaire, xxiii + 1514 pp., Vigot Fieies, Paris.

NiSHiGORl, M. 192.J.— On the life history of Bepaticola hepati-
ca. Second Report, J. Formosa Med. Soc., t. 247: 3-4.

1928. — The factors which influence the external devel-
opment of Strongijlnidcfs stercoraJix and on auto-infection
with this para.site. Ibid., v. 277: l-.K).

NoE, G. 1908. — II ciclo evolutivo della Filaria gmssi, milii,
1907. Atti R. Accad. Lincei, Roma, Rendic. CI. Sc. Fis.,
Math. & Nat., an. 30.";, 5. s., v. 17 (.')), 1. semester: 282-
293, figs. 1-4.

Nolan, M. 0. and Rf.ardox, L. 193!.. — Studies on oxyuriasis,
XX. The distiiliution of the ova of Enlerobiiis rermicu-
lari^ in household dust. J. Parasit., v. 2.5: 173 177.

O'Connor, F. W. 1931.— Filarial periodicity with observations
on the mechanism of the migration of the microfilariae
from the parent worm to the blood stream. Puerto Rico .1.
Pub. Health & Trop. Med., v. 6: 2(33-272.

Okada, R. 1931. — Experimental studies on the oral and per
cutaneous infection of Anchylostoma caiiiniim (Four Re-
ports), Jap. J. Exper. Med., v. 9: 209 280.

Olt, a. 1932. — Das Aneurysma vermlnosum des Pfcrdes und
seine unbekaunten Beziehungen zur Kolik. Deutsch. Tier-
artzl. Wochenschr., v. 40 (21): 326-332, figs. 13.

Ortlepp, R. J. 1922. — On the hatching and niigrMfion in a
mammalian host of larvae of ascarids normally parasitic in
cold-blooded vertebrates. J. Trop. Med. & Hyg., v. 2.5:
97-100.

1923. — The life history of Syrigamiis Irachea (Mon-
tagu) V. Siebold, the gapeworm of chickens. J. Helm.,
v. 1 (3): 119-140.

192;'). — Observations on the life history of Triofhni-
tophorus tenuicoUis, a nematode parasite of the horse.
Ibid., V. 3: 1 14.

1937. — Observations on the morphology ;itid life his-
tory of Gaigeria pachi/ttcclis Raill. and Henry, ISIO: a
hookworm parasite of sheep and goats. Onderstepoort J.
Vet. Sc. & Anim. Indus., v. 8 (1) : 183-212.

Pavlov, P. 1937. — Recherches cxperimentalcs sur le cycle evolu
tif de Si)"Hn'lii<'i"ilii'< capillaris:. Ann. Parasit., v. l."i: ."lOO-
503, pl."l4.

Pereira, C. v., Vianna Dias, M. and de Azevebo, P. 1936. —
Biologia do nematoide Pyocamallanvs cearrnsis n. sp.
(English summary, p. 225). Arch. Inst. Biol., Sao Paulo, v.
7: 209-22G.

Philpot, F. 1924. — Notes on the eggs and early development
of some species of Oxyurides. J. Helm., v. 2: 239 252.

Pkommas, C. and Daengsvang, S. 1933. — Preliminary report
of a study on the life cycle of Gnatliostoma spiiiigenim.
J. Parasit., v. 19 (4): 287-292.

1936. — Further report of a study on the life cycle
of Gnathostoma spiiiioerum. J. Parasit., v. 22 (2) : 180-
186.

1937. — Feeding experiments on cats with GitaDiustoma
spinigeriim larvae obtained from the second intermediate
host. Ibid., v. 23 (1): 115-116.

Railliet, A. 1899. — Evolution sans heterogonie d'un angios-
tome de la couleuvre a collier. Compt. Rend. Acad. Sc,
Paris, V. 129 (26) : 12711273.

Ransom, B. H. 1906.— The life history of the twisted wire
worm (Hacmonclius contortu.i) of sheep and other rumi
nants. Bur. Anim. Indus., U. S. Dept. Agric, Cir. No. 93.

1907. — Prdbstmayria vivipara (Probstmayr, 1865).
Ransom, 1907, a nenmtode of horses heretofore unreported
from the United States. Tr. Am. Micr. Soc, v. 27: 33-40.

1911. — The nematode parasites in the alimentary tract
of cattle, sheep and other ruminants. Bur. Anim. Indus
U. S. Dept. Agric, Bull. No. 127.

Ransom, B. H., and Ckaji, E. B. 1921. — The course of migra-
tion of Ascari.'i larvae. Am. J. Trop. Med., v. 1 : 129156
2 pis.

Ransom, B. H. and Foster, W. D. 1917. — Life history of As-
caris lumbricoid rs and related forms. J. Agric " Res v
11: 395-398.

1920. — Observations on the life history of Aticari.i
lumhricoides. U. S. Dept. Agric, Bull. No. 817, 47 pp.

Ransom, B. H. and H.all, M. C. 1916.— The life history of
Gongylonema scutatum. J. Parasit., v. 2: 80-86.

Rbfuerzo, p. G. and Gariia, E. V. 1938. — The crustacean in-
termediate hosts of Giiatinislomiim spinigenim in the
Philippines and its pre- and iuter-crustacean develop
ment. Philippine J. Anim. Indus., v. 5 (4): 351-362,
5 pis.

RouBAUD, E. and Descazeaux, J. 1921. — Contributions a I'his-
toire de la mouclie domestique comme agent vecteur des
habronemoses des equides. Cycle evolutif et parasitisme do
I'Habronema megastoma (Rudolphi, 1819) chez la mouche.
Bull. Soc Path. "Exot., v. 14: 471-506.

1922. — Evolution de I'Habionema miiscue Carter chez
la mouche donu'stiijue et de \'H. microstominii Schneider
chez le stomoxe. Note preliminaire. Ibid., v. 15: 572 574.

1922. — Evolution de \'Hubroiidiia mtiscae Carter che ■,
dans leurs rapports avec 1 'evolution des Habrouemes
d 'equides. Ibid., v. 15: 978-1001.

Roberts, F. H. S. 1934. — The large roundworm of pigs, Ascari.i
Itimbricoideii L. 1758. Anim. Health Sta., Queensland
Dept. Agric & Stock, Bull. No. 1, 81 pp., 11 figs., 2 pis.

1937. — Studies on the biology and control of the
large roundworm of fowls, Ascaridia qaUi (Schrank, 1788).
Ibid., Bull. No. 2, 106 pp., 7 pis.

Ross, I. C. and Kauzal, G. 1932.--The life cycle of Stepliaim-
rus dentatus Diesing, 1839; the kidney-worm of pigs;
with observations on its economic importance in Australia
and suggestions for its control. Austral. Council Sc. &
Indus. Res., Bull. No. 58, 80 pp., illus.

Sandground, J. H. 1926. — Biological studies on the life cycle
in the genus Strongiiloides, Grassi, 1879. Am. J. Hvg.,
V. 6 (3): 337-388.

1939. — Cephalobus j-arasUicus n. sp. and pseudostron-
gvloidiasis in Macaca irns morda.r. Parasit.. v. 31 (1) : 132-
137.

Schwartz. B. 1922. — Observations on the life cycle of AKcaris
vitiilorum, a parasite of bovines in the Philippine Islands.
Preliminary Paper. Philippine J. Sc, v. 20 (6): 661669.
1 pi.

1925a — Two new larval nematodes belonging to the
genus T-orrocaecum from mammals of the order Insect i-
vora Proc U. S. Natl. Mus., v. 67, Art. 17. 8 pp., 1 pi.

1925b — Preparasitic stages iu the life history of the
cattle hookworm (Bunostomiim phlfbotomnm) . ,1. Agrir.
Res., V. 29: 451-458.

1931. — Nodular worm infestation of domestic swine.
Vet. Med., v. 26: 411-415.

Schwartz, B. and Alioata, J. E. 1929. — The development of
Metastrongylus eloTigatus and M. piidendotectiis in their
intermediate hosts. | Abstract). J. Parasit., v. 16: 105.

1936. — Life history of Loiigistriata miisctiU, a nema-
tode parasite of mice. J. Wash. Acad. Sc, v. 25 (3) : 128-
146.

Schwartz, B. and Price, E. W. 1929.— The life history of the
swine kidney-worm. Science, v. 70 (1825) : 613-614.

1931. — Infection of pigs through the skin with tMe
larvae of the swine kidney worm, Stephaniiriis dcntatiiii.
J. Am. Vet. Med. Assoc, v. 79: 359-375.

1932. — Infection of pigs and other animals with kid-
ney worms, Stepliaiiiiriis dciilatiis, following ingestion of
larvae. J. Am. Vet. Med. Assoc, v. 81, n. s., v. 32 (3) :
325-347.

Soott, J. A. 1928. — An experimental study of the develop
ment of Ancylostoma catiiniim in normal and abiutrmal
hosts. Am. J. Hyg., v. 8 (2): 158-204.

Seurat, L. G. 1920a. — Historic naturelle des nematodes de le
Berberie, Algiers. 221 + vi pp., 34 figs.

1920b. — Developpement embryonnaire et revolution
du Strongylacantha glyciirliiza Beneden (Trichostrong.v-
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Shorb, D. a. 1931. — Experimental infestation of white rats
with Eepaticola hepatica. J. Parasit., v. 17: 151-154.

Spindler, L. a. 1933. — Development of the nodular worm oeso-
phagostomnm lonqicaiidum in the pig. J. .\gric. Res., t.
46: 531-542.

St.wbli, C. 1913.— Trichinose. In Haiidb. Path. Mikmorg.,
Kolle u. Wassermauii, Aufl. 2, Bd. 8, pp. 73120, 3 pis.

300

Stktanski W. iiiul SiKANKOwsKi, M. 1SI31). — Sur \in cas do
I>eiirtr;ition du stionKlt' K>'"iit dans la ri-iii droit du I'liicii.
Aim. I'arasit., v. 1-t: ,').'i 00, 1 jil.

StiI.F.S, C. \V. ami HassaI.I,, a. lSi)i>.— Iiiti rnal iiarasilrs of
till' fur seal. In Jordan, 1>. S, of »l. The fur seals and
Kur Si'iil Islands of tin- North Pncitic Ocean. Pt. H, i>i).
!Utl77, tigs. 1100. WashiuKton.

SlwiMERS, \V. .\. 1940. — Fleas as aeeeptalile iiiternu'di.ite hosts
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4.")0.

Swales, \V. E. Iit3.^. — A review of Canadian helniintholoK.v.

II. .\dditions to Part I, as determined from a study of
|>arasitie lielmintlis eoUeeted in Canada. Catiad. .1. His.,
iSeet. I>, V. S {:<): 47N 4SL'.

Hyiii.—Titramtrc.i crami Swales \'XV,\. a nematode
parasite of ducks in Canada. MorpholoKical and bio-
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Tavi.OK, K. Ij. 1!'2S. — Siiiit/initiix liiirliiu fmni th/ st;irliiig
transferred to tin' chicken, and some iih.vsiological varia-
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318.

1!I3."). — Syiipamiis traclna. Tlie longevit.v of tlie in
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Thom.\s, L. J. 1029. — Phihtini Ini iioiliilo/ici nov. spec., with
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1937a. — On the life cycle of Coiitriicacriim .iiiiriiH-
genim (Rud.), Ibid., v. 23: 429 431.

19371). — Further studies on the life cycle of Contra-
caecum xpiciitificnnii. Ibid., v. 23: 572.

1937e. — Life cycle of Kliaphiilasraii.i caiiadiiixiK Snied
lev, 1933, a nematode from the jiike, E.sox lucitis. Ibid.,
V.' 23: .->72.

Tkavassc.*;, L. 1920.- -Entwicklung d s lUiiihtlius fullrbtinii. n.
sp. Arch. SchifFs- u. Tropen Hyg., v. 30: 594-602.

Troisier. J. and Deschiens, R. 1930. — T/Hcimticoliase. .\nii.
Med., v. 27: 414-425.

UXDERWOOD, P. C. and Hakmood, p. D. 1939.- -Survival and
location of the microfilariae of Dirofilaiia immitis in the
dog. J. Parasit., v. 25: 23 33.

Van' Durme, P. 1902. — Quek(ucs notes sur Ics cmbryons de
Strongyloides i),testiiialix et leur penetration par le peau.
Thompson Yates Lab. Rpt., Liverpool, v. 4 (2): 471 474,
pi. 7.

Veglia, Frank, 1910. — The anatomy and life-history of the
Hacmoiicliiis contorius (Rud.), Dept. Agr. Union S. Africa,
3d & 4th Rpts. Director Vet. Res., pp. 349-500, figs. 1 60.

VoGEL, H. 1930. — XTeber die Orgauotropie von Uepaticola li< pal-
ica. Ztschr. Parasitenk., v. 2 (4): 502-505.

Vox Braxd, T. 1938. — Physiological observations on a larval
Euslrongylides (Nematoda). J. Parasit., v. 24: 445-451.

White, R. H. 1920. — Earthworms — the important factor in the
transmission of gapes of chickens. Md. State Coll. Agric,
Bull. No. 234, pp. 103-118.

Walker, H. D. 1886. — The gapeworm of fowls (Syngamus
trachralis), the earthworm (.Lumbriciis lerrestris) its origi
nal host, etc. Bull. Buflalo Soc. Xat. Sc, v. 5 (2): 47-71.

W.\LTON, A. C. 1937. — The Xematoda as jiarasites of Amphibia.

III. Studies- on life histories. J. Parasit., v. 23: 299-
300.

WiiiK, K. K. I'.i3(;. - Karlhuornis as transmitters of Capillaiia
iiiiniiliihi, the cropworm of chickens. N. .\ni. W't,, v. 17 (8):
IS 20.

1937. — Observations on thi' cl(vilo|iiiiiril of the poul-
try gapeworm. Syitgoiiin.i tinrlmi. 'I'r. Am. Micr. Soc, v.
50: 72-78.

1939. — Stu<lics on the ilcvchipnHiit of the |>igeon capil-
larid, Capillarui ruliiiiilini. \' . S. Dept. .\gric.. Tech. Bull.
No. Ii79. 19 pp.

Wktzi;!., H. 1930. — On tin- biology <if the fourth stage larva of
(l.ryuri.i itiiii (Schrank). .1. I'arasit., v. 17: 95-97.

1931. — On the biology <if the fimrth stage larva of
Ihymatoxy.i rrligcra (Rudolphi, 1819) Schneider, 1860,
:in oxyurid parasitic in the haii'. Ibid., v. IS; 40 43.

1:138. rntersnchungen iiber die Kntwicklung der
I'ferdestrongyliden. Sitzungsb. Gesellsch. Naturf. Frc-
unde, Mar. S, 1938, 18- 19.

193S. — Zur IJiologie und systematisicben Stellung deS
|i;iclislungenw\irines. Livro Jnb. Travassos, pp. 531-535,
1 pi.

Wktzki, R. and lOxiiiK, K. 1938a. — Wandern die Larvender

Palisadenwiirmer (Strongylus spec.) der I'ferde durch die

Lungen? Arch. Wiss. & Prakt. Tierheilk., v. 73 (2): 84-93.

1938b. — Zur Biologie von Dictyoctiiihi.s anificldi, den

l.UMgewnnn der Kinhufer. Iliid., v. 73 (2): 94-114.

\Vi rzi 1. i;. ami .\l ii.i.Kii, I'. K. 1935. — Hie Lebensgeschichte des
schachtelhalmformigen Fuchslungenwurmes C'rcno,90)H(j
ndpix und seine liekamiifung. Deutsch. Peltztierziichter, v.
19: 361-365.

WiviUHT, W. H. 1935. — Observations on the life history of
Toxaxcaris Uonina (Nematoda: Ascaiidae). Proc. Helm.
Soc. Wash., v. 2: 56.

Wi'LKER, G. 1929. — Der Wirtwechsel der parasitischen Nema-
toden. Verhandl. Deutsch. Zool. Gellsch., v. 33: 147 157.
(Zool. Anz., Suppl. 4).

YoKOOAWA, S. 1920. — On the migratory course of Trichosomo-
ides crassicauda (Bellingham) in the body of the final host.
J. Parasit., v. 7: 80-84.

1922. — The development of Hcligmosomum miiris
Y'okogawa, a nematode from the intestine of the wild rat.
Parasit., v. 14: 127-160.

1920. — On the oral infection by the hookworm. Arch.
Schiffs- u. Tropen-Hyg., v. 30: 063-679.

1938. — Investigation on the mode of transmission of
Wiichereria bancrofli (Preliminary Report). Tr. Soc. Path.
Jap., V. 28: 019 624.

YoKOUAWA, S. and OlSO, T. — Studies on oral infection with
Ancylostoma. Am. J. Hyg., v. 0 (3): 484-497.

YOSHIDA, S. 1934. — Contribution to the study on Gnathostomum
spinigcrum Owen, 1830. Cause of esophageal tumor in
the Japanese mink, with especial reference to its life
history. Tr. 9th Cong. Far East. Assoc. Trop. Med.,
Nanking, v. 1 : 025-030.

YosHlDA, S. and Toyoda, K. 1938. — Artificial hatching of As-
caris eggs. Livro Jnb. Tiavassos, Rio de Janeiro, pp. 569-
577.

Zawadowsky, M. M. and Schalimov, L. G. 1929. — Die Eier
von Oxyuris vcrmicularis und ihre Entwieklungsbedingun-
geu sowie ueber die Bedingungen unter denen eine Auto-
infektion von 0.\yuriasis unmoglich ist. Ztschr. Parasit-
enk., V. 2: 12-43."

aoi

CHAPTER VII

EPIDEMIOLOGY AND SANITARY MEASURES FOR THE CONTROL OF
NEMIC PARASITES OF DOMESTICATED ANIMALS

T. W. M. CAMERON, Institute of Parasitology, Macdonald College, Quebec, Canada

The parasitic existence of a nematode is dependent on its
finding a suitable environment in which it can mature and re-
produce and this involves four sets of factors:

(a) SuccESSFUi, Admission to the Host. — The host must
traverse the ground where the free stages of the parasite are
found, it must eat suitable foodstuffs in or ou which tlie
larval stages occur; it must be exposed to the intermediate
host, and so on. Even slight differences in habits; e.g., such
as exist between a sheep and an ox in eating grass, may
make all the difference in the parasite gaining admission.
The anatomy of the host, including the thickness of the skin
is a factor to be considered under this head.

(b) Suitable Environ ment.\l Conditions in the Host. —
Once inside the host, the parasite must find a suitable habitat
— type of mucosa in the intestine, length of intestine, pres-
ence of suitable food, and so on.

(c) Possession of a Suit.able Protective Mechanism
Against the Normal. Metabolic Processes of the Host. —
When the parasite lies in the alimentary system, it must
possess some means of preventing itself being digested or
being passed out by peristalsis, etc.

(d) Absence op a Host Reaction that Would Interfere
WITH THE Normal Metabolism of the Parasite. — This fac-
tor applies most obviously to parasites that leave the lumen
of the alimentary tract at some period of their life, but it may
apply to all. If there is any host reaction, the parasites must
be able to resist its effects.

Under natural conditions, nematodes are more or less spe-
cific to a single species or a group of closely related species
of animals. In general, it may be taken that nematodes of
ruminants are not transmissible to horses, pigs, poultry, nor
those of the latter to each other. However, many parasites
of wild ruminants are transmissible to domesticated ruminants,
of wild carnivores to dogs, cats and foxes, of wild birds to
domestic ones, and so on. The important exceptions to this
generalization include the Trichina and some members of the
genus Tricltostrongyhis.

Very few parasitic nematodes can complete their entire life
cycle within the same vertebrate animal, any more than they
can live a free independent existence. At one stage or an-
other they must leave the host to undergo some form of devel-
opment outside of it — either free, or in an alternate or inter-
mediate host. In effect, this means that a single young nema-
tode develops into a single adult only; there is no multiplica-
tion as in the case of bacteria. In both groups, disease de-
pends upon numbers, but whereas the entrance of a single
bacterium into the body may cause disease, the entrance of a
single larval nematode usually does not. Parasitic disease de-
jiends on actual numbers entering the body.

The stages which leave the body, are never immediately
infective. Some essential development must take place before
they are ready to re-enter and this development takes a definite
period of time and requires a definite set of conditions — heat,
moisture, oxygen, presence of correct intermediate host and
so on — before they are able to infect. Once the infective
stage is reached, they are often able to live for a long period
before re-entry; while the minimum time necessary outside of
the body can be fairly accurately ascertained, the maximum
time is much more difficult to determine.

In many cases, after entrance to the body, complicated
migrations through various organs are an essential part of
the life-cycle and the greatest damage to the host is often
caused at this period. We know of no means of preventing
these migrations and we know of no therapeutic agents which
can affect the nematodes during migration . Accordingly,
prevention of ingress is of the greatest importance.

Scientific control consists in making development as difificult
as possible and so depends essentially on a knowledge of the
life history and bionomics of the parasite involved. This
necessitates the correct identification of the nematode con-
cerned. The need for correct identification is most important
as not only are no two parasites quite alike in their biology,
but treatment is often different.

In determining control methods it is important to remem-
ber that there are economic aspects of the problem to be con-
sidered. The cost of control may be excessive and it must be
balanced against the loss to the stockowner — and loss should
include not only actual, but potential future loss. It is often
accordingly necessary to adopt several methods of control

simultaneously rather than to employ a single method. Control
may be nationwide or it may be individual. Individual con-
trol is at best a palliative, and campaigns directed over a
wide area and infinitely more satisfactory. This not only in-
volves cooperation between veterinarians, agriculturists, ad-
ministrators and parasitologists but it involves careful co-ordi-
nation as well. A central authority and enabling legislation
are almost essential, but the legislation to be successful must
come as the result of a demand from the majority of the
farmers involved. A central laboratory with a good informa-
tion service is also desirable, with adequately staffed branch
or associate laboratories throughout the country.

Control measures aim at breaking at some point the essen-
tial life-cycle of the parasite. If more than one point is at-
tacked, the chances of successful results are increased. These
measures will be discussed convenientl.v in several groups, al-
though it must be understood that such a hard and fast divi-
sion as is here adopted does not occur in nature and that
methods described under one may be equally applicable under
another. The parasite may be attacked at one or other of the
following points in its life cycle: —

1. While in the ovum or as a young developing larva.

2. During the developed infective stage, which does not
grow and ' ' rests ' ' until it enters the host.

3. Before entrance of this larva into the host.

4. Within the intermediate host or vector, within which
1 and 2 may be found and which may be the means of
entry to the host.

-■). During the parasitic stages in the host.

1. Methods of Destroying the Eggs of Pre-Infective
Larvae

These are those stages passed in the faeces as well as the
subsequent stages which develop therein. (In a small minority
of cases the larvae are not passed in the faeces, but may
leave by the mouth or the urinary system or be abstracted
from the blood b.v blood-sucking animals, or may come to rest
in the host's muscles). As we know of no efficient method of
destroying the eggs in the host, this section is accordingly
mainly concerned with manure and its treatment. It is not a
new subject, having been advocated for years in connection
with human hookworm disease, but curiously enough, very lit-
tle indeed has been done about it in connection with nema-
todes of animals in which it is infinitely more important.

There are two ways of treating manure. The first is to
disregard its parasite content and concentrate on its dispersal
in such a manner as to keep it out of harm's way. The sec-
ond is to treat it in such a way that its parasite content is
destroyed. Some twenty years ago, the late Dr. Maurice
C. Hall stated that this subject offered a field for a large
amount of investigation but this investigation has not been
done.

"Broadly speaking," he said, "one would have to deter-
mine how long the larvae and eggs of the various species of
worms involved live in manure piles, in spread manure, in
closely packed manure; the effect of sunlight, of moisture, of
various chemicals, the chemicals in turn being of a nature
not to injure the fertilizing value of the manure. There are
practically no data on this and little could be surmised with-
out such data. ' '

Since that was written a considerable amount of investiga-
tion has been carried out on this subject and it may be con-
sidered under the following headings:

1. Storage. The prompt daily collection of all manure in
the stables is an essential routine in farm practice and if
correctly carried out is a valuable preventive measure. If this
manure were stored in a proper container for a suflScient length
of time, without any other treatment all eggs and larvae would
be destroyed. Unfortunately, the time factor is too long to be
practical and resource to additional methods is necessary.

'2. Heating. In piles of horse manure, all eggs and larvae
of the strougyle type are destroyed in 4 days by the natural
heat generated, with the exception of those in the outer 6
inches. As a temperature as high as 107 degrees F. is generated
in the central zone, all other parasites should be destroyed
also, although we are without definite knowledge of this. If

302

rill' inaiiiirc is contiiU'd witliiii wmnli'ii hoxi's oitlii'r :ili<ivi' (ir
lielow Kroiiiul — all except the o\iter layer of It iiielie.s heroines
hot enough to destroy the panisites, while if the womleii
lioxes are doiihle walled with sawdust lietweeii, all are killed
ill a week. Kxperiiiieiits with artitieial heat, have shown
that steam, at l."i lbs. pressure, destroyed in itO luiimtes all
e^Ks and larvae in a special niaiiiire box.

While these data indieate that iiiainire can In' I'lVcctively
sterilized, the iiicthods with the exception of the first, have
the disadvantage of leipiiriiiii special a|)paratus. This en
tails expense and limits their application to well eciiiiiiped
stables. However, a compact manure pile, which has the
outer (> inches turned in every .'> days or so, will iiiHloiiliteilly
kill a very high percentage of the eggs and larvae.

3. Drying. This is a method which is only occasionally
possible and the drying of large (piantities of manure is
l>ractically confined to countries with a hot, dry climate wlu're
dried dung is used for fuel, or where its value is secondary
to military conditions and it may be spread out in the hot sun.
Ill the latter case, however, imincdiate daily <lrying is essen
tial as only the eggs and jire infective stages are easily
destroyed by this method. Drying is of some value also
in destroying larvae on bare ground. Iturning of manure is
the logical extension of drving it, but this is seldciru i>raiti
cable.

In a rather dilTerent way this method has been used to
combat the lung and intestinal nematodes of silver foxes in
Canada. There the animals are raised on floorboards which
are easily kept dry by being roofed. This inhibits develop-
ment of the eggs and larvae of the worms so effectively
that it is now almost routine practice.

In the open, short grass assists drying and is frciiuentl.v of
value ill reducing the infectivity of p.'istures, as of course, is
drainage. Very wet iiasturos, however, are not suitable environ-
ments for the development of most nematodes (except Did ylo-
raiiliix of horses, sheeji and oxen). Damp pastures are more
generally favourable for parasitism and every effort should be
made to render them unsuitable for the development of eggs
into larvae.

4. Chemical Tre:atmext. Comparatively little has been
done to find chemical methods of destroying the free-living
stages of parasites. It is a problem which presents many diffi-
culties, probably the greatest of which is the faet that the eggs
and larvae are always in close contact with faeces, soil or grass,
and many chemicals which might be used, are iiartially or com-
jiletely counteracted by contact with organic matter. Never-
theless, chemical control of all the free-living stages does ap-
pear to have considerable practical possibilities.

It offers the opportunity of using the faecal material as
manure and even of enriching the manurial value and it does
not necessitate special equipment.

The method has been sporadically used with a certain limited
success in some human hookworm areas, the chemicals employed
being kainit, lime and some nitrogenous fertilizers such as
nitrate of soda, sulphate of ammonia, and calcium cyanamide.

The addition of a chemical to faeces containing nematode
eggs, may have varied effects on the eggs and larvae depend-
ing not only on the nature but also on the quantity of chemical.

1. It may increase the percentage of larvae which reach the
infective stage and which continue to survive. Even in small
cultures of fresh horse faeces in sterilized containers, fungi
parasitic on nematodes have occasionally become established
very rapidly and in a short time have destroyed all the larvae.
The evidence suggests that some chemicals may destroy or
retard the growth of these fungi without harming the larvae;
flowers of sulphur is an example. Other evidence suggests
that some chemicals, which are lethal to eggs or larvae when
mixed with faeces in a certain i)roportion may, in a lesser
proportion, be lethal to the fungi without harming the larvae;
it follows that these chemicals may, if used too s])aringly,
actually increase rather than decrease the number of larvae
which survive. Fungi are more likely to be common in manure
pits and similar locations than in cultures and may be of
practical importance as a method of natural biological con-
trol. It is probable that there are many chemicals of quite
different types which possess this danger. A chemical may also
decrease putrefaction which may be lethal to larvae.

2. It may have no effect at all on the eggs or larvae. The
majority of the chemicals which can be added to faeces without
afTecting the eggs or larvae, are those which are most inert;
exam])lcs are ferrous sulphide, ferric oxide, ground limestone,
rock phosphate, basic slag, derris root, white hellebore, and
pyrethrum powders.

3. It may allow larvae to reach the infective stage but
cause many to exsheath. Some chemicals cause larvae to ex-
sheath without necessarily causing their immediate death, al-
though most of these chemicals are lethal in higher propor-

tions. I,ap;ige has shown that the factors which are impor-
tant in causing I'xshcathment when free of faeces, include age
of the larvae and |ill of I heir environment, and that chlorine
and sulphides make the sheath more permeable. Iji the pres-
ence' of faeces, some chloriib'S and sulphates, sodium and potas-
sium hydroxide and potassiuui peruiang.-inate occasionally
cause exsheathment. Tln'se cliemicals, in slightly greater pro-
portions, gener.'illy cause the death of larvae.

4. It may allow many l.nrvae to reach the infective stage
but subse(iuently cause their death. Many chemicals mixed with
faeces in certain proportions, allow a considerable number of
the eggs to hatch and the larvae to reach the infective stage
and then kill them comparatively rapidly. The most ontstand
ing exami>les so far noted with this property are (piicklime,
(in qu:uitities too small to I'.'iiise death through tin' heat of the
clieiuical reaction), cupric, ferric and ferrous sulphates, zinc,
cupric nitrate, sodium fluosilicate, and oxyquinoline sulphate.
Wlicn ajiplied to fresh faeces, in some cases only a third of
the quantity of chemical may be required to cause delayed
deiith compared with the (luantity required to cause death
ln'fore the infective stage is reached. Numerous other chemi-
cals (but to a lesser extent) have the characteristic of causing
dcl.-iyed death under certain conditions; examples arc nicotine
suliiliate, trisodium phosphate, sulphate and chloride of man-
gaiu'se. so<liuin and magnesium borates, strong cresol, phenol,
anil calcium liypt)chIoritc.

."i. It may allow a few larvae to survive. It is probable
th.it the thickness of the sheath may be an important factor in
lircventing the action of some chemicals on the larvae. If this
is so. it would account for the fact that, in spite of careful
mixing, a few larvae survive in cultures treated with sufficient
(or more than sufficient) chemical to kill most of them. In
many cases when a few larvae have survived they have been
mainly the larger sclerostome larvae. (In some cases the posi-
tion of the eggs, e.g., in the centre of a lump of faeces, may
have enabled them to survive.)

G. It may rapidly kill all the eggs or free-feeding larvae.
When a chemical is highly lethal its method of causing death
may be of considerable practical importance. Chemicals which
are lethal but insoluble — they are not common — and which kill
by contact would be difficult to use in practice, because many
larvae would escape by remaining away from the chemical,
e.g. inside a lump of faeces. These chemicals would, there-
fore, be especially useless in dry conditions. Applied dry,
chemicals which are deliquescent have more prospect of being
of practical value, for the moisture which they attract may
also attract the larvae. With solutions it is much easier to
obtain effective contact with eggs or larvae scattered through-
out the manure, especially if the chemical is sufficiently lethal
to be effective when applied as a very weak solution. With
very lethal chemicals such as iodine salts, it has been found
that very considerably less chemical is necessary to produce
sterilization with a very weak rathei' than with a very strong
solution. In extreme cases a chemical applied as a 1:2 solu-
tion may require from 20 to even 50 times the amount neces-
sary when applied as a 1:300 or a 1:1,000 solution.

Some chemicals — including some which are very effective
(such as chloropicrin, calcium cyanide, naphthalene, Ortho- and
Para-dichlorbenzene) — can be used as gases. Application of
this class of sterilizing agent should have many practical
advantages, provided that a suitable container is available
and that the faeces are not packed too tightly for the gases to
permeate them, but results suggest it is possible for a small
percentage of eggs or larvae to avoid gases, again probably
when they are in the centre of a lump of faeces. However,
whether this class of chemical is applied as a solid or fluid,
it is probable that the chemical will distribute itself effectively
through the faeces. Unfortunately, some of the most effective
gases are dangerous or at best, most unpleasant, to man him-
self.

Apart from the efifectiveness of a chemical and ease with
which it can be applied, the practicability of its use depends
largely on its cost. When sufficient urine is available it has
practically all the possible advantages. The next most prac-
tical group of agents is the artificial fertilizers, since if care is
taken to avoid loss of nitrogen, part or all of their cost may
be recovered in increased manurial value.

Occasionally it may be possible to use a chemical which is
not only lethal to nematode larvae, but also to other pests, such
as fly larvae; if this can be done the advantages are obvious.
Unfortunately, it by no means follows that because a chemi-
cal is lethal to fly larvae, it also kills nematode larvae. For
example, hellebore, borax, aniline and pyridine have all been
shown to be effective in fly control. Hellebore, however, is
not lethal to sclerostome larvae, while borax has to be used in
larger quantities than for fly control and in greater quantities
than are jiracticable if the faeces are to be used as fertilizer
(because of the toxicity of an excess of borax to plants). Ani-

303

(in weak solution")

(in very weak solution)

(in weak solution)

Jine and pyridine, on the other hand, are both vor3- lethal to
the free-living stages of sclerostomea.

The cost of treating faeces can also be reduced if a lethal
by-product is available or if a chemical is being bought in
bulk for other purposes. In these eases the possibility of the
presence of impurities must be considered, as they may alter
the lethal value of the chemical or they may make it unsuit-
able by containing a plant poison.

A large number of chemicals has been tested at the Insti-
tute of Parasitology for their effect, under controlled labo-
ratory conditions, on the pre-infective stages of horse sclero-
stomes. The more ' ' practical ' ' of these are given in the fol-
lowing table, with the percentage required to completely steril-
ize small quantities of horse manure:

Percentage Chemical Brmarls

0.04.'5 Chloropicrin

0.19 Calcium cyanide

0.2.T Paradiihlorbenzene

0.33 Formalin

Sodium fluoride
0.37 Phenol

Naphthalene

0.62 Cresol (in weak solution)

0.75 Urea (in strong solution)

1.0 Sodium borate (in weak solution')
Zinc chloride (in weak solution)
Ammonium thiocyanate (in medium solution)

1.25 Calurea

1.5 Potassium cyanate

1.9 ' ' Powdered' ' Cyanamide

2.5 "Granular" Cyanamide

Sodium chloride (in medium solution)

Sodium hydroxide

3.1 Carbon disulphide

Calnitro (in medium solution")

Ammonium nitrate (in medium solution)

Kaiuit (in medium solution)

3.75 Sodium nitrate (in medium solution)

4.4 Potassium nitrate (in strong solution)

4.5 Nitro chalk (in medium solution)
5.75 Calcium hypochlorite (in strong solution)
6.0 Ammonimum sulphate (in medium solution)
6.25 Carbonate of potash (in medium solution)
8.0 Carbon tetrachloride

14.0 Sulphate of potash (in strong solution)

20.0 2i)'/c Superphosphate

Phenothiazine
23.0 Dog urine

Horse urine
37.0 Cow urine

40.0 16% Superphosphate (in strong solution)

50.0 Quicklime

65.0 Hydrated lime

Of Xo Value

Flowers of sulphur

Ground limestone

Raw rock phosphate

Basic slag

Pyrethrum powder

Derris powder

White hellebore powder
Among the numerous other chemicals tested, in attempts to
find reasons for the lethal factors, compounds of iodine were
found to be of a very high efficiency indeed ; thus for example,
0.01% of methyl iodide (in a dilution of over 1:200) was com-
pletely etfeetive. Iodine salts, however, are expensive.

On farms the most easily obtained (in efficiently drained
stables) is urine; in addition there are many artificial fertiliz-
ers with lethal properties, part or all of the cost of which may
be recovered in added manurial value.

The chemical and lethal composition of urine varies consid-
erably, not only according to the species, but also according
to the food and health of the animal from which it is taken.
In a few cases its lethal value may be almost nil, but generally
speaking, about 30 to 40 percent of the weight of urine to
fresh faeces kills the free-living stages of selerostomes. Of the
artificial fertilizers, urea is the most potent, requiring about
three-quarters of 1 percent by weight of the fresh faeces to
sterilize them against selerostomes. Calurea should be used at
the rate of 1% percent, while about 2 percent of powdered
cyanamid is needed and another half of 1 percent if used in the
granular form. A high grade kaiuit is one of the next most
lethal fertilizers and it should be used at the rate of 5 lbs. to
100 lbs. of manure. Closely following in potency are many
other artificial fertilizers which should be iised at the rate of
about 6 percent or slightly over, compared with the weight of
fresh faeces.

It must be remembered that the addition of some alkali fer-
tilizers to faeces will cause the loss of ammonia. With urea
and calurea, much ammonia escapes as gas.

The quantities mentioned above would be too great in many
cases for common manurial practice if the whole manure heap
had to be treated, but since the heat of fermentation, lack of
oxygen and other factors, prevent the development of larvae
in the centre of a well-built heap, is should only be necessary
to treat the top and sides, provided that the faeces are put
there as soon as they are passed, that the fertilizer is immedi-
ately well mixed in, and that the pile is sufficiently well-
packed and protected to keep the fertilizer in contact for
some time.

The use of a well constructed manure pit is highl3' desirable
and ideally should be divided into two portions — one to con-
tain manure under treatment while the other is being filled;
the first portion is then emptied and the procedure reversed.
The size and design will depend on local circumstances. Ma-
nure stored in yards, no matter how stored, should be inaccessi-
ble to stock.

Selective Dispos.\l. As there is normally a marked speci-
ficity shown by the parasites of various species of animals, the
manure, especially if untreated, should be used on ground
which is inaccessible to the species of animal from which it
came. Thus, horse manure should not be used for top-dressing
liastures to be used by horses, but it is safe — or reasonably so
— to use it for pastures used by cattle and sheep. It may also
be used for growing crops — except hay crops which will subse-
quently be fed to horses.

Plowing Under. Wherever possible, manure should be
plowed under. However, this procedure cannot be guaranteed
to keep eggs and larvae below ground. Earthworms bring some
to the surface and strongyle larvae are capable of a certain
degree of upward migration. The horse selerostomes have
practically no migrating ability in clay soil (provided that
there are no cracks in the soil), but in sandy clay they can
migrate 4 inches and in sandy loam '< inches upwards; more-
over, they can live for over 4 years under these circumstances..
The sheep nematodes Osterlagia and Xematodirus can regain
the surface after being plowed under and survive for S to 10
months; Hacmonchus survives less well. Plowingin may
actuallj' assist development by breaking up the soil and faeces.

Fly Destructiox. Flies are important in connection with
manure as mechanical carriers of worm eggs (e.g. Ascari.s) and
as actual essential intermediate hosts of worms (e.g. Habro-
iiciiia) ; the part they play as mechanical carriers is probably
of secondary importance.

From the second point of view, flies must be prevented from
feeding on horse manure; this, if perfect, would completely
eradicate Eabrotieina from horses. Cleanliness in stables is
essential, even small quantities of manure being removed daily.
Spraying manure with hellebore (V-i lb. dissolved for 24 hours
in 10 gallons of water, will treat 10 cubic feet) or powdered
borax (at the rate of 1 lb. to 16 cubic feet) are recommended
by the United States Department of Agriculture for the pre-
vention of fly breeding. The hellebore has no injurious effect ;
the borax also is not injurious if the manure is not used in
excess of l."i short tons to the acre. Creosote oil also has been
recommended as a deterrant ; it is mainly useful under war
conditions and for dead horses.

The heat generated in the centre of a well-constructed ma-
nure pile or throughout the manure in a box will destroy many
maggots. The outer layers of the pile, however, will not be-
come sufficiently hot and will require treatment.

Comparatively few eggs or larvae leave the host other than
in the faeces. Those that do include the pinworms, trichina
worms, kidney worms and microfilaria.

Pinworms. The female O.ryuris equi, the only known pin-
worm of importance in domestic mammals, leaves the host to
deposit her eggs on the perianal skin or stable furnishings;
sometimes she is evacuated in the faeces or, dying in the rec-
tum, her eggs are so passed, but this is exceptional and the
few cases in which it occurs are provided for by the usual
procedures. Most eggs are actually laid on the skin and al-
though very little is yet known of their bionomics, it would
seem that excess of water is quickly fatal to them. Accord-
ingly, washing of stable, stable furniture, grooming kit and
perianal skin, would reduce the possibilitj' of reinfection. The
removal of eggs from the skin by washing will also reduce the
local irritation and render reinfection less i)robable, while in
heavy infections, warm water enemata will remove gravid fe-
males mechanically and so reduce the egg output. Infection is
by swallowing the embryonated eggs either directly from the
skin (where the irritation causes the horse to bite) or as a
contamination in food. General cleanliness and the use of hot
water (as for Ascarids) will undoubtedly reduce infections.

Trichina. While a few larvae pass in the faeces of car-

304

nivores mid pigs, tlirx ild not :i|>|U'iii' capaMc nt' Ihtoiiuiik in
t'cotivo. Tliosf wliii'h will lu'cnino iiitVctivc puss into tlio imis
I'K'S. Control lies ontirclv in :ippi'(>pi'i.'itt< fecdin);. I'lKS must
not lie pcrmitti'd to cat iincookiMl inont foods.

KlPNKYWOKMS. Till' fggs of tlu' snino ki<lni'.v worm nri'
passoil ill the nriiio and cxposuro to drviiij; and 8iiidi);lit will
dostroy them. This can often l)C done liy the iirovision of a
l>are lot around the hoK h>t, kept free from grass or shade and
well drained. The ckks of the kidney worm of carnivores are
also passed in the urine hut m)thinf; is yet known of their
I'ionomics and so no control measures can he adopted.

Mu'iiO>'il,.\Ri.v. Few lilaria worms are important in stock.
.Ml depend, however, on their removal from lilood or skin l)y
a hlood sucking insect. Control accordinijly deiieiids on insect
control, screening of houses and related measures.

2. Methods of Destroying Infective Larvae
(free or enclosed in egg shells)

(a> Disinfection

(i.) Chemical — There is no good chemical disinfectant for
larvae enclosed in their vgg shells (e.g. Ascarids^ and disin
fectaitts for this ])uritose are jiractically useless; in f:ict they
may assist the larvae hy destroying fungi and bacteria which
are themselves harmful to the ]iarasites. The use of chcmi
cals against free lai*\"ae has lieeu discussi'd ahovc as it is not
po.ssihle to separate the actions of chemicals on the preinfectivc
l.-irvae from the action on infective larvae, although in general
the latter are more resistant.

(ii) Urat is lethal for all forms of parasites and, in the
form of very hot water or live steam, is one of the most efti
sient disinfectants at our command. It is the only one of any
practical value against -X.scarids and its use is fundamental in
the control of these very serious parasites in awine and car
nivores. It can be used either as hot water (with lye or soap
to loosen the dirt) or steam. Its use is recommended in all
kinds of stables as it kills every kind of larva. While its value
has been recognized for many years, it is only reci'utly that
accurate knowledge has been obtained on the amount of heat
required and it was found that ascarid eggs could be killed in
1 second at 158° F., "J seconds at 140° F. and ." seconds at
140° F.

(iii), Cleanliiics.i both of animals and of ijuarters, is of
great value in reducing numbers of parasites. Washing of
udders of sows with warm water and soap removed man.v infec-
tive ascarid eggs. Washing of stables (including window-sills
and other places where dust lies) mechanically removes selero
sfome larvae which have very great powers of resisting drying
and which otherwise would be blown on to the animals' feed
or water.

(b) Pasture

Little work has yet lieeu done on the control of parasites on
pasture and arable land although the sub.ject is of great impor
tance in all parts of the world. Pastures cannot l>e treated
daily as can a manure liejt]) and so it is uminly infective larvae
which have to be killed. They are then in position in which
destruction is difficult. Chemical treatment has many dis-
advantages— cost being one of the most obvious. Nevertheless
some chemicals have been tried; copper sulphate, bleaching
powder and lime have jiroved unsatisfactory in practice. The
mo.st promising appear to be those which could be applied as a
gas and retained on the ground by a mulch of paper, a tarpau-
lin trailed behind a tractor or some similar method. Such gases
as chloropicrin (a tear gas), calcium cyanide and others men-
tioned have at least possibilities in that direction. .Mternately
it may be practical to use a delii|uescent salt alone or mi.xed
with a very lethal chemical so that the larvae may be attracted
toward the moisture.

These are suggestious for the future; meanwhile, the only
effective way is to collect the droppings daily before the larvae
can migrate to soil or grass. Obviously this method has very
considerable limitations, but it has been done on stud farms.

.\s infective larvae of bursate nematodes do not feed but live
entirely on foodstuffs stored up in their bodies, their life can
be shortened by causing them to use up this source of eiu'rgy
more quickly than usual. Modeiate warmth and light are
natural stimulants and, as continual spreading and harrowing
e.xposes them to these physical ageuts, it is of assistance in
reducing the numbers but will not completelv eradicite them.
It is especially effective in dry, warm climates.

The burning of grass — often a valuable agricnitur.il practice
- — theoretically must destroy some larval worms on the pasture
aud in the ground beneath; it cannot be relied uijon to destroy
them all aud it may also give the larvae access to the more
succulent grass beneath. It does, however, help to raise the
nutrition plane of the animals.

.\ II worm lai'vac icqniii' ,-i degree of moisture for develop-
ment, allhongli only » few (e.g. Did jiiirniiliiK) .are capable of
de\cIopment in w:iter :ilone. Drainjige, an essential step in the
control of these luiigworms, is always of general value In damp
pastures, it impro\-es the (piality of the gr'ass ami so improves
the resistance of the host, but it is donbtfnl if it di'strovs many
larvae.

Drying of larvae has very variable results. Oidin.ary drying
is quickly leth.il to uuiny of the lu'uiatode larvae of slieej) but
only slightly so to other larvae and forms enclosed in egg shells,
like .\scari<ls. Ten per cent of sclerostouie larvae can survive
4 nuinths air drying in an incubator at 7.")° to HU° F. and they
have been f(Uind alive in window dust in stables out of use for
several ye.ars. ()rdin;uy drying distroys only some larvae but
it may destr<iy sufficient to prevent disease.

Urought has not nece.ss;irily the .same effect as draining of
|i;istures. In dry seasons grass is short and scarce, more must
be eaten, (especially by sheep) it is eaten "short" and a
greater area of the pasture is grazed daily. Larvae of some
worms tend to live near the roots of the grass and .so under
these conditions m;iny more reach the host: the i)arasite intake
varies directly with the time of grazing. The resistance of the
host, through poorrii'ss of the feed, is lowered and so serious
disease may result.

.Moreover, embiyouated but uidiatched eggs of sheep gastro-
intestinal nematodes are often very resistant to drought aud so
these tend to accumulate. When the drought breaks they hatch
simultaneously, and if the moist weather continues for a week or
so, they may cause an explosive outbreak of disease. However,
short jieriods of drought interrupted by short showeis have an
ojiposite effect.

Heavy rain is inimical to the development of sclerostome
larvae in their ])reinfective st;iges ; whether this is due to the
fact that subsecpient drying is easier, is not yet known. Heavy
rainfall in hill country often has the effect of mechanically
washing Larvae and faeces off' the hillsides and so reduces the
number of infective larvae; this is especially true in troi)ical
islands and uplands where rainfalls are often very heavy. How-
ever, it may concentrate infections in the valleys. In fiat country
the larvae are washed off the grass but quickly crawl back
again. (It should be noted that an excessive growth of grass
may encouiage sheep to feed between the tall grasses. It is in
this ])osition that most larvae are found and so heavy infections
ma.v result ) .

Continued exposure to extreme cold undoubtedly has a serious
effect on the free stages of parasites but in many cases we
cannot rely on the natural cold of winter to act as an important
agent. Destruction dci)ends at least to some extent on snowfall.
Where the snow is adequate, the temperature of the grouiul be-
neath is almost independent of the air temperature, and even
when the air temperature falls to 0°F., the ground temperature
is still little below freezing. The type of winter most destruc-
tive is the siioiflixx winter and a comparatively mild winter
with little snow, is much more destructive than a severe one with
a heavy snowfall.

Moreover, in countries with a normally cold winte~, animals
of all kinds are stabled during cold weather and the parasites
can be carried over as adults in the host or as eggs in the ma-
nure in the barn.

In countries with a mild winter climate, frost may actually
increase the life span of the parasites, although repeated freez-
ing and thawing is much more lethal than continued freezing.
There is little accurate knowledge yet available on the lower
thermal death points of parasites. It is known, however, that
some forms, such as horse .sclerostome larvae, can survive very
low temiieratures (-3t)°F.) for long periods; others such as
sheep nodular worms, are easily killed by cold. Each species
has its own critical temperature or range of temperature and
this tends to control its distribution independently of man.
However, man may often jiermit a parasite to survive in an
otherwise unfavourable environment — by suitable methods of
animal husbandry. Eastern Canada has a hot summer and a
cold winter, but animals are housed for the coldest months of
the yea I'. This i)ermits of the existence of such parasites as
Orsopliai/fislfnninn c'lliunbinintni in eastern Canada, although it
is absent from British Columbia and Great Britain, both of
which are less extreme in temperature.

Sunlight is harmful to most nematodes but whether because
of light or heat or both is not definitely known. Its value in
destloying larvae of pig kidney worms is well recognized.

Dung feeding insects such as beetles, are known to destroy
many worm I'ggs but in some cases, the eggs appear to pass
through them and they may act as distributors rather than
destroyers. Such insects may act as true vectors of some
worms.

Mixed glazing on pasture is usually of great value, as horses
will eat and digest the larvae of worms which mature in cattle
and so on. In this way, the number of infective larvae swal-

S05

lowed by eat-h kind of host is greatly reduced. This simple
procedure often causes (|uite startling results and may, by it-
self, be sufficient to prevent actual disease. Thus, on heavily
infected horse pastures, sheep may remove 100,000 eggs per
head daily.

Hay often has the effect of mechanically removing a large
number of infective larvae from a pasture.

Actual removal of the turf and re-so«ing to permanent pas-
ture may be and has been used in extreme cases. But this can
only be recommended when heavily infested but very valuable
land is concerned or where the tu:f may be sold for urban
purposes.

3. Avoidance of Infection of the Host and Prevention
of Ingress of the Parasite

(a) General Hygiene — This is of the utmost importance.
Many horses are confined to stables throughout the year and
when they are kept clean and permanent litter avoided, the
worm infections are at a decidedly low level. Ordinary methods
of cleanliness alone can be of great value. This indeed is
one of the basic principles underlying the very successful Mc-
Lean County Sanitation System for controlling Ascarids in
pigs; in its essentials, this system simply requires cleanliness
of sow and breeding places and avoidance of exposure of the
young animals to infection.

(b) Disinfection — Small quantities of faeces, overlooked in
general cleaning of stables are important sources of infection.
These may be sterilized by very hot water or steam. The gen-
eral bactericidal disinfectants are not very good for this jiur-
pose, the least ineffective being 3 percent lye and .l percent
lysol. These are of value both for horse and sheep strongyles,
but require an hour's contact to destroy them. They are prac-
tically useless against A.scarids and related worms, however.
Lye in its usually applied strength (about 1 percent) is quite
useless iis a disinfectant for any kind of worm, although it is
useful in freeing parasite eggs from dirt and making them
more readily available to the destructive action of other agents.

(c) Permanent Pastures — There is no doubt that permanent
pastures form the greatest single danger to stock and that
Maurice Hall's dictum "Permanent pastures perpetuate para-
sites'' is still of the utmost importance. The pastures con-
centrate eggs and larvae, and improved pasture culture, by in-
creasing the stock-carrying capacity, still further increases
the danger. At present there is no effective method of pre-
venting infection on them.

It was once believed that temporary pastures, plowed in and
re-sown would overcome this difficulty, but recent work has
shown that heavy infections of sheep may result from such a
practice. The eggs and larvae plowed in are protected from
sun, heavy rain and drought and many emerge with the new
grass.

So far attempts at altering the pasture flora to produce an
environment less suitable for development, or a type of grass
less suitable for migration of the worms and so less likely to
cause an infection, have been comparatively ineffective but are
still being tested. Taylor finds that larvae climb higher on
clover than on grass and that such fertilizers as basic slag,
by encouraging clover growth, increase parasitism. On tlie
other hand, sainfoin carries only 5.50 larvae per pound, under
conditions where grass carries 1,1)00, probably because of the
relatively slight contact with the ground which the large sain-
foin plant makes.

Manuring a pasture by nitrates encourages rapid growth of
grass and may lead to a reduction in larvae per pound of grass
and so produce a smaller intake. However, a dense growth of
grass provides favourable cover for parasites and infection is
proportional to density of cover; sparse growth permits natural
agencies to reach them.

(d) notations. Rotation of permanent pasture when this is
possible, is of value but it postulates a large amount of pasture
land and much fencing as the animals have to be moved on
before the eggs they have passed give rise to infective larvae
(5 to 7 days) and kept away from the "used" land until all
larvae are dead; this period varies with the parasite con-
cerned, the soil and the climate and no general rules are yet
possible. The cleanest land should always be reserved for grow-
ing stock which is more susceptible to worm disease than older
stock.

However, a certain amount of rotation of stock may be prac-
ticed. Not only may horses follow ruminants, but cattle may,
to some extent, follow sheep and old animals follow young
ones. Under these circumstances, a shorter fallow period is
possible as subsequent animals eat many of the larval parasites
of their predecessors.

It is often practicable to graze lambs on clean pasture and
follow them by old sheep which have some degree of resist-

ance to gastro intestinal nematodes. In choosing a rotation
such as this (or such as cattle following sheep) care must be
taken to know which parasites are concerned as only some may
thus be treated. The simultaneous grazing of several kinds of
animals (such as horses and sheep) is only an extension and
improvement of this method.

(e) Bare Lots — The use of bare lots for young stock has
much to recommend it. There is no grass for them to eat and
conditions for development of worms are highly unfavourable,
iloreover, as the animals must be watered from troughs the
danger of infection is further decreased.

This method has enabled lambs to be raised in districts where
worm infections are so high as to kill a large percentage of ani-
mals raised on pasture.

Partial bare lots in pig pastures, in lands where the kidney
worm is prevalent, are of assistance in controlling this parasite
also. Faeces also are concentrated, making their removal or
treatment easier.

(f ) Fencing — Fencing is of value in dividing pastures for ro-
tation, or to ensure uniform grazing and to avoid overgrazing
of certain parts. Temporary fencing (as in folding) so ar-
ranged to allow lambs (but not ewes) to reach new pastures
in a progressive system of feeding, is also of value, but entails
a certain amoui\t of labour, as the fences must be moved weekly.
In this case the lambs, if they are not weaned, have the run
of the pasture ahead as well as the one in which the ewes are
kept, or, if they are weaned, the one ahead only. The very
greatest care must be taken to prevent the lambs gaining ac-
cess to old ground already grazed by the ewes and from which
they have been moved on. If this is not done a heavy infec-
tion is extremely probable.

(g) Limitation of Numbers — Limitation of numbers is really
an attempt to return to nature from artificial conditions of
modern farming. It is the rational method with permanent
pastures where over-stocking has such disastrous results. A
reduction of .50 percent in numbers on a pasture means a much
greater reduction than that in parasites. It also spreads out
the rate of intake of parasites and allows resistance to de-
velop. Moreover, overstocking decreases the food yield of the
pasture and encourages closer grazing and a higher worm in-
take. The poorness of the food supply decreases body resist-
ance and so encourages parasitic disease.

(h) Night Housing — Night housing is often valuable as most
strongyle larvae are able to climb on to grass but do so only
when it is damp, retreating towards the soil as it dries. Heavy
dews are very suitable for this upward migration and the simple
procedure of keeping stock — especially young stock — off the pas-
ture until the dew has evaporated, has frequently made all the
difference between health and disease. Husk in cattle is often
caused by early grazing and night housing is particularly use-
ful with that disease.

(i) Saised Troughs — Feed racks, raised troughs and clean
water — especially in connection with bare lots and permanent
pastures which are heavily stocked — is valuable in reducing
intake of parasites. It is of value also in stables where
the floors are often heavily contaminated with infective larvae
and it is especially valuable for young stock.

(j) Silage and Folding — The use of silage helps to reduce
numbers of larvae taken in by the host, and the temjierature
generated in its preparation may destroy some larvae and shor-
ten the life of others; in general, silage does not carry the
heavy infections that grass does.

Folding on green crops, with the aid of hurdles, is also of
value, provided the same ground is not used too often for
this purpose. The animals must be moved every 6 days or so
and the young must have first choice — even going one fold ahead
of the adults — and must not under any circumstances be per-
mitted to enter old, used folds.

Eotational grazing (e.g., nitrogenous stimulation of grass
which is grazed on successive fields) may cause a heavy infec-
tion but generally increases resistance to disease.

The penning of stock on arable ground is more dangerous
than the free ranging of stock on permanent pastures as they
tramp faeces into the ground and so improve the chances of
the parasites developing; under these conditions sandy soil
is probably more dangerous than clay.

Food cabinets, as recently developed, afford a method for
the quick growing of green crops under circumstances which
preclude any infection at all. The animals, if housed on con-
crete and kept clean, need never acquire aii.v intestinal para-
sites at all with this system. The food cabinets permit of
the growing of "grass" in a week from seed without the aid
of soil. This is done by using perforated trays of certain
grains (notably barley, wheat and maize) in a constant tem-
perature cabinet and exposing them to the action of moisture
and artificial fertilizer daily. By a suitable rotation a constant

306

output of (Tinss is tliiis olitjiiiu'd. fnc fmni iliscasc oi'|;!>>>>"<"'<
mid iiidopoiidont of rliiiiatr.

(k^i Cookinii — Larvai" cani'.-d liv food aiiiinalH arc dcsl roved
liy lii'atinK and so all meat and tisli foods fed to pitjs or car-
iiivori's should bo cooked unless free from siispicion ; this is
liiKlilv important in the control of the trichina.

U) Flourboarils — The use of floorlKUirds, wire or concrete
Hoors for i>iKs, carnivores and poultry, provided they are kept
clean, niit only iiermits of ellicient I'nj; destruction lu elitnina
tion, liut prevents infection, or .it least reduces it very con
sideralily.

(ni^ Qiuiraiitiiii — New stock should not be introduced to a
worm controlled farm, until it has tieen carefully cxainincd
for parasites. A single boar, for example, may introduce
ascarids to a worm free pigBeiy. Kiioiin c.irriers of any
kind of parasites already present should be treated, iso-
lated or at least excluded from common crazing. Wild aiii
mals which harbour parasites communicable to domestic nni
mals should be denied access or be destroyed.

Vectors

Many roundworms of domesticated animals, require essen-
tial intermediate hosts. These may be arthropods, earth-
worms, snails, or vertebrates such as fish, amidiibia, and
even other mammals. A knowledf;'' of the life history of
both carrier and parasite is essential before control can be
nndertaken. This may involve not only destruction of the
vector but avoidance of infection of the vector, in many
oases a procedure of almost equal importance.

Destruction of infective larvae in vertebrates may be un-
dertaken by meat inspection and physical or chemical de-
struction of condemned material. Cooking of all garbage
fed to pigs is an invaluable means of controlling Trichina
in pigs and so in man. In the case of pork for human con-
sumption, thorough cooking until the flesh turns white, is a
perfect safeguard; pork is often eaten undercooked. Where it
is eaten raw. it should be subjected to chemical treatment,
chilling or heating (as laid down in the regulations of the
I'nited States Bureau of Aiiiinal Industry).

Earthworms carry a considerable number of parasites to do-
mestic animals and their control is extremely difficult. Chemi-
cals and sand have been used but more successful results are
obtained by avoidance of. infection.

Insect destruction is almost as difficult. Most of the im-
portant carriers are dung feeders and are not easily attacked.
Many of the usual contact or stomach ]ioisoiis are available but
their use has been extremely limited. A more rational means
of control is an attack on the breeding places and this is
feasible for house flies, mosquitoes and ectoparasites.

Avoidance of infection of the vectors is almost as im-
portant as their destruction. This can be effected not only
by proper manure disposal and treatment, but by means de-
signed to keep animals and vectors apart. Thus, for ex-
ample, the lungworms of swine are carried by manure-fre-
quenting earthworms; if swine faeces are disposed of in
situation where the swiue themselves cannot reach the para-
sites can be controlled. Swine confined entirely to proper
concrete pens, should never have lungworms.

In cases where the larvae are actually removed from the
bodv by biting flies, protection from these will not only
prevent vectors becoming infected hut will prevent the hosts
being infected in turn. In addition, of course, measures for
the control of these insects (mo.squitoes. midges, black flies
and stable flies) should be undertaken.

As the spirurid nematodes are carried l;irgely by dung-fre-
quenting insects, manure treatment and disposal will help to
reduce infections.

Destruction Within the Host

Antiparasitic drugs are used for two purposes — to treat
clinical cases or to provide a clean herd. The first requires the
removal of only sufficient parasites to relieve the symptoms;
the second postulates a much more efficient drug, one which
would destroy all parasites being the ideal. There are few such
drugs availalde as yet and such as are, may be used with suc-
cess against a comparatively small number of species; fortu-
nately, however these include some of the important forms.
Where these drugs are available, for either internal or external
parasites, their use as a means of control is highly important.
All members of the herd should be treated regularly until all
parasites have disappeared and no residual infection left to act
as a starting point for re-infection.

This mass treatment, where it has been employed correctly
and under strict supervision, has given excellent results. It is

ncccssaiy to emphasii'.c the necessity for strict supervision. .Ml
drugs used to destroy parasites ari' animal poi.sons, at least to
sonic exii'iit. and their indisi rimiii.'ili' use by l;iyinen is apt not
only to nullity their results but to be actii.-illy dangerous to
the animals. Their use ;iccordingly requires the aid of the
practicing vi'terinarian. No other jierson knows the h.'ibits and
location of the parasite, the physiology of the host, the correct
drug to use, the technique of its administration and its contra-
indications. If this jirinciple is accepted, it follows that co-
(qierative district schemes, involving panels of jiractitioners,
.•ire essential. It is useless, as a control measure, to er;idicate
any |iarticular parasite on one farm if the next remains lic;ivily
infested. The first sti'ps to be taken must be those of an cdii
cational nature to be followed by some cii.'ibling order frinii a
higher .•luthoiity ; this order, however, should come only as the
result of a demand from the district itself. Thereafter, by a
suitably designed veterinary jianel treating animals in groujis
in sub districts, the entire population in the district can lie
treated ipiickly, cheaply and efficiently.

Reservoir Hosts

NVild aitiin.'ils belonging to the s;iiiu' major groiijis as domcsti
cated ones, often harbour jiarasites transnii.ssible to them and
there are innumerable cases on record of such animals or even
animals more distantly related, acting as reservoirs of infec-
tion as well as transmitters of new species to domestic :.ni-
mals. It is of ini])(irtaiice to know what parasites occur in the
wild fauna of a cdinitry or district and to take such stejis
as may be possilile to keep those parasites ivithin control.

At present only one or both of two jilaiis of action are avail-
able; cither to destroy all the wild carriers or to prevent their
intermingling with domestic ones by suitable segregation.

Indigenous wild mammals and birds not only possess jiara-
sites transniissilile to man and to domesticated stock but may
become infected from the introduced stock and act as uncon-
trolled reservoirs of the new iiarasites. An adequate knowledge
of the parasitic fauna of the indigenous wild animals is an es-
sential steji in controlling parasites of domestic stock. It is
surprising how little has been done. The Institute of Parasi-
tology in Canada is conducting such a parasitological survey to
ascertain the distribution and intensity of infections in all
forms of animal life in the Dominion. A large amount of
voluntary assistance in collecting has been readily given by
all classes of persons — official, commercial and private — and
although many years must pass before the survey is even aji-
proximately complete, it has already yielded invaluable re-
sults. This survey has also been extended to the West Indies
and it is to be liojied that other countries will take similar
steps and enable a world map to be prepared showing the dis
tribution and importance of all parasites in all kinds of animal
life.

Avoidance of Parasitic Disease

Effective control of any species of parasites will eliminate
the disease caused liy it, but even when this cannot be done,
steps should be taken to reduce or avoid the disease. With a
very few obvious exceptions, disease depends on numbers of
parasites present but we are unable to state the exact point at
which clinical disease begins, even if we admit the theoretical
concept that even a single jiarasite causes some disease. There
is too little real knowledge aliout the action of parasites and
too many factors involved, including nourishment, resistance
and presence of other parasites.

In general, however, it may be stated that any attemiit to
reduce the number of parasites ingested, to increase the re-
sistance of the host or to raise the standard of fitness of an
animal offsets the effects of the parasite to some extent and
helps to reduce parasitic disease even if it does not eliminate
parasitism.

(a) Prireutivc Licks — The theory underlying the use of pre-
ventive licks is that a small daily dose of some drug taken in a
mineral lick, will either kill the larvae taken in the food or
else render their environment so abnormal that they will not
develop; it is not suggested in this way to administer drugs
against adult parasites. There is no conclusive proof yet that
preventive licks are .satisfactory. Good results have been
claimed with tobacco and bluestone, but the subject must still
be considered as in the exiicrimental stage.

There is no doubt that the efficiency of some of the older
worm medicines was due to their "tonic" action on the liody
and that this was particularly the ca.se with such elements as
iron, copper, cobalt, arsenic, phosphorus and calcium. These
appear to be used by the body to repair or counteract damage
done by the parasites, as well as in some cases to destroy the
parasites themselves. A supply of such materials in mineral
licks is often of great importance in jireventing the develop-

307

ment of disease symptoms. It not infrequently happens that
animals fed on a " natural ' ' diet may be receiving insufficient
phosphates or calcium or other elements, and the use of licks
containing these substances immediately increases the general
condition of the animal and so assists in control of parasitic
diseases.

(b) Diet — It is extremely difficult to separate many para-
sitic diseases from those caused by deficiencies in diet. There
is evidence to suggest that in many cases the two are so closely
interwoven as to be inseparable and that their effects are mu-
tually cumulative. There is no doubt that in very many cases,
a sufficient, well balanced diet, balanced in all its accessory
factors as well as its main constituents, will prevent parasitic
disease and will often actually reduce the numbers of para-
sites harboured. Pasture treatment, such as "top-dressing,"
is often a valuable way of doing this. This adequate diet is
jiarticularly important for immature animals and every effort
should be made to secure this. This is, of course, true for all
preventive measures to be taken but is especially important, ia
connection with diet.

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1938b. — Observations on the bionomics of strongyloid
larvae in pastures. I. The duration of infection in pasture
herbage Vet. Rec. v. .50(40): 1265-1272.

1939. — The role of pastures in the development of the
strongyloid diseases of grazing animals. Ibid., v. 51(1S):
495-504.

308

CHAPTER VIII
EPIDEMIOLOGY AND SANITARY MEASURES FOR THE CONTROL OF NEMIC PARASITES OF MAN

WILLIAM W. CORT, Department of H.lminthology, School
of Hygiene and Public Health, the Johns Hopkins Univer-
sity, Baltimore, Md.

ELOISE B. CRAM, Division of Zoology. National Institute of
Health, U. S. Public Health Service, Washington, D. C.

DONALD L. AUGUSTINE, Department of Comparative
Pathology and Tropical Medicine, School of Medicine and
Public Health, Harvard University, Boston, Mass.

General Discussion
W. W . C.

.Xt'tor the disfdvi'ry of :i liuiiuiii piujisito the next st("]> in flic
si'<|»oiUH' loading to ofFective control must he the detcrniiiuitioii
of its life cvclc and method of luinian infection. Such iiifor
mation suggests the liroad lines along which control measures
can be developed, but needs to be sii|i|ilcmented by eiiidemi
olugic studies to gain information on tlic vjirious factors in-
volved in dissemination in population groups. These factoi's
differ greatly for the different nemic jiarasites of man, which
vary in their host relations and life cycles.

In those species in which eggs or larval stages have a free
life, vis., the hookworms, asearis, trichuris, enterobius, etc.,
knowledge is essential on the effect of general environmental
factors, such as temperature, moisture, and physical and chemi
cal conditions of the soil; for only when the environment out-
side the host is favorable can these free stages persist and in-
fect nuiu. The relations of these factors depend on the anu)unt
of development <mtside the host necessary before the infective
stage is reached and vary greatly between snch species as en-
terobius and the hookworms. In those si)ecies with interme-
diate hosts the relations outside the definitive host are still
more complicated, since they involve all the factors related to
the infection of the intermediate host and the transmission by
it of the parasite. Thus all the relations of Trichi/irlla spiralis
to the rat and pig become of vital significance in its tranmis-
sion ; with the guinea worm, Dractinculus medinensis, the Cy-
clops is brought into the picture: and in the filariae the rela-
tions of mosquitoes and certain other blood sucking flies must
be considered.

Equally significant in epidemiologic studies of nemic para-
sites is the consideration of human habits in relation to trans-
mission. For those species in which the eggs pass out with the
feces, habits of excreta disposal are of great significance.
Kqnally important also are all the human habits that make
jiossible the entrance of the free stages into the human body.
With those nematodes which have intermediate hosts the human
habits that are related to spread are entirely different and vary
greatly with the species. In the filariae, habits that bring about
exposuie to the bites of the insect vector are important both
in relation to the infection of the insect and in the transmission
of the parasite l)ack to man. In certain cases the human rela
tions may be very peculiar. As for example with TricliiiitlUi
.spiralis where the methods of feeding pigs and habits in rela-
tion to pork eating have to be considered; or with the guinea
wonn where transmission depends on the drinking of water
containing cyclops, in which infected individuals have waded
or washed their feet.

.\nother phase that cannot be neglected is the host parasite
relations. For example, the development of a specific immunity
or the presence of an age resistance may be important in de-
termining the distribution of the parasite in the population ;
or undernourished individuals may be more snsceiitible than
are those on a good diet. We know least about these factors
and in the present state of our knowledge their relation to
epidemiology is difficult to evaluate.

It is evident that the more extensive is the understanding of
the epidemiology of a parasite, the more effective the control
program can be made; thus, weak links in the cycle of trans-
mission can be more effectively discovered and mistakes avoided.
Most effective in control are ,'ittempts to ch.ange human habits
that make possible transmission. In fecal borne infections the
improvement of sanitation to prevent soil pollution is most
important. Where transmission is by insect vectors, control
measures are chiefly concerned with the jirotection of tlie peo
[lie from their bites and with their eradication from areas near
liuman habitations. Where treatment is eflFective and easily ap-
plied to large groups, mass treatment may be an efficient con-
trol measure in breaking the cycle at the stage passed in the
human body.

In the following discussion only the most important and best
kiu)wn of the nemic iiarasites of man will be considered, viz.,
the hookworms, .liiciirlosloma iliioilinalr and Ncrator amrri-
callus: the large round worm, Asearis liimbricoitlis ; the whi|)
worm, Trichuris trichiiira: the pin worm, Eiitrrohiiis rcrnii-
ciilaris; the flesh worm, 'I'ricliiiii lla siiiralis; the guinea worm,
DraciDiciilus iiiiiliiiciisis ; and the most impoitant of the filariae,
ll'iiclicrcria baiicrofti. Onchocerca volvulus, and Microfilaria
nialaiii. For most other human nematodes there is little in-
formation on epidemiology or control methods, and they are
for the most part of minor significance as human parasites.
.\lso, the knowledge iiresented on the more important forms
gives a backgiound for understanding similar relations for the
other sjiecies.

The Hookworms
W. W. C.

In ancient Egyptian, .\rabian, and Greek writings are founl
descriptions that may possibly have referred to hookworm dis-
ease. .-Vlso, accounts in medical treatises of the 17th and ISth
centuries from Brazil, Guadeloupe, and Jamaica almost cer-
tainly referred to this disease. Modern knowledge dates from
the description of Ancylostoma diiodrnalr by Dubini (1S43).
In 1S7S Grassi and the brothers Parona demonstrated that
hookworm infection could be diagnosed by fecal examinations.
Leichtenstern in 1887 demonstrated experimentally that infec-
tion could be brought about by the ingestion of larvae. Looss
(1898) first discovered infection by skin penetration with mi-
gration through the lungs and over a period of years carried
out extensive investigations on hookworm biology which cul-
minated in his Iftll monograph.

By tlic beginning of the lIlUli century the scene had shifted
to the Western Hemisphere, where Lntz in Brazil, .\shford in
Puerto Rico, and .Stiles in the Ignited States had demonstrated
the importance of hookworm disease. Of especial significance
was the discovery by Stiles (1902) of the second species of
human hookworms, \rcator americaniis. Very important also
was the work of the Puerto Rico .\nemia Commission from
1904 to 1908 (Ashford and Gutierrez, 1911) which carried out
the first extensive investigation and control program in a trojii
cal country. Later (1909 to 1914) came the campaign of the
Rockefeller Sanitary Commission in the southern United States,
which was followed in 1914 by the establishment of the In-
ternational Health Board of the Rockefeller Foundation, which
in the next few years extended hookworm control campaigns
widely into other parts of the world.

The true human liookworms, Aiici/lostoma ihiodcnalr and Xic
ator americaniis, are widely distributed between the 3t5th paral
U'l north latitude and the 30th parallel south. Within this belt
there are extensive regions where the combination of favorable
temperatures and rainfall make possible the development of
widespread heavy infections and clinical disease in populations
living close to the soil under iiriniitive conditituis of sanitation.
Such populations are still found in very limited areas in the
sonthein t'nited States and more extensively in the West In
dies. Central America, northern South .\merica. Tropical -Af-
rica, and in certain parts of southern Asia and the East In-
dies.* While A. (liioilenale and N. americaniis are present to-
gether in a considerable part of the hookworm belt they show
important differences in geographical distribution and appear
to have origiimted in different parts of the world (Darling,
1920).

A. diiodcnale and N. americaniis differ greatly in the mor-
phology of the adults. The former is larger, appears to be more
injurious to its host and is harder to eliminate with anthelmin-
tics (Darling, Barber, and Hacker, 1920). The female of A.
duodcnalc produces about 22,000 eggs every 24 hours while

*For a detailed discussion of the geographical distribution of hook-
worm disease see Chandler, 1929. pp. 18-54.

309

that of N. americanus only about 8,000 to 10,000 (Super, 1927)
Also the infective larrae of the first species are slightly larger,
of different structure, and more resistant to environmental con-
ditions than those of the second (Svensson, 1925). In experi-
mentally infected human volunteers, the adults of A. duodenale
lived almost 7 years and those of X. americanus over 5 years
(Kendrick, 1934). In these infections, however, the egg counts
in the individuals infected with the first species fell to a very
low level in less than 2 years, and in those harboring the sec-
ond species they were greatly reduced in about a year. In spite
of all these differences, both species are very similar in their
host relations and life cycles; and the symptomatology, epi-
demiology, treatment, and control of the diseases they produce
are alike in all essential particulars.

Although in a few cases the human hookworms have been re-
ported incidentally in other hosts, and A. americanus appears
to be a normal parasite of anthropoid apes, there is at present
no good evidence that such animals serve as true reservoir hosts.

Besides the true human hookworms there are several others
that have some relation to man. The dog and cat hookworms,
.4. caninum, A. braziliense, and Uucinaria sienocephaia have
been extensively used in studying host-parasite relation prob-
lems. The larvae of the last two have been shown to produce
linear skin lesions in man, and A. braziliense is the causative
agent of creeping eruption which is especially prevalent in
certain parts of the southern United States (Fiilleborn, 1928;
Kirliy Smith, Dove, and White, 1929). N. suiUus, described
by Ackert and Payne (1923) and by some workers considered
as a synonym of A. americanus, has received consideration in
relation to'the possibility that its host, the domestic pig, may
serve as a reservoir host for humau hookworm disease.

FACTORS AFFECTING THE FREE STAGES OF THE
HOOKWORM LIFE CYCLE

Development of hookworm larvae can be completed at tem-
peratures ranging from about 12° to 37° C, with the optimum
from about 2.5° to 30° C. (Stiles, 1921; McCoy, 1930). Below
22° C. the development is greatly slowed up; and at tempera-
tures approaching 37° C, although development is very rapid, a
considerable proportion of the larvae either fail to develop or
soon die. The eggs and larvae are quickly killed by tempera-
tures above 40° C. and have little resistance to temperatures
close to freezing (Looss, 1911; Svensson, 192.")). The injurious
effect of low temperatures on hookworm eggs and larvae is the
determining factor in limiting the distribution of hookworm
disease almost entirely to tropical and subtropical regions.

All the free stages of the hookworm life cycle are quickly
killed by desiccation. Therefore, in regions of low rainfall in-
fection is absent or kept at a low level (Chandler, 1926-1928;
Sawyer, 1923; Docherty, 1926). On the other hand, while the
eggs and infective larvae will live for a considerable period
under water, they will not develop eitlier under water or in cul-
tures that are saturated with moisture. Therefore, in areas
where the soil is flooded for a part of the year hookworm in-
fection may be kept at a low level (Chandler, 1926; Barnes and
O'Brien, 1924). Hookworm larvae require the presence of
oxygen for development (McCoy, 1930) and it is probably its
absence that prevents their development in a saturated medium.
Also, they require a loose porous culture medium and do not
develop well in clay soils (Stoll, 1923b). Soil relations are
very important in the southern United States where infection
is almost entirely absent in areas with clay soil and is par-
ticularly intense in those with a loose sandy soil (Augustine
and Smillie, 1926; Rickard and Kerr, 1926).

The developing larvae can apparently feed normally only on
living bacteria, which must be present in considerable numbers
for development (McCoy, 1929). It seems probable that the
growth of enough bacteria for the needs of the larvae depends
chiefly on the mixture of feces with the soil and if the eggs
become separated from the fecal material in which they are
passed development will be checked.

Epidemiologic studies of recent years have given illustrations
of the types of field conditions that are suitable or unsuitable
for the development of the hookworm larvae in the soil. Loose
porous humus, sandy, or loam soils that are well shaded give
the best development. Places of intense soil infestations under
such conditions have been reported in fields of sugar cane in
Trinidad (Cort and Payne, 1922). in coffee groves in the hills
of Puerto Rico (Cort, Riley, and Payne, 1923), and in fields
of cultivated mulberry trees in the Yangtse Delta region of
China (Cort, Grant, and Stoll, 1P26). In clay soil not covered
b.v a layer of humus or a growth of grass almost no larvae
will develop even where the rainfall is considerable (Cort and
Payne, 1922). Even on soils of loose texture in regions of
abundant rainfall, development of soil infestation will be great-
ly inhibited if there is no shade, since exposure of the soil sur-
face to the sun's rays produces alternate periods of wetting and

drying which quickly destroy a large proportion of the larvae
(Augustine, 1923c). Unshaded areas covered with a thick
growth of grass have in some cases been reported as very favor
able for development (Korke, 1925). In hookworm infected
population groups, therefore, significant sources of infection
may be limited, even where there is extensive soil pollution, to
the Comparatively few places where the eggs are deposited on
a loose soil that is well shaded.

When the larvae develop in the soil they migrate toward the
surface and are found frequently singly or in clumps extending
from the particles (Augustine, 1922b; 1923b). In only a few
cases have they ever been reported at depths below the super-
ficial surface layers (Baermann, 1917b). When covered with a
loose soil they can migrate vertically from considerable depths
(12 to 36 inches), while in a water soaked or stiff clay soil
almost no upward migration occurs (Payne, 1922 and 1923).
Lateral migration is very restricted and they will not spread out
from the place of development unless carried by water or ani-
mals (Augustine, 1922a; Chandler, 1925). After the second
molt they no longer feed and will continue to live only as long
as their reserve of food material lasts. Therefore, the more
active they are the shorter will be their life. Under artificial
conditions in water, however, infective hookworm larvae have
been kept alive for as long as 18 months (Ackert, 1924). In
the soil in the tropics their life may be limited to only 6 to 9
weeks, with the great majority dying in 3 or 4 weeks (Augus-
tine, 1922c and lS23c). Under conditions less favorable for
activity they may persist in the soil for periods up to 4 to 6
months (Hirst, 1924; Baermann, 1917b). There is also evi-
dence that the larvae of A. duodenale live somewhat longer
than those of X. americanus (Svensson, 1925).

A consideration of the activities of the infective hookworm
larvae in the soil lead to certain practical considerations iii
relation to the epidemiology and control of hookworm disease.
The larvae tend to remain in "nests'' where the stools are
deposited ; so only limited places are sources of infection.
Further, the burying of feces except under a very stiff clay
soil is dangerous because the larvae will soon reach the surface.
There is no evidence, however, that they will migrate out of
latrines (Payne, 1922). Finally, where soil pollution is
stopped, sources of infection will be naturally sterilized in a
comparatively short time b.v the death of the larvae.

HOST RELATIONS TO HOOKWORil INFECTION

The penetration of the infective hookworm larvae through
the skin produces lesions which are commonly known as ground
itch. Secondary bacterial infection frequently increases the
severity of this condition. Also, the type of reaction suggests
in many cases an allergic condition associated with the pres-
ence of immunity. Thus Sarles (1929) noted a much more
severe skin reaction to hookworm larvae in old resistant dogs
than in susceptible puppies.

Lung symptoms produced by the migrations of the larvae
have frequently been noted. They are only occasionally at all
severe except in extremely heavy infections, suggesting that the
larvae usually enter a few at a time.

In the intestine, the hookworms bite deeply into the mucosa
and appear to suck blood constantly throughout their adult
life (Wells, 1931; Nishi, 1933). It seems evident that they
feed chiefly on elements derived from the blood (Hsii, 1938).
They move" from place to place and, therefore, when numerous
injure the intestinal wall over considerable areas. Blood con-
tinues to flow from the lesions even after they have moved
away. Disturbances of the digestive system which are com-
monly present in moderate as well as heavy infections have
been "explained chiefly in relation to the injury of the intes-
tinal mucosa produced by the worms.

Anemia is the most prominent symi)tom of hookworm disease.
Indeed, most of the long train of symptoms found in chronic
hookworm patients can be related to the presence of long
standing anemia. The etiology of hookworm anemia has been
the subject of considerable controversy. A review of the liter-
ature indicates that there is no convincing evidence that it is
caused by toxic products of the worms. Recent investigations
have emphasized the importance of blood loss in the production
of the anemia. In experimentally infected dogs the blood pic-
ture follows exactly that produced by artificially induced hem-
orrhage (Foster and Landsberg, 1934; Landsberg and Cross,
1935; Landsberg, 1937). Apparently, blood loss produced by
the worms is only one factor in the production of the anemia
in hookworm infected populations. Disturbances produced by
dietary deficiencies, particularly lack of iron, have been em-
phasized as important additional factors (Rhoads, Castle, Payne,
and Lawson, 1934 a & b; Cruz, 1934). More recent work,
however, stresses general dietary deficiency rather than lack of
iron alone (Otto and Landsberg, 1940; Payne and Payne,
1940). Anemia produced by other diseases especially malaria

310

may hIso W a oonipliiatinK faotnr. It .sivms rvidriil alsi> that
the clironic lilood loss imnjiu'cd liy the wmins aiiKlit in ccitaiii
t'asos be ouo of tin- t'ai'tors that would (iiially lead to the dovol
opiuont of oiif of the • ' idiopalhio " aiiomiaH. In addition, it
si'onis oi'itaiii that aiicmlas of a variety of ctioloKii'S are fre
(luently referred to hool<\vorm infeetion ia eases where the few
worms present have litth> if any part in the prodnetion of the
anemie eondition lAndrews, liMlU.

Reeently it lias lieen shown that a speeifio imninnity is ae
((Uired hy dogs in response to repeated infections with .1. <-<nii
iiiim in wliieh antil>odies are formeil ehielly in response to [\[<-
secretions and excretions of the worms (Kerr, ISlHti; Otto and
Kerr, ISlH't; Otto. 1!I40). It seems practically certain that a
similar immunity develo|>s in man in response to hookworm
infection. In fact, several workers have recently expressed the
view that host immunity must play an important role in the
regulation of human hookworm infection ( KiiUeborn, Dios, and
Zuccarini, 1!I2S: FiiUcliorn. \'.^-2'.^; fort, 1!132; Pessoa and Pas
eale, 1937 a & h; Cort and Otto, \'.)iO) . Such a postulation
makes it easy to explain the relatively moderate infections and
slight evidence of hookworm disease found in many individuals
and groups of jieople who appear to live under conditions giving
constant opportunity for the invasion of the larvae. Severe
cases, especially in children, might perhaps be explained in
part by exposure to infections so extrenu' that the develoimu'iit
of the immunity is prevented. Also, it seems probable that
uadernourishment or other debilitating factors prevent the de
velopment of the immune reactions. In experimental infections
in young dogs either undernourishment or too rapid infection
which weakens the host from extreme blood loss will prevent
the immune response (Otto and Kerr, 1!)39); and the immu
nity already developed in highly resistant older animals is
easily broken down by placing them on a deficient diet { Foster
and Cort. I!i3l2; l!l3.'i). If the same relations hold in human
infection, individuals or groups that are badly debilitated liy
undernourishment or other factors may be expected to acipiire
heavy norm burdens arui will also be less able to compensate
by the regeneration of new blood for the losses caused by the
norms. It seems probable also that malaria and other diseases
are more important than is at present realized in weakening
the defense mechanism against hookworm infection. In fact,
the hypothesis has reeently been suggested that widespread
chronic hookworm disease of the type found specially in tropical
countries seldom results from uncomplicated hookworm infec-
tion, but is produced by hookworm infection plus undernourish-
nu'nt or other debilitating factors that weaken the host defense
(Cort and Otto, l<t4ii: Cort, 1940).

HUMAN HABITS I.\ RELATION TO HOOKWORM
DISSEMINATION

Insanitary methods of excreta disposal and activities bring
ing about contact with infested soil are the most important
human habits in hookworm dissemination. Careless depositing
of stools on the ground (soil pollution) is a widespread habit
among most of the i)opuiation of the world especially in tropical
and subtropical regions. Recently, epidemiologic evidence has
emphasized soil pollution in the general vicinit.v of dwellings
as important in hookworm infection. Adults and older chil
dren arc apt to go for defecation to protected places not far
from their houses and often the most important contact with
infested soil appears to come about during the act of defeca-
tion (Cort, 192.5; Cort, Stoll, Sweet, Riley, and Schapiro, 1929;
Chandler, 1928). Young children usually defecate in the door-
yards close to the houses or even under or in the houses them-
selves, where the soil conditions are usually not suitable for the
development of hookworm larvae.

It is usuall.v difficult to determine the extent to which field
work brings the laborer into contact with sources of infection.
People living near cultivated areas such as vegetable gardens,
banana groves, sugar cane fields, or coffee groves, may by their
defecation habits produce concentrated places of soil infestation
that will infect field laV)orers. Usually, however, stools passed
by laborers at work are widely scattered and would be only
occasionally sources of infeetion, as compared with the con-
stant exposure in the defecation areas near the houses.

Some occupational relations especiall.v important in hook-
worm dissemination have been noted. Coffee picking in the
hills of Puerto Rico has been shown to be responsible for ex-
tremely heavy infection (Ashford and Gutierrez, 1911; Cort,
Riley, and Payne, 1923). Here groups of people work in the
groves for long hours and spread their stools widely when they
pick the coffee at weekly intervals for (! or 7 weeks. Toward the
end of the picking season the soil of these groves becomes so
impregnated with infective larvae that extensive infection of
the workers occurs. In places in the Orient where human excre
ment is used as fertilizer, the practices in connection with the
cultivation of particular crops determine the extent of hook-

\Miini dissemination. In regions in China where sericulture is
important hookworm infection m:iy be widespread because the
mi'thods of f<'rtili/,ing the mulberry trees nnike po.ssible the
developnu'nt of intense soil infestation ((^ort, (irant, and Stoll,
I!i2(>): fr<nn such places the iieople who pick the mulberry
le.ives to feed the silkworms ln'come intensely infected. Other
"i-cnpational relationships that |iroduce sources of infection
might be cited, but as we consider the cviileni'c it beconu's nu)re
.Hid niori' evident th;it, except when' lunnan excrenu'nt is used as
feililizcr, soil iiollntion in tin' vicinity of the <lwellings is by
I'ai the must irnporlant f;ictcir in hookworm di.sseminatiori.

iiisrijii-.rTioN or hookwor.m infection within

I'OITI.ATIONS

The use of the Stoll dilution egg counting method in the
extensive epidemiologic stinlies of hookworm disease of the
last two decades has given a large anjount of information from
different parts of the world on the distribution of hookworm
infection in population groups. Estimates of worm burdens by
this niethod have made it possible to compare (|uantitatively
the infection according to age, sex, occupation, race, and other
categories, as well ;is to comp.-ne the ilistribution in populations
living under ilifti'rent conditions. Thus d;it;i can be obtained
for a .scientific planning of control progr.-inis ami the results
of the campaigns in reducing the intensity of infection can be
measured. Attention has, therefore, been turned from the per
centages of positive cases ;ind has been focused on the number
of worms harbored (worm burden).

There has been an increasing emiihasis on the importance of
a proper evaluation of the lightly infected cases, especially
those that might be considered as carriers or subclinical, as
compared with the heavier cases. A high incidence of hook
woiin infection nuiy occur in groups where the number of
worms present is so small that they have little if any injurious
c'ffect. Such situations may be found, as in certain parts of
North China (Cort, (irant, and Stoll, 192li) and Egypt (Scott,
1937) where human habits are favorable for hookworm disseni
ination but climatic conditions are unfavorable. Similar wide
spread, practically sub-clinical infections are also jiresent
where sanitation and treatment have reduced the intensity of
infection to a low level, but where widely scattered light
sources of infection still exist. It is not possible to indicate
definitely the actual number of worms necessary to produce
clinical symptoms since this would vary in relation to a variety
of factors; also it is not easy to accurately evaluate the injury
to a population produced by widespread light infections. It caii
be .said, however, that light infections are of but little conse-
quence as compared with heavy; and that hookworm disease
becomes a real i)ublic health problem only in groups with
fairly heavy worm burdens.

The individual family except when isolated is not nearly so
much the unit of hookworm infection as is the case with
ascaris. This appears to be due to the fact that sources of
infection are fairly widesjiread and because defecation places
near dwellings are commonly shared by more than one family.
Frequently almost all the individuals in even large populations
are infected.

The relative intensity of infection in the sexes and in differ-
ent age groups varies greatly in different iiopulations. Usually,
however, infection is almost completely absent in children under
3 years of age, gradually increases up to 10 years and reaches
the adult level somewhere in the early teens or even later
(Smillie, 1922; Payne, Cort, and Rile.v", 1923). It may vary
considerably in the different age groups of middle life and
most often has a tendency to decline in older people. Females
usually have a distinctly lower level of infection intensity than
males (Carr, 1926; Hill, 1927a; Cort, Stoll, Sweet, Riley, and
Schapiro, 192S). It has been suggested that this type of age
and sex distribution is most t.vpical of situations where in-
fection comes from soil infestation in the general vicinity of
the houses. It can be suggested that in most situations the
children only have considerable exposure to infection when they
begin to visit adult defecation places. Greater activity of boys
than of girls brings greater contact with infection; and adult
males usually have more contact with sources of infection
away from home than do females. Unusually heavy infection
in very young children has been noted in certain groups in
Panama (Cort, Stoll, Sweet, Riley, and Schapiro, 1929), in the
Argentine (Fiilleborn, Dios, and Zuccarini, 192S), in Puerto
Rico (Hill, 1927a), and in southeastern (ieorgia (Andrews,
1940). This seems to occur only where soil conditions in the
dooryards are favorable for the development of hookworm
larvae. Heavier infections in women than in men have been
found in a few places like the areas of coffee cultivation in
Puerto Rico (Cort, Riley, and Payne, 1923) and in certain
groups engaged in sericulture in China (Cort, Grant, and Stoll,
192()) where the women are eng;iged to a greater extent than

311

the men in oeeupatioiis that bring thcni into contact with nn-
usually intense sources of infectiou. In parts of the southern
United States the level of infection rises rapidly from 6 to l.i
vears and then declines rapidly until after 20 years the «-orni
burden is almost negligible (Smillie and Augustine, 1<J2...
Chart 4) Such a situation cau probably be attributed to the
wearing of shoes and the greater use of sanitary facilities by

the adults. , , . j. ■■ i

Evidence on racial differences m hookworm mteetion and
disease is rather conflicting. It does, however, seem clear that
negroes in the southern United States have much lighter mtec-
tious than whites (Knowlton, Um-. Smillie and Augustine,
19-1.) • Keller, Leathers, and Densen, 1940). It seems possible
that this difference is due to a true racial immunity m the
negro race, although further investigations are needed b 'tore
differences in environment and nutrition can be completely
ruled out. There is also evidence that suggests that groups
with negro and negro-indian blood are more resistant to the iii-
iurious effects of the worms than those of the white race
(Gordon 192.-> ; Cort, Stoll, Sweet, Riley, and Schapiro, 1919).
However', it is difficult to rule out other factors and here also
the whole question needs much further investigation.

CONTROL OF HOOKWORM DISEASE

Four different methods of preventing the spread of hook-
worm infection have been generally recognized, viz., (1) disin-
fection of feces or infested soil, (2) the encouraging of wear-
ing shoes, (3) anthelmintic treatment, and (4) improvement
in sanitation. Extensive experimentation has shown that hook-
worm eggs in feces and the larvae in the soil can be killed
bv the application of salt, lime, or other chemicals. Such
methods are useful in limited areas such as mines (Fisc-lier,
19'>8) or in sterilizing human excrement which is to be used as
fCTtili'zer (Cort, Grant, and Stoll, 19l2(i). The wearing of shoes
has been shown to be a potent factor in keeping hookworm in-
fection at a low level (Smillie, 1922; Davis, 192.'.; Chandler,
1929 pp. 208-211, 380-3S2). However, attempts to increase the
wearing of shoes in hookworm infected populations by propa-
ganda or legal requirements do not seem to have been very
effective Hookworm control campaigns, therefore, have been
organized chieflv around treatment and sanitation. The use of
anthelmintics improves the health of the people and reduces
soil infestation. The sanitary phase of the program is a fight
against soil pollution and involves education and the introduc-
tion of latrines. Much work has been done in developing sani-
tary conveniences suitable for people of different types. The
pit" latrine (privy) has been most widely used in the Western
Hemisphere: and the recently developed bored-hole latrine
(Teager, 1931 and 1934) seems to be best adapted for the
jieoples of certain countries of Asia and Africa.

In the early hookworm campaigns in Puerto Eico and the
southern United States the so-called "dispensary method
was used This consisted of the examination and treatment
of large groups of people who flocked to the numerous dis-
pensaries that were set up. Significant results were attained
in the treatment of severe cases and in preliminary education,
but only a beginning was made in the reduction of infection
and in the improvement of sanitation.

\s a reaction against the inadequacy of the "dispensary
meUiod " the "intensive method" was developed by certain
members of the field staff of the International Health Board ot
the Rockefeller Foundation. Its ob.ieetive was the complete
eradication of hookworm infection by a systematic program of
sanitation and treatment to "cure" of all infected individuals
(Howard 1919). First, every effort was made to get latrines
installed in every house in a given area. Then, after systeinatic
stool examinations, the positives were given treatment. Ihey
were later reexamined, and those still infected were given a
second treatment. Reexamination and retreatment were sup-
posed to be continued until the stool samples of all the people
of the area were negative for hookworm eggs. Sometimes as
many as 9 or 10 treatments were required for "cure." Efforts
to improve the sanitation were continued during and after the
treatments. Although hookworm infection was never completely
eradicated from any area by this method, striking results were
obtained in a number of places. Least defensible of the pro-
cedures of the intensive method was "treatment to cure" in
which much effort and money were wrstcd in treating very
light infections and in trying to remove tlie last few worms by
retrcatments. On the other hand, the emphasis on intensive
sanitation especially before treatment and on a careful follow-
ing up of the sanitation after treatment, was an important
contribution to hookworm control procedures.

The "mass treatment" method came as a reaction against
the complete ineffectiveness of the intensive method to cope
with the situation in a large country such as Brazil. As advo-
cated by Darling (1922) mass treatment required first the de

termination of the index of infection (approximate womi inir-
deu) by the examination by worm counts of a representative
sample of the population. Later, the development of the Stoll
dilution egg counting method (Stoll, 1923a) made it possible
with much less effort to obtain a better estimate of infection
intensity. Then, wherever incidence was high, a whole group
was simultaneously given anthelmintic treatment of known
efficacy without a previous diagnostic examination and without
reexamination. Thus large groups of people could be rapidly
treated. An adequate sanitary program was sometimes com-
liined with mass treatment. In many jilaces, however, the great
emphasis on treatment and the rapidity with which the cam-
paign moved brought about a neglect of sanitation. Whenever
this was true reinfection occurred at a rather rapid rate as
suggested bv the investigations of a number of workers (Baer-
niaiin, 1917b; Sweet, 192.3; Docherty, 1926; Hill, 192.J, 1926,
1927b). Mass treatments, therefore, were particularly effective
if repeated at intervals of 2 or 3 years (Rice, 1927; Lambert,
1928). Perhaps of greatest importance was the emphasis on
the quantitative viewpoint ; the object of the campaign was to
reduce the worm burden of the population and not to cure
cases. Also important was the idea that a preliminary survey
was needed to estimate the ' ' index of infection ' ' before control
wink was started.

A campaign against hookworm disease at the present time-
can be planned on the basis of the wealth of experience of the
last 2.') years. Such a campaign under ideal conditions might
include five steps which have actually been utilized in cam-
paigns; and to these a sixth might be added. (1) a presurvey
to evaluate the problem quantitatively; (2) presanitation to-
reduce soil pollution as much as possilile before treatment; (3)
mass treatment to reduce the worm burden of the group to a
.subclinical level in as short a time as possible; (4) follow-up
sanitation to keep soil pollution at a low level; and (5) a post-
survey to measure quantitatively the results of the campaign.
Finally (6), every effort possible should be made to improve
the general health by the correction of dietary deficiences and
the elimination of other diseases.

The central feature of the presurvey should be an examina-
tion by the dilution egg-counting method of a representative
sample of the population to obtain information on the quanti-
tative distribution of hookworm infection in the population
and on the extent of true hookworm disease. Investigations of
the amount of sanitation present and of soil pollution habits
wiU aid in planning the program for sanitar.v improvement
which in most situations is by far the most important part of
the campaign. In regions where hookworm infection is found
to be chiefly at or near the subclinical level, even if its inci-
dence is high, control work may well be limited entirely to
sanitation. When the preliminary survey shows heavy infec-
tion and \videspread disease every effort should be made to re-
duce soil pollution to the greatest possible extent before treat-
ment is started by the introduction of latrines and education
in their use. This is done in order to reduce the amount of
reinfection after treatment.

A course of treatments should be chosen which has been
shown by quantitative study on a group of considerable size to
reduce the worm burden by at least 90 percent. If the inci-
dence of infection shown by the preliminary survey is over 90
percent, treatment without diagnostic examination according
to the mass treatment method may seem desirable. Such a pro-
cedure, however, should not be applied to the youngest age
group where infection is almost always least and danger f rom ■
treatment greatest. Mass treatment should be given by popu-
lation units so that all the people living in the same environ-
ment would be freed of their worms as nearly at the same time
as possible. Individual examinations after treatment and re-
treatments cannot be justified where the object is to reduce the
worm burden as much as possible with a given amount of treat-
ment. In tropical regions treatments toward the end of the
dry season, when the soil has been unsuitable for a considerable
period for the development of the larvae, will have more last-
ing value than those given during the rainy season, when rein-
fection is very extensive (Chandler, 1929, pp. 40.5-408; Me Vail,
1922) ; and in colder regions treatments at the end of the win-
ter will be most eft'ective.

Even in the best organized campaigns a varying percentage
of the worm burden will he left after treatment. Whether in-
fection will soon return to a high level again depends on the
extent to which the people are prevented from returning to
their former habits of soil pollution. Real success in hook-
worm control, therefore, will be achieved only where efforts to
improve sanitation have been permanently organized and effec-
tively continued over long periods of time as part of the per-
manent public health program.

The final step in an ideal program for hookworm control
would be a resurvey carried out about 2 or 3 years after the

312

■cdiiililetion of the tieatiiioiits by the same methods used in tlu'
preliminary survey. Such an investigation will make it [los
silile to elieek the sanitation and to determine whether the
level of infection has retnri\ed to a jioiat where further treat-
ment is needed.

Most important iii .-ittaikint; the hookworm problem is the
acceptance of the quantitative point of view and the nsiiij; of
(juantitative methods to determine the "hookworm index'' in
the preliminary survey and the resiirvey. Much effort and
money have been wasted in trying by active treatment cam
liaigns to reduce hookworm infection in poi)ulations whi're it
ivas already close to the subclinical level. Most fundamental
perhaps of all is the changed objective of the modern hook
worm campaign, which is to reduce hookworm infection to a
subclinical level by treatment and to keep it tlu're by per
mauent improvement in sanitation.

Finally, certain new viewpoints need to be developed on ac-
count of the recent ticw information on the significance of ac
quired immunity in hookworm infection and its relation to un-
dernourishment and other debilitating factors. If the immune
respons'- in man to his hookworms proves to be of the same
grade as tliat of the dog to .1. en )i i ii ii iii , measures to remove
factors that interfere with the normal host responses are just
as important in hookworm control as those directed against
the spread of infection. In fact, it seems altogether likely that
if it were possible to eliniin:ite dietary deficiencies from a
population suffering from hookworm disease by furni.shing an
adequate food suppl.v, the restoration of the normal host resis
tancc would in itself strikingly reduce hookworm infection and
disease (Otto and I,andsl)erg, n)40 ; Cort and Otto, 1940).
Emphasis in hookworm control, therefore, should be placed not
on isolated spectacular treatment campaigns, but on the at-
tempt to reduce hookworm infection by all the methods that
will improve the sanitation and raise the general economic and
health level of the infected populations.

Ascaris lumbricoides

W. W. C.

References to human ascaris are found in the ancient medi-
cal literature of the Chinese, Egyptians, and Greeks. Edward
Tyson in 1683 and Francesco Redi in l()8-t studied the anatomy
of this parasite, distinguished the sexes, and expressed the view-
that it reproduced by eggs and not by spontaneous generation.
From that time on, ^l.s'ror/.< liimbricnirles became a favorite ob-
ject for study, and investigations on its anatomy laid the foun-
dation of our present knowledge of nematode structure. Al-
though much information on the prevalence, pathology, and
geographical distribution of ascaris in man has been long avail-
able, it is only recently that much attention has been paid to
the epidemiology of ascariasis in relation to control.

PATHOLOGY AND SYMPTOMATOLOGY
In laboratory animals and in pigs the migrations of ascaris
larvae are known to produce lesions in the intestinal wall,
liver, Ivmph nodes, and especially in the lungs (Ransom and
Foster," 1920 ; Yokogawa, 102,S ; Martin, 1926; Roberts, 1S34).
The lesions in the lungs consist of petechial hemorrhages and
inflammatory processes. In heavy infections the lungs may be
very extensively involved, being edematous, hemorrhagic, and
even completely consolidated. The picture is that of a multiple
lobar pneumonia, which frequently causes the death of experi-
mental animals. A disease of young pigs known as "thumps"
has been identified as ascaris pneumonia (Ransom, 1920). In
man severe pulmonary symptoms may l)e produced by hea^'y
infections (Koino, 1922) and in some tropical regions lung sym-
toms, especially in children, have been attributed to ascaris in-
fection. In most infected populations, however, it is extremely
difficult to assign a definite symptomatology to the lung mi-
grations of ascaris (Keller, Hillstrom, and Gass, 1932).

It is not easy to define clearly the symptoms produced by
the worms in the intestine. Perhaps the most common com-
plaint is an intermittent intestinal colic. Normal digestion
may be disturbed and there may be loss of appetite and in-
somnia. Nervous sym))toms are particularly common among
heavily infected young children. Individuals having a special
sensitivity may develop a generalized toxemia or specific ner-
vous symptoms. In young children very heavy infections may
cause severe illness or even death. Large numbers of ascarids
may produce intestinal blockage. Also, the migrations of adult
worms sometimes produce penetration of the intestinal wall
and severe injury to the appendix, liver, lungs, or other or-
gans. However, only a small proportion of infected individuals
show symptoms that can be definitely attributed to ascariasis.

DI.'!TRIBI'T10X .^XD EPIDEMIOLOGY
Doling tlie last 1." years our knowledge of the factors in-
fluencing the dissemination of ascaris has been very greatly in-

creased by a number of siiecific epidemiologic studies in differ
ent i)arts of the world. The distribution of the worm burden
has been studied by the StoU dilution egg counting method,
and attempts have been made to get at the sources of infec-
tion liy the observation of soil pollution habits and by the iso
lation of eggs from the soil (Spindler, 1929a; Majilestone and
Mukerji, 193(i). Data from these investigations and infornm
tion on the factors influencing tlie«development and viability
of ascaris eggs outside the body of the host have given a fairly
good body of ei)idcmiological knowledge on wliich to base con-
trol measures. In addition, recent studies indicate that host
relations may be of importance in determining the distribution
of ascaris in populations.

DISTRIBUTION

.1. Iiimbricoidffi in man has a world wide distribution and
appears to rival Eiitcrohiiis rcniiinilnri.': for the distinction of
being the commonest of all human parasites. It has been found
within the Arctic Circle and in regions where almost desert
conditions i)revail. It is most abundant in tropical countries
with a heavy rainfall and is especially widespread in the Orient,
although extensive endemic centers are also present in Europe
and in the United States (Otto and Cort, 1934a; Denecke, 1937;
Girges, 1S34).

Recently the information on the distribution of ascaris within
population groups has been greatly increased. The family is
almost always the unit of infection (Cort, Stoll, Sweet, Rih'v,
and Schapiro, 1929; Cort, Otto, and Spindler, 1939; Otto, Cort,
and Keller, 1931). This is true in urban as well as rural areas
(Headlee, 1936; Winfield and Chin, 1938). Only in Egypt
(Scott, 1939) and In certain special institutional situations
(Caldwell, Caldwell, and Davis, 1930) was a larger group in-
dicated as the unit. In numerous situations negative or lightly
infected families are found living close to those that are heav-
il.v infected. With few exceptions (Scott, 1939) about •")n per-
cent of the total worm burden of any population group is con-
centrated in about .5 percent of the infected individuals. These
heavy cases are largel.v found in a small number of families,
the so called "ascaris families." Usually the peak of the in-
fection curve comes early in life, sometimes even in the o to 9
age group, and the worm burden in adults is only a fraction
of that in children. Also, women of child-bearing age are fre-
quently more heavily infected than men of the same age groups.
However, heavy infections are sometimes found in adults, es-
pecially in certain places in the Orient (Cort and Stoll, 1931).

Ascaris is in general a parasite of people on a low economic
and social level. "Ascaris families" are usuall.v among the
poorest and most degraded of the population. Not infrequently,
however, infections in children, sometimes rather heavy, are
found in families of a higher type living under favorable en-
vironmental conditions. In the Orient, also, ascaris is often
widespread in people of the better classes (Mills, 1927). It is
not primarily a parasite of rural districts since in many jjarts
of the world it is present and sometimes very common in cities
of various sizes. The reasons for most of the pecularities in
the distribution of ascaris which have just been summarized
become clear when the knowledge available on the various fac-
tors that influence dissemination is considered. These factors
may be grouped under (1) host relations, (2) general environ-
mental factors, and (3) human habits.

HOST RELATIONS
In this connection one of the important problems is the re-
lation of the ascaris of pig to human infection. Extensive
investigations have shown no differences between the ascarids
of these two hosts in morphology or in physiological and bio-
chemical relations (Schwartz, 1920; Bakker, 1921; Barker,
1923). Almost all attempts to infect pigs with eggs from hu-
man sources have been unsuccessful fPayne, .\ckert, and Hart-
man, 192."); Martin, 1926). Also, the attempts to infect man
with the pig ascaris have given negative results (Koino, 1922;
Payne, Ackert, and Hartman, 292.'i; Buckley, 1931). Several
workers have expressed the view that the human and pig as
carids are physiological or host varieties which have each lost
their infectivity for the other host. As Lane (1934) has sug
gested, however, the evidence from these experimental infections
is not very conclusive because of the lack of adequate controls
and because of the difficulty reported by a number of workers
of infecting pigs with the pig ascaris (see also Roberts, 1934).
Also, de Boer (193."ia & b) reported that he succeeded in infect-
ing suckling pigs with eggs from both pig and human sources
and Hiraishi (1928) and others in .Japan have infected pigs
deficient in vitamin .\ with human ascaris. It is difficult, how-
ever, to escape the conclusion that under field conditions in-
fection of man with pig ascaris is at least very infrequent. In
fact, no evidence has been found in the reports of epidemiologi-
cal studies of undoubted human infection from pig sources. At-
tention has also been called to areas in which differences in the

313

incidence of the pig and human asearis are very great under
conditions that would seem to favor cross infection (Payne,
Aekert, and Hartman, 1925; Caldwell and Caldwell, 192(3; Mar-
tin, 1926; Roberts, 1934). Therefore, until some evidence can
be 'presented of human infection with asearis from the pig, it
hardly seems reasonable to consider the domestic pig as a
reservoir host of any significance in the dissemination of asearis
in human populations.

There is some evidence that a specific immunity is acquired
to infection with A. himbricoiiles. Some of the studies showing
this have been made on abnormal hosts and, therefore, involve
only the stages of the cycle through the lung migration (Kerr,
1938). Other workers have reported experiments that sug-
gested the development of immunity in pigs (Morgan, 1931;
de Boer, 193(ib; Roberts, 1934). In pigs abo infection is very
much greater in young than in old animals (Ransom and Fos-
ter, 1920; Roberts, 1934). Such differences might be explained
as the result of an immunity produced by repeated infection.
There is some suggestion also that in older animals poor nutri-
tion may increase susceptibility (Morgan, 1931; Hiraishi,
1928). Possibly in man a part at least of the reduction of in-
fection in adults as compared with children may be due to the
development of an acquired immunity, although difference in
habits cannot be excluded. Also, it seems not unlikely that
undernourishment or other debilitating factors may influence
susceptibilitv to this parasite.

There is some suggestion that A. Iiimbricoidcs is not well
adapted to its host. This has been suggested by several work-
ers because of the difficulty of producing experimental infec-
tions in pigs (Ransom and Foster, 1920; Martin, 1926; Hirai- .
shi, 192S; Roberts, 1934). A similar relationship in man may
explain the rarity of heavy infections. Another significant
host relation is the rapid turnover of the infection and the con-
stant loss of worms in infected populations (Otto, 1930). In-
dividuals frequently pass worms; heavy worm burdens are only
kept up by constant reinfection; and groups removed from ex-
posure to "reinfection soon lose their worms (Keller, 1931). It is
not clear whether this instability of infection is due to lack
of attachment of the worms or to immunity reactions of the
host. Finally, it seems probable that host reactions have a
part in keeping asearis infections in human populations at a
low level except under extreme conditions of exposure to infec-
tion, and in establishing the peculiar age distribution of this
parasite.

GENERAL ENVIRONMENTAL F.\CTORS

The eggs of A. lumbricoidrs live for long periods of time
and are remarkably resistant to most external conditions. They
have been kept alive for 4 to 't years (Davaine, 18.")8 and 1863;
Martin, 1920) and under natural conditions will live for 1 to
2 years and survive the winter (Brown. 1928; Roberts, 1934).
Under field conditions, where they would be exposed to a larger
variety of factors, it seems probable that they remain viable
for somewhat shorter periods, although it is evident that in-
fested soil renuiins dangerous for a very much longer time
than is the case with hookworm.

Asearis eggs have been shown to have a remarkable resistance
to a wide variety of chemical agents (Yoshida, 1920; Ransom
and Foster, 1920). It seems evident, therefore, that in nature
they would rarely if ever meet chemical conditions in the soil
that would be unfavoralile. The eggs require a constant supply
of oxygen for their development, they can, however, live for
several weeks under anaerobic conditions and can develop in
cultures where oxygen tension in the surrounding water is only
a fraction of saturation (Brown, 1928a). It seems evident,
therefore, that under natural conditions they can readily find
oxygen enough for development except in polluted water or
saturated media where bacterial growth would use up the

supply.

Asearis eggs in all stages of development can withstand freez-
ing temperatures for surprisingly long periods of time (Cram,
1924; Nolf, 1932) and will develop slowly at temperatures as
low a's 12° C. The optimum temperature for development seems
to be about 30° to 33° C. and development is almost completely
inhibited at temperatures of about 37° C. Higher temperatures
are very iniurious to the eggs and at temperatures above W° C.
they are killed in a short time (Ogata, 192."i; Nolf, 1932).
Desiccation is also an important factor in killing asearis eggs,
although they will remain viable for several days when dried on
glass slides and kept at a relative humidity of about ."JO percent
(Otto, 1929; Roberts, 1934). On the dry surface of soil they
survive much longer (Caldwell and Caldwell, 1928; Brown.
1928b). Their resistance to desiccation is also greatly increased
by low temperatures (Martin, 1920). They will develop nor-
mally when air dried on glass slides and kept in an incubator
with" a relative humidity above 80 percent (Otto, 1929). A
number of authors have reported that direct sunlight is lethal
to asearis eggs, although in many of the experiments the effect

of high temperature vias not excluded. There is, however, defi-
nite evidence that sunlight per sc docs in.iure the eggs since
Nolf (1932) demonstrated that they were quickly killed by ultra
violet light. Under conditions in the field, a combination of
high temperatures with desiccation is probably most important
in killing the eggs as is shown by the rapidity with which they
die when exposed to direct sunlight on certain types of soils
(Brown, 1927b; Otto, 1929).

The resistance of the eggs of the human asearis to external
environmental conditions accounts for its wide geographical dis-
tribution. Studies in the United States (Otto, Cort, and Keller,
1931) have shown that they can develop and persist on the hard-
packed clay soil of unshaded dooryards where the eggs of tri-
churis and hookworm are soon killed. Certainly, A. lumbri-
coides is less restricted in its spread by clinuitic and soil con-
ditions than any other human parasite with free stages. Of
course, tropical and semitropical countries with a high rainfall
oft'er the most favorable conditions for its spread; but where
human habits are particularly favorable a high incidence with
heavy infections may occur in regions, such as in certain places
in North China, where there is low lainfall and a long cold
winter (Cort and Stoll, 1931; Winfield, 1937a).

HUMAN HABITS AND SOURCES OF INFECTION
Studies of the last few years in such widely separated regions
as tropical America, the southern United States, North China,
and the Philippine Islands, have shown that the chief sources
of asearis infection are from eggs deposited Ijy young children
in the yards, under the houses, and even within the houses them-
selves (Brown, 1927a; Cort, Stoll, Sweet, Riley, and Schapiro,
1929; Cort and Stoll, 1931; Cort, Otto, and Spindler, 1930;
Nair, 1935; Otto and Cort, 1934a; Tubangui, Basaca, and Pas-
co, 1934; Winfield, 1937 a & b). This household pollution by
young children results in the accumulation of large numbers of
viable eggs in the dooryards which are frequently carried into
the houses. Under these conditions eggs can easily contaminate
food and water and also infect directly by hand-to mouth trans-
fer the youngest children who play in the dirt and are most
careless in their habits. More general areas of concentrated
soil infestation are frequently found such as those near unsani-
tated schools or in the yards of institutions (Caldwell, Cald-
well, and Davis, 1930). In Egypt the sources of infection ap-
pear to be chiefl.v from eggs on the floors of the houses (Scott,
1939). The point has been repeatedly stressed that heavy in-
fection of a family can only be brought about by the grossest
type of soil pollution close to the house combined with very
careless habits, especially in the children. Families without
infection have frequently been found living next door to heav-
ily infected "asearis families." Also, in certain regions, as
for example western Tennessee, where there is little or no
sanitation in some of the rural areas, asearis infection may be
at a low level or absent where the stools are deposited at some
distance from the dooryards (Otto, Cort, and Keller, 1931).
Sucli relations, and the rarity of heavy infections, can only be
explained by postulating that in man, as has been shown in
the pig, infection is difficult. The ingestion of large numbers
of eggs is evidently necessary to produce even moderate infec-
tions of adult worms. When the constant loss of worms is also
considered, it is easy to understand why constant exposure to
intense infection is necessary to produce heavy infections.

The contamination of drinking water has been frequently
suggested as a method of infection with asearis. In most of
the epidemiological studies that have been made in the United
States, Tropical America, and the Orient the possibility of in-
fection from this source has been practically ruled out. In cer-
tain parts of India, however, evidence was found that the
contamination of shallow pools of water was a factor in infec-
tion (Chandler, 1928). Recently the suggestion has been made
(Lane, 1934) that the breathing in of dust containing viable
asearis eggs might be a source of infection of considerable sig-
nificance. While infection in this way seems possible, it could
hardly be a method of major importance except under very
unusual circumstances.

It has been commonly considered that vegetables fertilized
with human feces are an important source of asearis infection
(Mills, 1927; Yoshida, 1925; Walker, 1927; Khalil, 1931; Rob-
ertson, 1936). This would explain, as suggested b.v Mills
(1927), the distribution of asearis among all ages and classes
of the population in Korea. Several workers in the Orient have
found viable eggs of asearis clinging to vegetables that are
used for food uncooked (see summary by Winfield and Yao,
1937). Also, where human excrement is used as fertilizer, the
storage, transportation, and distribution of night soil on the
fields would serve to scatter the eggs of asearis widely in the
general environment of the villages. However, definite evidence
has been presented in studies in China that pollution by chil-
dren in the yards and streets of the villages is a very common
and perhaps the most important method of asearis dissemina-

314

tioii iCiirt aiui Stiill. ]'X\\ ; W iritiold. l<):f.'ili ; Wiiiticld and e'liiii,
l!i;iS). Also, ill North C'liina, Wiiiliold and Yao (I'.CiT) eould
tiiid no evidence of asearis eggs on vegetables after they were
prei>ared for food, and expressed the opinion that infection
from this source was of little if any significance in this part
of China. It seems clear, however, that the use of human ex
crenieiit as fertilizer does spread asearis probably in a number
of different ways, since in China, Korea, and Japan infection
witli this parasite appears to be more common, especially in the
atlults, than anywhere else in the world.

CONTROL OF ASCAEIASIS

Treatment of infected populations and improvement in house-
hold sanitation are the obvious suggestions for the control of
ascariasis. On account of the enormous numbers of eggs pro-
duced and their great resistance to chemicals, sterilization of
sources of infection \vould seem to have a very limited value.

In spite of the availability of effective nntlieliuintics (Brown,
]!'34), there is clear evidence that mass treatment of infected
pojuilations is not an effective control measure against asearis
because of rapid reinfection (Cort, Schapiro, and Stoll, 1929;
Otto, 1930; Otto and Cort, 1934b). Perhaps if the treatments
could be made almost 100 percent effective in removing the
worms, and if they were administered at the end of a dr}'
season or winter when the numbers of viable eggs in the soil
would be reduced (Cort, Schapiro, Riley, and Stoll, 1929), they
might have some real value as a control measure. At any rate,
treatment in ascarisinfected populations is imi)ortant for re-
lieving heavily infected individuals, especially young children,
of dangerous worm burdens.

There are also certain difficulties to be met in the attempt to
control asearis by improved sanitation (Cort, 1931, p. 137).
It was found in Panama (Cort, Stoll, Sweet, Riley, and Scha-
piro, 1929) that in certain areas sanitary improvements that
had definitely reduced the level of hookworm infection did not
appear to limit the spread of asearis. Also, more than half of
the families with heavy asearis infection that were studied in
the mountains of Tennessee had privies which in almost all
cases were in use (Otto, Cort, and Keller, 1931). Examples have
also been reported from cities of families with flush toilets
connected with the sewage system in which the children had
considerable asearis infection (Otto and Cort, 1934a; Headlee,
193(5). Under all these conditions the infection is kept up be-
cause the young children fail to use the sanitary facilities and
deposit their stools in the yards close to the houses.

In attempts to improve sanitation in rural districts certain
practical points of special importance in the control of asearis
seem to have been entirely overlooked in a number of places.
First, the latrines should lie placed near enough to the houses
so that they can be reached by the young children, and in the
second place they should have special seats for the children.
Usually seats are designed only for adults and are difficult or
even dangerous for children to use. In addition, real progress
in asearis control will have to depend on the instruction of the
children and their parents in the homes and in the schools in
the dangers of soil pollution and in the minimum requirements
of a proper household sanitation. In most places widespread
asearis infection is associated with general low standards of
living, and any raising of standards will have a tendency to
reduce infection.

Trichuris trichiura
W. W. C.

The whipworm, Tricliiiri.i tricliiiira, was first described by
Roederer in 1761, although it was apparently observed much
earlier. Davaine (18.")S and 18(53) studied the development of
the eggs. Leuckart (1866) demonstrated experimentally the
direct development of the trichuris of the sheep and pig, and
Grassi (1887) produced experimental infection with T. tricliiiira
in man. About the liegiuning of the 20th century the patho
genie role of trichuris was greatly emphasized and it was con-
sidered to be an important factor in infection with such dis-
eases as typhoid fever, cholera, appendicitis, and dysentery
(Guiart, 1911). More recently, however, these views have been
discounted by most workers. The extensive surveys of the last
three decades by fecal examination have greatly extended the
knowledge of the distribution of trichuris. Also, considerable
information on the factors influencing its dissemination has
been obtained, chiefly in connection with field studies on as-
earis and hookworm.

The adults of T. trichiura are most frequently found in the
caecum, vermiform appendix, and colon with their long at-
tenuated anterior ends sewed into the superficial mucosa. The
great majority of infections with the human trichuris involve
only a few worms, but in occasional cases hundreds may be
present. The length of life of the adult worms is not definitely
known, although it appears to be much greater than that of

ascaiis. .Mso, there is no evidence of the constant loss of worms
and rapid turnover of infections found in that species. There
is some evidence that an acquired immunity is developed in
trichuris infections (Suzuki, 1934; Miller, 1941).

PATIIOGKNECITV
The adult worms produce some injury to the int<'stinal mu-
cosa and when present in large numbers may cause considerable
inflammation. Therefore, in the heaviest cases they may pro
duee rather severe intestinal disturbances. There is no real
evidence that they serve as a "lancet of infection" for other
diseases as suggested by many earlier workers (Guiart, 1911)
and their relation to the production of anemia is rather doubt-
ful (Otto, 1935; Swartzwelder, 1939). In most cases their
presence would pass unnoticed except for the finding of the
characteristic eggs in fecal examinations.

DISTRIBUTION AND EPIDEMIOLOGY

Trichuris trichiura is widely distributed in the world and
is frequently found, especially in tropical and subtropical re-
gions, associated with both asearis and hookworm. Its range
is not as extensive as that of asearis, especially in the temperate
zones and it is absent in the colder regions. In the majority
of places where both these parasites are found together the in-
cidence of trichuris is lower. In the mountain regions of the
southeastern United States, where the incidence of asearis is
several times that of trichuris, families are common that harbor
only asearis, but almost always where trichuris is f(Hind as-
earis will also be present (Otto, Cort, and Keller, 1931). There
are, however, many situations where examinations have shown
the incidence of trichuris to be equal to or even higher than that
of asearis. Such situations are usually in tropical or subtropical
countries, but there are a number of places in Europe, especial-
ly in the U. S. S. R., where the incidence of trichuris is sur-
prisingly high.

Examinations of the last few years by the dilution egg-count-
ing method have given us considerable information on the dis-
tribution of trichuris within population groups, especially in the
United States (Cort, Stoll, Sweet, Riley, and Schapiro, 1929;
Otto, Cort, and Keller, 1931; Cort and Otto, 1937). Its dis-
tribution resembles that of asearis in having the family as the
unit of dissemination, and in the concentration of a large pro-
portion of the worm burden in a small percentage of heavy
cases, usually grouped in families. Also, the distribution of
trichuris according to age and sex is much like that of asearis
except that the peak of infection comes almost always at a
somewhat later age. Usually adult females are more heavily
infected than males of the same age groups.

The human habits involved in the spread of trichuris and
asearis appear to be exactly the same. Differences in egg
production, susceptibility of hosts to infection, stability and
persistence of infection in the hosts, or in immunity relations
cannot be evaluated in the present state of our knowledge in
relation to differences in the methods of dissemination or dis-
tribution of these two parasites. Therefore, in attempting to
explain such differences we must concern ourselves chiefly with
the differences that have Iteen found in the resistance of
their eggs to external environmental factors. The eggs of tri-
churis are much less resistant to low temperatures than are
those of asearis, and are somewhat less resistant to high tem-
peratures (Nolf, 1932). They are also less resistant to desic-
cation, require slightly more moisture for development, and de-
velop more slowly when the moisture is reduced (Caldwell and
Caldwell, 1928; Spindler, 1929 a & b; Nolf, 1932; Onorato,
1932). They are very long lived and like those of asearis are
very resistant to chemicals, and they are considerably more
resistant than the eggs of asearis to ultra violet light (Nolf,
1932).

The differences just discussed in the resistance to external
environmental conditions of the eggs of asearis and trichuris
appear to exjjlain .satisfactorily at least some of the differences
in their distribution. Certainly the absence of trichuris in cold
regions and its scarcity wherever there is a long cold winter
can be explained on the basis of the lack of resistance of its
eggs to low temperatures. It seems unlikely that the eggs of
trichuris on the soil could live through even a short period of
freezing temperatures.

Following suggestions that trichuris is limited more in its
distribution by dry conditions than asearis (Sweet, 1924;
Chandler, 1928), this relation was first carefully studied by
Spindler (1929b) in the United States. It was found that in
the mountains of southwestern Virginia trichuris occurred in
a much lower incidence than asearis except in a few limited
localities, where dense shade in the yards produced moist con-
ditions where the eggs were deposited. This finding led to the
suggestion supported by a careful review of the literature that
the incidence of trichuris tends to be as great or greater than
asearis onlv where there is a considerable amount of moisture

Sl.j

Ill tlic soil due to Iieavy rainfall or protection by dense vege-
tation. Later epidemiologic investigations elsewhere in the
United States supported this view by showing that in other
areas where the incidence of ascaiis was much higher than
trichuris, infections with the latter were largely limited to
households where dense vegetation or poor drainage produced
moist areas around the dwellings where the eggs were deposited
(Otto, Cort, and Keller, 1931; Otto, 1932); Cort and Otto,
1937).

Certain field studies in the United States (Cort and Otto,
1937; Otto, 1932; Caldwell, Caldwell, and Davis, 1930) were
made of situations where the incidence of trichuris was higher
than ascaris. In these places the soil where the eggs were de-
posited was moist and appeared very favorable for develop-
ment. The soil pollution in the yards and close to the houses,
however, seemed to be considcrabl.v less than that found asso-
ciated witli heavy ascaris infections. It was suggested, there-
fore, that given favorable conditions for the development of
the eggs the advantage in dissemination would be in favor
of trichuris on account of its longer life and greater stability
in the host. Undoubtedly, other differences in the life cycle,
host relations, and general environmental relations of these
two parasites also produce differences in their distribution.

Finally, since the human habits responsible for the spread of
trichuris and ascaris appear to be the same, control measures
would be the same for both.

Trichinella spiralis
E. B. C.

The old Mosaic law against eating pork is perhaps traceable
to suspicions regarding the casual relationship between pork
and the disease later called trichinosis. From very earlj' days
epidemics were recorded with symptoms strikingly similar to
those of trichinosis; Glazier (1881) refers to such a disease
among the Carthaginians sent (B. C. 427) to subjugate Sicily;
descriptions of outbreaks from the l.^ith century on, in Ger-
many, France, the British Isles, and America correspond so
closely with those of trichinosis that there is now no doubt
as to the etiology. However, it was not until the 19th century
that evidence was produced as to the cause of the disease.

The principal hosts of TrichineUa spiralis are swine, rat and
man. In addition, however, the following other animals either
have lipen fmiiid naturally infected or have been experimentally

infected. Naturally infected: mice, rabbits, beaver (coypu),.
domestic eat, palm civet, dog, wolf, coyote, fox, pole cat, martin,
ferret, European and American badgers, raccoon, polar bear,
common bear {Ursiis sp.), and mongoose. Experimentally in-
fected: guinea pig, monkeys, sheep, cattle, horse, young chick-
ens, pigeons, magpies, and rooks. In young chickens the larvae
in the muscles soon die (Augustine, 1933; Matoff, 1938). Lar-
vae developed to the infective stage in very young [ligeon.s
(Matoff, 1936; 1938) and in adult pigeons affected by avita-
niinosis (Pavlov, 1940). In the latter case infectivity was
demonstrated 32 days after the feeding of trichinous meat to
tlie pigeons (personal communication). Coldblooded animals
are apparently immune (Pavlov, 1937).

DIAGNOSIS

During life, diagnosis of trichinosis may l>e made from the
clinical history, the differential blood picture, and immunologi-
cal tests. Other tests, sometimes used but less reliable, are
the following. Stool examination: the evidence indicates it is
of little or no value. Biopsy: a bit of muscle excised usually
from the deltoid, biceps or gastrocnemius is examined as a
fresh press preparation and by digestion, as the trichinae are
thus more easily detected than in sections. This method has
the limitation of being not deiiendable until the end of the third
week after infection and in addition a negative biopsy does
not exclude trichinosis. Examinatinn of blood and cerebrospinal
fluid for larvae: For a period of about 3 weeks, beginning
about 1 week after infection, the larvae may be present but
are not always easy to find.

Immunological reactions, consisting of intradermal and pre-
cipitin tests, are more reliable when properly used and inter-
]>reted. Bachman (1928) initiated both tests; they have been
somewhat modified by Augustine and Theiler (1932) and other
workers. Bozicevich (1939) developed an improved antigen,
sujierior in having larvae with a miniinum of debris and in
being extracted with neutral O.S.'i percent solution of sodium
chloride, without preservatives; the result is much greater speci-
ficity and impioved maintenance of potency. With the im-
proved antigen a positive skin test in ralibits may be obtained
8 or 9 days after infection; however, in man positive reactions
are seldom obtained until after the second week of infection.
Both skin and precipitin tests should be used for diagnosis,
even though the skin test is negative. Positive precipitin re-

Tablb 9. Findings of trichinae in local stirveys in the United States

Author Date

Whelpley 1891

Thornbury 1897

Williams 1901

Queen 1931

1937*

Riley and Scheifley .. 1934

Hinman 1936

McNaught and Anderson 1936

Magath 1937

Sawitz 1937

Pote 1937

Scheitiey 1938

Walker and Breckenridge . 1938

Evans 1938

Hood and Olson 1939

Sawitz - - 1939

Butt and Lapeyre .. 1939

Gould 1939

Gould - 1939

Harrell and Johnston 1939

Oosting 1940

Catron 1940

Totals

•Reported by Scheifley, 1938.

Place

St. Louis, Mo.

Buffalo, N. Y.

Buffalo, N. Y.

Philadelphia, Pa.

Baltimore, Md.

1 >enver, Colo.

Rochester, N. Y.

Boston, Mass.

Denver, Colo.

Minneapolis, Minn.

New Orleans, La.

San Francisco, Cal.

Rochester, Minn.

New Orleans, La.

St. Louis, Mo.

Minneapolis & St. Paul, Minn.

Birmingham & Tuscaloosa, Ala.

Cleveland, Ohio

Chicago, 111.

New Orleans, La.
Los Angeles, Cal.
Eloise, Mich.
Eloise, Mich.
Durham, N. C.

Dayton, Ohio
Ann Arbor, Mich.

Number of

Number

Percent

examinations

positive

positive

20

1

5.0

21

3

14.3

362

21

.^.8

7

0

0.0

126

5

4.0

10

1

10.0

344

59

17.2

58

16

27.6

431

70

16.2

117

20

17.1

200

7

3..T

200

48

24.0

220

17

7.7

200

10

.").0

1,060

163

15.4

118

15

12.7

100

33

33.0

100

36

36.0

208

12

5.8

220

25

11.4

200

14

7.0

170

31

18.2

90

11

12.2

410

82

20.(1

44

0

0.0

6

0

0.0

55

3

.').4

134

27

20.1

300

.-,.-.31

44

774

14.7

13.9

Method

Microscopic

Microscopic

Microscopic

Microscopic

Microscopic

Microscopic

Digestion

Digestion

Digestion

Microscopic

Digestion

Digestion

Microscopic

Micros. & digestion

Sections

Microscopic

Micros. & digestion

Micros. & digestion

Digestion

Digestion & micros.

Micros. & digestion

Digestion

Digestion

Micros. & digestion

Digestion

Microscopic

Micros. & digestion

% Digestion ; %

Micros. & digest.
Digestion and 270

microscopic

316

mictions appear usually at the end of tlie thiid week. Liuiita
tions of the use of these reactions for diagnosis of the disease
should l)e kept iu mind; after an attack of trichinosis, a posi-
tive skin test may he obtained for as long as 7 years and a
I)()sitive precipitin reaction for as long as 2 years. In addition,
persons with subclinical trichina infections may also give posi-
tive skin and precipitin reactions.

For postmortem diagnosis, the compressor method and the
digestion-Bacrmann method are used. The former consists of
direct microscopic exauiination of a press preparation of mus-
cle. The l;itter method consists of the digestion of muscle in
jirtificial gastric .iuice, the digested nmterial being put through
the Baermann apparatus and examined microscopically for lar-
vae. Either of the two methods has special value and certain
limitations for certain types of infection, the two methods
being supplementary (Hall and Collins, 1!I37). Both methods
have therefore been used in recent surveys and on a quantita-
tive basis of trichinae per gram of diaphragm muscle examined.
The two methods have been described in detail by Nolan and
Bozicevich.

Investigation (Sawitz, 1937; Schapiro et al, 1938) has shown
a correlation between the skin test for diagnosis of trichinosis
in living persons and postmortem findings.

SYMPTOMATOLOGY

Trichinosis is characterized by lack of regularity in its course
(Ransom, 191:1; Hall, 1937; Kaufman, 1940). A history of
eating raw or undercooked pork containing trichina may or may
not be followed by a gastrointestinal disturbance, including ab-
dominal pains, nausea, vomiting, diarrhea or constipation or one
succeeding the other, and intestinal henu>rrhages. Eosinophilia
of 10 to 45 percent and at times OS to 7S percent may be
present ; on the other hand it may not be present at all. There
may be edema (usually periorbital), high fever, myositis and
l>neumonia. The heart may be involved. There may be ner-
vous derangement, including encephalitis, meningitis and de-
lirium. The variegated clinical picture results from differences
in intensity of infection, organs invaded and resistance of the
patient. A clinical but nonfatal case may show at biopsy as
few as 8 larvae per gram of gastrocnemius (Ferenbaugh et al).
Hall (1937) tentatively designated as "heavy to critical" cases
showing 101 to 1,000 larvae per gram. Conclusions concern-
ing man can not be drawn from quantitative data from labora-
tory animals, as in man (Xevinny, cited by Roth, 1939) inflani-
matorj- and other injurious processes are more pronounced and
extensive, than in those animals. Schwartz (1938) found that
experimentally infected hogs showed no symptoms when there
were less than 800 to 900 larvae per gram of diajihragm muscle
tissue.

EPIDEMIOLOGY

In California outbreaks of trichinosis have resulted from the
eating of jerked bear meat (Walker, 1932; Geigcr and Hob-
maier, 1939) and in Europe from the meat of the polar bear
and the dog (cited by Kaufman, 1940) and the Coypu (Rubli,
1936;. These cases are rare, however; swine are the principal
source of infection to man and it is probable that most cases
of infection of other animals could be traced back ultimately
to swine.

The incidence of trichinae in swine varies according to the
locality and manner of feeding, the principal source of the
infection being uncooked pork scraps fed to swine in garbage
or swill ; the eating by swine of infected rats or of carcasses of
infected pigs are very minor sources. Hall (1937a), Schwartz
(1938) and Wright (1939) have analyzed the data from dif-
ferent parts of the United States; trichinae were found in only
about 0.5 percent of swine fed on cooked garbage and southern
swine which range the fields and woods and get little garbage;
in 1 to 1.5 percent of swine iu the Central West, where feeding
of grain predominates over garbage feeding; in 4 to (5 percent
of swine fed on uncooked garbage; and in 10 to 20 percent of
swine fed on slaughter house offal, this last group now being
small.

As regards the incidence in man, data have been inadequate;
due to the variability of symptoms, cases are frequently un-
recognized. To reports of outbreaks of acute trichinosis, which
have often involved large numbers of persons, and those of
sporadic cases must be added necropsy findings which detect
subclinical infections as well as previously undiagnosed clinical
cases. In the 94 year period, 1842-1936, according to Sawitz
(1938), there were between 5,000 and 6,000 clinical cases of
trichinosis diagnosed and recorded in the United States. Stiles
(1901) found that in Germany between 1860 and 1898 there
were reported 14,820 cases of trichinosis with 831 deaths, a
mortalitj' of 5.6 percent. Hall (1938a) points out that iu the
1880 's competent authorities maintained that the incidence of

tricliinae was mucli greater in the United States than in
Europe and that these oi)iuions, long neglected, were borne out
by later findings which indicate that the United States has the
greatest trichinosis problem of any country in the world. The
incidence here is about 5 times greater than in middle Europe
(Magath, 1937), or even higher (Hall, 1938a). Comiiarative
data are Lacking from many parts of the world. A very low
iiu-idence has been found iu England (Van Someren, 1!I37).
Eleven clinical cases arc known from the Hawaiian Islands
(Alicata, 1938); trichinae have been found in the rat, mon-
goose and wild .-md domestic pigs there. Apparently only
one hunmn case has been reported from Chiim although the dog,
cat and swine have been found infected there (Ch'n, 1937).

Early examinations of necropsy material were confined to
direct microscopic examination of muscle by the compressor
method and for the most part did not represent real surveys.
In more recent years a digestion method has also been used;
there is evidence that either technique alone fails to detect one-
third of the infections, so that a correction figure of 33% per-
cent should be applied if only one method is used. Local sur-
veys have been nmde in various parts of the United States
(Table 9) and a nationwide surveys of unselected cases from
various population groups (Table 10) is in progress. To date
the findings from necropsy examinations of over 9,000 persons
show that 15 percent were infected with trichinae, and the ac-
tual incidence figure would be higher if corrections could be
made to eliminate all variables. As regards severity of infec-
tion, the majority of 488 positive cases (Wright, 1939) showed
less than 11 larvae per gram of diaphragm but 2.5 iierceiit of
the cases had between 101 and 1,000 larvae per gram.

An analysis of the findings according to sex, age, lace, oc-
cupation and social-economic status of 2,000 individuals
(Wright, 1939) failed to show any special correlation in most
of the groups represented. However, a geographical correlation
is indicated, especially as regards reported cases of cliiiical
trichinosis; the heaviest incidence is found along the North
Atlantic coast and along the Pacific coast, correlated with gar-
bage feeding. In New York, Massachusetts and California from
501 to over 1,000 clinical cases per state were reported up to
1938 (Hall, 1938) ; these are areas where there is extensive
feeding of uncooked garbage to swine.

CONTROL

With regard to trichinosis, the significance of chemotherapy
is decidedly different than in the case of most other helminth
infections, "as in oxyuriasis (p. 324). In trichinosis it is en-
tirely therapeutic, administered only for the patient's sake; in
oxyuriasis it is both proi)hylactic and therapeutic, preventing
reinfection of the patient and infection of others.

Since human trichinosis results from the operation of two
factors (Hall, 1938), its prevention lies in control of those
faetors— namely, (1) food habits of the individual, including
infection from accidents and failures of cookery, and (2) the
frequency of occurrence of live trichinae in swine supplying
the pork. It is evident from necropsy findings as well as from
numerous sporadic cases and occasional outbreaks of trichino
sis, that a very large number of persons have eaten unprocessed,
uncooked or undercooked infected pork. The great majority of
swine are free from trichinae; pork from a small minority of
swine serves as the principal source of both human and porcine
trichinosis. This source may be combatted (Hall, 1936; 1937a;
1938a; Schwartz, 1938; Wright, 193S) by (1) meat inspection;
(2) avoidance of the use of raw or inadequately cooked pork or
pork products; (3) the swine sanitation system; (4) cooking
of garbage; and (5) rat destruction.

In Germany microscopical inspection of pork for trichinae
was instituted iu 1875. Exclusion of American pork from Ger-
many caused a loss of millions of dollars to farmers and ex-
porters in the United States and led to diplomatic complica-
tions. Stiles' (1901) study of the German system indicated
that inspection can not detect all infected meat, that there was
a false sense of security from inspected meat and that the
system was very elaborate and expensive. In the United States
tiiere has never been federal meat inspection for trichinae in
pork intended for domestic consumption. The principal mea-
sures relied upon have been education as to cooking pork thor-
oughly, and the preparation under meat inspection of pork
products customarily eaten raw. Freedom from infective
trichinae is assured "by cooking at 137° F. (that this tempera-
ture requirement, originally set by Ransom and Schwartz
(1919), is adequate has been verified by Otto and Abrams,
(1939), by refrigeration at 5° F. for not less than 20 days
(Ransom, 1916), or by special processing of the pork (Ransom,
Schwartz and Raffensperger, 1920). That the intradermal test
be applied to all hogs killed in all slaughter houses, for the
detection of trichina infections, has been advocated (Nelson,
1939) but the evidence (Spindler and Cross, 1939; Lichterman

317

and Klcemai), 1939) indicates that the test does not detect all
trichina infected swine.

The evidence shows that the control measures of the past
have been palliative and casual and have not controlled trichi-
nosis; a basic program should aim at elimination of tlie prin-
cipal source of infection of swine — namely, pork scraps in gar-
bage or slaughter house waste. The swine sanitation system
is of great value where used; pigs are raised on pasture, are
not fed swill or garbage, and have little or no opportunity to
eat rats or other pigs. As alread.v noted, the incidence of por-
cine infection is correlated with the method of feeding pigs.
Localities, as England (Van Somereii, 1937), which require
cooking of any garbage fed to pigs have a low incidence. A
survey made by Wright (1940) shows that in the United States
over 50 percent of reporting cities having a population of
10,000 or over dispose of municipal garbage in whole or in
part by feeding it to swine. Very few cities cook it ; it is
evident therefore that municipalities are contributing substan-
tially to the spread of trichinosis. The problem of control
clearly lies in that field.

Table 10. — Findings of trichinae in Xational Institute of

Health nationwide survey*

Direct microscopic and digest ion-Baermann methods

Number of Number of
diaphragms diaphragms Percent
Series examined positive positive

Base (10 hospitals in Washington,

D. C, 2 Marine and 4 Naval

hospitals in eastern seaboard

cities) ___ _ 3,000 488 16.3

Random (diaphragms selected at

random from hospitals selected

at random throughout U.S. A.) 436 80 1S.3

Negative (from States in which

clinical trichinosis has never

been reported) 140 26 18.6

Traumatic (persons suffering

traumatic death and not hos-
pitalized) - _.._ 212 3S 17.9

Jewish (orthodox and unorthodox

Jews) _... 134 1 0.7

Totals 3,922 633 16.1

*As reported by Hall and Collins, 1937; Nolan and Bozice-
vich. 193S; Wright, 1939; Kerr, 1940; and Kerr, Jacobs and
Cuvillier (in press).

The F'tlariae
D. L. A.

The superfamily Filarioidea contains a large number of spe-
cies of which Wnchereria bancrofti (Colibold, 1877) Seurat,
1921 and Onchocerca rolrnlns (Leuckart, 1893) Railliet and
Henry, 1910, are important pathogens for man. Less important
species that infect man include Loa hia (Cobbold, 1864) Cas-
tellani and Chalmers. 1913; Dipelaloiiema perstans (Manson,
1891) Yorke and Maple.stone. 1926; and ilansnneUa oszardi
(Manson, 1897) Faust, 1929. Several other species have been
reported from man which are known only in the immature
stages. Of these only Microflnria malai/i (Brug, 1927) appears
to be of clinical importance. The following discussion will be
limited to the first two species named and Microfilaria malai/i.

1. BANCROFTIAN FILARIASIS

The enormous enlargements of parts of the body, particularly
of the legs and external genitals, so frequently accompanying
Bancroftian filariasis were noted and much studied long before
the etiological agent, Wnchereria bancrofti, was discovered.
According to Menon (193.1), the first, and a very good descrip-
tion of these conditions was written about 600 B. C. by Susliruta
in India. The disease was probably also well known in Persia,
Arabia, Egypt, and parts of Africa at that time. Hillary
(1766) gives a very good account of its occurrence in Barliados,
describing the recurring attacks of fever, the lymphangitis, the
lymphadenitis, and the slowly increasing swellings of the af-
fected part up to the stage at which typical elephantoid appear-
ances become definite and iironiinent. Hillary was certain
that the disease had been brought to the West Indies from
Africa by Negro slaves and, at his time, was observed to be
"too frequent among them and among the white people also."
Neumann (O'Connor and Beatty, 1938) estimated that 6 per-
cent of the population of St. Croix, Virgin Islands, had elephan-
tia.sis in 1881.

Obsei-vations demonstrating the etiology of elephantiasis were
initiated in 1863 by the French surgeon Demarquay, who found
microfilariae in chylous urine of a person who had lived in
Cuba, were continued by the investigations of Lewis (1879) in
India and by others, and culminated in the research of Patrick
Manson in China between 1876 and 1900. Early in his inves-
tigations Manson discovered filarial periodicity and experimen-
tally demonstrated that a mosquito. Cule.r fatigans, was an es-
sential intermediate host and the agent for dissemination of
the parasite. More recent investigations have been largely epi-
demiological and pathological. Noteworthv among these arc the
studies of Bahr (1912), Low (1913), O'Connor (1923; 1931),
Anderson (1924), Fiilleborn (1929), Iyengar (1938), and Payn-
ton and Hodgkin (1938).

The adult worms are parasites only of the lymphatic system
of man. They maj' occur at any level of the system, but are
found most frequently in the limbs, scrotum and inguinal re-
gions. The two sexes are frequently coiled together in the
periglandular tissues, the lymphatic vessels of the capsule and
in the cortical sinuses. In heavy infections they may also oc-
cur in the medulla.

The microfilariae (for life history see p. 288) occur in the
lymph, the blood stream, and, under certain conditions (chy-
luria), may be found in the urine. Tliese larvae characteris-
tically exhibit a marked nocturnal periodicity. They are found
in greatest numbers between 10 o'clock in the evening and 2
o'clock in the morning, but during the day they may be en-
tirely absent from the blood. In the Philippine Islands and
largely throughout Polynesia, however, the microfilariae show-
no periodicity; while in Australia and New Guinea, periodicity
is the rule, but both types do occur. As far as is known botli
types represent one and the same species. In order to continue
their life cycle microfilariae must be taken up by an appropriate
mosquito.

GEOGRAPHICAL DISTRIBUTION

IVnchcreria bancrofti is practically world-wide in distribu-
tion, but is largely limited to tropical and subtropical coun-
tries. Its spread necessarily depends on the extent of the mi-
grations of individuals showing microfilariae in the blood, and
on the presence or absence of appropriate mosquitoes in new
areas to serve as intermediate hosts. The parasite is eharac-
teristicall.y found in island populations or along more or less
broad low-lying coastal areas of larger islands and continents.
In Asia it is established along coastal areas from Arabia to the
Shantung Province in Eastern China, and cases have been re-
ported as far north as Manchuria. It is prevalent in the islands
of the East China Sea, southern Japan, southern Chosen and
throughout Oceania. In Australia its distribution is mainly
along the Queensland coasts.

Bancroftian filariasis is common across tropical Africa,
Madagascar, Mauritius and neighboring islands and along the
Mediterranean shores. It has been reported to be indigenous in
Spain, Hungary and Turkey. It is of very common occurrence
throughout the West Indies, the Guianas. and Venezuela, and is
less frequent in northern Colombia and eastern Brazil (Bahia).
It appears not to have become established along the Pacific
coast. A small endemic focus was reported in 191.5 and again
in 1919 in North America near Charleston, South Carolina
(Francis, 1919). Sporadic cases of infection have been noted
from time to time in various parts of the United States, but
these, invariably, were of foreign origin or from the Charles-
ton area. Thus, it is evident that Bancroftian filariasis has
a world-wide geographic distribution. Its distribution within
any given country is, however, characteristically and markedly
spotted and discontinuous due to the local physical factors and
the differences in social standards and .sanitation.

PATHOLOGY

It is generall.v held that living microfilariae are not patho-
genic. It has been observed that microfilariae readily pass
through lymph nodes without phagocytic filtration (Drinker,
Augustine and Leigh, 193.5). 'They are exceedingly active in
the blood stream. They are not only passively carried about
with the blood stream but actively move against the lilood
stream in the arterioles, making slow progress by bracing them-
selves through the crests of the alternate undulations of their
bodies against the walls of the vessel. They frequently- occlude
the capillaries and then make their way through the stagnated
column of blood cells to reenter the active circulation. They
apparently never make permanent plugs or form emboli (Au-
gustine, Field and Drinker, 1936; .\ugustine, 1937).

The serious disorders are brought about by dead micro-
filariae and the living and dead adult worms. These disorders
in every case can be traced to interference with the lymphatic
system. Living worms, however, apparently cause little damage
other than varying degrees of blockage of the afferent approach
of the vessels in which the3- lie. However, when the adult

318

worms dio tlu'y Iiecoino forciK" bodies. Inflamiiiation follows
their death and degeiieiation. s"'i"K rise to lymphangitis,
lYnii)liadenitis, intlammatovy varicose j^roin glands, abscess and
fever. The obstructed and dilated lymphatics sometimes rup-
ture, with escape of chyle into the bladder, and less frequently
into the intestine and the abdominal cavity, and thus (j'^'c ''se
to chyluria, chylous diarrhea and cliylous ascites. Without
ru|)ture of the vessel, superficial or deeji lymph varices may
develop, such as varicose (flands of the );roin or axilla, h.ydrocelo
and lymph scrotum.

All active changes are associated with the defeneration and
absorption of dead parasites. The end result is always fibro
sis with complete occlusion of the parasitized vessel. Elephan-
tiasis, one of the commonest lesions, is the result of long and
widespread lymphatic obstruction.

Pyogenic Ijactcria, streptococci and stajihylococci have been
isolated fairly frequently from the region of the lymphedema.
Their responsibility in the disease syndrome, however, is not
clear. Drinker, Field and Homans (1934) and Drinker (1936)
have shown experimentally that loss of lymph circulation pre-
disposes to streptococcic infection, that these liacteria cause
attacks of severe chill and high fever, and usually can be iso-
lated from the tissue fluids only in the early stages of the
seizures.

The diagnosis of infections with W. bancrofti is made by
finding the characteristic microfilariae in the blood. Many
cases, however, having clinical symiitoms show no microfilariae
in the blood nor in the contents of the dilated vessels. In such
instances the infection is usually of long standing and either
the adult worms have died or the lymphatics draining the af-
fected area have become obstructed by the worms and their
products to such an extent that the microfilariae cannot pass
along the vessels to enter the circulating blood.

EPIDEMIOLOGY

Bancroftian filariasis characteristically occurs in low lying
coastal areas and along the shores of lakes and rivers. In-
digenous infections are seldom to be found in the foothills or
beyond coastal ranges. The incidence of infection and clini-
cal manifestations in endemic regions vary greatly in adjoin-
ing areas. The incidence of infection is always in direct rela-
tion to the prevalence of the mosquito concerned; and, in turn,
the prevalence of these mosquitoes in an area is in direct rela-
tion to the favorableness of that area for moscpiito breeding.
The parasite is naturally limited to the range of its insect
vectors, and local physical factors, such as temperature, hu-
midity, porosity of the soil, prevailing winds, and character
of the vegetation which may influence the development and
presence of the vector, will also indirectly influence the inci-
dence and intensity of filariasis in the human population.

O'Connor (1923) found a very low incidence of filariasis
and but a very few mosquitoes on some atolls of the Ellice
group having narrow, broken land strips and lacking depth of
bush favorable to Aerlr.t rarirgaUi.i. On other atolls with larger
land areas, the central lagoon reduced to a swamp, and cov-
ered with d?nse, dark bush, Aedrx raruiiatiis was obs?rved in
swarms throughout the day, and over 70 percent of the in-
habitants over 16 years of age showed some sign of filarial in-
fection. Again, a favorable high temperature with a suitable
amount of moisture is absolutely necessary for the development
of the parasite in the mosquito and for its transfer from the
mosquito to the human skin. The low incidence of infection
or absence of infection in many places, particularly in the in-
terior of China where proved mosquito carriers are present, is
attributed to cold or to dryness and high temperature (Feng,
1931). Thus, local conditions may have a marked influence on
the distribution of the infection within an endemic area.

While the mosquito is the sole vector of W iichrreria bancrofti,
as in malaria, the transmission is accomplished with much less
certainty and promptness in the case of filariasis. There is no
.multiplication of filaria larvae in the intermediate host. There
develops but one infective larva from each microfilaria sucked
in by the mosquito, whereas the malaria parasite multiplies
enormously and the chance of the infection being returned to
man is by thousands of times more likely. The actual number
of microfilariae sucked up by the mosquito is also relatively
small in comparison with the number of malarial organisms in
the blood which may be taken up in a similar manner. A high
mortality occurs among the microfilariae which actually reach
the .stomach of the mosquito.

O'Connor and Beatty (193S) estimated that about 3.5 per-
cent of the microfilariae ingested by mosquitoes die within 20
hours after an infective meal in the stomach blood clot, that a
very heavy mortality of larvae may occur after their arrival
in the thorax, and that many infected mosquitoes may die dur-
ing the first f^ew days after such feeding. Of ,").nOO wild Culex
fatiganx collected over a period of 12 consecutive months in St.

Croix, V. I., fr(un within and near dwellings occupied by per
sons with filariasis, only 2.3 percent were found to contain
fully "infective" larvae. These authors believe that the ])er-
centage of C. fatiflaii.s which actually transmit the infection to
man is much smaller, due to death of mosquitoes from various
causes such as strong winds, torrential rains, spiders, bats, liz-
ards and chickens. Chickens wandering into the laboratory
were observed to search and eagerly devour mosquitoes resting
in the darker corners of the room. It was also observed that
r. fali(/a)i.s readily feeds upon domestic fowl. It is probable
that many parasites are deposited on the skin or feathers of
birds and thus liecome lost.

Bancroftian filariasis char.'icteristically occurs in small, dense
ly populated and poorly .sanitated villages. It is particularly
common in the overcrowded dwellings of poor people, and the
incidence and morbidit.y in a given family ma.v be striking.
Infection is usually commoner in males than in females, which
difference in China is attributed to the custom among women
of wearing more clothes while sleeping at night, and thus ex-
posing less body surface to the attack of mosquitoes (Lee,
1926). The severity of the disease characteristically increases
with advancing age, thus indicating absence of any develop-
ment of immunit.Y in filarial infection. All races of mankind
appear to be equall.v susceptible. Differences noted, particu-
larly absence of infection or lighter infection among North
Americans and Europeans residing in the area are due to their
better sanitary conditions, better protection against mosquitoes,
and homes removed from the over crowded dwellings of the
native population. Better housing is always essential in control.

In view of the fact that the parasite is transmitted solely
through the bites of mosquitoes, its prevention is primarily
one of mosquito control, and measures taken against these
insects in the control of malaria and yellow fever are eciually
effective against infections with TTuchereria bancrofti. Culex
fatifiann is a domestic mosquito which breeds near dwellings
in cisterns, rain liarrels, discarded tin cans, sullage drains,
ditches, etc. Tight screens and gauze coverings will prevent
mosquito breeding in cisterns, vats and rain barrels. Discarded
pots, tins and other utensils should be buried or destroyed, and
drains arid ponds kept clear of vegetation in order to effect
proper mosquito control. All breeding places should receive
weekly treatment with larvicides. In the Oceanic Islands,
where Ai^des variegatus is the most important vector, attention
must be centered on discarded cocoanut husks and shells, natu-
ral and artificial cavities in trees, tin cans, and other possible
containers of clean water. O'Connor (1923) observed that the
Pacific rat makes breeding places for A. variegatus in trees by
gnawing and cutting young cocoa-pods. The pods then die,
become dry, and form hanging breeding places for the mos-
quito.

With modifications to meet local conditions, the methods ad-
vocated by O'Connor and Beatty (193S) to reduce Bancroftian
filariasis in Christiansted, St. Croix, might be effectively ap-
plied elsewhere. They include the following recommendations:

-4. The general measures adopted should be as follows:

1. The incidence of persons with microfilariae should be de-
termined at the same time for the whole population.

2. The percentage of infective mosquitoes should be deter-
mined in tlie same houses and outhouses, etc. The mosquito "in-
fective" incidence may be more valuable than the mierofilarial
incidence, partly because while some natives do not readily sub-
mit to having blood taken from them, yet when the reasons
are explained to them they rarely ob.iect to their mosquitoes
lieing collected. Furthermore, a person with microfilariae hav-
ing been infected in another locality may be in a place where
there are few or no mosquitoes and so will not be a serious
menace. On the other hand, the repe.'.ted finding of infected
mosquitoes is proof positive that one or more persons with
microfilariae is near l)y.

3. These studies might well be repeated aliout every 3 years.

B. In houses of high human and mosquito infectivity inci-
dence, the following local measures should be carried out:

1. The nature of filariasis, its transmission and prevention
should be completely and simply explained to the occupants of
the house where control measures are in.stituted.

2. Suitable containers for potable and other water supplies
should be adequately .screened with wire netting. Where con-
tainers are not suitable they should be replaced.

3. The use of the mosquito net should be demonstrated. (If
the occupants cannot afford them these should be provided from
public funds.)

4. The proper maintenance and us? of all screening should be
supervised at intervals by the existing sanitary officers.

5. When possible occupants should be encouraged to keep
fowls in their yards near the house.

6. The number of mosc|uitoes in the houses and the percentage
of these which are infective should be recorded from time to

319

time in order to evaluate the results of preventive measures.

7. Efforts to have adult mosquitoes killed daily by the in-
habitants wliile highly desirable will usually be found imprac-
ticable. This measure would be too expensive for government
maintenance, but where full cooperation is assured it should be
adopted to supplement the foregoing.

The control of filariasis in the Orient is complicated by the
presence of another filariid, quite recently discovered, which has
long been confused with IViichercria bancrofti. This species.
Microfilaria inalayi, was discovered in 1927 by Leichtenstein in
the Dutch East Indies. Leichtenstein had failed, after numer-
ous attempts, to infect Ciilex fatigans and other eulicine mos-
quitoes with microfilariae of the area, and noting the absence
of acute forms of the disease, although elepliantiasis of the leg
was common, it occurred to him that he might be dealing with
a new species of filaria. Brug (1927) examined Leichtenstein 's
material, found morphological characters distinct from Ban-
croftian microfilariae, and proposed the name Filaria malayi
for the parasite. Brug's observations have since been confirmed
by various workers, and the species now appears established on
morphological characters of the microfilariae and extensive epi-
demiologic studies, although the adult worms are yet to be
discovered.

Thus far. Microfilaria malayi appears to be strictly oriental
in geographic distribution. It is known to occur in the Fed-
erated Malay States, Sumatra, Java, Ceylon, parts of India,
Indo-China and in north-eastern Chekiang Province of China.
It is often the dominant species of a given region and occurs
typically in rural districts along river or forest settlements.
Elephantiasis of the feet and legs is typically associated with
J/, malayi infection. The genitals and upper extremities are
rarely involved as in Bancroftian filariasis. The microfilariae
show nocturnal periodicity, but do not disappear entirely from
the peripheral blood during daytime. Mosquitoes of the genus
Manxotiia, subgenus Maiisonioidcs, are the principal vectors,
particularly M. (Monsonioides) annulifera. These are noc-
turnal feeders and are most active during the evening from
7 p.m. to S p.m.

Recently, extensive studies have been made on the control of
filariasis in India, particularly in Travancore, where Microfilaria
malayi is chiefly concerned (Sweet and Pillai, 1937; Iyengar,
1938). It was demonstrated by these investigators that the
presence of a floating plant, Pistia stratioitcs, is essential for
tlie breeding of Maiismiia. The female mosquito does not or-
dinarily lay eggs except on the leaves of Pi.'<tia, and the larvae,
being structurally adapted to obtain their supply of oxygen
from the air cavities in the root, are not capable of living apart
from this particular plant.

In experimental areas the clearance of ponds and tanks of
Pixtia markedly reduced the incidence of Maiifioiiia mosquitoes
and checked further spread of the infection. Pistia plants can
be cheaply and effectively removed by hand. Here we have an
excellent example of the suppression of a mosquito-borne disease
by a strictly limited S])ecies control of the carrier.

2. ONCHOCERCIASIS

Onchocerciasis in man is caused by Onchocerca volviihi.<<
(Leuckart, 1893), the adult forms of which are characteris-
tically found in prominent, subcutaneous, fibromatous tumors.
The microfilariae aiipcar in large numbers in the skin, especial-
ly in the skin in the vicinity of the tumor, the eyes, the con-
.iuMctivao and the cornea, and in the central portion of the
tumor with the adult worms. They do not appear in the cir-
cnlation but may rarely occur in the deeper tissues and viscera
(Rodhain, 1937). When seen in fresh sections of the epidermis
or conjunctiva they are actively motile and possess no sheath.
Two types are clearly distinguished. It has been suggested
that the smaller forms with a more compact arrangement of
the nuclei may represent male, and the longer ones female
microfilariae.

It is believed that the tumor results from the irritation pro-
duced by the presence of the adult worms and the products
of their metabolism. Unencapsulnted adult worms have, how-
ever, been noted (Sharp, 1927; van den Berghe, 193li). The
microfilariae have been considered to be a cause of an erysipela
tons condition of the face and head and of disturbances in
vision, iritis, punctate keratitis and total lilindness. The part
tliat these microfilariae play in the production of these condi-
tions is not clear.

Onchocerciasis is very common along the west coast of Africa
from Sierre Leone to the Congo liasin and extending eastward
through the Congo into I'ganda, Anglo-Egyptian Sudan and
Kenya. It also occurs endemically in southern Mexico and
Guatemala upon the Pacific or southern slopes of the volcanic
ranges at altitudes between 2,000 and 4,500 feet (Caldernn,
1920). The parasite in Central America was discovered by
Robles in 191.5 and named Onchocerca cacculieiif: by Brumpt

in 1919, who considered the American form distinct since, in the
great majority of cases, the tumor was located upon the scalp or
in the region of the face, whereas the tumor in African cases
was generally found on the body. Further, the disease in America
was observed only in areas mainly inhabited by native Indians
and into which regions the negro, apparently, had never been
introduced. Later studies by Strong and associates (1934)
have shown that the Central American form cannot be sep-
arated from the African form on either morphological charac-
ters or on biological criteria. The two forms are now gen-
erally regarded as belonging to the same species, 0. volvulus.

Blackloek (1926) demonstrated that the black-fly Simulium
(lamnosum is particularly concerned in the transmission of
onchocerciasis throughout tropical Africa. S. ncavci, however,
is said to be the chief, if not the only carrier of the parasite
in the Lubilash-Sankuru region in the Province of Lusambo
(Kasai). S. metaUicum, S. caUidum and S. ochraceum are the
vectors in endemic regions of Mexico and Guatemala (Strong
et al, 1934). The development of the parasite in these flies
and its transmission to man are essentially the same as the
development and transmission of W uchercria bancrofti in and
liy mosquitoes.

The control of onchocerciasis in Africa is exceedingly diffi-
cult due to its widespread distribution and the general topog-
raplo' of the country, dense vegetation or forests and running
streams, ideal environments for the breeding of Simulium.
Vegetation is usually cleared only in the vicinity of the vil-
lages and plantations. This limited clearance of vegetation is
probably of little value in control since these flies are capable
of fl.ying great distances. The people are attacked by the flies
most frequently while defecating at the edges of streams (a
common and usual practice), while collecting water for drinking
jiurposes or while engaged in agricultural pursuits, rice, cotton
or coffee cultivation which bring them into the immediate
environment of the fly.

Measures of individual protection against the bites of these
flies, such as wearing of fly-proof clothing and masks, proper
screening of houses and bed nets, the use of smudges and re-
pellents, are to be recommended, but are usually not practical
and are rarely applied by native populations. It is obvious
that effective control of onchocerciasis rests in the eradication
of Simulium flies but, as yet, there is no practical method
known to destroy their eggs, larvae or pupae which abound
under stones in the swiftly-flowing streams of the endemic
areas.

In Central America attempts Imve been made to control the
human carriers which infect the flies. Surgical removal of the
tumors containing adult worms has been a public health proce-
dure of importance, and where a systematic attempt has been
made to eradicate the disease in sharply circumscribed areas,
the late of infection has been greatly reduced. It is recom-
mended (Strong et al, 1934) that, under local conditions as in
Guatemala, periodic microscopic examinations should be made
in each individual after operation to detect the number of
microfilariae which may persist and, if large numbers of micro-
filariae are present, the patient should be regarded as a dan-
gerous carrier and be isolated, or removed to a region where
Simiiliitm does not occur, until the parasites disappear.

Dracunculus medinensis
W. W. C.

Although the guinea worm, Dracunculus nicdini iisis, has
been known since ancient times nothing was understood of its
life cycle until Fedtschenko (1871) implicated Cyclops in its
transmission. Since that time various species of cyclops have
been infected experimentally and recently Moorthy (1938) has
given an adequate account of the developmental stages in this
liost. Leiper (1907) re])orted the experimental infection of a
monkey and the finding of two immature males, and recently
experiments with dogs (Issajev, 1934a; Moorthy and Sweet,
1936 & 1938) have made possible the adequate description of
the male (Moorthy, 1937) and added nmch to our knowledge
of all the stages in the definitive host. The researches of
Fairley and Listen (1924a), Fairley (1924), and others have
served to give a picture of the pathology and symptomatology
of dracontiasis and numerous and widely scattered publications
have given the present conception of its geographical distri-
bution, epidemiology, and control. In spite of numerous sug-
gestions no treatment of real value is yet known. Although the
extent of the studies on this parasite is impressive, much more
needs to be done to bring our knowledge even up to the level
of that of the other important human helminths.

Natural infections with worms identified as D. medinensis
have been reported from a number of mammals including dog,
horse, cattle, jackal, wolf, leopard, monkey, deer, baboon, rac-
coon, mink, and fox (Leiper, 1910; Turkhud. 1920; Chitwood,

320

in3;<). While some of those records niiiv he due to eoiit'usion
of elosoly rehited species, there is no reason to donlit th;it in
some ciises the worms actually were 1). mcdininsis. There is no
evidence, however, that any of these animals are si{;riilicant
reservoir hosts in the endemic areas. Infection in aniumls, liow
ever, might serve to spread this jiarasite into new areas as
suggested by its presence in animals in Chimi (Ilsii and Watt,
VXV.>.) and in the United States (Chitwood, 1!)33) where en-
demic cases in man have never been reported.
INJURY TO HOST

There appears to be no evidence that the guinea worm appro
ciably injures its host during tlu- developmental period in the
deep connective tissues. Just before the female worms reach
the skin they secrete toxins which produce general symptoms
such as urticaria, nausea, vomiting, diarrhoea, severe dys]Hiea,
and syncope. These symptoms disapjjoar after the worms have
established an opening through the skin. Later injury to the
host is produced by secondary infection and by tissue reactions
to the worms liefore and after their deatli. Severe inflammation
is produced if the worms are broken in the tissues and the
embryos freed. The iiresence of the guinea worms may also
produce permanent joint injuries (Pradhan, liiHO).

Tn endemic areas dracontiasis is often a medical and public
health jiroblem of great importance. Large numbers of people
are iru'apacitated for 3 to <i months of the year; severe sulier-
ing and occasionally death are produced; and the economic life
of the community is often severely disturbed. For example,
Moorthy (1932a) stated that iu certain villages in the endemic
areas of Mysore a large jjercentage of tlie people were more
or less completely incapacitated for ."i to li months of the year
and that outside labor had to be imported. The statements of
other authors indicate that this samp situation holds in the
enormous number of villages in various parts of India where
this parasite is endemic. Also over large areas of Tropical
Africa the guinea worm is a real scourge.

GEOGRAPHICAL DISTRIBUTION*

Dracontiasis is widely distributed in a number of parts of
Tropical Africa and is endemic over large areas of India. It
is also found in Arabia, Iran, Afganistan, and Russian Tur-
kestan. It is supposed to have been introduced into the West-
ern Honiisphere with slaves from the Gulf of Guinea. It was
formerly thought to have become endemic in Curacao, Demerara,
and Surinam but seems now to have disajipeared; it is only in
a limited region in the state of Bahia, Brazil, that it is still
endemic. There is other evidence that the guinea worm is not
easily spread to new regions. Although it has been constantly
introduced into the Dutch East Indies it apparently has never
been establislied (Brug, 1930) and no evidence was found of
endemic centers along the north coast of Africa and in southern
Europe.

In Africa are located the most widespread and perhaps the
worst endemic areas of guinea worm infection in the world.
In general it can be said that almost all the important endemic
centers in Africa are north of the equator and south of the
Tropic of Cancer. In West Africa they are in general scat
tered from Mauritania to Gabun, especially in Mauritania.
Senegal, Upper Volta, Ivory Coast, Gold Coast and Northern
Territories, Togo, Dahomey, Nigeiia, and Cameroon. East of
this region endemic areas are known especially East of Lake
Chad, over much of the southern part of the Anglo-Egyptian
Sudan and in Uganda.

In Arabia the guinea worm is present along the shore of
the Bed Sea and in some places in the interior; it is endemic
in certain jiarts of Russian Turkestan, Afganistan, and in Iran
it appears to be almost entirel.v limited to certain towns and
villages in the province of Laristan, wiiicli is located in the
.south on the Persian Gulf (Lindberg, 1930).

Next to Africa the real home of the guinea-worm is India.
Imjiortant endemic centers in this country are limited to the
western half of the peninsula, little infection being found east
of Delhi and the Central Provinces. In Rajputana and Central
India the infection exists almost everywhere except in a few
desert regions; in the Central Provinces it is prevalent in all
the districts except a few on the eastern side; in the Bombay
Presidency it is widely distributed except in the sea coast
area south of Bombay; in the iladras Presidency it is preva
lent except for a few districts on the western coast; in Hydera-
bad 9 out of 16 districts liave the infection; in Mysore it is
practically limited to one district in the north ; it is also pres-
ent but with lower incidence in the valle.v of the Indus and
the Northwest Frontier Provinces; elsewhere in western and
central India there are a few limited centers.

*Infortnation gathered by questionn.iires and suniiiied up in a recent
work by E, B. lIcKinley (]9;^5) suppleniented the numerous luiblica-
tions found in the lite ature on the distril)Ution of dracontiasis in vari-
ous parts of the wfirld. A personal communication from Dr. V. N.
Moortb\' gave ^the latest information on India.

'I'hcn' are certain general iioints of iiitori'st in regard to the
geogra|ihical distribution of dracontitisis. It extends from the
tropics in -Xfrica and southern liuiia well up into the tem-
perate zone in Russian Turkestan, Afgaiii.stan. .and the innth-
western frontier i)roviiK'es of India. Even where it is wide-
spread .as in tropical .\frica north of the e(iuator and in west-
ern and ccntr;il India, its distribution is very discontinnous, and
importtmt endemic centers are often separated by wide areas
where it is not present. In limited regions too its distribution
is very si)otted. In Mysore, for examide, the infection is al-
most entirely limited to the Chitaldrug district, and in this
district itself there w-as only a small iiroiiortion of infected
villages which are widely scattered (Moorthy, 193:ia). The
same spotted distribution has been noted by other authors in
the other endemic areas of India. The same type of distribution
has been noted by vari(uis workers in different parts of Africa,
where guinea worm villages may be close to others where the
parasite is absent. It has also been noted that in an infected
village itself only part of the families suffer. Even more sur-
prising is the point emphasized by Moorthy (1932a) and Trewn
(1937) that in infected families, where there appear to be no
differences in habits, some Individuals will remain entirely free
from infection. All these peculiarities of distribution suggest
that the factors involved in the dissemination of the guinea
worm are very complicated.

EPIDEMIOLOGY

In general it may be said that the guinea worm can only
spread where infected individuals wade or bathe in drinking
water in which Cyclops are present. While most of the endemic
areas are in hot countries there is no evidence that tempera-
ture per se is a determining factor. This parasite is chiefly
prevalent in regions where there is a low annual rainfall. This
seems to be related to the fact that in such regions the people,
during at least part of the year, are forced to depend for their
drinking water on open pools, wells, or cisterns in which the
population of Cyclops becomes concentrated. In a personal
communication Dr. V. N. Moorthy recently made the follow-
ing statement in regard to the distribution of dracontiasis in
India: "The most significant fact to note in this distribution
is that the intensity of infection appears to vary directly with
the scarcity of water supply during the season of infection.
In provinces like Bengal and Assam where there is a plentiful
supply of water all through the year dracontiasis hardly exists
at all." Roubaud (1913) and others have also pointed out
that in the forested regions of west equatorial Africa where
the rainfall is abundant, as the lower Ivory Coast and the
Congo Basin, guinea worm has not been observed.

A number of authors have noted a seasonal relation in guinea
worm infection. Since the development of the worms takes
about a year, the yearly period when the people are suffering
from the disease coincides with the conditions most favorable
for its transmission. In India the outbreaks are almost en-
tirely limited to the first half of the year with most of the
infection coming in March, April, and May. This is the driest
season just before the Monsoon. In Dahomey, Roubaud (1913)
found the disease most frequent also in the driest months of
the year which are from December to February. The same
author noted, however, that in the endemic areas of the Lake
Chad region it occurs almost entirely in the rainy season,
which is in the middle of winter. He explains this by the use
during this period of water from little cisterns and pools
which are temporarily filled. Davis (1931) lujted that epi-
demics of dracontiasis occurred in southern Sudan during the
rains from April to June. In Iran, Lindberg (193(3) found
the season of infection to be from March to August with the
maximum in June, which are the hottest months of the year
just after the rainy season. It is evident, therefore, that the
seasonal incidence of dracontiasis varies greatly in different
endemic areas and is related to the water supply of the people
and not to general climatic conditions.

Little significant information is available on the relation of
the distribution of the various species of cyclops to the epi-
demiology of dracontiasis. These copepods are widely dis-
tributed over the world and immerous species occur wherever
they are found. In general, therefore, it seems possible that in
most regions ivhere the guinea worm would be introduced and
where the human habits are favorable for its spread, suitable
intermediate hosts would be present. Only certain species of
cyclops can serve as intermediate hosts. Chatton (1918) tried
to infect four different species of Cyclops in Tunis with larvae
from introduced cases. One of these, Cyclops macrnrus, was en-
tirely refactory to infection. In three others, C. viridis, C.
prasiniis, and an undetermined species, the larvae were ingested
and penetrated into the body cavity but failed to develop al-
though they remained alive for from 40 to .10 days. In India,
Lindberg (193:"i) fouiul that C. multicolor dies quickly after

321

ingesting guinea noira larvae and noted no development after
7 days.

We know little also of the relation of the reactions of the
definitive host to this dissemination of this parasite. If any
immunity is produced bj' the presence of worms it must be
quickly lost after the completion of development because re-
peated infection of the same individual year after year is a
common phenomenon. Moorthy (lS32a) recorded that out of
a total of 1,363 patients suffering from draeontiasis 83 per-
cent gave histories of having suffered in previous years. He
also noted that certain individuals seem to be entirely lacking
in susceptibility to infection and escape the disease year after
year, although they live in the same houses and drink the same
water as those who become infected. He suggested from in
vitro studies that in such individuals there might be physiologi-
cal factors, such as hypo- or hyperchlorhydria, which would
prevent the freeing of the infective larvae from the cyclops in
the stomach or which would kill them before they could pene-
trate into the tissues.

As suggested above, the character of the water supply is
of the greatest importance in the dissemination of draeontiasis.
Infected individuals must have access to drinking water that
contains suitable species of Cyclops. Absence of this parasite
in people who obtain their water supply from rivers or
smaller streams can probably be attributed to the absence or
scarcity of the proper species of Cyclops (Lindberg, ISS.j).
Small open collections of water such as step wells, cisterns,
or small pools in which the people frequently wade or bathe
are chiefly implicated. For example, in the Gold Coast
surface collections of rain water and shallow open wells
are considered to be the sources of infection (Leiper, 1907) ;
in the upper Volta, village ponds and hollows made by the
natives in obtaining mud for building their huts (LeDentu,
1024) ; in the Lake Chad basin, temporary cisterns or pools
(Roubaud, 1913) ; in southern Sudan, shallow wells or drink-
ing pools (Davis, 1931); in Iran, cisterns of rain water
(birkehs) or washing basins in the mosques (Lindberg, 1936) ;
a,nd in India, the step wells and village pools (Turkhud, 1919;
Pradhan, 1930; Moorthy, 1932a: Lindberg, 1936). Such bodies
of water only become of considerable danger in spreading the
infection when the water is low and the Cyclops are present in
large numbers and concentrated near the surface (Turkhud,
1912; Pradhan, 1930; Lindberg, 193.i). This explains the sea-
sonal cycle of infection in India because the season of great-
est infection (March to May) is near the end of the dry sea-
son when the water is lowest. It also explains the greater
prevalence of guinea worms in those villages with the poorest
water supply. The epidemiological data makes clear the diffi-
culty that the guinea worm has in finding conditions in human
populations suitable for its spread and goes far to explain
the discontinuity of the endemic centers, the failure of the
disease to spread readily into new territory, and its spotted
distribution over the endemic areas. All these facts on epidem-
iology suggest obvious methods for control and indicate that
any serious attempt to apply control measures should bring
rapid and permanent results.

CONTROL

It is obvious that prophylaxis and control of draeontiasis in
the endemic areas can either deal with habits of the individual
or with community relations to the water supply. Boiling, filter-
ing, or even straining the drinking water through a cloth would
be effective in individual protection. The rapid extraction of
the gravid worms from infected individuals and their exclu-
sion from the water supply would help in preventing the in-
fection of the C3-clops. However, all the workers who have
considered the problem are in agreement that permanent con-
trol in an infected community can be achieved only by chang-
ing the water supply to eliminate sources of infection. Thus
Leiper (1907) pointed out that on the Gold Coast the fencing
of the pools, the building of parapets or covering the open
wells, and the digging of draw wells would permanently elimi-
nate the disease. Turkhud (1919) argued that the changing
of all step wells in the infected villages in India to draw
wells would save many times the cost of the pumps by eliminat-
ing the economic losses from the disease. Moorthy (1932b)
found that where this was done in the Chitaldrug "district of
Mysore great reduction and in some cases entire elimination
of the disease resulted.

Where for some reason it is not possible to change the coii-
struction of the wells or pools the employment of methods to
kill the Cyclops have been suggested. Such measures have to
be used repeatedly since they serve only to eliminate the Cy-
clops temporarily. A number of authors have experimented on
the use of chemicals to kill cyclops. Davis (1931) recom-
mended lime, either unslaeked or slacked, in proportions of 1
to 1,000. In fact in the previous year Pradhan (1930) had

already reported an extensive lield experiment in which the
use of lime (about 1 drachm per gallon of water) in 27 in-
fected step wells had reduced the incidence of guinea worm in
the people using them 21 to -l-j percent. Moorthy (1932b) re-
ported that when perchloron (3 lbs. per 100,000 gallons) in
combination with copper sulphate (1 lb. per 200,000 gallons)
was used in wells they could be rendered completely free of cy-
clops for about a month. He advocated the use of this method
during the infection period (March to June) as a good method
of reducing the number of cases in areas where permanent con-
trol methods could not be undertaken.

Several authors have suggested the "biological control" of
guinea worm infection by the introduction into the wells or
ponds of fish that feed on cyclops, but Moorthy and Sweet
(193fic) appear to have been the first to report on the success-
ful use of this method. They found a number of cases in
which people using wells containing certain species of small fish,
particularly of the genus Barbus, were entirely free from guinea
worm infection. This led to the development of methods for
raising and introducing fish into the step wells. Use of this
control method in 3.") infected villages in 1934 and 193-5 caused
complete elimination of draeontiasis in six and a marked reduc-
tion in four. Their results led to the conclusion that the use
of fish was not only cheaper but much more effective than chemi-
cal methods.

Finally it seems clear from all the evidence in the literature
that prospects for the control of draeontiasis are excellent in
any endemic area where a systematic effort can be made. It
is very encouraging that Moorthy and Sweet (1936b) were able
to report that from 1S29 to 1936, by the introduction of draw
wells, the use of chemicals, and the introduction of fish, dra-
eontiasis was entirely eliminated from all but 25 of 112 in-
fected villages in the Chitaldrug district of Mysore, India.

Enterobius vermicularis
E. B. C.

The human pinworm or seatworm, Enterobius rermiciilaris
(Linn., 17."iS) Leach, in Baird, 18.13, was one of the first of
the intestinal helminths to be described from man, a fact easily
understood since it comes to the exterior and there produces
local sj-mptoms which would lead to its discovery. According
to Schmidt, it was discussed by Hippocrates, Aristotle, Galen
and others under the name Ascaris, before Linnaeus gave it its
specific name.

E. vermicularis is apparently restricted to man. In view of
Cameron's (1929) study indicating that in primates one species
of Enterobius is restricted to hosts of one genus, reports of E.
vermiculari.<i from primates other than man must be regarded
with suspicion unless supported by unimpeachable evidence.
This parasite occurs in the intestine but is not limited in loca-
tion as are many other intestinal nematodes. It occurs, in va-
rious stages of development, from the lower ileum through the
rectum and gravid females migrate through the anus to the
perianal region to lay eggs.

SYMPTOMATOLOGY AND PATHOLOGY

Symptoms are extremely variable in nature and degree being
apparentlj' absent in some cases and severe in others. There is
mechanical stimulation and irritation of the gastrointestinal
tract, occasionally with nausea and vomiting, and of the ex-
ternal surfaces during migration, producing pruritus ani and
vulvae, in some cases apparently allergic in nature (Brady and
Wright, 1939). By transporting organisms during migrations,
the parasites may induce vaginitis and even peritonitis and may
cause the formation of cysts in the female genital tubes or in
the peritoneal cavity, with resulting irritation (summarized by
Africa, 1938). Probably there is slight eosinophilia. The role
in appendicitis is debatable (Bachman, 193.5; Driiner, 1921;
Penso, 1939; and others) but worms apparently may give rise
to the .syndrome of appendicitis without characteristic histo-
logical changes (Botsford, Hudson and Chamberlain, 1939).
Restlessness and others secondary effects in behaviorism, in-
cluding scholastic difficulties, feeling of shame and poor social
attitude, may be pronounced.

DIAGNOSIS

The most reliable method of diagnosis is by the microscopic
detection of eggs in scrapings made from the perianal region.
This technique has been standardized by the use of a cellophane-
tipped swab (Hall, 1937; Folan, 193"9), known as the NIH
(National Institute of Health) swab (Fig. 201) ; the cellophane
is detachable for mounting and examination under the micro-
scope. Swabs should be made during the night or first thing
in the morning, preferable on at least 7 days if first results
are negative.

322

ruiber st^pnf

*— Tmst tube

- Rubber band

v_y

Kig. 201.
N-I-H swab (National Institute of Health) for the detection of Ente-
robius infections.

T.Mii.K 11. — IiifiiUiicc of Jiiitcrbiiis vcrmiculan.'i
By use of various kinds of swabs and scrapers

Date

published Country

Population
group Race

Age

No.
e,\am.

No.
posi-
tive

posi-
tive

1886-

Germany

Children

W

Under IB 3,.")06

2,068

59

1925

Militia

W

Adult -too

76

19

1926-

U.S.S.R.

Various

\v

All 7,074

4,255

GO

1931

1933-

Sweden

.\svluni

w

? 60

42

70

1936

('liildrcii

w

Under 1.1 340

123

36

1905-

Finland

Various

w

All 2,7.13

81

3

1911

Children

w

Under 16 300

95

32

1935-

U.S.A.

Ment. hosp

.w

15-60 282

62

22

1937

Boys inst.

w

12-20 213

3

1.4

Boys inst.

N

J2-20 187

3

l.(>

Summary

1886-
1937

5 countries Various Mostly All 15,115 6,808 45
groups white

By use of NIH swab — Institutionalized persons

Date
pub-
lished

No. % Swabs
No. posi- posi- per
Locality Race Age Sex exam, tive tive person

U

nited Stata

1937

D. C.

N

14-20 F

23

0

0

1

W

14-20 F

4

0

0

1

1939-

40

Louisiana

W

6-14 MF

365

302

83

7

N

6-14 M

63

53

84

7

N

6-14 F

63

10

16

1

1939

Alabama

W

All M

384

317

S3

(2 or

W

All F

2.53

98

39

more)

1941

Georgia

w

Adults F

100

31

31

av. 2.9

w

Adults F

65

52

80

6

1941

D. C.

w

6-8 M

17

14

82

4

1941

Puerto Rico

■»

5-19 M

52

6

12

4

*

6-19 F

50

15

30

4

1940

Canada
Toronto W

2 14 MF

140

98

70

av. 3.7

Smnmary

1937-
1941

6 localities WN
N. America

All MF

1,579

996

63

1 to 7

Fig. 202.
Egg of Enterohiiis vermirularis.

EPIDEMIOLOGY

Critical investigations, based on examination of perianal
scrapings, have been made in European countries, in the United
States, including Puerto Rico, in Canada, and in the Philippines.
The results of these investigations are summarized in table 11.
These results show that examinations of 22,376 persons revealed
pinworm infections in 9,703 persons, or 43 percent.

Additional studies, differing in method or scope and not
shown in table 11, include .stool examination of 495 children of
preschool age in Brazil (Moniz de Aragao, 193S) ; E. venni-
ctdaris was found in 49 percent, an extremely high figure con-
sidering the method of diagnosis. In Spain, Darriba and de
Cardenas (1935), from examination of feces, anal scrapings,
finger nails and nasal mucus, found 11 of 46 children, or 34
percent, infected with pinworms; in Greece, Pandazis (1937)
reported pinworms in 28 percent of infants and 6 percent of
adults, apparently from fecal examination supplemented by
finger nail examination.

FACTORS INFLUENCING PREVALENCE

R.\cE. As noted previously, the Negro race has shown a
lower incidence than the white race. Although Sawitz, D'An-
toni, Rhude and Lob concluded from a small group of boys of
the same ages in institutions of similar environments that the
incidence was almost identical in the two races, the eonsideralily
lower incidence found in Negroes than in white persons in the
general population of Washington, D. C, is contrary to what
would be expected if environmental conditions are the deter-
mining factor. The significance of the racial factor deserves
further study; that many persons classed as Negroes in the
United States are mulattoes should be kept in mind, in this
connection. Of Interest are racial differences in the relative
frequency of pinworms in 2,317 appendices removed surgically;
the incidence was 2.88 percent for the white population, 10.04
percent for Indians of the United States, and 23.91 percent
for Eskimos and Aleutians.

Age appears significant only to the extent that in the general

By use of NIH swab — Nouinstitutionalized persons

Date

No.

%

Swabs

pub-

No.

posi- posi-

per

lished

Locality Race
United States

Age

Hex

exam.

tive t

ive

person

1937-

11 D. C. W

All

MF

2,895

1,202

42

(Usually

N

All

MF

1,099

142

13

2 to 4)

1939

Sample W

12-19

M

166

21

13

1

from va- N

12-19

M

137

0

4

1

rious parts W

12-19

M

198

40

20

av.4

of U.S.A. N

12-19

M

105

9

9

av.4

1940

Phila. W ?

To 12

?

144

36

25

1 to 3

1941

Florida W

Philippines

6-12

MF

438

71

16

1

1939

Manila W

Mostly

500

376

75

1

6-10

MF

Summary

1937-41 U.S.A. and WN
Philippines

All MF 5,682 1,903 33 1 to 4

'Mixed group of white, mulatto and Negro persons.

population the incidence is highest in children of school age,
next highest in those of preschool age, and lowest in adults
(Cram and Reardon, 1939; Chanco and Soriano, 1939). There
is evidence that the school is the determining factor in these
differences; the incidence in children of so-called "preschool"
age who attended nursery schools has been found as high as
that in older children (Table 12).

Sex. The incidence in males has usually been found slightly
higher and in an Alabama institution was much higher, but in
the Philippines was slightly lower, than in females. Consider-
ing both sex and age, Sawitz et al found the peak of infection
at 9 years; after that there was a drop in incidence in females,
probably correlated with stricter sanitary habits, whereas in
males the incidence remained relatively constant up to 15 years
of age.

The factor of crowding is important in the spread of pin-
worms. The familial nature of the infection has been empha-

323

si/.ed (Schmidt, IIIU; Loiitze, lilST); Wright and Cram, 11)37;
Hall and Cram, 193!)). From a study of about 300 piinvorm-
infected families in Washington, D. C, it was apparent that
multiple eases are the rule rather than the exeeption and that
frequently all the children of the family, and one or both par-
ents, may be infected. Bozicevich and Brady (1938) found a
correlation between the size of the family and the incidence
of Enterobiiis, easily explained in that the larger the number of
persons in a family, the more chance there is for introduction
of the infection into the household and, once introduced, the
easier its spread, the infection increasing in a geometrical, not
an arithmetrical rate. Under institutional conditions Sawitz
et al found the incidence of infection much lower among chil-
dren occupying rooms with one or two beds than where larger
groups were quartered in dormitories. Families with pinworm
infections are found most numerous in older, comparatively
congested residential sections but are by no means confined to
those sections (Cram and Reardon, 1939); the social-economic
status is not limited to any one level.

T.\BLE 12. — liwicJeticc of Enterobiiis vermicidaris according to
age and race of children in camps and iiiirxirii sclioolt:.

Reported by

Waxhington. D. C.
Race Age

Xum- % Swabs
ber posi- per
.Sex exam, five person

Bozicevich White' 6-18 M 230 31 1

Bozicevich & Bradv White' 618 M 504 57 2 4

Cram White (Jewish)' 6-12 MF 147 25 4

Negro" 6-12 MF 63 21 4

Ciam & Nolan White" 2- 5 MF 91 -55 av. 9

Cram White"' 2- 5 MF 62 52 4

Negro' 2- 5 MF 68 ^19 4 _

'Camps. "Private nursery school. 'Public nursery schools.

CONTROI.

Control of pinworm infection is extremely difficult. The
number of eggs deposited may be enormous, one worm being
capable of producing from 5,000 to 17,000 eggs (Reardon,
1938), and the time of development of eggs on the skin of the
perianal region is short, as little as 6 hours. The infected
individual may contaminate the hands while scratching or when
using the toilet and subsequently carry the eggs to the month
or may contaminate other objects. Eggs which fall off of the
person develop more slowly, depending on temperature and
humidity; they can pass through cloth and there is considerable
evidence that airborne infection is a possiliility (Lentze, 1932;
Oleinikov, 1929; Nolan and Reardon, 1939; Sondak, 1935).
In households and schools with infected members pinworm eggs
have been found in dust from a large variety of locations and
objects at various levels. The eggs may float on the surface
of water and a certain proportion would therefore remain on
the sides of wash bowls, bath tubs, laundry tubs and similar
containers when they are emptied.

The eggs are very resistant to i)h3-sical and chemical agents.
Temperature and humidity influence the length of their sur
vival. Lentze (1935) found that a temperature of 55° C. and
above killed the eggs in a few seconds; at the optimum tempera-
ture (36° to 37° C.) on a damp base, as on the human skin,
especially under the nails, eggs survived for about 10 days.
Jones and Jacobs found that temperatures above 28° C, with
humidities below 50 percent, detinitely aft'ect the eggs within
24 hours; less than 10 percent of eggs survived after 2 to 3
hours and none survived after 16 hours at a temperature of 3))°
to 37° C. and relative humidity of 38 to 41 percent. On the
other hand, at lower temperatures, 20° to 24%° C, and higher
humidity, 62 to 91 percent, 30 percent of eggs survived 6 days;
on water at 3° to 5° C. a maximum of 93 percent survived 18
days. According to Sondak (1935), eggs were still viable after
drying at room temperatures averaging 10° to 12° C. for 3
weeks but not viable after 35 days. Exposure of eggs to mea-
sured quantities of monochromatic ultraviolet radiation (Hol-
laender, Jones and Jacobs, 1941 ; Jones, Hollaender and Jacobs,
1941) showed an increased sensitivity of the eggs at wave-
lengths below 2400A. As regards the effect of chemicals, Son
dak (1935) found that eggs were not killed by formalin in
strengths of 1, 2, 5, and 10 percent; by corrosive sublimate
1:1,000; by saturated solution of corrosive sublimate and cop-
per (eupric sulphate) ; by 5 percent antif ormin ; by 1 and 2
percent solutions of carbolic acid or by 1, 2, and 5 percent
lysol solutions, but they were killed by 5 percent carbolic acid
and by 10 percent lysol.

Because of the large numbers of eggs scattered by an infected
individual and because of the resistance of the eggs, hygienic
measures alone can not be relied upon to control the spread of

pinworm infection. This was pointed out by Wright and Cram
(1937) and was given a practical demonstration by D'Antoni
and Sawitz (1940) who put in force a vigorous cleanliness pro-
gram for (i weeks in one of the institutions studied by them;
at the end of that period swab examination showed an increase
from 38 percent to 51 percent in incidence of pinworms. The
greatust promise for control lies in medicinal treatment admin-
istered over a period which is sufficiently long to cover the
period of survival of eggs in the surroundings, tlms preventing
reinfection of the individual.

Bibliography

THE HOOKWORMS

ACKERT, J. E. 1924. — Notes on the long.nity and infectivity of
hookworm larvae. Am. J. Hyg., v. 4(3) :222-225.

AcKERT, J. E. and Payne, F. K. 1923. — Investigations on the
control of hookworm disease. XII. Studies on the occur-
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1922b. — Idem. IX. On the position of the infective

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1922c. — Idem. X. Experiments on the length of life
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1923a. — Idem. XIX. ObservatioTis on the completion
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1923b. — Idem. XXII. Further obseivations on the
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1923c. — Idem. XXIII. Experiments on the factors
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Babrmanx, G. 1917a. — Eine einfache Methode zur Auffindung
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Cakk, H. p. 1926. — Observations upon hookworm disease in
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Chandler, A. C. 1925. — The migration of hookworm larvae lu
soil. Indian Med. Gaz., v. 60(3) :105-108.

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1926. — Idem. Part V. Tea estates of Assam and Ben-
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324

C'OKT, \V. W. :iiul c-ii-Wdikcis. !lli:i: l!lL>."i.— liivrstig:iti(iMs cm the
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CoRT, \V. W., KiLEY, W. A. and P.\yne, G. C. 192;!.— Idem.
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325

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326

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DRACXINCULUS MEDINENSIS

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TRICHINULLA SPIRALIS

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trichinosis epidemic of sixty four eases. J. Am. Med.

Assoc, V. 110:1434-1436, 2 figs.
Gbigbr, J. C. and Hobmaier, M. 1939. — Trichinelliasis and

carnivorous mammals (Bears). Calif. & Western Med., v.

51(4):249-250.

Glazier, W. C. W. 1881.— Report on trichinae and trichinosis.
Prepared under the direction of the Supervising Surgeon-
General (U. S. Marine Hospital Service). 212 pp., 87
figs. Washington.

Hall, M. C. 1937a.— Studies on Trichinosis. III. The com-
plex clinical picture of trichinosis and the diagnosis of the
disease. Pub. Health Rpts., U. S. Pub. Health Service, v.
52(18) :539-551.

1937b.— Idem, IV. The role of the garbage-fed hog
in the production of human trichinosis. Ibid., v. 52(27):
S37-886, 1 fig.

1938a. — Idem, VII. The past and present status of
trichinosis in the United States, and the indicated control
measures. Ibid., v. 53(33) :1472-1486.

1938b. — Idem, VI. Epidemiological aspects of trichi-
nosis in the United States as indicated by an examination
of 1,000 diaphragms for trichinae. Ibid., v. 53(26) :1086-
1150, 1 fig.

Hall, M. C. and Collins, B. J. 1937. — Studies on trichinosis.

I. The incidence of trichinosis as indicated by post-mortem

examinations of 300 diaphragms. Pub. Health Rpts., U. S.

Pub. Health Service, v. 52(16) :468-490.
Kaufman, R. E. 1940. — Trichiniasis: Clinical considerations.

Ann. Int. Med., v. 13(8) :1433-1460.
Kerr, K. B. 1940.— Public Health Aspects of the trichinosis

problem in the South. South. Med. J., v. 33(5) :511-516.

329

Kerk, ii. B., Jacobs, L. and Cuvillier, E. Studies on trichi-
nosis. XIII. The incidence of human infection with
trichinae as indicated by post-mortem examination of 3,000
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ice, v..j6(16) : 836-8.3.").

LiCHTERMAN, A. and Kleeman, I. 1939. — Detection of Trichi-
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McCoy, 0. R. 1932. — Experimental trieliiniasis infections in
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Magath, T. B. 1937. — Encysted trichinae. Their incidence in
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Matoff, K. 1936. — Bei Taulien auf entcralcm Wege erzengtc
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1938. — Zur Frage der Muskeltrichinellose beim Ge-
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Mauss, E. A. 1940. — Transmission of immunity to TrichincVa
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1937b. — Recherches experimentales sur la trichinose

des volailles et des vertebres a sang froid. Ibid: 440-447.
1940. — Le role de I'avitaminose dans 1 'infestation du

pigeon par le Taenia echinococciis (les pigeons ages sont-ils

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1916. — Effects of refrigeration upon larvae of Trichi-

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1936. — Ueber das Vorkommen pranatalen Trichinenii-
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1938. — Prevalence of trichinosis in the United States.
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1939b. — Idem. IX. The part of the veterinary pro-
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1940. — Idem. XIV. A survey of municipal garbage
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1941. — Idem. IX. The familial nature of pinworm
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330

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Lentze, F. a. 1932. — Febcr die Verbreitung von Spul-und
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193.5. — Zur Biologic des Oxyuris vermicularis. Cen
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Leuckart, K. G. F. R. 1868. — Die menschlichen Parasiten and
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1939.— Idem (Abstract). Trop. Dis. Bull., v. 36(7):
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1941. — Incidence of Endamoeba histolytica and intes-
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Sawitz, W., D'Antoni, J. S., Rhude, K. and Lob, S. 1940.—
Studies on the epidemiology of oxyuriasis. South. Med. J.
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Diagnostizierung der Oxyuriasis gibt es und welche ist
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Smith, W. H. Y., Gill, D. G. and McAlpine, J. G. 1939.—
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331

CHAPTER IX

ANTHELMINTIC MEDICATION FOR NEMIC
DISEASE OF DOMESTIC ANIMALS AND MAN

WILLARD H. WRIGHT, Washington, D. C.

and

PAUL D. HARWOOD, Ashland, Ohio

History

The use of remedies for the removal of worms dates far
back into aiiticiuity. As primitive man became aware of his
intestinal parasites by observing the passage of such a large
nematode as Ascaris or the proglottids of large cestodes such
as Taenia saginata or Taenia solium, he no doubt sought from
his limited armamentarium weapons for the removal of these
undesirable boarders. Since most of his medicines were de-
rived from the plants found in his circumscribed environment,
he turned to them for his worm treatments. He chose so well
that derivatives of some of these plants in one form or another
are still in use as anthelmintics. Thus male fern, a frequently
employed taeniafuge, was known to the early Greek physicians,
if not before them; Jerusalem Oak, Chcnopoditim anthdininti-
cuin, was used as a worm remedy by the North American In
dians; and a decoction of the leaves of Mallotus pliilippinrnsis.
from which the taeniafuge kamala is obtained, was employed
by the early Ethiopians.

Developments in anthelmintic medication have been divided
aptly into three epochs: The first, comprising centuries of un-
critical empiricism; the second, comprising several decades of
critical empiricism; and the third and last, comprising a rela-
tively few years of critical experimentation.

The first epoch marked the period of primitive groping and
the centuries of acceptance of its empirical findings without
any marked advance being registered in the field.

The second epoch followed the discovery of the Old World
hookworm, Ancitlostoma duodenale, by Dubiui in 1843, and the
gradual uufoldment of knowledge regarding the importance of
the parasite and the recognition of ancylostomiasis as a disease
entity. Gricsingcr's association of the hookworm with Egyp-
tian chlorosis, Wucherer's work which showed its relation to
tropical anemia in Brazil and Perroncito's discovery of hook-
worm as the cause of the St. Gothard tunnel disease stimulated
interest in the hookworm problem. These discoveries, followed
by Sonsino's classical observations, demonstrated the need for
specific therapeusis and prepared the way for the development
of a number of anthelmintics which, if not thoroughly efficient,
provided useful treatments; these held their place for a period
of four decades and until the epoch of critical testing provided
more specific and more effective drugs. The year 1881 marked
Perroncito's proposal of male fern as a hookworm treatni/nt.
the introduction by Bozzolo of thymol, and Baumler's unfavor-
able report on oil of chenopodium for this purpose. Male fern
had only limited use as a hookworm treatment but thymol
proved to have considerable efficacy and enjoyed a long vogue.
In fact, the latter drug was used more extensively than any
other until Schiiffner and Verwoort reintroduced oil of cheno-
podium in 1913 and showed that Baumler's conclusions, which
were apparently based on the treatment of only one ease, were
erroneous. In the meantime, Bentley in 1904 reported his
findings with betanaphthol and advocated its use In hookworm
disease.

In 1905 Herman introduced a mixture of chloroform, eucalyp-
tus and castor oil as a treatment for ancylostomiasis in miners
at Mons, Belgium. The mixture was later modified by Phillips
and others and was subsequently employed extensively in the
treatment of hookworm disease in many parts of the world.
Schultz later found chloroform to be the active ingredient of
Herman's Mixture and reported the drug to be effective against
hookworms in the dog.

In the meantime progress was being made also in the field of
anthelmintics for veterinary use. As early as 1894 Perroncito
and Bosso discovered the efficacy of carbon disulphide for the
removal of bots, Gasternphihis spp., from the horse. In fact,
the first critical testing of anthelmintics was actually carried
out by Grassi and Calandruccio in 1884 and 188.5 and by Per-
roncito in 1885 and 1886 in establishing the value of male fern
for the destruction of liver flukes in sheep by post-mortem
examination of treated animals. However, this method of test-
ing found no further advocates for a quarter of a century.

A work of far reaching economic importance was the dis-
covery by Hutcheon in South Africa in 1891 of the efficacy of
copper sulphate solution for the removal of the common sheep

stonuich worm. Hai iiioiicJius niniui-lus. The wireworm remedy
of copper sulphate and sodium arseuite worked out by Theiler
in 1912 and Veglia in 1920 has also been used extensively in
South Africa and was an important contribution to anthel-
mintic therapy. In the United States, Lewis and Guberlet
added a tobacco infusion to the copper sulphate solution ; Lam-
son introduced nicotine sulphate solution; and Curtice com-
bined copper sulphate and nicotine sulphate into the "Cu-Nic"
solutiou with an increase in efficacy against the common stom-
ach worm and some other gastrointestinal parasites of rumi-
nants. In general, however, it may be said that the four dec-
ades of critical empiricism produced less progress in the de-
velopment of veterinary anthelmintics than in anthelmintics
for human use. It was not until 1915 that substantial progres.";
was achieved in the former field.

The year 1915 marked the practical beginning of the epoch
of the critical testing of anthelmintics. Hall laid down the
basic principles of this method and together with his associates,
including Foster, .\very, Snead, Wolf, Wilson, Wigdor and
Shillinger, checked critically the efficacy of empirical anthel-
mintics and developed new compounds of far reaching and
fundamental importance in both human and veterinary medi
cine.

The method which Hall adopted was to administer known
doses of drugs to test animals of various species, collect all
worms passed in the feces for a given period of time, identify
and count these worms, sacrifice the test animals and make
thorough post-morten examinations with the recovery, the iden-
tification and the counting of all worms remaining. This
method gave specific information concerning the number of
worms present, the number removed and the number left after
treatment and provided an accurate index concerning the effi-
cac.v of the drug tested. The method was relatively ponderous
and time consuming compared to the favored process of drop
ping ascarids or some other easily collected invertebrate into
solutions of drugs and calculating the anthelmintic efficacy of
the drug by observing the ultimate fate of the animal in the
solution. However, critical testing developed precise informa-
tion whereas in vitro tests were often entirel.v valueless.

The method of critical testing was of particular value in
veterinary medicine. It enabled an accurate assay of drugs
whose value was often more traditional than real, and its use
confirmed in many cases the efficacy- of empirically selected
anthelmintics and enabled dependable information to be ob-
tained concerning their therapeutic dose rate, their margin of
safety, the contraindications for their use and the type and
mode of purgation most suitable to promote the efficacy of the
drug and to protect the patient.

Many of the tests, especiall.v those on dogs, provided results
which were applicable with but slight modification to human
medicine. The outstanding discovery in this connection was
that by Hall in 1921 of the value of carbou tetrachloride for
the removal of hookworms from the dog. Hal! immediately
suggested the use of the drug in the treatment of hnmai] hoo!<
worm disease, a suggestion which was forthwith adopted by
a number of investigators particularly Laml)ert and other
physicians on the staff of the International Health Board. It
was soon found that the efficacy of carbon tetrachloride ex-
ceeded that of all other drugs in this condition and it was
adopted practicall.y as a standard treatment and used in mil-
lions of cases in various parts of the world. Another discovery
less spectacular but actually of greater importance was that
of Hall and Shillinger in 1925 of the value of tetrachlorethy-
lene for the removal of hookworms. Because of its greater
safety and the fact that it produces little or no hepatic or
renal damage, tetrachloreth.vlene is replacing carbou tetra-
chloride in human ancylostomiasis and for many parasitic in-
fections of domesticated animals.

Using the method of critical testing, Hall and his coworkers
established or confirmed the value of many anthelmintics in-
cluding copper sulphate for Ilaenwiiclnis contortus, oil of
chenopodium for ascarids in dogs and swine and for strongyles,
cyclicostomes, and pinworms in horses; carbon disulphide for
bots and ascarids in equines; carbon tetrachloride for stomach
worms and other worms in sheep and for a-scarids and

332

Stroiifrvli's ill liorsrs: tctr:irlili)ii'tlivK'iio for iM'rtaiii slircp p.-ira-
sites; and other troatnicnts.

The method devised li.v Hall has since been widely adopted
and employed by nnini'rous iiivestiRatois in establishing the
value of many other anthelmiTitics.

Except in the rase of eondenmed eriniinals who will volun-
tarily submit to tist, till' nu'thod of eritieal testing cannot be
used in man. t)ther metliods have necessarily been adopted for
evaluating the ei^cacy of anthelmintics for nematode infections
in this host. One of these, the use of a so-called standard
treatment, was based on the administration of the test drug,
the screening of the stools an<l the recovery of worms, followed
witliin a suitable period by the administration of the standard
treatment, the relative efTicacy of which was known. Worms
passed following this treatment were collected and counted and
a comparison between .the results obtained with botli treatments
enabled the investigator to arrive at sonu' evaluation of the
efficac.v of the test drug. While the method necessarily had its
limitations, its use led to findings of value particularly when
applied to relatively large numbers of persons to obviate the
margin of error in individual differences. Under these con-
ditions, the standard treatment method was used effectively by
Caius and Mliaskar in their extensive investigations in connec-
tion with the hookwtirm in.jury in the Madr'as Presidency and
similarly by Darling, Rarlicr, Hackett, Smillie and other physi
cians on the staff of the International Health Board in their
far-flung search for the most effective treatment for hookworm
disease.

Following the discovery by Stoll in 1!)2.3 and Stoll and
Hausheer in lS)2(i of a method of counting nematode ova in
feces with some degree of accuracy, the Stoll count has been
used extensively in evaluating anthelmintic treatments in man.
With due regard for the limitations imposed upon it by the
varying factors involved, the method has been of marked value
in gauging the efflciency of certain anthelmintics particularly
those designed for the treatment of Asearin and hookworm in
fections in man. Because of its greater reliability and its ease
of application, this method has replaced largely the use of the
standaid treatment method. Hall and .\ugustiiie in 1920 sup-
plemented the Stoll count with a count of worms passed fol
lowing treatment in evaluating certain anthelmintic treatments
for man.

At times it is protit.-ible to employ several different methods
of research. Lamson and his associates used in vitro testing,
critical testing and the Stoll egg-counting method in their ex-
tensive investigations into the anthelmintic value of the alkyl
h.vdroxy benzenes and related compounds. In this case, com-
parable in vitro tests on Jscaris linnbriroides with large num
bcrs of compounds gave leads which could be developed further
by the employment of other methods.

Mode of Action

Little information is available concerning the manner in
which anthelmintics act on worms. An extensive use of in i'i(ro
tests in this field of investigation may yield some data but,
since it is difficult, if not impossible, to simulate in vitro the
environmental conditions of the parasite in its natural host, re-
sults obtained in this manner must be used with great caution.
The physiology of nematodes in itself is an almost totallj' un-
explored field. In the absence of precise knowledge concerning
the life processes of a parasite, it is not likely that we shall
know in what manner toxins act on the organism. The meager
information which is available throws little light on the prob-
lem in hand.

According to their mode of action, anthelmintics may be
divided roughly into the following groups:

1. Narcotizing or paralyzing agents.

2. Compounds exhibiting a destructive action on protein.

•S. Compounds containing enzymes capable of digesting nem-
atode tissues.
4. Anthelmintics of unknow^n action.

The first group contains such well known anthelmintics as
santonin and the chlorinated hydrocarbons. Worms eliminated
following the administration of these anthelmintics may ex
hibit more or less movement. This characteristic is so marked
with santonin that earlier authors were led to describe this
drug as a vermifuge, a term which originally designated an
anthelmintic that irritated the parasites and drove them into
the colon where they might be removed with a brisk purge.
(Trendelenburg, 191.T.) However, as Lo Monaco demonstrated
in ISilfi and as Chopra and Chandler (1928) have pointed out,
santonin is highly toxic to ascarids in vitro if the test solutions
are properly prepared. If santonin is partially dissolved in
suitable quantities of normal liexane, a chemical which in it-
self is innocuous, the drug causes in vitro successive stages of

sliiiiiil.-ition and profound paralysis. Therefore, it is now con-
sidered that .santonin |iarlially paralyzes the jiarasites, which
in that condition are unable to maintain their position in the
alimentary canal. The prompt elimination of the parasites by
the action of a pnrgalivi- may increase the efficacy of santonin
as shown by Morris and Martin (li):U) and by others.

The chlorinated hydrocarbons contain several well known
compounds which exert an anesthetic action on worms. In vitro
the parasites gradually lose their motility and, if exposure to
the drug is continued after iinmotility sets in, the parasite may
be killed. However, if removed from the solution promptly,
it may recover. The authors have observed hookworms and
a.scarids moving feebly when removed from dogs with drugs
belonging to this series.

On the other hand, oil of chenopodium belonging in the
first group apparently has a paralyzing action on the mus-
culature, an effect which almost always results in the death of
the nematode.

The largi' group of hydroxy benzenes are examples of those
aiithelinintics in the second group. If solutions of egg albumin
are treated with these compounds, the iiroteins are promptly
precipitated. With the more water soluble coniponnds of this
series, such as phenol, the preeijiitation is relatively com-
plete; with comjiounds such as thymol and hexylresorcinol, the
precipitation is partial; while the extremely" insoluble com-
pounds precipitate only small quantities of the protein. In
vitro, he.xylresorcinol exerts a searing effect on the cuticle of
A.'icaris liimbricoidef!. resulting in the destruction of tissue; if
the exposure is closely controlled, blisters may be formed. In
solutions of hydro-xy benzenes which are not quickly fatal,
Ascaris exhibits a marked stimulation of activity greater than
that observed in solutions of santonin or of the halogenated
hydrocarbons. Since Lamson and Ward (1932) have described
a blistered condition of the cuticle of ascarids removed from
patients treated with hexylresorcinol, tin. mode of action in
VIVO may be identical with the action observed in vitro.

In connection with the third group, Robbins (1930) has
shown that the anthelmintic activity of leche de higueron, the
sap of the Central and South American fig tree, Ficiis laiiri-
folia, is correlated with the presence of a proteolytic enzyme,
which he has named "ficiii." Asenjo (1940) has shown re-
cently that the destructive effect of fresh pineapple .juice on
Ascnris liimbriroi/lrx in vitro is probably associated with the
action of the proteolytic enzyme, bromelin. However, there is
no evidence as yet that the above-mentioned .jiiice has any an-
thelmintic value.

The fourth group probably includes the ma.jority of anthel-
mintics. Any comments regarding the mode of action of these
drugs would be speculative for the most part. For instance,
we do not know how trivalent antimony compounds act on
somatic nematode parasites, although in the case of "Fouadiu"
the action of the drug is cumulative on iJirofilaria immitis and
the adult worms succumb very gradually. Some observations
of the senior author seemed to indicate that sterilization of the
adult female worms is due to fatty degeneration and necrosis
of the reproductive cells of the ovary and perhaps the drug
acts similarly on the somatoplasm.

Little is known concerning the nature of the anthelmintic
activity of various dyes. Gentian violet stains the tissue of
such nematodes as Strong/iloidcs and Enterobinx. against which
it is effective. In Enterobiii.i passed following treatment, the
cuticle is usually slightly stained, the digestive tract more so,
and the reproductive organs, particularly in the female, are
intensely stained. The dye no doubt has a cumulative action
since some stained gravid female pinworms will migrate in
the early stages of treatment. Furthermore, the prolonged
course of treatment necessary to eradicate infections with both
of these nematodes supports the view that the anthelmintic is
not one of the contact type.

Similarly, worms eliminated following the administration
of phenothiazine are stained reddish, but there is little reason
for thinking that the action of this drug is in anyway cumula-
tive, as prolonged treatment seems to be relatively less effective
than a single large dose. Many worms eliminated following
treatment with this drug are alive and move feebly, a circum-
stance which suggests that phenothiazine should be classed
with the narcotics and para].yzants.

The manner in which anthelmintics reach the tissues of the
parasite is as little known as is the action of drugs on these
tissues. One assumption has been that nematode parasites with
their well developed digestive tract ingest the anthelmintic in
solution with the food and absorption therefore takes place
from the oesophagus or through the cells lining the wall of
the intestine. However, evidence for such a hypothesis is not
convincing. For instance. Well's (1931) striking demonstra-
tion of the blood sucking proclivities of the dog hookworm has
shown that the parasite may take up as much as 0.S4 cc. of the

333

host's blood in 24 hours. The blood passes rapidly through the
digestive tract and apparently is not subjected to any material
amount of digestion. Consequently, the worm probably uses
as food diffusible substances in the plasma. In spite of the
marked diffusibility of carbon tetrachloride, the drug has
little or no action on hookworms when injected intravenously.
Wright and Underwood (1934) cite work with Bozicevieh in
which repeated intravenous injections of carbon tetrachloride
failed to have any effect on the microfilariae or adults of
Dirofilaria immiiis. While it is probable that this parasite
takes only a limited amount of nourishment orally because of
the atrophied digestive tract, yet it is bathed continuously in
the blood plasma. Even under these conditions of intimate
contact, the anthelmintic had no effect.

The studies of Mueller (1929) indicated that carbon tetra-
chloride penetrated the cuticle of Ascaris and was not taken in
through the digestive tract. Mueller believed that fat soluble
compounds such as chloroform and carbon tetrachloride exert
an anthelmintic effect by reason of their action on the fat
content of the muscle cells.

Brown (1937) has reported the results of some ingenious
experiments designed to ascertain the manner in which certain
anthelmintics reach the tissues of Ascaris lumbricoidcs. While
the results were in part inconclusive because of the difficulty
of handling worms without injuring them traumatically, the
evidence seemed to indicate that oil of chenopodium and car-
bon tetrachloride in solution are absorbed through the body
wall. Brown was able to show that Ascaris will ingest solutions
of carbon tetrachloride in mineral oil but will refuse to ingest
dilute solutions of chenopodium. Brown did not believe that
the drugs tested acted directly on the nervous system of the
parasite even when injected in the region of the nerve ring.

The experiments of Strong (1918), Lambert (1923), Hall
and Sliillinger (192.")) and Fernan-Nihiez (1927) may be cited
as bearing on this problem. Strong injected oil of chenopo-
dium intramuscularly for the removal of whipworms without
success. Lambert was equally unsuccessful with intramuscular
injections in two eases in man but obtained better results in a
third case. However, when used intravenously, the drug had
a marked vennicidal action again.st Trichiiris, little action on
Ascaris and none on hookworms. Hall and Shillinger obtained
very indift'erent results on dogs but Fernan Nunez reported
marked success against Trichiiris in man with intramuscular
and intravenous injections. The manner in which whipworms
derive their nourishment is still a deliatable point although
Garin (1913) was able to demonstrate lilood in th^> intestinal
contents and Schwartz (1921) reported a hemolysin from Tri-
chiiris viilpis. The evidence from the above-mentioned experi-
ments would seem to indicate, however, that the drug was
possibly absorbed through the digestive tract in view of the
little likelihood that under these conditions it would have been
in adjacent tissues in sufficient concentrations to have been
absorbed through the cuticle. Recently Trum (1938) found
that oil of chenopodium injected intravenously was very toxic
for horses, but had very little effect on the blood sucking
strongyles present in these animals.

Correlation Between Chemical Structure and
Anthelmintic Efficacy

Compounds comprising the group of cft'ective anthelmintics
and those for which some anthelmintic efficacy has been re-
ported are associated with such widely divergent chemical
groups that no general correlations can be drawn between aii-
thelmic efficacy and chemical composition. As a rule, anthel
mintics are very specific in their action, exhibiting their opti-
mum efficacy against one species of parasite or at best against
closely allied species of parasites. Drugs specific for the re-
moval of nematodes are seldom effective for the removal of
cestodes. The one glaring exception to this rule is carbon tet-
rachloride which is a fairly effective treatment for Taenia and
Diphyllobnthriiim lafiim infections of man although of little or
no value against other cestodes. On the contrary, there is no
taeniafuge which is effective for the removal of nematode
parasites.

The specificity of anthelmintics is conditioned not only by
the anatomy and physiology of the parasite but also in part by
the anatomy and physiology of the host. In this connection,
drugs effective for the removal of strongylid parasites from
carnivores fail to a great extent when employed against simi-
lar parasites of ruminants. Such drugs are frequently held
in the rumen with a resultant dissipation of their action long
before they reach the object of their attack farther down in
the complicated digestive tract. On the other hand, the
anthelmintic value of copper sulphate solution against Hacmon-
chus contorUis in ruminants is associated with the peculiar
stimulus which the drug exerts in bringing about the closure

of the oesophageal groove thus permitting the solution to be
diverted directly into the abomasum.

The optimum action of two effective drugs is often lost or
markedly reduced when such drugs are combined in a single
dose. Frequent efforts have been made to develop a single
method of treatment which would be effective against both in-
testinal nematodes and cestodes. These efforts have nearly
always resulted in failure. In such cases, drugs -which are
effective against nematodes and cestodes, respectively, lose
much of their efficacy when combined. Fnder these varied cir-
cumstances, attempts to correlate anthelmintic efficacy and
chemical structure must be made on the basis of a selection of
closely related compounds on a single species of parasite.

Hall and Wigdor (192(i) were apparently the first to carry
out studies of this sort. Their work was carried on in 19lV
and 1918 but was interrupted by military service. Their lim-
ited study was made with terpenes and certain other aromatic
hydrocarbons. Unfortunately, the study provided little infor-
mation of value partly because of the divergent structure of
the compounds tested and partly because of tlie feeble anthel-
mintic activity of many of them.

Cains and Mhaskar's extensive investigation into the value
of hookworm remedies was a thorough piece of work. How-
ever, here again too many compounds (70 in all) of too di-
vergent a character were employed. In the summary and
conclusions of their work, Cains and Mhaskar (1923) stated
that the effective hookworm treatments studied by them dif-
fered so much in molecular composition and structure that no
general correlations could be said to exist between anthelmintic
properties and chemical composition. They concluded that
anthelmintic action on hookworms is specific.

Wright and Sehaffer (1932) selected a series of chlorinated
alkyl hydrocarbons, a feiv of which had been .studied by Hall
and his associates. The previousl.v unstudied compounds were
tested critically for their anthelmintic efficacy against hook-
worms and general correlations were drawn l>etween anthel-
mintic efficacy, chemical structure and physical properties.

In the homologous series, there was a rise in anthelmintic
efficacy against Anciilostoma caniiniiii with an increase in the
length of the hydrocarbon chain from the low member of each
group to the next higher member. In each case, there was an
accomjianying decrease in solubility from above the optimum
solubility range to a solubility within that range. In one
homologous series (normal monochlor compounds) a iieak of
anthelmintic efficacy was teached. It was pointed out that in
a similar way other homologous series would no doubt each
have a peak of anthelmintic efficacy, for the reason that a
point will be reached Avhere the solubility of a higher member
will be so slight as to result in little or no anthelmintic effi-
cacy. It was concluded that although the addition of — CH2 —
groups to the hydrocarlion chain results in a progressive change
in solubility from one member to the next in homologous series,
a progressive change in anthelmintic efficacy does not neces-
sarily follow.

An increase in anthelmintic efficacy against A. canininn did
not always result with an increase in the number of chlorine
atoms in the molecule or with an increase in the relative per-
centage weight of chlorine in the molecule. In those cases
where a high degree of anthelmintic efficacy was associated
with increase in the chlorine content, the resulting compounds
without exception possessed a solubility within the optimum
range. Further, the siireading of the chlorine atoms in the
hydrocarbon molecule did not invariabl.v result in an increase
or decrease in anthelmintic efficacy.

Differences in position of the chlorine atom in the molecule
resulted in changes in anthelmintic efficacy and the accompany-
ing change in water solubilitj' was an important factor in
determining anthelmintic efficac.v. Even among comjiounds
with the same number of carbon, hydrogen and chlorine atoms,
changes in the position of the chlorine atom resulted in com-
pounds showing marked differences in anthelmintic efficacy for
hookworms. In addition, differences in iinthelmintic efficacy
were exhiljited when the methyl radical was introduced in dif-
ferent positions in the clilorinated liydrocarlicju molecule.

Wright and Sehaffer concluded that antlu'lmintic efficacy of
chlorinated alkyl hydrocarlions against A. ciiniinnii is intimately
linked with water solubility which varies with the chemical
structure of the molecule and that the anthelmintic efficacy is
not solely dependent on the halogen concentration or on the
position of the chlorine atom or atoms in the molecule. With a
single exception those compounds having water solubilities be-
tween 1:1250 and 1:.5300 showed a high degree of anthelmintic
efficacy for hookworms in the dog regardless of the halogen
concentration or the position of the diloiine atom or atoms in
the molecule. Water solubility is, therefore, the factor most
definitely correlated with the anthelmintic efficacy of chlori-
nated alkyl hydrocarbons for hookworms.

334

It is intcrfStiiig to note that tho al>ovo iiu'iitioiu'd coni'lusidiis
did not apply in tlie case of aiitlu'lniintie efficacy of the com-
pounds asainst To.vocara caiii.s and Tuxuscari.s Iroiiina.

In critical tests on doRS with nionolironi hydrocarbons,
Wright, Schaffer, Bozicevicli and Underwood (li)37) fovuid that
an increase in the hydrocarbon chain was associated Avith a
]irogressive decrease in water solubility from one member to
the next without a progressive change in anthelmintic cfti
cacy against JnciiluKtoiiia canhiKin. The jieak of anthelmintic
efficacy against hookworms was reached with n butyl bromide,
the efticacy thereafter declining. This compound was the only
member of the series possessing a water solubility lying within
the optimum solubility range of chlorinated hydrocarbons. It
appeared probable that an optimum solnbilit.v range similar
to that for chlorinated hydrocarbons exists among lironiinated
hydrocarbons so far as anthelmintic efficacy against hookworms
is concerned. These authors concluded that water solubility
api'earcd to be the factor most definitely correlated with an-
thelmintic efficacy of bromiuated hydrocarbons for hookworms,
as it is with chlorinated hydrocarbons. Wright and Schaffer
(lil.31) came to similar conclusions in connections with mono-
iodated compounds.

l.amson and his associates (1934, 1935) studied extensively
the anthelmintic value of a large number of phenolic coni-
jionnds, most of the comparalde tests having been carried out
on AKcaris Uimhricoidfs in I'itro. These compounds included
(1) alkyl resorcinols, (2) alkyl phenols, (3) alkyl eresols, (4)
polyalkyl phenols, and (5) phenols with other than normal
alkyl side chains. The authors concuded that the ascaricidal ac-
tivity of phenolic compounds is related to the local irritating
action although all phenols exhibiting such action are not
necessarily active ascaricides. To be effective as an asearicide,
it was found that a phenol should lie a liquid or a substance
which will lifjuify or emulsify in the intestinal tract. Such
substances were found to have a melting ])oint of not over 7.5°
C. The solubility range of ascaricidal phenols was found to
lie between 1:1,000 to 1:35,000, although the most effective
anthelmintic of this type in the large number of compounds
studied was hexylresorcinol with a water solubility of 1:2,000.

It was found that the ascaricidal properties of phenols and
resorcinols are increased by the introduction of alkyl radicals.
Such properties become more marked with the lengthening of
the alkyl chain and reach a maximum which differs in differ-
ent series, thereafter declining rapidly. The ascaricidal value
of dihydroxybenzenes was not strikingly different from that
of mouohydroxybenzenes. No significant differences were
found between ortho and para alkyl phenols. The introduction
of single normal chains into the nucleus was more effective
than the introduction of multiple chains with the same total
number of carbon atoms. Normal chains in general were more
effective than branched chains, although exceptions were noted,
such as the increased efficacy of thymol over that of n-propyl
meta cresol. Some of the differences in activity were thought
to be accounted for by the higher melting point of the branched
chain compounds over that of normal compounds. Cyclic side
chains behaved similarly to forked chains.

From the evidence at hand it may be concluded that little
or no correlation can be drawn between the anthelmintic effi-
cacy and the chemical constitution of compounds differing
widely in their chemical structure. When closely allied com
pounds have been tested against a single species of parasite,
the results have indicated generally that there is a rise and fall
in anthelmintic activity within the homologous series, the ac-
tivity reaching a peak and then declining. In the case of
liquids, the anthelmintic efficacy is definitely linked with the
water solubility and in the case of solid compounds with the
water solubility and the melting point. In general, in homolo-
gous series compounds with normal chains are usually more
effective than those with branched chains. Finally, the evi
denee, meager as it is, emphasizes almost dramatically the
extreme specificity of anthelmintics.

Chemical Classification

The following classification showing the various chemical
groups to which anthelmintics belong is taken mainly from the
excellent summary of Lamson and Ward (1932). The listing
includes for the most part the compounds more commonly em-
ployed against nematode parasites and contains mainly those
drugs which have been shown by adequate test to possess
marked anthelmintic properties. For information concerning
the chemical grouping of other drugs, including those employed
in cestode and trematode infections, the reader is referred to
the more detailed classification of Lamson and Ward.

1. Inorganic substances
Bismuth subcarbonate
Copper sulphate

.\ntimony i)otassiuni tartrate
Colloidal iodine
Sodium arsenite
(^;irbon disulphide
Hydrogen peroxide

2. Hiilofii nuUil Itydrocarbons
a. Alipathic

(1) Saturated
Chloroform
Rromoform
Carbon tetrachloridi'
n Butyl chloride
n-Butylidene chloride
n-Butyl bromide

(2) Unsaturated
Tetrachlorcthylene

3. PItcnols

a. Monoliydric phenols

uHexylm cresol
Thymol
Carvacrol
Betanaphthol

b. Diliydric phenols

n Hexylresorcinol
n-Heiitylresorcinol

4. Oiiionic acids and their salts or esters
Aluminum subacetate

5. Orijnnic dioxides
Disuccinyl perovide

(i. Organic antimomi coiiiponnds

Sodium antimony III jiyrocatechin disulphonate of sodium

' ' Filsol ' '

"Stibsol"

7. Terpcnes

a. Bridged ring
(1) Peroxides

Ascaridol

b. Sesquiterpenes
Santonin

8. Alkaloids
Nicotine
Pyrethrine

9. Enzymes
Fie in
Bromelin

10. Plant products
Leche de higueron
Digenea simplex
Oleum chenopodii
Oleum eucalypti
Oleum terebinthinae
Quassia

Tobacco

11. Dyes and similar conij)ounds

a. Thiaziu
Phenothiazine

b. Triamino triphenyl methane
Gentian violet

c. Phthalein
Mercurochrome

General Principles of Anthelmintic Medication

Elscwliere in this discussion we have emphasized the specific-
ity of anthelmintics, a thing which is of prime importance
from a medical standpoint. It is not only a waste of time and
effort to employ a nonspecific treatment against a given para-
sitic infection but it is a hazard to the safety and well being
of the host. Specific treatments cannot be chosen unless an
accurate diagnosis is made. Hence any anthelmintic medica-
tion should be predicated on such a diagnosis. Even today when
the average physician or veterinarian is far better qualified
than formerly in the field of parasitolog.y, we find practitioners
administering anthelmintic treatment on the basis of a clinical
diagnosis without proper laboratory checks. No parasitic in-
fection is characterized by pathognomonic symptoms and the
shifting sand of the clinical picture is not a sufficiently firm
foundation upon which to base treatment with drugs which at
best have only a small margin of safety.

In the past, mass treatment of large population groups has
been a popular method of attack against a given parasite.
The benefits anticipated from such a procedure have not been
generall.v realized for all too frequently the important sub.iect
of prophylaxis has not been given sufficient attention. Under
such circumstances, the population groups involved have con-
tinued to indulge in the habits responsible for their parasitic

335

infection and after a suitable period of time are again ready
for further treatment.

With improved techniques for determining the presence of
most parasites and for evaluating the relative degree of in-
fection with many of them, mass treatment is no longer justi-
fied in the field of medicine. Even in veterinary medicine it
can be condoned only in the case of large flocks or herds in
which individual diagnosis would be economically unsound.

The question is frequently raised as to whether an infection
with a given number of worms is of clinical importance and
thus warrants treatment. No categorical answer can be given
to such a question. An infection with a certain number of
worms might be injurious to the health of one individual with-
out aft'ecting in any appreciable degree the well l)eing of an
other individual. No one has been able to define the line of
demarcation between a clinical and a sub-clinical infection.
In mass treatment such finesse of judgment is not required or
at least is not exercised but in medical practice it is best that
due cognizance be taken of the relative degree of parasitism.
If the patient has only a few worms, such as hookworms, he
liad better go without treatment rather than be subjected to
the potential hazards of anthelmintic medication. However,
with such a circumscribed environmental parasite as Enterobiiis
rr.rmicularia, it is necessary from a control standpoint to treat
siniultaneou.sly all infected individuals in the household re-
gardless of the degree of infection or the presence or absence
of clinical symptoms. Otherwise, untreated individuals provide
direct avenues of reinfection for treated individuals.

Methods of Application. Anthelmintics are administered
in a great many different ways, depending on the kind of
parasite, its location within the host and the species of host
animal. In man, palatability is a matter of some importance
and it is desirable to administer the drug in a manner least
distasteful to the patient. While the esthesia of taste is not
usually considered in the case of lower animals, palatable doses
of drugs are more apt to be retained by dogs and cats in
which the vomiting reflex is acutely sensitive. Many of the
anthelmintics now on the market are dispensed in soft gelatin
capsules. Hard gelatin capsules are still employed by some
practitioners who prefer to fill the capsules at the time they
are used.

For certain parasites located far down in the digestive tract,
the use of enteric-coated tablets is an advantage. However,
most of the enteric coatings employed become harder with age
and are less apt to dissolve in the digestive tract. A new type
of water-soluble coating has recently been devised to obviate
the disadvantages of the usual enteric coating. The new coat-
ing permits timed disintegration of the tablet witliin c^'rtain
definite periods after administration and radiographic evidence
in support of this has been furnished by Worton, Kempf, Bur-
rin and Bibbins (1038).

For ruminants, certain anthelmintics such as solutions of
copper sulphate and nicotine sulphate are given as a drench.
In fact, Ortlepp and Miinnig (1936) have shown that the ad-
ministration of a dose of copper sulphate solution immediatel.y
))rior to the use of other drugs has the effect of closing the
oesophageal groove and permitting the drug to reach the abom-
asum directly. This is of marked advantage in connection with
some treatments against ruminant parasites. On the other
hand, some anthelmintics, such as the sodium arsenite-bhiestoiie
mixture for the common sheep stomach worm, are given in
j)owdered form.

The duodenal tube method of administration is an advantage
in some instances and is particnl.'irly valuable in stubborn
cases of strongyloidosis in man in which ordinary methods of
administration fail.

Somatic helminths, when they can be reached at all, are
usually attacked through the intramuscular or intravenous
route. Lungworms in domestic animals are susceptible to some
extent to anthelmintics introduced intratrachcally and good
results have been reported in this connection by certain workers
in the Soviet Union. The inhalation method was used by
Wehr, Harwood and Schaffer (193S) in the attack against
Symgamus trachea in chickens with barium antimonyl tartrate
dust.

Parasites in the lower bowel are subject to attack per rec-
timi. The employment of enemas is a common practice against
Entcrohins vrrmiciihirix in man. The method has been used by
Miinnig in South Africa and by others in removing nodular
worms from sheep, while intracecal injections have been advo-
cated and employed with some success for the expulsion of
whipworms from the dog. In a like manner, HcteraMs galUnae
can be reached with anthelmintics injected by way of the
cloaca.

The individual anthelmintic treatment of farm animals has
never appealed to the livestock owner and there has always
been keen demand for an anthelmintic which could be given

with the feed. Other than the tobacco dust or nicotine treat-
ment for Ascaridia in poultry, anthelmintics administered in
tlie feed are generally ineffective. The method has the disad-
vantage that some animals ingest too much and others too little
of the drug. More recent tests with phenothiazine seem to in-
dicate that for some parasites this drug may be of value when
given with the feed. If results are substantiated in further
trials, the method will no doubt find widespread use.

While most anthelmintic therapy is based on the use of single
dose treatments, it is sometimes of advantage to employ divided
doses. The dose of chenopodium for man is occasionally divided
into two or three parts administered at one half to one hour
intervals. When given in this way, the efficacy of tlie drug
against hookworms is believed by some workers to be slightly
enhanced. If toxic symptoms are manifested by individuals
having an idiosyncrasy for the drug, dosage can be discontin
ued. However, the purgative is usually withheld until the last
portion of the dose has been administered and under these
conditions increased absorption of the anthelmintic is apt to
occur.

Repeated treatment over a period of time is required for the
eradication of such parasitic nematodes as Strongyloides ster-
coralis and Enterobiiis vcnnioilaris. Likewise some degree of
efficacy can be secured against whipworms by repeated dosing
with a drug such as santonin which exerts little or no action
against these parasites when given in a single dose.

The above citations will be sufficient to indicate to the reader
that anthelmintic warfare against parasites, whether in man or
the lower animals, requires the employment of varied methods
of attack based on the nature of the lio,st terrain and the ac-
cessibility of the parasite to the range of the weapon or
weapons available. Some parasites can be overcome by a
single anthelmintic onslaught but others are expelled from
their position only after repeated attacks. The method of ap-
plying treatment is therefore an important factor in anthel-
mintic medication.

Prelimin.\ky Fasting. It is custoniary usually to fast the
jiatient before the oral administration of most anthelmintics
with a view of emptying the stomach and reducing the bulk of
the intestinal contents. In the treatment of Axcaris and hook-
worm infections in man, the patient is usually given a light
supper the night before and the anthelmintic administered in
the morning, no food being permitted until adequate purgation
has ensued. Dogs and cats are usually fasted overnight. Various
periods of fasting are prescribed for larger domestic animals.
Swine should be fasted for 24, and preferably, 36 hours. For
equines it is advisable to withhold feed for 18 hours prior to
anthelmintic medication for parasites in the stomach and small
intestine and 36 hours for parasites in the large intestine.
Conditions are somewhat different in the case of ruminants.
Even prolonged fasting will not entirely reduce the bulk of
the contents of the rumen. Formerly, it was customary to fast
animals for 12 to IS hours but more recently Clunies, Ross and
Gordon (1934, 1935) have shown that there is no increase in
the efficacy of a number of drugs used for the removal of the
common sheep stomach worm in animals fasted for 24 hours as
compared to the efficacy of the same drugs in nnsfarved sheep.
Consideration op the Patient. Since tlie safety of the pa-
tient is of paramount importance, it is the duty of the prac-
titioner to satisfy himself that no contraindications for anthel-
mintic treatment are present. This calls for an adequate physi-
cal examination to rule out general contraindications and a suit-
able inquiry to ascertain the possible presence of specific con-
traindications for the drug of choice. General contraindications
include febrile conditions, extreme youth or old age, chronic
debilitating diseases, pregnancy, gastro-intestinal disturbances,
chronic constipation and alcoholism. The presence of one or
more of these conditions does not necessarily mean that treat-
ment should be withheld but it does mean that due regard
should be taken with respect to the type of drug and the dosage
employed. The practitioner must decide whether the injury
from parasitism is sufficient to warrant the risks attendant on
treatment and must weigh the advisability of substituting a
less specific but safer drug for a more specific but more dan-
gerous drug. In patients who are poor risks for adciiuate doses
of specific drugs, it is advisable to reduce the dose and remove
a few worms at a time rather than hazard injury to the patient.
In persons with severe hookworm disease, it is questionable
whether anthelmintic treatment should be resorted to until the
anemia has been corrected by .suitable doses of iron.

In particular, doses of anthlemintics for children should be
computed very carefully and apparent age rather than chrono-
logical age should form the basis of computation. Since the
evacuation habits of children are not always regular, the ad-
ministration of a high soapsuds enema on the morning of
treatment often helps to prevent reactions to such anthelmin-
tics as the chlorinated hydrocarbons.

336

The pr;u-liti(iiu'r 's iibligatiiiii t(i tlic |i;itieTit has not been
fiiltilli'd until a suitablo cliofk is made on the results of the
tioatiui'iif. In the case of most parasites, it is advisable to
wait two weelis before a reexamination since some anthelmin-
tics definitely inhibit egg production in some parasites. With
such a specialized [larasite as Enlfrobiiis vcrniicularis a longer
period of time is needed to determine freedom from infection
following treatment. In evaluating the efficacy of any treat-
ment due cognizance slionld be taken of the possibilities of mi
grating larvae developing to maturity and also of possible
exposure to reinfection following treatment.

Choice of tub Anthelminxic. An ideal anthelmintic would
be one which could be given with complete safety to the pa-
tient; would be nontoxic in all cases; would be effective in re
moving all of the i^articnlar kind or kinds of worms against
which it was directed; could be easily administered even in
large scale treatments; and would be sufficiently cheap that
cost would be no obstacle to its use.

In spite of the exuberant enthusiasm of some investigators,
the ideal anthelmintic has yet to be discovered. Drugs which
on first test seem to fulfill such specifications are usually found
wanting in some rcsjject when submitted to adequate field trials
on large numbers of individuals.

Keeping in mind the general specificity of anthelmintics, it is
best to select the most effective drug available provided no
general or specific contraindications exist for the use of that
specific drug. If contraindications are present, they usually
modify either the selection of the anthelmintic or the dose em-
ployed. The presence of more than one nematode parasite or
concomitant infections with cestode or trematode parasites fre-
quently changes the picture. In the latter case the administra-
tion of a single drug will seldom be effective in eradicating such
diverse helminths. Even in multiple nematode infections treat-
ment with a single anthelmintic may not be effective. In the
case of certain parasites, a combination of two drugs may be
of value such as the chenopodium-tetrachlorethylene mixture in
concomitant ascarid and hookworm infectious in man. In other
cases, different kinds of parasites have to be attacked by means
of separate treatments.

One method of attack has been suggested as being of value
for the removal of all intestinal helminths in certain animals.
DeRivas (1926, 1S>27. 1936) advocated the use of trans-duodenal
lavage with hot water or hot saline for parasites in the small
intestine and colonic lavage with l:.'iOOO copper sulphate solu-
tion for parasites in the large bowel. He carried out experi-
ments on dogs and man and reported that the use of two liters
of hot saline at temperatures of 4.5° to 47° C. resulted in the
elimination of worms with little discomfort to the patient. Hall
and Shillinger (1926) used the method on dogs with water
having an initial temperature of 49° to .52° C. in the container
and cooled to 47° to 48° C. at the time of administration. The
use of 2 to 4 gallons of fluid resulted in an efficacy of 97.7
percent against ascarids, 77 percent against hookworms and
51.6 percent against tapeworms. However, the treatment re-
sulted in the death of half the experimental dogs and was re-
sponsible for hemorrhage, enteritis and intestinal edema in
those surviving. The safety of this method of treatment does
not seem to be well established and perhaps for this reason
the technique has never become popular.

Somewhat the same method of treatment was used by Whit-
ne3- (1939) for removing various species of intestinal parasites
from dogs. He employed a 1.5 percent solution of hydrogen
peroxide in warm water and injected this solution per rectum
under pressure until the act of vomiting indicated that the
material had passed through the entire gastro intestinal tract.
The treatment was said to be highly effective against all of
the helminth parasites commonly found in the gastrointestinal
tract of the dog. Reactions were encountered in some of Whit-
ney's cases. Serious after effects in the form of gastro enteritis
and paralysis have since been reported by some veterinarians
following the use of the treatment. Apparently, the treatment
does not have an adequate margin of safety.

PURQ.^TION. The administration of a purgative in connection
with anthelmintic medication is of the utmost importance in
the case of most drugs. Usually the purgative acts to promote
the efficiency of the anthelmintic by distributing it throughout
the intestinal tract and by aiding in the prompt expulsion of
the parasites. In most cases, purgation is of marked value in
safeguarding the patient by reducing the absorption of the
anthelmintic. Some purgatives also give local protection against
the irritating action of certain drugs.

The choice of the purgative is conditioned by the method
of treatment and the drug or drugs employed. The use of the
chlorinated hydrocarbon group of anthelmintics requires the
administration of saline purgatives, since fats and oils tend to
increase the ab.sorption of such compounds, a thing which re-
sults in more marked reactions to the treatment. In the ease

of oil of chenopodium, castor oil is the purgative of choice
even though saline jiurgatives have been used with this drug.
Castor oil not only i)romotes promjit expulsion of the drug
and reduces absorption but it also exerts a local emollient ac-
tion and protects the intestinal mucosa against the irritating
properties of chenopodium.

Purgatives are usually administered concomitantly with the
anthelmintics but practice in this regard varies with the host,
the parasite and the drug employed. In treating large numbers
of hookworm patients at one time, it is customary to give
carbon tetrachloride or tetrachlorethylene in a solution of
magnesium or sodium sulphate. However, in this case the drug
may be given in gelatin capsules and immediately preceded or
followed by the purgative. In the treatment of Ascaris infec-
tions in man w'ith hexylresorcinol, it is the usu.al practice to ad-
minister the purgative 24 hours after the drug. Calomel has
always been the time honored purgative for use with santonin
but it is probable that better results would follow the employ-
ment of a saline purgative.

Adequate protection presupposes the administration of full
doses of the purgative. Perhaps more injury has followed the
use of inadequate doses of purgatives in connection with anthel
mintics than has come from over dosing with the anthelmintics
themselves. By this we mean that over doses of anthelmintics
will frequently be tolerated if accompanied by adequate doses
of purgatives whereas many fatalities have resulted from stand
ard doses of certain anthelmintics used without adequate pur-
gation. Therefore, in using nearly all anthelmentics, attention
should be given to gauging accurately both the dose of the
anthelmintic and the dose of the purgative.

In event that adequate purgation does not ensue within a
reasonable time, prompt measures must be taken to protect the
patient. High enemas should be resorted to and, if necessary,
an additional dose of the purgative should be given by duo
denal tube. Warm applications to the lower extremities and
to the abdomen will hasten evacuation. The point of most im-
portance in such circumstances is the rapid institution of cor-
rective measures. Every effort should be made to stimulate
bowel movements and promote prompt expulsion of the anthel-
mintic. If the patient is permitted to go unaided, increased
absorption of the anthelmintic will ensue and the life of the
individual may be endangered.

No doubt much of the distress following the administration
of many anthelmintics is caused by the purgative and not by
the anthelmintic. Malloy (1926) showed that the nausea, dizzi-
ness, headache and abdominal pain following the administration
of carbon tetrachloride in magnesium sulphate solution was
due in most cases to the purgative and not to the anthelmin-
tic. Wright, Bozicevich and Gordon (1937) found that reac-
tions to the tetrachlorethylene treatment in children were
markedly reduced when magnesium citrate solution, a more
pleasant and palatable purgative, was used instead of mag-
nesium sulphate. In most cases, the symptoms described above
are not alarming and usually pass off rapidly after the bowels
move.

Anthelmintic Medication for Nematode Parasites
of Man

TREATMENT TOR ASCARIS LUMBRICOIDES INFTtCTION

HEXYLRESORriNOL. This is the drug of choice since it is
highly effective and is safer than other drugs formerly em-
ployed for this purpose.

Proper fasting is important since hexylresorcinol combines
with protein and is rendered inert insofar as its anthelmintic
action is concerned. The patient should be given a light sup-
per on the evening before treatment and the drug should be
administered on an empty stomach the following morning.
Hexylresorcinol is used in the form of Caprokol pills, each of
which contains 0.2 gram of the drug. The dosage for adults
consists of 5 pills or a total of 1.0 gram. The dosage for
children is, as follows: Under six years, 2 pills; six to eight
years, 3 pills; eight to twelve years, 4 pills; over twelve years,
.5 pills.

The pills should be swallowed with a little water; special
care should be taken that they are not chewed since the drug
is a local irritant and produces annoying burns. Children in
particular should be observed closely to make sure that the
pills are properly swallowed. Food should be withheld for 4
hours following administration of the drug. A saline purga-
tive should be given 24 hours after treatment to sweep out
the dead worms.

As a usual thing there is little or no discomfort from the
drug although some patients may complain of nausea and
slight abdominal pain. Occasionally a slight burning sensation
in the epigastrium is noted but this soon passes off.

337

There are no well established contraindications for hexylre-
soreinol therapy. However, it is advisable for the patient to
abstain from alcohol immediately before and after treatment.
As a precautionary measure, it is probably well to avoid treat-
ing persons suffering from gastric or duodenal ulcer and any
form of gastroenteritis.

Oil of Chenopodium. This drug has had widespread appli-
cation in the treatment of aseariasis and hookworm disease
but its margin of safety is small and it has prol>ably been re-
sponsible for more fatalities than any other single anthelmin-
tic. However, its efficacy against ascarids is very high.

The active principle of chenopodium is ascaridol which varies
in content with different oils. Effort has been made to stand-
ardize the ascaridol content at 70 percent in order to have
available a uniform product but various oils on the market
may vary in the content of the active principle.

In using chenopodium, the ijatient should be given a light
evening meal. If constipated, a saline purge is indicated fol-
lowed by a high soapsuds enema the next morning. These pre-
cautions are important in the ease of constipated individuals
since chenopodium itself tends to produce constipation.

The drug is given on an empty stomach and no food should
lie allowed until the bowels move. The adult dose should not
exceed 1.5 ce. The dose for children is based on 0.0.3 ce. for
each year of apparent (not chronological) age. The drug may
be given in gelatin capsules and immediately preceded or fol-
lowed by adequate dose of a saline purgative. Some authorities
recommend dividing the dose into two jiarts and administering
the doses 2 hours apart, in which case the purgative is given im-
mediately after the last dose. If the patient shows any signs
of reaction, the second half of the dose should be omitted and
the purgative given immediately. The advisability of the split
dose method is problematical since increased absorption and
toxicity may result when the purgative is thus delayed.

The preferred method of administering chenopodium is to
mix it with castor oil and give as a single dose. One to 2 ce.
of castor oil should be given for each year of apparent age
in children. The larger dose provides more adequate protection.
The oil not only produces adequate purgation but protects the
intestinal mucosa against the irritating action of the drug.

When chenopodium is measured by the drop method, there is
a wide variation in dosage. Measurement should be made by
a standard 1 cc. pipette graduated into tenths in order to
avoid errors in dosage.

Toxic symptoms manifested in chenopodium poisoning are
nausea, vomiting, dizziness, a tingling sensation of the ex-
tremities, muscular incoordination, stupor, profound collapse,
cyanosis and respiratory failure followed by death. Severe
and even permanent deafness may result. If purgation does
not ensue within a reasonable time, strenuous efforts should be
made to evacuate the bowels as promptly as possible. Any delay
in instituting rigorous measures maj' seriously endanger the life
of the patient.

Contraindications for chenopodium therapy include gastro-
enteritis, chronic constipation, alcoholism, pregnancy, deljilitat-
ing diseases, and moderate to severe cardiovascular-renal dis-
ease. Very young children or aged individuals are poor risks
for treatment.

S.'INTONIN'. Santonin is a time honored remedy for the re-
moval of large intestinal roundworms, although its efficacy in
single doses does not approach that of either hexylresorcinul
or oil of chenopodium. However, it is non-irritating and easily
administered and can be used to advantage when there are defi-
nite reasons for avoiding the two other drugs.

The patient should be given a light evening meal and the
dose of santonin administered with an equal amount of calomel
at 10.00 p.m. The next morning before breakfast, a saline
purgative should be given. The dose of santonin for adults is
3 to 5 grains (0.2 to 0.3 gram). For children, the dose rate is
based on 1/6 grain (0.01 gram) for each year of apparent age.
Santonin is more effective when given in repeated treatments
over a period of time. A satisfactory routine is to give 1 to 2
grains (0.06 to 0.12 gram) for adults" and % to % grain (0.015
to 0.03 gram) for children daily over a period of 7 days. The
drug is given with an equal amount of calomel and no other
purgative employed. With continued treatment, the patient
should be observed carefully for any evidence of toxicity.

Santonin is responsible in some cases for disturbances in
perception and there may result yellow, green, and occasion-
ally, blue vision. Symptoms of toxicity are evidenced by nau-
sea, vomiting, dizziness, diarrhea, hematuria and convulsions.
The drug is contraindicated in nervous disorders such as epi-
lepsy. Fats and oils should be avoided as they increase ab-
sorption. The factor of safety for santonin is considerably
greater than that for chenopodium but the drug is not without
its hazards. Some authorities recommend that a single dose of
3 grains for adults be not exceeded.

TREATMENT FOR THE KE.MOVAL OF HOOKWORMS, ANCYLOSTOM.^
DUODENALE AND NEGATOR AMERICANTJS

TBTRACHLORf;THYLENE. Because of its greater safety, this
drug is largely replacing carbon tetrachloride and other treat-
ments for hookworm disease.

The patient should be given a light evening meal and should
receive the drug on an empty stomach the following morning.
No food should be allowed until aftei- the bowels move. The
dose for adults is 3.0 ec. and for children 0.1 to 0.2 ec. for
each year of apparent (not chronological) age. Better results
are obtained with a dose of 4.0 cc. for adults but the larger
dose is apt to be followed by more severe reactions. The drug
may be administered in gelatin capsules followed immediately
by an adequate dose of magnesium or sodium sulphate. In
mass treatment, tetrachlorethylene is given with the purgative.
In such cases, the mixture should be stirred while the patient
is drinking it so that the tetrachlorethylene will be distributed
evenly throughout and not sink to the bottom of the container.
The purgative should lie dissolved in a liberal amount of water.
One of the preferred methods is to use 30 ec. of a saturated
solution of the saline purgative plus 60 cc. of water for an
adult patient. As previously noted, a solution of magnesium
citrate meets with less objection on the part of children and
apparently causes less disagreeable reactions. In constipated
individuals, it is best to give a saline purgative the night be-
fore treatment followed the next morning by a high soapsuds
enema.

In the hands of various investigators, tetrachlorethylene has
sliown a degree of efticacy varying between 75 and 95 percent.
T^ike carbon tetrachloride, it is more effective against Necator
than against Ancylci.il oma.

Following treatment, patients frequently complain of dizzi-
ness, headache, nausea, vomiting and abdominal pain. Experi-
ence indicates that these reactions are less severe if the pa-
tient remains quietly in bed and for safety's sake it is best
to insist on his doing so. Reactions usually disappear rapidly
following action of the jiurgative. If the bowels do not move
within the expected period of time or if minatory symptoms
develop, prompt measures should be taken to hasten evacuation.

Tetrachlorethylene is contraindicated in cases of gastro-
enteritis, chronic constipation and concomitant infections with
A.tcaris himbricoidrs. Fats and oils should lie withheld from
the diet for 48 hours prior to the administration of the drug
since they increase absorption and add to the toxicity. Pa-
tients receiving arsenical treatments are poor risks.

Hexyresorcinol : This drug, administered as for Ascaris, is
about 50 to 60 percent effective for the removal of hookworms.
Because of its relatively wide margin of safety, it can be
used to advantage in cases in which the physician might hesi-
tate to employ tetrachlorethylene.

TREATENT FOR CONCOMITANT ASCARIS AN"D HOOKWORM
INFECTIONS

Tb;trachlorethvi,ene and Oil of Chenopodium. A mixture
of these two drugs can be used in cases in which both kinds of
parasites are present. By itself, tetrachlorethylene should not
lie given when Axcaris is present because the drug tends to
stimulate clumping of the worms with possible intestinal ob-
struction.

The dosage of the mixture for adults is 1.0 cc. of oil of
chenopodium plus 2.0 cc. of tetrachlorethylene. For children,
the dose rate is based on 0.05 ec. of chenopodium and 0.1 cc.
of tetrachlorethylene for each year of apparent (not chrono-
logical) age. The mixture is given in one dose and followed
immediately by a saline purgative as outlined for tetrachlor-
ethylene. The contraindications and precautions are those noted
in connection with the use of chenopodium for Ancaris.

Hexylresorcinol. Because of its greater safety, this drug
is to be preferred over the above-mentioned mixture for the
treatment of combined hookworm and A.trarix infections. The
method of administration is the same as tli:it for the latter
]iarasite.

treatment for trichuris trichiura infection

While various anthelmintics in single doses will remove a
small percentage of these worms, treatment is generally un-
satisfactory. Repeated doses of santonin, as outlined under
therapy for Aficaris himbricoidcf!, represent the most practical
treatment at the present time. Even this regimen of treatment
may have to be repeated on several different occasions to ap-
proach any considerable degree of efficacy.

Hexylresorcinol and tetrachlorethylene each will remove small
numbers of worms, as will oil of chenopodium. Leche de
higueron, the sap of the Central and South American fig tree,
Ficv.i Jaiirifolia, is a fairly effective treatment when given in
doses of 30 to 60 ce. However, this material is not usually

338

availnliU' oiitsuk' of tlic iiativi' lialiitat of the tiou siiu-o thv
sap undoigoi's rapid fcriiu'iitatioii ami becomes very uiipalata
ble at ordinary temperatures. Kffort is being made to preserve
the material in a way whieli will jiermit of its transportation
and storage. Fiein, the proteolytic enzyme isolated from the
sap by Robbins. cannot be used safely in man because of its
marked jiroperty of digesting the mucosa of the gastro-intesti-
nal tract in the presence of abrasions.

TKK.VTIIK.NT FOR STRONG YLOIBES STERCORjUjlS INFECTION'

Kwa Tjaon Sioe (1928) and de Langen (1928) introduced
gentian violet for the treatment of infectious with this para-
site and the treatment was further developed by Faust (l!t30).
For adults, Faust recommends a dose of 1 grain (04 mgm.)
three times a day before meals over a period of 10% days or a
total dose of CO grains. For children, the drug ma.v be given
at the rate of 1/0 grain (10 mgm.) per day for each year
of apparent age or approximately V2 grain (32 mgm.) for each
3 years of apparent age, given over a similar period of time.
Gentian violet is procurable in % grain and 3/20 grain enteric-
coated or water soluble coated tablets.

Some Sirongyloidcs cases are refractory to oral therapy with
gentian violet and for such cases Faust recommends the duo
deual intubation of 2."i cc. of a 1 percent solution of the dye.
The patient should remain quietly in bed after this treatment
as nausea and vomiting are apt to ensue.

About one-third of the patients treated with gentian violet
experience reactions consisting of one or more of the follow-
ing symptoms: Nausea, vomiting, diarrhea, headache, dizziness
and abdominal pain. These reactions are usually not of a seri-
ous character and can be controlled by reducing the dosage
for a short time or discontinuing treatment for a day or two.

Contraindications for gentian violet are not clearly defined
but as a precautionary measure the drug should not be given
to patients suffering from gastroenteritis, moderate to severe
cardiac, hepatic or renal disease and concomitant infections
with Asearis liimbricoidcs. Pregnant women are apt to be
markedly nauseated by the treatment. The consumption of
alcohol should be prohibited during the period of treatment.

TREATMENT TOR ENTEROBIUS VERMICULARIS INFECTION

The ease with which many individuals become constantly re-
infected with pinworms makes eradication of the parasite an
extremely difficult matter. The failure in many cases to achieve
control by the rigid application of hygienic measures calls
for supplementing such measures in most cases with suitable
therapeutic procedures.

It is probable that man3' of the failures to control pinworm
infection are attendant on the fact that treatment is usually
administered only to those persons in the household who show
clinical symptoms. Frequently, other members of the family
may be infected without being aware of the fact. Under such
circumstances, these persons serve as reservoirs of infection
which is again acquired by the treated individuals. Wright and
Cram (1937) have emphasized tlu> importance of carr.ying out
adequate diagnostic tests on all members of a household and
treating all infected individuals simultaneously with the view
of eliminating at one time all sources of infection within tin-
home.

The literature probably contains a greater array of drugs
recommended for the removal of pinworms than for any other
parasite. Single dose treatments are not well adapted for
combating this parasite. Tetrachlorethylene, probably the best
of these, is less than .50 percent effective. In general, better
results follow the employment of repeated doses of drugs over
a period of time sufficient to allow for desiccation of ova in
the patient's surroundings and thus reduce opportunities for
reinfection.

Santonin in repeated doses as for Asearis has been used fre-
quently, although its efficacy is somewhat less than 50 percent.
Enemas, medicated or non-medicated, are of value particularly
in young children but they must be carried over a period of
time sufficient to care for the possibilities of reinfection.

Brown (1932) obtained good results in a small series of pa-
tients with hexylresorcinol enemas administered at varying
intervals and supplemented by oral therapy with Caprokol
pills. Wright, Brady and Bozicevicli (1!I39) treated 27 patients
without oral therapy and found 18 negative on post-treatment
swabs, although some of the negative patients failed to fur-
nish an adequate number of such swabs. A preliminary soap-
suds enema was given at bedtime followed immediately after
its expulsion by an enema consisting of a 1:2000 solution of
hexylresorcinol in water. The above-mentioned workers found
that satisfactory results in most cases required the administra-
tion of at least 10 such enemas over a period of 3 weeks. No
doubt more consistent results would follow more prolonged

treatment, it is possible that Caprokol orally once or twice-
during the jjcriod of treatment would add to the efficacy of
the regimen, although the preparation in single doses is not
effective in eradicating the worms.

It would appear that the drug coming closest to fulfilling
the requirements for a satisfactory treatment for oxyuriasis is
gentian violet as reported by Wright, Brady and Bozicevich
(1938) and Wright and Brady (l!i40). These investigators
completed experimental treatment on 224 individuals, of whom
84 percent were negative for pinworm ova on 7 consecutive
daily anal swab examinations taken at various intervals after
the end of the treatment.

The dosage for gentian violet is the same as that used for
the treatment of strongyloidosis. However, the regimen of
treatment is somewhat different, the patient being given the
drug over a period of 8 days, foUow-ed by a rest period of one
week and then another course of treatment for 8 days. The
contraindications and precautions are the same as those out
lined under therapy for strongyloidosis.

Recently Manson Bahr (1940) reported good results in the
treatment of pinwoi-m infection with phenothiazine. Of 6 chil-
dren and 3 adults, clinical cures were said to have been ob-
tained in all cases, although 3 individuals required a second
course of treatment. The following dosage was recommended:
For children under 8 years of age, 2 grams daily'for 7 days;
for children under 4 years of age, one half of the above-men-
tioned dose; and for adults, 8 grams daily for at least 5 days.
In the cases in question, results of treatment were not checked
by swab technique or other methods to determine disappear-
ance of infection. Nothing is said in Manson-Bahr 's paper con-
cerning the dangers of blood dyscrasias from the use of pheno-
thiazine, although DeEds, Stockton and Thomas (1939) re-
ported the occurrence of secondary anemia in 3 of 49 patients
given phenothiazine as a urinary antiseptic. The maximum to-
tal dose recommended by Manson-Bahr is greatly in excess of
that specified by DeEds, Stockton and Thomas as being with
in the limits of safety. It would seem that this treatment
should he used with considerable caution.

TREATMENT FOR WUCHERERIA BANCROFTI INFECTION

There is no specific medication for this condition. Various
drugs have been reported as being of value for the destruc-
tion of the microfilariae or preventing their appearance in the
peripheral circulation. However, evidence for the efficiency of
such drugs is meager as in many cases the larvae reappear later.
There is no known drug effective for the destruction of the
adult worms.

Chopra and Sundar Rao (1939) have reported on tests ex-
tending over 10 years with patients treated with a large num-
ber of different drugs at the Calcutta School of Tropical Medi-
cine. None of the compounds employed was of value in effect
ing the destruction of adult or larval worms. Soamin, an ar-
senical preparation, reduced the number of febrile and in-
flammatory attacks. Fouadin had a temporary sterilizing ef
feet on the parasite but microfilariae reappeared in the blood
after several days. However, the drug was said to be very
useful in controlling inflammation and fever over comparatively
long periods of time. In a few cases, chyluria disappeared even
after a single dose. Prontosil and its derivatives were found
of value in the treatment of secondary infection.

Roentgen ray therapy has been advocated as being of value
in filariasis but Golden and O'Connor (1934) were unable
to obtain consistently promising results.

In filarial lymphangitis and elephantiasis, surgical interven-
tion by means of the Auchincloss technique or one of its modifi-
cations will bring some temporary relief. Knott (1938) has
advocated prolonged tight bandaging. The use of the method
on 105 unselected patients in his series indicated apparently
that it is of value for the gradual removal of the lymphoedema
and in the prevention of the recurrent attacks of lymphangitis.

Anti-streptococcal vaccines have been reported to be effec-
tive in some cases but O'Connor (1932) pointed out that the
relief is only temporary and that any serum or vaccine produces
similar relief, indicating probably that temporary cure is due
to protein shock rather than to specific anti-bacterial action.

Anthelmintic Medication for Nematode Parasites of
Dogs, Cats and Related Carnivores

TREATMENT FOB ASCAKID INFECTIONS

Tetrachlorethylene. This drug in a dose of 0.2 cc. per
kilogram (2.2 pounds) of body weight is effective for the re-
moval of dog ascarids. In using chlorinated hydrocarbons in
the presence of heavy ascarid infections, particularly in pup-
pies and young dogs, it is advisable to follow the anthelmintic
in 3 or 4 hours by an adequate dose of castor oil, or to give

339

a saline purgative immediately following the treatment. The
purpose of this is to prevent clumping of the ascarids, which
are inordinately stimulated by these compounds, and a possible
intestinal obstruction which sometimes causes enteritis, necro-
sis and death. Tetrachlorethylene may be given to cats at
the same dose rate and in the same manner as for dogs. The
drug in doses of 1 cc. has been reported to be of value for the
removal of ascarids from foxes. In these animals, it is said
to cause a slight enteritis which is not of serious consequence.

Oil. of Chenopodium. Xumerous experiments have shown
that this drug is very effective for the removal of ascarids
from dogs. The rate of dosage is 0.1 ec. per kilogram of body
weight or 1.0 cc. for a 10 kilogram (22pound) dog. For prac-
tical purposes, this can be regarded as equivali'iit to th.' lol
lowing doses: For dogs weighing 10 pounds or 1 ss (except toy
dogs), 5 minims; for dogs weighing 10 to 20 pounds, 10
minims; for dogs weighing 20 to 30 pounds, 1.1 minims; and
for dogs weighing over 30 pounds, 20 minims. Toy dogs re-
quire small doses and considerable precaution should be ex-
ercised in treating such animals ; a dose of 2 or 3 minims is
advisable. The dog should be fasted from the afternoon of the
day previous to treatment and should be dosed the following
morning. The chenopodium should be accompanied by at least
an ounce (30 cc.) of castor oil. It is not advisable to give the
chenopodium in the castor oil. as chenopodium is salivating and
the combination produces a disagreeable slobbering effect. For
choice, the chenopodium should be given in gelatin capsules and
the castor oil administered immediately before or after the
capsules. The animal should not be fed until 3 hours after
treatment. If dogs show serious toxic effects, large additional
doses of castor oil should be given and enemas used to insure
prompt purgation. The contraindications for chenopodium have
been discussed in connection with the treatment of ascariasis
in man.

Chenopodium is very effective for the removal of ascarids
from cats but the drug is more toxic for these animals than
it is for dogs. The dose for the cat should not exceed O.O.") ec.
l)er kilogram (2.2 pounds) of body weight, immediately pre-
ceded or followed by an adequate dose of castor oil.

For fox pups, Young (1930) recommended 1-minim doses of
oil of chenopodium in castor oil and found this safe for pups
3 weeks old and effective for pups up to 8 weeks of age. He
preferred not to treat them until tlun- were 4 weeks old.

Santonin. When there are contraindications for other treat-
ments, santonin in repeated doses may be used to remove as-
carids from dogs. Experiments show that single doses of
santonin, even very large doses, such as '2 grain for each
pound of body weight, are less effective than a single thera-
peutic dose of chenopodium, but that smaller doses of santonin
daily for several days gives very good results. Small dogs may
be given Vn grain of santonin and an equal amount of calomel,
and large dogs double this dose, daily for a week. Tliis should
be given early in the morning and the animal not fed for 2 or
3 hours. As previously stated, a saline purge following single
doses of santonin seoms to increase materially the efficacy of
the drug.

N-BuTYL Chloride. The administration of tetrachlorethylene
to dogs is frequently followed by a temporary narcosis which
often embarrasses the veterinarian and alarms the client. Har-
wood, Jerstad, Underwood and Schaffer (1940) are of the
opinion that n-butyl chloride does not produce such reactions.
For the removal of ascarids, these investigators recommend the
following dosages: For dogs weighing 2.3 to 4..''i kilos (•") to 10
pounds), 2 cc; 4.."i to 9 kilos (10 to 20 pounds), 3 cc; 9 to 18
kilos (20 to 40 pounds), 4 cc; and 18 or more kilos (40 or
more pounds), 5 cc.

Hextlresorcinol. Lamson, Brown and Ward (1930) have
reported that hexylresorcinold is very effective for the removal
of dog ascarids. The drug is given in doses of 0.5 to 1 gram.
With hexylresorcinol, it is necessary to withhold food for 12
to 18 hours before treatment. Animals should not be per-
mitted to crush or chew capsules or pills of hexylresorcinol
since, as previously stated, the drug is irritant to the mucosa
of the mouth.

TRE.\TMENT FOR HOOKWORM INFECTION

Tetrachlorethylene. At the present time, this is the drug
of choice having largely replaced carbon tetrachloride because
of the toxicity of the latter. The therapeutic dose rate of
tetrachlorethylene for dogs and cats is 0.2 cc per kilogram
(2.2 pounds) of body weight, or 2 cc. for a 10-kilogram or 22-
pound animal. It is usually not necessary to give a purgative
in connection with tetrachlorethylene, but a purgative is ad-
vantageous as it helps to sweep out worms killed by the treat-
ment and to eliminate the drug rapidly from the intestinal

tract. It is advisable in coneomitant heavy ascarid infections,
particularly in puppies, to follow tetrachlorethylene with a
suitable dose of purgative. However, castor oil or other oils, or
fats, should not be given immediately preceding or following
tetrachlorethylene as they aid in tlie al)sorption of the drug.
Tetrachlorethylene has the disadvantage of causing in some
cases a transient vertigo or dizziness, which may be :ilarming to
the owner of the aninuil, hut which in fact is not serious and
which soon passes off. For this reason, as mentioned under the
section on the treatment of ascarid infection, n butyl chloride
may be used in place of tetrachlorethylene. The dosages sug-
gested for the removal of hookworms are the same as those
suggested for the removal of ascarids from dogs.

Tetrachlorethylene can be used to advantage in the removal
of U ncinaria slenocrphala from foxes. The dosage is the same
as that for dogs. However, foxes do not tolerate anthelmintic
treatment as well as do dogs, and particular care should be
taken to judge accuratel.v the dosage of the drug and to ap-
praise closely the possible presence of contraindications for
treatment. Care should be taken to see that capsules are not
broken in the mouth, as inhalation of tetrachlorethylene may
lead to serious complications, particularly in fox pups.

He.xylresorcinol. This drug can be used to advantage
when contraindications for other treatments are present. How-
ever, its efficacy falls below that of tetrachlorethylene and
many other halogenated hydrocarbons. The dosage is the same
as that given under treatments for the removal of ascarids.

TREATMENT FOR TRICHURIS VULPIS INFECTION

Numerous experiments on dogs indicate that a large number
of anthelmintics are potent in the removal of whipworms but
that a single dose of such drugs will rarely remove many
whipworms. The failure of single dose treatments is no doubt
due in part to the fact that the anthelmintic fails to enter the
cecum or enters it only in insufficient amounts. It is, therefore,
necessary to give a drug from day to day, until it does come
in contact with the worms in effective doses, or to give large
doses of relative^- non -toxic drugs to ensure the entry of the
drug into the cecum.

Santonin. For the [uirposes of repeated treatments, san-
tonin is a very satisfactory drug since it does not cause gastro-
intestinal irritation even when given over a period of time.
The drug may be given to dogs in a dose of '4 to 1 grain
each of santonin and calomel, according to the size of the
animal, daily for 7 days. The treatment may then be dis-
continued and repeated after an interval of a week.

Leche de Higueron. This drug has been described under
treatment for whipworms in man. While adequate tests have
not been carried out to estalilish its eflficac.v for the removal
of T. viilpix, it seems jirobable that it would be effective for
that purpose. However, until the material becomes more gen-
erally available, its use will l)e restricted to the geographical
areas in which the tree is indigenous.

N Butyl Chioride. Harwood, Jerstad, Underwood and
Schaft'er (1640) showed n butyl chloride to be over .')0 percent
effective for the removal of whipworms. While this degree of
efficacy is certainly not satisfactory, these workers pointed out
that the drug is superior nevertheless to anj- other single dose
treatment known at present. As it is highl.v eft'ective for the
removal of ascarids and hookworms, it seems worthy of trial
in whipworm infections. For whipworms, the above-mentioned
investigators recommend a dose of 3 to o cc. for dogs weigh-
ing ."1 pounds or less; 0 to 8 cc. for .j to 10-pound dogs; 10 to
12 cc. for 10 to 20-pound dogs; lo cc for 20 to 40-pound dogs;
and 2.J cc. for dogs weighing over 40 pounds. If the dog is
infected with ascarids, a saline purgative should be given im-
mediately following the anthelmintic*

Other Methods. Hall and Shillinger (1926) found that
mercurochrome gave fairly satisfactory results for the removal
of whipworms from dogs when the drug was given in doses of
2 to 5 tablets each containing l.'i grains (96 mgm.) daily for
') to 11 days. The drug removed 273 of 311 whipworms from
9 dogs, or 88 percent, and removed all whipworms from 4 of
6 infected animals. The safet.v of this treatment has not been
established. Although it has never come into general use, it
would seem worthy of trial.

The use of drugs injected into the cecum by means of a
catheter passed per rectum has been advocated for the removal
of whipworms. However, it is extremely difficult to pass a
fiexable rubber tube in such a way that the operator has any
assurance that the orifice of the catheter is opjiosite the ori-
fice of the cecum and that the drug actually enters that organ.
In critical tests, Underwood, Wright and Bozicevich (1931),

*Chitwood (personal communication) has obtained 100 percent effi-
cacy for whipworms when n. butyl chloride was administered in Ice
hard gelatin capsules at the rate of Ice per kilo body weight and with
no purgative. Purgatives appear to lower the efficacy of this drug.

340

using ti'tiju-liUiiotliyU'iic, oil of ilu'iiniuiiliuiii or ctliyluk'iu'
cliloriilf, olitaiiK'd an efHiiuy of 100 iioici'iit in one dog, H.l
pi'iTont. in a second dog but. complete fnihire in 11 other
animals.

Surgical intervention witli tlic removal of tlic cecum is prac-
ticed by some veterinarians who report veiy good results in
cases in wliich it is impossible to remove the worms by anthel-
mintic treatment. Symptoms of abdominal distress with alter-
nating constipation and diarrhea associated with whipworm
infection are said to l)e relieved permanently following re-
moval of the cecum. While this method will not obviate rein-
fection, subsequent infections in the colon are usually of very
light di'grec and not associated with clinical sym])toms.

•niK.\T.Mr.NT KOR iWPILL.iRIA .\EROPHn-.\ .\ND CHKNOSOM.V
VULPIS IXrECTIONS

Intratracheal injection of various medicinal substances has
been advocated in the treatment of these very serious parasites
of foxes on fur farms but it is doubtful whether any great
benefit has resulted. On the other hand, the develoinnent within
recent years of the tracheal swab-syringe and the tracheal
brush for the mechanical removal of Inngworms from the
trachea of the fox has provided a fairly satisfactory metliod
for the removal of worms which are actually in the trachea, the
instruments owing to mechanical difficulties being of little
value for the removal of worms from the bronchi or bronchioles.
Hanson (l!t33), who was largely instrumental in developing
this method of treatment to its present satisfactory state, has
l)ublishcd results of critical tests with the instruments and de-
tailed information concerning their use. This method of treat-
ment is more effective in the case of C. aerophila than with
Crciiosoma vulpLi, since the latter parasite is more frequently
located in the bronchi and bronchioles, where it cannot be
reached by the tracheal brush or swab.

Recently Russian investigators have reported that a solu-
tion consisting of iodine, 1 gram; potassium iodide, 2 grams;
and water, 1,;")00 cc. is effective for the destruction of these
parasites when injected intratraeheally. The animal is placed
on its back with the head elevated at an angle of 30 degrees.
One-half the dose is injected while the animal is rolled slightly
to one side; then the animal is rolled slightly to the other
side and the remainder of the dose injected. The treatment
is repeated after 8 da.vs. Maximum doses are 3 cc. of the solu-
tion. It is reported that maximum doses remove 80 percent of
the lungworms.

TRE.\TMENT FOR SPIROCEBCA LUPI INFECTION

There is no anthelmintic treatment of value in this condi-
tion. Treatment is symptomatic with the view of relieving the
cough and nausea and maintaining the condition of the animal.
Oil of chenopodium has been suggested but it is unlikely that
worms in the tumors would be affected. On theoretical grounds,
chlorinated hydrocarbons, such as carbon tetrachloride, should
be more penetrating and more effective than chenopodium.
Suehanek (1932) reported a case of spirocercosis in a dog
which was diagnosed by means of X ray and the esophagoscope.
The dog was placed under chloral hydrate narcosis, the blade
of a scalpel was fixed in a pair of forceps which were passed
through a tube and, with the aid of the esophagoscope, the
tumor was removed.

TREATMENT FOR PHYSALOPTEKA SPP.

Ehlers (lSi31) reported on the anthelmintic treatment for in-
fections with Physalopicra sp. in badgers {Taxidra laxits)
and it is probable that the treatments found effective can be
used also on other animals. Tetrachlorethylene in doses of
0.5 to 1 cc. (8 to 1(3 minims) failed to remove the worms but
a dose of 5 cc. killed all physalopterids although it proved fatal
to one animal. Ehlers stated that the drug deserves further
trial in doses of 1.3 to 2 cc. (20 to 32 minims). Carbon disul-
phide was found to be very effective in doses of 0.8 to 1 cc.
(12 to Ki minims), administered after a period of fasting for
18 to 24 hours, and followed in ti hours by a table spoonful
(1.5 cc.) of castor oil mixed with honey, a mixture which bad-
gers will eat readily out of a spoon. While the administration
of a purgative is desirable, no ill effects w^ere observed in
those animals to which a purgative was not given.

TREATMENT FOR DIROPILARIA IMMITIS INFECTION

Fouadin (sodium antimony III pyrocatechin disulphonate of
sodium ) has been used more extensively than any other drug
for this condition. As .shown by Wright and Underwood (1934).
a suitable course of treatment results usually in the permanent
disappearance of microfilariae from the peripheral circulation,
in the sterilization of female worms, and in the eventual de
stniction of some or all of the adult worms in the heart and

Body tfeiglit of dog

pulmonary aitery. The action of Foiuidin oTi adult worms is-
cumulative and is exerted over a relatively long period of
time. The destruction of any considerable number of adult
worms at any one time ina.v result in embolic pneumonia or in
an acute toxemia with consequent danger to the life of the
l)atient. Cons<'(|uently, heavily infected animals should be
treated with caution and in such animals treatment should not
lie administered rajiidly, or in large doses, or at too frequent
intervals. The adTuinistration of moderate doses of the drug
over a period of time results in a central necrosis of the liver
and in an acute toxic nephrosis. The liver damage may lead
to guanidine retention with a lowering of the blood calcium
level. Symptoms of calcium tetany should be combated through
the use of calcium gluconate. Considerable judgment must be
exercised in the administration of this treatment and due
weight should be given to the presence of chronic or acute
disease conditions which might influence the tolerance of the
animal for the drug. Wright and Underwood recommended the
following dose rates for intramuscular and intravenous injec-
tions for dogs in good physical condition and not suffering
from cardiac, hejiatic or renal disease: these dose rates have
been generally followed by most veterinarians.

IiilraitiKucuIar inject ioins

Daily dose Daily dose Daily dose
for first 6 for second after sec-
days 6 days and 6 days-
cc. cc. cc.
Under 10 kgms. (22 lbs.) 0..1 1.0 1.0
10 to ir, kgms. (22 to 33 lbs.) 1.0 1..5 1.5
l.T to 20 kgms. (33 to 44 lbs.) 1.0 1..5 2.0
20 to 25 kgms. (44 to 55 lbs.) 1.5 2.0 2.0
Over 25 kgms. (55 lbs.) . 2.0 2.5 2.5

Intravenous injections

Days of treatment

Body weight of dog 1st 3rd 5th 7th 8th 9th 10th 12th
['nder 10 kgms. (22

lbs.) - 0.5 0.5 0.5 1.0 1.0 1.5 1.5 1.5

10 to 15 kgms. (22 to

33 lbs.) - 1.0 1.0 1.0 1.5 1.5 2.0 2.0 2.0

15 to 20 kgms. (33 to

44 lbs.) -.- 1.5 1.5 1.5 2.0 2.0 2.5 2.5 2.5

20 to 25 kgms. (44 to

55 lbs.) 2.0 2.0 2.0 2.5 2.5 3.5 3.5 3.5

Over 25 kgms. (55

lbs.) 2.5 2.5 2.5 3.5 :\5 5.0 5.0 5.0

Intramuscular injections are without apjjreciable unfavora-
ble local reaction and are particularly applicable for use in
small dogs in which the subcutaneous veins are so small as ta-
make intravenous injections difficult. However, intravenous ad-
ministration permits the use of a smaller total dose in most
cases, and the results desired are obtained in a shorter period
of time.

In connection with other treatments, Hayes (1933) recom-
mended the use of an antimony preparation called "Filsol,"
the chemical composition of which has never been made public.
This preparation appears to be more toxic than Fouadin and
should be used with even greater caution.

Brown and Austin (1939) have published case reports on the
use of "Stibsol." said to be antimonial-3-catechol-thiosalicylic-
acid-sodium, and to contain 30 percent of antimony. The solu-
tion contains approximately 8.5 mg. of trivalent antimony per
cubic centimeter. These investigators recommend for this
compound the same dose rates as recommended by Wright and
Underwood for the intravenous injection of Fouadin. Evalua-
tion of the efficacy of this compound must await either the
publication of more extensive and more critical tests or the
results of field trials in relatively large numbers of cases.

Simonelli (1936) and Lucas (1937) have reported success-
ful results in the treatment of canine filariasis following the
use of emetine hydrochloride at dose rates varying from 10 to
60 mgm. per day, but more critical evidence is needed before
this treatment can be evaluated. The drug had been previously
used by MacCallum (1921) for this purpose.

Anthelmintic Medication for Nematode Parasites
of Swine

TREATMENT FOR ASCARIS SUUM INFECTION

On. OF Chenopodium. This is probably the most effective
treatment available at the present time. The drug is given at
a dose rate of V2 to 1 fluid dram (2 to 4 cc.) for a 100-pound
(45.5-kilogram) animal, immediately preceded or followed by

341

at least 2 fluid ounces (GO ee.) of castor oil, or the drug nun-
be administered with the oil. Doses for animals of various
sizes should be computed on a weight basis, though it is likely
that a dose of 2 fluid drams is adequate for animals weighing
300 to 400 pounds (136.4 to 1S1.8 kilograms). The drug mav
be given with a dose syringe or by stomach tube. The animals
should be fasted for 18 to 24 hours prior to treatment and
should not be fed or watered for 3 hours after treatment.
Oil of chenopodium should not be given to animals suffering
from gastroenteritis, constipation or febrile conditions, or to
very young animals or sows in advanced pregnancy. If a herd
is to be treated without regard to possible contraindications in
individuals, the lower dose rate of chenopodium should be used.

Santonin. Santoniu has been widely recommended as a
treatment for the removal of ascarids from swine. At various
times, it has been tested critically by Mote, Vadja, Shillinger,
and others, all of whom have found that santonin in the doses
commonly recommended and given in the manner usually rec
ommended exhibits a relatively low efficacy for the removal of
these worms. Under these conditions, the efficacy of santonin
does not compare favorably with that of oil of chenopodium.
More recently, Morris and Martin (1931) as well as Shcherbo-
vich (1935) have found that santonin administered in relative-
ly large doses and followed by an adequate dose of an active
purgative, such as magnesium sulphate or castor oil, will re-
move a large percentage of the ascarids from swine. Morris
and Martin administered santonin at dose rates varying be-
tween 1/6 to % grain (10.7 to 43 mgm.) per pound (4.j cgm.)
of body weight, followed in 12 hours by 1 dram (4 grams)
of magnesium sulphate per pound of body weight. It would
seem that adequate purgation is necessary and relatively large
doses required if satisfaetorj' results are to follow the use of
this drug

PHiiNOTHi.^ziNE. Swanson, Harwood and Connelly (1940)
have recently reported on the use of this drug for swine and
it appears to have considerable efficacy for the removal of as-
carids. However, better results were obtained in the removal of
mature ascarids than in the removal of immature forms. In
view of the marked efficacy of the drug for the removal of
nodular worms from swine, it could probably be used to ad
vantage in animals in which both kinds of worms are present.
The above mentioned investigators have suggested dose rates
of phenothiazine for experimental use in swine and these may
be found under the treatment for Oesophagostomum spp.

TREATMENT FOR THE REMOVAL Or HOOKWORMS

Satisfactory medication has not been established. On theo
retical grounds, some of the chlorinated hydrocarbons would
seem to be promising. However, Eaffensperger, as reported by
Wright and Raffensperger (1930), did not find carbon tetra-
chloride in a dose of 25 cc. in 75 cc. of castor oil for pigs
weighing 125 pounds effective for the removal of Gtobocephahis
urosubulatus. Tetrachlorethylene or n-butyl chloride might be
more promising since carbon tetrachloride is not well tolerated
by swine and is more soluble.

TREATMENT FOR THE REMOV.\L OF SWINE STOMACH WORMS

Bozicevich and Wright (1935) found that carbon disulphide,
administered in capsules or by stomach tube, at a dose rate of
0.1 cc. per kilogram (2.2 pounds) of body weight, or 4.5 cc.
for a 100 pound pig, was approximately 90 percent effective
for the destruction of Hyostrongylus rubidus and even more
effective for the removal of Ascarops strongylina. Food must
be withheld for 36 to 44 hours prior to treatment, as the
presence of food in the stomach interferes with the action of
the carbon disulphide and acts to reduce the efficacy of the
treatment. Lower doses of carbon disulphide were less effec-
tive. Pigs killed 2 hours after treatment showed a slight to
moderate gastritis but, as in the administration of carbon di-
sulphide to horses, this gastritis does not constitute a marked
objection to the use of the treatment as it probably clears up
rather quickly. It appears that this treatment should be effec
five also for the removal of Physocephalus sexalatus and other
nematodes occurring free in the stomach of awine.

TREATMENT FOR THE REMOVAL OF NODDLAR WORMS,
OESOPHAGOSTOMUM SPP.

Of a number of drugs tested for the removal of these worms,
none showed a high efficacy until Harwood, Jcrstad and Swan-
son (1938) and Swanson, Harwood and Connelly (1P40) dem-
onstrated the marked efficiency of phenothiazine for this pur-
pose. In experiments reported bj' the latter investigators, con-
ditioned phenothiazine removed 4,753, or 92.1 percent, of 5,162
nodular worms from 22 pigs. In other tests, recrystallized
phenothiazine showed approximately the same degree of effi

cacy. Swanson, Harwood and Connelly recommended the fol-
lowing dose rates for phenothiazine for experimental use in
swine :

tr eight of pig Size of dose

Up to 11.4 kgm. (25 lbs.) 5 gm. (1.2 drams)

11.4 to 22.8 kgm. (25 to 50 lbs.) 8 gm. (2.0 drams)
22.8 to 45.5 kgm. (50 to 100 lbs.) 12 gm. (3.0 drams)

45.5 to 91.(1 kgm. (100 to 200 lbs.) 20 gm. (5.0 drams)
Over 91 kgm. (200 lbs.) 30 gm. (7.5 drams)

Phenothiazine may be administered to swine in hard gelatin
capsules if the operator is sufficiently skilled to avoid lodging
the capsules in the pharyngeal pouch, or it may be adminis-
tered mixed with any ground feed to which the pigs are ac-
customed. Pigs varying greatly in size should not be treated
at one time in the latter manner, and the chemical should not
be offered to the animals except when they are sufficiently
hungry to consume the medicated food at once. The efficacy
of the drug when administered with the feed needs further
investigation but this promises to be a very valuable method
of treatment.

TREATMENT FOR STEPHANURUS 0ENTATUS INFECTION

No effective treatment is known for the destruction of swine
kidney worms. Turpentine has been recommended on the
ground of the great diffusibility of the drug but it has not
been established that the drug could reach the adult worms in
the perirenal fat. Kauzal (1932) interpreted his experimental
results with carbon tetrachloride as indicating that the treat-
ment was of some benefit, as no worms were found in the liver
of one of the treated animals, while worms in the liver of a
second animal were encapsulated. It is possible that this drug
might check the migration of worms or destroy migrating
worms in the liver, although it is probable that the drug would
have no effect on adult worms in the perirenal tissue.

TREATMENT FOR LUNGWORM INFECTIONS

Freeborn (1916) recommended the injection into the nostrils
of swine of 5 cc. of chloroform repeated at intervals of 3 to 5
days until the infection is controlled. However, there is no
critical evidence that this treatment is effective in the de-
struction of the worms.

Skrjabin and Schul'ts (1936) reported that one part of
chlorine in 30,000 parts of air had little effect on the host
after one hour and claimed that this exposure destroyed 73.3
percent of the lungworms present. The same authors also
recommended intratracheal injections of the iodine solution
described under the treatment of lungworms of carnivores.
The doses employed for swine are 0.25 cc. per kilogram of body
weight for small pigs and 0.5 cc. per kilogram of body weight
for average sized pigs.

The treatment which appears to be safest and best is good
nursing in connection with an abundance of good feed and
adequate shelter. In the absence of specific therapy, emphasis
should be placed on prevention and animals should be isolated
and removed from areas where the intermediate hosts are
prevalent.

TREATMENT FOR TRICHURIS SUIS INFECTION

Medication for whipworm infection in swine is entirely un-
certain and no effective treatment is known at present. Single
doses of various anthelmintics will remove a few whipworms
at times but consistent results are not obtained with any of
them. In the absence of more information concerning the
pathogenicity of this parasite, chemotherapy dors not s?em to
be a matter of any considerable importance.

Anthelmintic Medication for Nematode Parasites
of Equines

TRE.iTMENT FOR PARASCARIS EQUORDM INFECTION

Carbon Disulphide. This drug is probably the most effec
five treatment available. It should be administered in a dose
of 6 fluid drams (24 cc.) for a 1,000 pound animal, after a
fast of 18 hours, or at a dose rate of 1.5 fluid drams (6 cc.)
for each 250 pounds of body weight. No purgative is needed
but a saline purgative may be advisable in the case of heavy
infections; oils should be avoided as they increase absorption
and add to the toxity of the drug. Carbon disulphide should be
administered by stomach tube; if capsules containing the drug
are broken in the mouth, asphyxiation and death may result.
Capsules containing carbon disulphide adsorbed on various
kinds of powdered material are available; these capsules un-
doubtedly are safer to administer but fail to provide the same
high efficacy as exerted by the liquid drug. Carbon disulphide
produces a well marked inflammatory reaction in the stomach
and upper duodenum. This inflammation usually clears up in
a short time however. Carbon disulphide is contraindicated in

342

till' iiroseiioe of Ku^^tro entoiitis; it is luit indicated in the
treatment of pregnant mares.

C.VRBON Tetr^\chix)Kide. This is also an oft'cetive treatment
for tlie removal of asearids from horses. It is given in the
same manner as for the removal of strongyles, but in heavy
asearid infections it is advisable to follow the drug by a
saline iiurgative in order to sweep out dead worms and jire
vent their oluniiiing in the small intestine. This is particularly
indicated in the case of foals.

PllENOTHiAZlNH. E.xperiments indicate that this drug will
remove some asearids but more data are needed before it can
be established as a satisfactory treatment.

TREATMENT FOK THE RE.MOVAI, OF L/VRGE AND S.MAI, I. .STRONGYLES.
STRONOYLUS SPP., TRU'HONEMA SPP. AND RELATED GENERA

Oil OF Chenopodium. Chenopodium is very effeetive for the
removal both of large and small strongyles. Aninuils slumld
be fasted for 3ti hours and oil of chenopodium administered in
a dose of 4 to 5 fluid drams (16 to 20 cc.) for a 1,000 pound
animal, or at a dose rate of 1 fluid dram (4 cc.) for each 2.'i0
pounds of body weight, immediately preceded or followed by
1 quart of raw linseed oil. Cases of excessive jmrgation have
been reported in some instances following the use of raw lin-
seed oil. It is possible that this undesirable action is due to
impurities in the product ; consequently a good grade of oil
should be used. Veterinarians' of the V. S. Army have pro-
posed a substitute puigative of castor oil and mineral oil,
claiming that this mixture provides snitalde purgation fol-
lowing treatment with chenopodium and is without undesirable
effects. The following are the doses of the mixture recommend-
ed: For weanlings, castor oil 4 to 6 ounces and mineral oil
1 pint; for yearlings and 2year-olds, castor oil 6 to 8 ounces
and mineral oil 1 pint ; for 3-year-olds and older, castor oil 8
to 10 ounces and mineral oil 1% pints. Oil of chenopodium is
contraindieated in the presence of constipation, gastroenteritis
and febrile conditions, and in pregnant mares.

Carbon Tetrachloride. This drug is effective for the re-
moval of large strongyles but only about 50 percent effective
against small strongyles. It should be given in capsule or by
stomach tube in a dose of 6 to 12 fluid drams (2.'') to 50 cc. )
for a 1,000-pound animal after fasting for 24 to 36 hours. The
drug need not be accompanied by a purgative but if one is
used, sodium sulphate is to be preferred. If linseed oil is used,
it should be given 4 to 5 hours after carbon tetrachloride. The
administration of carbon tetrachloride to equines is followed by
a fall in the blood calcium level and by a marked increase of
bilirubin in the blood. In carbon tetrachloride intoxication, it
is advisable to use calcium gluconate. The drug is contrain-
dieated in animals suffering from hepatic disease or from cal-
cium deficiencies, such as rickets or osteomalacia.

N-Butylidene Chloride. In a dose of 0.2 cc. per kilogram
of body weight, this compound is very effective for the removal
both of large and small strongyles. It is probable that the
dose could be reduced to 0.15 cc. per kilogram without ma-
terially aifecting the efficacy of the treatment; this dose is
equivalent approximately to 70 cc. for a 1,000-pound animal.
As n-butylidene chloride is constipating, it is advisable to fol-
low the drug in 5 hours by raw linseed oil in a dose of 1 quart
for a 1,000 pound animal.

N-BUTYL Chloride. Because of the relatively higher cost
of n-butylidene chloride, Harwood, Underwood and Schaffer
(1938) tried n-butyl chloride for the removal of strongyles.
In a dose of approximately 0.2 cc. per kilogram of body weight,
the compound proved very effeetive for the removal of small
strongyles and reasonably effective for the removal of large
strongyles. In the tests in question, the drug was given in 10
times its volume of raw linseed oil. In tests by the above-
mentioned workers, two horses succumbed to treatment with
doses ten times the therapeutic dose. It would appear that
the compound is not as safe as is n-butylidene chloride and that
further tests are needed to clarify this point.

Phenothiazine. This is a very effective drug for the re-
moval of strongyles from horses. Several authors have reported
excellent results following the use of doses varying from 30 to
100 grams for adult animals. However, the only critical ex-
periments reported thus far were by Harwood, Habermann,
Roberts and Hunt (1940) and Habermann, Harwood and Hunt
(1941). In the tests described in the latter paper, it was
found that this drug in doses varying from 50 to 100 grams
per equine removed practically all of 362,797 cylicostomes and
96 percent of 137 Strongyliis spp. These authors concluded
that the dose per adult equine should be held at 50 grams
pending additional critical experimentation with smaller dos-
ages. In some instances, a dose of 50 grams failed to remove
a few of the Strongyliis spp. present In the treated animals
and, since these are the most pathogenic of the nematodes
present in equines, it does not seem advisable to employ dos-

ages of ;i(i giams per horse such as recommended by Taylor
and Sanderson (1!I4I)) on the basis of tests checked by the egg
count method alone.

Single doses of ])henothiazine as high as 500 grams have
been given to horses without producing alarming symptoms,
but these dosages may cause pronounced cloudy swelling of
the liver, the formation of methaemoglobin, and anemia (La-
page, 1040; Habermann, Harwood and Hunt, 1941). Single
doses of 1,00(1 grams have produced fatalities in horses. Since
the toxic manifestations appear to be associated with the de-
struction of the erythrocytes, it is advisable to administer the
drug cautiously to horses suffering from anemia. The Bureau
of Animal Industry has issued a press release terming poor,
weak animals and those suffering from infectious anemia as
bad risks for treatment and it would appear that the drug
. should be employed with considerable caution in such cases.

Hatcher (1941) reported the death of 5 of 12 horses, each
of which was given a dose of approximately 120 grams of
phenothiazine as an anthelmintic. Under experimental condi-
tions, doses of this size have caused no symptoms other than
discoloration of the mucous membranes, transient loss of ap-
petite and a temporary anemia. Grahame, Morgan and Sloane
(1940) administered 100 grams to each of 35 horses without
accident, and others have reported similar results. Possibly
under certain conditions horses may prove more sensitive to
phenothiazine than present experimental evidence suggests. As
a measure of precaution, wholesale treatment should be avoided.
The Bureau of Animal Industry recommends that when large
numbers of animals are to be treated with this drug, one or
two, the least valuable of the lot, be treated first to determine
tolerance for the drug. Such animals should be kept under
observation for a week before others are treated. If no bad
results are observed, the remaining animals should be treated a
few at a time and the observations repeated. This procedure
should be followed until the entire group has been treated.

Phenothiazine may be administered to horses in gelatine cap-
sules or in a suitable suspension. In order to make a suspen-
sion of phenothiazine suitable for administration to animals,
it is necessary to use some chemical as a dispersing agent.
Numerous dispersing agents are known and many of these have
been employed ; however, few of these suspensions have been
given critical test. It is known that certain agents will greatly
reduce the efficacy of phenothiazine when such chemicals are
employed as suspending agents. Therefore, it is not advisable
to employ such mixtures unless they have been tested critically.
A formula which has been found satisfactory consists of
phenothiazine 50 grams (1.67 ounces), molasses 20 cc. (0.67
fluid ounces), and water to make 90 cc. (3 fluid ounces). The
molasses is thoroughly mixed with the phenothiazine, then a
small portion of water is added and thoroughly stirred in.
The process of alternately adding water in small quantities
and of stirring is repeated until a smooth suspension of the
required volume results. Also, phenothiazine may be mixed
with almost any ground feed. Since certain animals do not
take readily feed medicated with phenothiazine, the following
regimen may be employed :

For one week prior to the administration of the drug the
horse should receive no salt. During this time it should re-
ceive daily one pint of a mixture containing equal parts of
oats and bran to which 50 grams (about 2 fluid ounces) of
molasses have been added. For administration of the drug,
.50 grams (1.67 ounces) of phenothiazine is incorporated in
about 150 grams (about 5 fluid ounces) of molasses, and this
mixture is mingled thoroughly with 2 quarts of an oats bran
mixture. Two ounces of salt are added to this formula. While
fasting is unnecessary, the medicated mixture should not be
placed before the horse until the animal is hungry. If the
horse hesitates to eat the medicated mixture, it may often be
encouraged to do so by sprinkling a small quantity of untreated
oats or corn over the surface of the mixture. Even if the drug
is administered in the feed, it is better to treat horses indi-
vidually rather than to attempt mass treatment.

treatment for lungworm intection

Skrjabin and Schul'ts (1936) and Kulikov and Tamarin
(1937) have advocated the use of iodine in a solution of po-
tassium iodide for the removal of lungworms from horses. The
material is injected intratraeheally while the horse is on its
back, slightly inclined to one side for the first half of the
injection, and to the other side for the remainder. The dose
is 250 to 300 cc. of a 0.1 percent solution of iodine in a 0.2
percent solution of potassium iodide.

trb^tment for oxyuris equi infection

Oil of turpentine is an effective treatment for the removal
of pinworms from the horse. Animals should be fasted for

343

36 hours and the drug administered in a dose of I! fluid ounces
(60 cc.) for a 1,000-pound animal, immediately preceded or
followed hj 1 quart of raw linseed oil. The drug should not
be given to animals already suffering from renal disorders.

Oil of chenopodium, as administered for large and small
strongj'les, is effective also for the removal of pinworms.

TREATMENT FOR THE REMOVAL OF STOMACH "WORMS

Carbon disulphide in a dose of 6 fluid drams (24 cc.) for a
1,000-pound animal, preceded by gastric lavage with S to 10
liters of a 2 percent solution of sodium bicarbonate, is very
effective for the destruction of Eabroncma muscae and H.
microstoma, as determined by Wright, Bozicevich and Under-
wood (lt)31). Without preliminary lavage, the drug gave less
favorable results in the tests of these investigators. Appar-
ently the alkaline solution serves to remove excess mucus from
the stomach wall and permits the drug to reach the parasites
more effectively. Furthermore, the solution seems to give
some protection against the irritating action of the carbon
disulphide. In the above-mentioned experiments, Draschia
megastoma in stomach tumors was not affected by the treat-
ment. It is advisable, though not necessary, to siphon oft the
sodium bicarbonate solution ."> to 10 minutes after its admin
istration. The contraindications for the treatment are the
same as those listed under the discussion of this drug for the
removal of asearids.

While not determined by critical tests, it would appear that
carbon disulphide would be a fairly satisfactory treatment for
the destruction of Irk-)iost>oiigi/his axci in the stomach of the
horse.

Anthelmintic Medication for Nematode Parasites
of Ruminants

TREATMENT FOR STRONGVLOIDES PAPILLOSUS INFECTION

There is no established treatment for strongyloidosis. The
parasite appears to be resistant to most of the anthelmintics
commonly employed in sheep and even prolonged dosage with
some of these drugs fails to eradicate it. Gentian violet, the
only known drug which has shown any specificity against
worms of this genus, has not been tried in ruminants.
TREATMENT FOR INFECTION WITH TRICHURIS SPP.

Like whipworms in other animals, those forms occurring in
ruminants are difficult to remove. Occasional whipworms will
be removed by many of the anthelmintics used for the removal
of other worms from sheep but there is no specific treatment
available at the present writing. The enema treatment de-
scribed under therapy for oesophagostomiasis is said to be
fairly effective against T. oris. However, in view of the lack
of evidence concerning the pathogenicity of the parasite, there
would be little need for the use of the treatment in uncom-
plicated infections.

TREAT.MENT FOR INFECTIONS WITH OESOPHAGOSTOMUM SPP.

Phenothiazixe. The introduction of phenothiazine by Har-
wood, Habermann and Jerstad (1939), provided the first an
thelmintic which is useful for the removal of 0. columbiauiim
when administered orally in a single dose. These investigators
found that the conditioned drug administered as 20 percent of
a meal of concentrates after a period of fasting at a dose rate
of 0.5 gram per pound of body weight removed 90 percent of
the nodular worms, almost SO percent of the Haemonchus, 76.7
percent of the hookworms, and apparently 100 percent of the
Ostertagia. Subsecjuent investigations in the U. S. Bureau of
Animal Industry (Habermann and Harwood, 1939; Haber-
mann, Harwood, and Hunt, 1940) demonstrated that either
rccrystallized phenothiazine or the ci'ude non-conditioned drug
was even more effective than the product which had been con-
ditioned for use as an insecticide and which was employed in
the earlier tests. A dose of 25 grams has been recommended
for adult sheep. These results have been confirmed by a num-
ber of other workers, including Swales (1939), Roberts (1939.)
and Gordon (1939).

Swales administered phenothiazine in an enema without ob-
taining any efticacy for the removal of Chabcrtia ovina or 0.
culumbiaiiiim. This finding would .seem to confirm the view
of Harwood and his associates that the drug probably under
goes some chemical change in the digestive tract of the host
which acts to promote its efficacy. Failing to find that sheep
regularly consumed mixtures of the anthelmintic with the feed.
Swales reduced the bulk of the commercial product by prepar-
ing compressed tablets according to the following formula :

Commercial phenothiazine (pulverized) SO parts

Starch ( pulverized 1 S parts

Effervescent salt (sodium bicarbonate, ."0 parts,

dehydrated tartaric acid, 45 parts) 9 parts

Dried ox gall 2 parts

Phenolplithalein _ _ __. 1 part

The individual dosage of sheep at the rate of 0.3 gram of
phenothiazine for each pound of bod^' weight in Swales' ex-
periments was very effective for the removal of H. contort ux,
Bunostomuiii trigonoccphaUim, 0. colKiiibiarium, Chabertia
uviiia, Ncmatodirus sp., Cooperia sp. and Ostertagia sp. The
treatment was approximately 50 percent effective for the re-
moval of Tricliontroiigi/Uix spp. but was apparently ineffective
against Strungijloidcs and Capillaria longipes.

Roberts (1S>39) tested Thio.x, a commercial preparation con-
taining 93 percent phenothiazine, on a large number of ani-
mals and found that satisfactory results were secured against
0. cohimbianum with a dose rate of 0.15 gram per pound of
body weight given immediately after previous stimulation of
the oesophageal reflex with 2 cc. of a 10 percent copper sul-
phate solution and following a 24-hour fast. Without fasting
or the use of the copper sulphate, a dose of 0.4 gram per
pound was effective. Good results were obtained also against
H. contortus but the treatment failed to remove Trichuris par-
vispiciilum and T. globulosa. In certain of Roberts' tests some
of the sheep failed to respond to treatment even with the higher
dose rate of the drug.

Gordon (1939) confirmed also results against II. c(iiitortii.i
and nodular worms. He found also that phenothiazine in a
dose of 0.6 gram per kilogram (2.2 pounds) of body weight
reduced the egg counts of Triclio.stroiigi/liis spp. by 90 peicent
or more. Small daily doses of the drug ( 1 gram daily for -5 ■
days) were effective against the common stomach worm and the
nodular worm.

Insoluble Copper Salts. A treatment which was developed
by Monnig (1935) in South Africa is of considerable value
against 0. cohimbianum but does not approach the efficacy of
jiheiiothiazine. This treatment consists in the administration
of certain insoluble salts of copper in the proportions and
doses given below :

Dosage in grams for sheep

of various ages

Over 6
3 to 6 and under Over
Drug Parts months 18 months IS mo)ilh.i

Copper arsenate __ 2 0.2 0.36 0.5

Calcium hydroxide 3 0.3 0.54 0.75

Copper tartrate 5 0.5 0.9 1.25

Total dose in grams 1.0 1.8 2.5

In an effort to deliver the mixture into the abomasum, the
sheep are given 2.5 cc. each of a 10 percent solution of copper
sulphate and this is followed immediately by the appropriate
dose of the mixture. Sheep should be watered immediately be-
fore treatment but should be fasted for 48 hours prior to dos-
ing and 24 hours after dosing. Water should be withheld for
1 to 2 hours after treatment. Recommendations call for ro-
peating the treatment on the following day. The treatment
is said to have a fair degree of efficacy against E. contortus
and Moniezia crpansa.

Enema Treatment. This treatment, originally recommended
by Brumpt 35 years ago, has more recently been developed
further by South African and Australian workers. The tieat-
ment consists of a solution of 2 grains (125 mgm.) of sodium
arsenite per liter of water. The solution is administered by
enema in the following doses:

Lambs up to 4 months of age 1 pint

Lambs 4 to 6 months „. 1.5 pints

Six months old to 2-tooth sheep 1 quart

Aged sheep _ _ _ . 1.5-2 qts.

Sheep should be fasted for 24 hours before treatment. The
solution may be allowed to flow by gravity, may be given by
syringe, or may be injected by a specially devised apparatus.
The forced in,iection of the solution involves some risk and
deaths have followed its use. This method of treatment is time
consuming and ill adapted to large scale application.

Swauson, Porter and Connelly (1940) found that uncondi-
tioned phenothiazine removed 99. S percent of 0. radiatum from
calves when the drug was administered in doses varying from
50 to 80 grams (0.44 to 1.1 gram per kilogram of body weight).
While it is not possible to make definite therapeutic recom-
mendations on the basis of these preliminary experiments, it
would appear that phenothiazine is of considerable promise for
the removal of nodular worms from cattle.

treatment for CHABEHiTIA OVINA INFECTION

As previously stated. Swales found phenothiazine 100 percent
effective for the removal of these worms from a limited num
ber of animals. Habermann and Harwood (1939) reported

344

lator tliat iioii coiuiitiHiii'd plionotliiaziiio in doses of ['.' Id 12
grains lemoved 2<i.7 i)eri-oiit of 12(5 Clutbcrda from li slieep; in
dosos of In to 2(1 grams, 47.9 lu'reont of 4S worms from .'i
slioep; and in doses of 22 to 2G grams, i)3.8 percent of 32
worms from 3 slieep. The enema treatment described under O.
foliiiiihidiiKm is .said to be satisfactory also.

TRE.^TMKNT FOR (l.\IGERI.\ PACHYSCELIS INFECTION

Ortlepp (193.1) found tetrachloretliyleiie effective for the
removal of these worms when given in a dose of 10 cc. in 10
to 20 cc. of liquid paraffin and immediately preceded by a dose
of 2..") cc. of a 10 percent solution of copper sulphate to stimu-
late closure of the oesophageal groove. Smaller doses should
be used for lambs and young sheep. Fasting is not necessary.
Treatment should be repeated twice at intervals of 10 to 14
days. Some reactions may be encountered with this relatively
large dose of tetrachlorethylene.

To reduce the number of reactions, Ortlepp and Monuig
(193(i) investigated a number of preparations containing tetra-
chlorethylene. The results of a limited number of experimen-
tal trials suggested that an emulsion consisting of 25 cc. of an
aqueous solution of 7.7 grams of soft soap, 37.5 cc. of tetra-
chlorethylene and 37. .J cc. of liquid paraffin might be satisfac-
tory-. Later croton oil was added in a dose of 1 cc. to each
40 cc. of the emulsion which contained 10 cc. of tetrachlor-
ethylene, this amount of the emulsion being the dose for an
adult animal.

Subsequently, certain disadvantages were encountered in the
use of this emulsion and Mbunig and Ortlepp (1939) conducted
further experiments in order to devise a more satisfactory
vehicle for the tetrachlorethylene. The formula finally worked
out was made up, as follows: To -"iOO cc. of tapwater heated to
70° C. are added 6 grains NaOH and then 40 grams of casein
is rapidly stirred in. The solution is then heated to S.l" C. and
40 grams of ground resin is stirred in rapidly. A highly sa-
ponifiable resin should be emplo.ved and this should be ground
to a fine powder. The solution should be kept at S."i' C and
stirred for about Id to 20 minutes until complete combination
of the alkali with the other ingredients has occurred. It is
then made up to SOO cc. with cool water. The tetrachlorethy-
lene is added in successive small quantities while mixing pro-
ceeds in the proportion of 7.3 cc. of tetrachlorethylene to 2.j cc.
of the emulsifier. The emulsion is issued in concentrated form
and is diluted with an equal quantity of water before use.
The dose for an adult sheep is 20 cc. of the diluted emulsion
(i.e. 7.5 cc. of tetrachlorethylene) for adult animals; 15 cc.
for lambs 6 to 12 months old, and 10 cc. for lambs 3 to 0
months old. The remedy is given after a preliminary dose of
2.5 cc. of 10 percent copper sulphate solution. This treatment
is said to be effective against Hacmonchus coiitortiis, Tiiclio-
utronffybis spp., A'ematodirus spp., Gaigeria pachijscrlix and
Bunostomum irigonocephalinn.

While no tests are on record, it would seem that phenothia-
zine would be effective against Gaigeria.

TREATMENT FOR BUNOSTOMUM TRIOONOCEFHAI-UM INFECTION

The phenothiazine treatment, as described under nodular
worms, is the most effective available at the present time.
Tetrachlorethylene, as used against Gaigeria, is also quite ef-
fective but is probably more hazardous. The "Cu-Nic" solu
tion, described under treatment for the common stomach worm,
will usually remove a high percentage of hookworms.

Little is known concerning removal of B. phU'botomum from
cattle but it is probable that the "Cu-Nic" solution would
be of value. For dosage, the reader is referred to treatment for
H. contortus. Swauson, Porter and Connelly (1940) reported
that phenothiazine in dosages of 50 to SO grams removed 1,160
of 1,729 B. phlebotomum from 6 calves. In these limited tests,
the unconditioned drug at a dose rate of 0.44 to 0.55 gram
per kilogram of body weight in calves weighing over 91 kilo-
grams (200 pounds) was less effective against this species than
when given to lighter calves at a dose rate of 0.66 to 1.1
grams per kilogram of body weight. The drug is promising
but more information is needed concerning its exact efficacy
;ind its safety for cattle.

TRBLYTMBNT FOR HAEMONCHUS CX)N"l'ORTUS INFECTION

Copper Sulphate. The treatment which has been used most
extensively is the copper sulphate solution devised by Hutcheon
(1891) in South Africa. In the United States a 1 percent
solution has been employed most commonly and this is admin-
istered in a dose of 50 cc. for sheep up to a year old and 100
ce. for mature sheep. The dose for calves is 100 cc, for
yearlings up to 200 cc, and for mature cattle up to 1 liter.
Where sheep cannot be adequately protected against severe in
fection by light stocking, pasture rotation and other measures,

tre;itiiieiil slioiilcl lie repeated in tcm])erate climates under con-
ditions of moderate stocking at intervals of 3 weeks. In warm
climates with heavy stocking of pastures, it is necessary to re-
peat treatment every 2 weeks. It is usually necessary to con-
tinue treatment throughout the wanner months of the year
and in warmer climates it may be of value to continue dosing
during the winter. Tlie repeated administration of copper
sulphate is apparently not detrimental to sheep and in fact
there is some evidence to indicate that animals so treated make
better gains that non-treated animals. Wright and Bozicevich
(1931) found that the 1 percent solution of copper sulphate
may be administered in the usual doses as often as once a week
without harm to sheep. When so administered, there is a
marked increase in the copper content of the liver after a
period of time with no appreciable pathological changes. In
view of the relationship of copper salts and liver to anemia,
the increased amount of copper in the livers of sheep treated
frequently with copper sulphate solution may be beneficial
rather than detrimental to the health of the animals.

The 1 percent solution may be made up on the basis of 1
gram of copper sulphate to 99 cc of water, or by dissolving
Vi pound of copper sulphate in 1 pint of boiling water and
adding cold water to make 3 gallons of the solution. This lat-
ter will make a quantity sufficient to dose 100 sheep, allowing
10 percent for waste. Only clear blue crystals should be used
in preparing the solution. Porcelain, enamelware or wooden
vessels should be employed, as copper sulphate solution will
corrode metal.

Various writers have advocated the use of a 1.5 percent
solution or stronger solutions of copper sulphate. As shown
by Cluiiies Ross (1934) and Monnig and Quin (1935) solutions
of this salt stimulate the closure of the oesophageal groove in
sheep with a resultant delivery of the solution directly into the
abomasum in a considerable proportion of the cases. No doubt
this quality of copper sulphate is responsible to a considerable
extent for its efficacy against H. contortus. Gordon (1939) has
shown recently that the usually prescribed dose in Australia,
i.e., 1 fluid ounce of a 4 percent solution of copper sulphate,
is not an efficient treatment against H. contortti.<i in adiilt sheep.
His investigations indicated that a dose of 2 iliiid ounces of
a solution of this strength was very effective in adult sheep.
Gordon (1939) determined also that the copper sulphate treat-
ment is relatively ineffective against immature Haemonchiis
and stated that apparent failures of treatment in severe out-
breaks of haemonchosis in the field could be explained on this
basis. As a result of the findings, Gordon suggested that in
flocks heavily infected with the parasite, treatment with copper
sulphate should be applied every 10 to 14 days.

Copper Sulphate and Nicotine Sui,phate. As previously
stated, the copper sulphate and tobacco solution of Lewis and
Guberlet and the nicotine sulphate solution of Lamson have
been replaced largely by the "Cu-Nic" solution developed by
Curtice. This latter solution is made up by adding 1 ounce
of 40 percent nicotine sulphate to each gallon of a 1 percent
solution of copper sulphate. The dose of the combined solu-
tion is 3.5 ounces (100 cc.) for adult animals and 1.5 ounces
(50 cc.) for weanling lambs. Experience has shown that this
solution is occasionally toxic for weak animals or for very
young lambs. Furthermore, the operator should be certain that
the precipitate, which forms in this mixture, is not allowed
to settle in the container from which the sheep are being dosed.
If there is any reason to believe that animals will not tolerate
the treatment, the dose should be reduced or trial treatment
should be made on a few animals to establish tolerance. For
cattle, the "Cu-Nic" solution may be used in the same doses
as for the 1 percent solution of copper sulphate. For sheep,
the solution is effective against immature as well as mature
Haemonchiis and in addition is a fairly satisfactory treatment
for the removal of hookworms, small trichostrougyles and
Monicsia expansa. In uncomplicated stomach worm infections,
it is probably of no great advantage over copper sulphate solu-
tion because of its greater toxicity.

Carbon Tetrachloride. While the use of this drug in un-
complicated stomach worm infections has been largely dis-
continued in the United States, it is still popular in Australia,
especially in concomitant liver fluke infections. In the United
States, it is usually given in gelatin capsules in a dose of 5
cc. for adult sheep and 2.5 cc. for weanling lambs. In Aus-
tralia, the doses employed are 2 cc. for adult sheep, aud 1 cc.
for lambs under 6 months of age, the drug being mixed with
4 parts of liquid paraffin. Not infrequently losses follow the
use of carbon tetrachloride in sheep and for this reason it
should be used with caution. Where the drug is used, precau-
tion should be taken to place the sheep on a diet rich in avail-
able calcium for 2 to 3 weeks prior to treatment. Changes in
feed other than to provide calcium should not be made for
several weeks prior to treatment ; animals appear to suffer

345

fewer reactions when maiutaiiied for several weeks ou pasture
prior to and subsequent to treatment with carbon tetrachloride.

Tetrachlokethylene. This treatment, tirst tested by Hall
and Shilliuger (unpublished data), has been employed exten-
sively. In the United States, the drug is admini.stered iu gela-
tin capsules in a dose of 5 cc. for adult sheep and 2.5 c.e. for
lambs. In Australia, it is combined with equal parts of liquid
paraffin. While several investigators have reported it to be
very effective against the common stomach worm, there is
some divergence of opinion on this point with the probability
that its efficacy does not approach that of carbon tetrachloride.
However, tetrachlorethyleue is a much safer treatment. In
repeated treatments over a period of time, it is of some value
in mixed infections involving stomach worms, hookworms and
small trichostrougyles.

Copper Sulphate and Sodium Arsenite. This mixture in
powder form has long been employed in South Africa, where
it is known as the "Government Wireworm Remedy." It is
composed of 4 parts of copper sulphate, partly dehydrated,
and 1 part of sodium arsenite. Special measuring spoons are
employed to insure correct dosage, which is as follows: For
lambs 2 to 4 months old, 0.2 gram of the mixture; 4 to 6
months old, 0.25 gram; 6 months to 2-tooth animals, 0.375
gram; 2-tooth sheep, 0.5 gram; 4-tooth sheep and over, 0.625
gram. The remedy is said to be contraiudicated in the pres-
ence of heavy Trichostrongylus infections; smaller doses should
be used when the sheep are in poor condition or when they
are grazing on young grass in the spring. All animals should
be kept from water for at least 7 hours before and after treat-
ment; otherwise rapid absorption of the drug may occur and
lead to arsenical poisoning.

Phenothiazine. Evidence presented under the discussion
of the treatment against nodular worms indicates that this drug
represents an effective treatment against H. contortus. While
its use on more animals may disclose some limitations or con
traindications, it appears to be of great value, particularly
because of its eiBcaey in concomitant infections with many of
the other gastrointestinal parasites which are commonly found
in sheep. If onlj- the common stomach worm is present, doses
as small as 10 grams per adult sheep may be employed; how-
ever, if other species are present, it is probably advisable to
use a dose of 25 grams.

treatment for infeptions with small trichostronoyles,

trichostrongyles spp., ostertaoia spp., cooperia spp., and

nematodirus spp.

On the basis of present evidence, phenothiazine is the treat-
ment of choice for the removal of worms of these genera from
sheep. From tests carried out to date it would appear that in
sheep phenothiazine is probably less effective against Cooperia
spp. and Nematodirus spp. than against these other genera.
However, the general utilitarian value of the drug against
most nematode parasites of the gastrointestinal tract of sheep
ranks it above all others at present. English investigators
(Taylor and Sanderson, 1940; Lapage, 1940) have reported
that sheep treated with doses of phenothiazine varying from
5 to 30 grams gained more rapidly than untreated controls;
Ostertagia spp. were the principal nematodes encountered in
the test animals.

The "Cu Nic" solution will freciuently remove satisfactory
percentages of these various worms. In Australia, Gordon and
Clunies Ross (1936) found that sheep exposed to continual
heavy infection with Trichostrongylus spp. were adequately pro
tected by routine treatment at intervals of 3 weeks with a 2
percent solution of copper sulphate and commercial nicotine
sulphate. Similar protection was obtained by the use of 15
ec. of a 2 percent solution of copper sulphate followed imme-
diately by 2.5 cc. of tetrachlorethyleue repeated at the same
intervals. The recommended dose of the 2 percent copper
sulphate and nicotine sulphate solution is as follows:

Adult sheep 2 ounces (60 cc.)

Sheep 12 to 18 months 1.5 ounces (45 cc.)

Lambs 8 to 12 month 1.0 ounce (30 cc.)

Lambs 4 to 8 months 0.75 ounce (22 cc.)

Lambs under 4 months 0.5 ounce (15 cc.)

Treatment for the removal of worms of the above-mentioned
genera from cattle is not well established. In limited experi
ments, Swanson, Porter and Connelly (1940) found that un-
conditioned phenothiazine administered to calves in doses of
50 to 80 grams (0.44 to 1.1 grams per kilogram of body weight)
removed all T. axci present. The treatment was approximately
84 percent effective against 0. ostertagi but only slightly effec-
tive against Cooperia spp.

TREATMENT FOR LUNOWORM INFECTION

Protostrongylnx and Mnellerivs infections are not susceptible
to treatment but numerous drugs have been recommended

against Dictyocauliis filaria, chiefly for administration by in-
sufflation or by intratracheal injection. Evidence for the use
of these preparations is not convincing. Orloff (1935) recom-
mended injections into the trachea on 2 successive days of 10
cc. of a mixture of 1 cc. of a 10 percent tincture of iodine, 50
cc. of glycerin and 150 cc. of distilled water. The sheep are
placed on the back and after injection are held in a sitting
position for half a minute. McGrath (1931) found Lugol's
solution of no value and responsible for the causation of
pneumonic lesions. McGrath believed that the intratracheal
injection of the mixture recommended by the New South
Wales Department of Agriculture provided good results. This
mixture consisted of chloroform 0.5 cc, oleum terebinthinae 1
cc, and olive oil 2 cc. However, Kauzal (1932) was not suc-
cessful in removing all worms with this mixture. Vein and
Zottner (1937) used a dose of 10 cc. of an aqueous solution of
1 mgm. of pyrethrin per dose ; this was repeated three times.
These treatments are for sheep but could probably be used
for calves also.

Until more substantial evidence is obtained for the value
of medicinal treatment, the most logical procedure is to give
infected animals good nursing treatment, remove them from
infected pastures and provide feed which will satisfy all nu
tritional requirements.

Anthelmintic Medication for Nematodes of Poultry

TREATMENT FOR STRONGVLOIDES INFECTION

Gentian violet exerts a specific action against Strongyloidcs
avium and, in birds in which treatment is indicated, this would
be the drug of choice. Wright and A^an Volkenberg (1937)
found that a dose of 1 grain (64 mgm.) three times a day for
10 days for birds weighing 3 to 4 pounds removed all of these
worms from the small intestine and the ceca. However, this
course of treatment resulted in inflammation of the digestive
tract. Single doses up to 10 grains were not effective.

TRflATSIENT FOR CAPILLARIA COLUMBAE AND C. RETUSA INrBCTIONS

There is no established treatment for the removal of capil-

larids from the lumen of the digestive tract. Carbon tetra-
chloride has been reported to be of value in chickens when
given in a dose of 1 cc and repeated in 1 week. However,
the evidence for this is contradictory as other investigators
have not obtained promising results with this drug either in
chickens or pigeons. Thymol has been recommended for pigeons
in a dose of 5 cgm., repeated on alternate days until 3 doses
have been given. The last dose is followed by castor oil. Per-
haps halogenated hydrocarbons other than carbon tetrachloride
might be of benefit, although to be of value any treatment
would probably have to be repeated several times. In any ease,
worms in the ceca would be particularly difficult to remove.

TREATMENT FOR ORNITHOSTRONGYLUS QUADRIRADIATUS INFECTION

Thymol has been reported to be of value though such reports
have not been confirmed. Tetrachlorethyleue in doses of 0.5
to 1 cc. will sometimes remove some of the worms, although it
does not constitute a dependably eft"ective treatment. In fact,
Cuvillier (1937) stated that the lack of any anthelmintic of
demonstrated efficacy against the parasite indicated the impor-
tance of applying preventive measures.

TREATMENT FOR AMIDOSTOMIIM ANSBXIS INFECTION

Schmid (1930) treated geese with carbon tetrachloride in
doses of 1 to 1.5 cc. in 8 cc of flour paste injected into the
crop and reported excellent results, the birds improving in
condition and the losses in the flock being checked. Schu-
mann (1930) had good results following doses of 1 ec of car-
bon tetrachloride administered in gelatin capsules. Jerstad
(1936) removed all of 11 Amidostomum from a goose ivith a
single dose of 2 ec. of carbon tetrachloride.

TREATMENT FOR SYNGAMUS TR.\CHEA INFECTION

Mechanical removal of the worms may be accomplished by
means of a fine wire, a barbed feather or other similar devices
commonly used by poultrymen. However, the method is te-
dious and time consuming and not adapted for flock treatment.
Several workers have recommended the intratracheal injection
of several drops of a 5 percent solution of Aniodol (trioxy-
methylene).

Wehr, Harwood and Sehaffer (1938) obtained an indicated
efficacy of 98 percent for the removal of these worms by in-
sufflation with barium antimonyl tartrate. The birds are
placed in a tightly closed container and the finely powdered
drug is dispersed throughout the air several times by means
of a blower.

346

■I'liKATJlKNT FOll llKTKRAKl.S (iAl.1.1 N AK INKKCTION

Siiisle doses of a lunubor of dviiRs luliiiiMisteiod iirallv will
ri'iuove some lieterakiiis but few of tlu'se drupts exliiliit a ilc
peudable efficacy. It is probable that in most eases tlie drus
does not actually penetrate into the ceca to any great extent.
Tlu' flock treatment for Ascaridia with tobacco dust mixed
with mash will remove some worms over a period of tinu^ liut
results are variable.

Recently McCuUoch and Nicholson (1940) reported that
phenothiazine in doses varying from O.O.") to 1 gram per bird
removed :;,0.">li Ilcterakis from 1:2 chickens and failed to re-
move 8S0, but of the worms not removed all except 121 had
been killed by the action of the drug by the time the birds
came to necropsy. Also in repeated doses varying from O.O.'i
to 0.5 grams per dose, phenothiazine removed 4,C(>3 worms from
l.") chickens. All of the 277 Hctcrakis not removed by the time
the birds came to necropsy had been killed by the action of
the drug.

Rectal injections by means of a hard rubber enema syringe
of a mixture of 0.1 cc. of oil of ehenopodium in 5 ec. of cot-
tonseed oil for a 1..5 pound (080 gram) bird were found by
Hall and Shillinger (1923) to remove 90 percent of the heter-
akids from chickens. Probably double this dose would be ef-
fective for birds weighing 3 pounds (1.36 kgm.) or more.
This mixture may be made up at the rate of 1 teaspoonful
(4 ce.) of oil of ehenopodium in li fluid ouncQS (180 cc.) of
cottonseed oil, and given at the rate of Vs fluid ounce (10 cc.)
for birds weighing 3 pounds or more, using a proportionately
small dose for smaller birds. The two ingredients should be
thoroughly mixed before administration. The tip of the syringe
should be passed along the floor of the cloaca and the mix-
ture injected slowly.

TRE.\TMF.N'T FOR ASCARIDIA OOLUMBAE INFECTION

Carbon tetrachloride in repeated doses of 0.5 to 2 ce. ad-
ministered in liquid paraffin on several consecutive days has
been found entirely effective in removing these worms from
pigeons. Tetrachlorethylene in a dose of 0.6 cc, preceded and
followed by sodium sulphate, is said to constitute an effective
treatment.

TRE,\TMENT FOR ASCAKIDIA GALLI INFECTION
Various treatments are available in single doses for the re
moval of these worms. Tetrachlorethylene in a dose of 1 cc.
for average sized birds is very effective. For young chickens,
the dose should be reduced in accordance with the weight of
the bird. Carbon tetrachloride is not as effective as tetra-
chlorethylene but n-butylidene chloride in doses of 2 cc. for
adult birds removed all ascarids from test birds. These drugs
may be administered in gelatin capsules but care should be
taken that the drugs do not enter the lungs.

Nicotine sulphate combined with Lloyd's alkaloidal reagent,
a selected diatomaceous fuller's earth, is a very effective
single dose treatment. Recommendations call for the adminis-
tration to each bird of a No. 2 capsule containing 35 cgm.
(5.45 grains) of a mixture of 6.6 cc. of 40 percent nicotine
sulphate solution and 16 grams (4 drams) of Lloyd's reagent.
Certain flock treatments are effective for the removal of
Ascaridia and obviate the individual treatment of birds. The
one recommended first by the California experiment station
calls for the addition to the mash of 2 percent by weight of
tobacco dust containing at least 1.5 percent of nicotine; this
mixture is fed for a period of 3 to 4 weeks and repeated at
3-week intervals. For a single flock treatment, the California
station recommended the use of 1 teaspoonful of oil of eheno-
podium, thoroughly mixed with moist mash, for each lot of 12
chickens.

TREATMENT FOR OXYSPIRURA MANSONI INFECTION

A treatment which has been found of value consists in the
administration of 1 or 2 drops of a 5 percent solution of creo-
lin under the nictitating membrane of the eye which is first
anaesthetized with cocaine or a 5 percent solution of butyn.
The creolin should be washed out promptly with water. The
worms killed by the treatment are usually carried down the
lacrimal duet. The use of a 10 percent solution of argyrol
as a supplementary treatment is of value in relieving the irri-
tation and in helping to control concomitant bacterial infection.

TREATMENT FOR DISPHARYNX SPIR.VLIS INFECTION
Whitney (1925) tried carbon tetrachloride and turpentine in
pigeons and believed the latter to be more effective. He gave
a No. 0 gelatin capsule filled with dry magnesium sulphate 12
to 24 hours prior to treatment; one No. 0 capsule of turpen-
tine was then given night and morning for 4 days, the last
dose being followed by 2 cc. of castor oil. Pigeons treated by
this method showed marked clinical improvement.

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348

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349

CHAPTER X
FEEDING HABITS OF NEMATODE PARASITES OF VERTEBRATES

J. E. ACKERT and J. H. WHITLOCK, Kansas State College. Manhattan, Kansas

'J'lit' obscured habitats of the parasitic nematodes preclude
ready observations upon their feeding haljits. Indications of
their nutritive needs have been gained from chemical analyses
of the worm bodies. Weinland (litOl) found that glycogen
made up one fourth to one-third of the dry substance of the
ascarid body. Flury (1912) was led to believe that ascarids
had essentially the same chemical constitution as other animals.
He found only such minor differences as a lack of uric acid,
creatinine and the substitution of a high molecular alcohol
(ascarjl alcohol) for glycerol in combination with fatty acids.
From these studies it seemed probable that the nutritive needs
of parasitic nematodes are fundamentally the same as those of
other animals, although Aekert (1930) has shown that there is
no evidence to indicate that Atirarklia galli needs Vitamin .\,
Vitamin B (complex), or Vitamin D.

As most of the research on the feeding habits of nematodes
has been upon adult forms, they will be discussed first; then
tl larval forms will be compared with the adults, and the sec-
tion will close with a brief review of digestion in the parasitic
nematodes. Although there are many diverse groups of nema-
todes, few methods of parasitic feeding have been evolved.
The similarity of these feeding habits in nematode groups
which are widely separated morphologically would make a dis-
cussion of nutrition from a primarily taxonomic standpoint
repetitious; hence the subject will be discussed from an eco-
logical and physiological standpoint rather than from that of a
morphological classification.

Ecologically, iiarasitie nematodes may be grouped as to
whether they are associated with the physiological interior or
exterior of the host body. The physiological exterior of the
body, as here considered, is marked by any epithelial mem-
brane lining a cavity which communicates with the exterior of
the host body.

Most of the parasitic helminths are associated with the physi-
ological exterior of the bodj', particularly the mucosae. This
group will be subdivided upon the l>asis of being attached to
the mucosae most of the time or usually unattached. Attached
nematodes maj- hold their positions by the buccal capsule grasp-
ing the mucosa {Ancylostoma, A'ecator, Strongylus) or by pene
tration of the mucosa (Fhysaloptcra, Trichuris). Nematodes
unattached to the mucosa may be closely associated with it
(Haemonchus, Mctastrongylns) or not closely associated with
it {A.icaris, Ascaridia, Hrtcrakis, Oxyuris). Nematodes in-
habiting the physiological interior of their hosts are best ex
emplified by Dirofilaria, Spirocerca and Strongyloides.

Nematodes in the Physiological Exterior of the Body

NEMATODES ATTACHED TO Ml'COSA BY BUCCAL
CAPSULE

The best examples of this group are the hookworms Aiii-i/hi
stoma and Necator which apparently remain attached to the
intestinal mucosa much of the time. The sucker-like oral open
ing and the adjacent teeth or cutting plates afford effective
means of attachment and bloodletting. Since the earliest
recorded observations, blood has been considered as a prob
able food of hookworms. Grassi, according to Leichtenstern
(1886), saw hookworms eject blood both from the mouth and
the anus. Leichtenstern thought, as did Grassi, that much
more blood is withdrawn by the parasite than is necessary for
its food. As the fecally deposited red cells seemed to be prac
tically unchanged, Leichtenstern inferred that the plasma must
be the main source of nourishment. In 1888 Ernst noted the
emission of blood from the mouth cap.sule and Whipple (1909)
observed the oral and anal emission of blood in both Xecator
and Ancylostoma. Whipple believed that there was a rapid
ingestion of blood by the parasite. Aekert and Payne (1923)
who took Necator suillus repeatedly from the intestines of
freshly killed swine frequently noted female specimens v\-ith
bodies colored red from ingested blood. On the other hand
some workers, notably Looss (190.5) and Ashford and Igara
videz (1911), maintained that blood is not the normal food of
hookworms. They observed worms lacking blood even when
they were attached to the intestine. They found tissue ele
ments and shreds of mucosa in both the esophagus and intestine
and concluded that the parasites fed primarily on the mucous
membranes; the blood in the tract was thought to be due to
accidental hemorrhage from hookworm bites. Support for the
view that portions of the mucosae serve as food for such worms
was given by Hoeppli (1930), who found that Ancylostoma
duodenale is more than a blood sucker. The piece of mucous
membrane taken in )iy the mouth capsule is rasped by the teeth.

Blood from surface vessels pours into the buccal capsule where
.secretions from the esophageal glands partially digest the
blood and loosened portions of the mucosae. "After this di-
gestion has taken place, the liquefied masses are swallowed by
the worm." Evidence that disintegration had taken place wa.s
furnished by staining the tissue at the bottom of the mouth
capsule and in the lumen of the esophagus.

Wells (1931) in a series of ingenious experiments was able
to observe living Ancylostoma canitium in the act of feeding.
He was able to observe the attachment of the hookworms to
the mucosa, study the details of the blood-sucking process, the
passage of the blood through the intestine of the worm, and
its ejection through the anal orifice. From the volumes of
blood withdrawn by the parasite and the rapid rate at which it
passed through the intestine. Wells was of the opinion that the
food of the hookworm consists of simple dift'usable substances
in the host blood.

In studies upon the food of the dog hookworm, Ancylostoma
caniiiiim, Hsii (1938) made serial sections of hookworms taken
from living hosts and found red blood cells in all worms; ho
also found fragments of host tissue and white blood cells all
of which were in stages of disintegration. As further evidence
of blood as food for the hookworms, Hsii reported the find g of
pigment granules in the cytoplasm of the worms' intestinal
cells, which gave positive iron reaction. These granules, which
were found in large quantities throughout the whole intestine,
the author interpreted as owing their origin to the breaking
down of red blood corpuscles. Hsii did not find intestinal con
tents of the host, worm eggs, or bacteria in the hookworms'
intestines. He concluded that the food of A. caninum consisted
of blood and mucosa cells.

Other nematodes that attach by means of buccal capsules in-
clude such forms as Strongyhis, Chabertia and Camallanus, all
of which are known to draw intestinal epithelium into their
mouths. From the disintegrated condition of the tissue so
drawn in, it is probable that epithelial tissue and blood form
a portion of their food. Whitlock (unpublished), who has
worked extensively with living equine strongyles, has noted in
the worm intestines material resembling partially digested
blood. Wetzel (1931b), studying Chabertia ovina (Fab.) in
sheep colons, found that the nematodes feeds on the propria
mucosae which it draws into its buccal capsule. The tissue
fragments which are loosened by the gnawing of the nematode
are partially digested, according to Wetzel, by secretions from
the dorsal esophageal gland.

Support of the view that C. ovina attacks the mucous mom
brane is afforded by the work of Kauzal (1936) who found
numerous small hemorrhages on the mucous membrane of the
large intestine of sheep which he attributed to C. ovina. He
examined 250 of these specimens quantitatively for iron which
he assumed to be derived from haemoglobin. The presence of
the haemoglobin and the reddish tint of the intestinal con
tents of the immature C. ovina led Kauzal to infer that thi.s
nema ingests considerable quantities of blood. That the at
tachment to the intestinal mucosae by the buccal capsule is a
widespread feeding phenomenon among the Strongyloidea is
further shown by Magath (1919) for Camaltanus amcricanus in
the turtle intestine and by Hoeppli and Hsii (1931) t'oi- h'ul-
icephalus sp. in the enteric caual of snakes.

NEMATODES ATTACHED MUCH OF THE TIM 10 I'.V
PENETRATION OF THE MUCOSA

Typical examples of this group are Trichuris and Physalop-
tera. The food of Trichuris apparently is secured while the
anterior extremity is imbedded in the mucous membrane of
the large intestine. Christofferson (1914) who reviewed the
literature on Trichuris (Trichoccphalns) up to 1914, observed
a peculiar cell transformation about the imbedded anterior por
tion of these nematodes. Hoeppli (1927) found such changes
in human and baboon intestines in which the Trichuris made
tunnels in the mucosa parallel with the surface of the intestinal
lining. Surrounding the anterior ends of the trichurids in
these tunnels, the epithelial cells, according to Hoeppli, were
transformed into syncytial-like structures with eosinophilic
homogeneous protoplasm and pycnotie nuclei as a result of the
action of a liquifying secretion from the worm. Hoeppli 's
studies (1927, 1933) led him to believe that the liquified syn-
cytial material was taken by the trichurids as food.

That Tricliuris may take blood was indicated by the studies
of Guiart (1908) who found blood-engorged trichurids. Garin,
cited by Otto (1935), likewise found Trichuris filled with blood
and reported that blood was found in the stools of 50 out of

3.50

.'>4 tricliuris iiit'i'c-tod patients. In support of tlie view that
these nematodes may feed on lilood were the tindinjjs of Li
(1933e) and Chitwood and C'hitwood (My^l) that the adult Tri-
chtiria bears a stylet capable of insertion suflieient for drawing
blood. Chitwood and Chitwood (ISU?") showed that the anterior
muscular [lart of the trieluiroid esophaKUs possesses uiuselcs
capable of the dilation necessary for .sucking. Moreover, they
found by serial sections a large number of red coipuscles in Ihc
esophageal lumen of Trichi(ri.i. While Smiruov (1936), after
a comprehensive study of the literature and of serial sections
of worms, concluded that there was no convincing evidence
that trichurids feed on blood, the fact remains that Whipple
(IIHH)) and Garin (1913) reported the occurrence of hemolytic
enzymes in Trichiiris. From the various studies made it ap-
pears that trichurids secure their food from the intestinal
mucosa and that it may consist of liquified mnco.sal tissue and
Idood elements.

Studies on the food of Tricliim Uti xpiralix were made by
Heller (1933) who introduced encysted trichina larvae enclosed
in collodion sacs into the snuiU intestines of cats and rats.
While the meat around the larvae was digested in 0 to 8 hours,
they made no growth in 1 to 3 days. Trichiiiella larvae en-
closed in fine silk bags and thus kept away from the intestinal
mucosa likewise did not develop. That these nearly adult
trichinae do not feed on intestinal contents seems likely also
from other tests by Heller who fed India ink along with meat
containing encysted larvae, but failed to find any ink in the
worms' intestines. Sections of intestinal tissue made after
the encysted trichinae were fed showed that the freed larvae
penetrated the intestinal mucosa, where the maturing trichinae
doubtless secure their food.

Following the work of Heller, McCoy (1934) injected sterile
TrichineUa larvae from digested rat muscle into the amniotic
sac of chick embryos li to 1.5 days old. Definite growth of the
maturing larvae occurred in only about 1 or 2 percent of the
trichinae. A single female developed to sexual maturity. Bet
ter success was attained in a second series of experiments in
which the sterile larvae were injected into the amniotic sacs of
rat embryos on approximately the 14th day of gestation. In
2 to ,■) days, practically all worms were developing at nearly
the normal rate and on the fifth day, numerous female trichinae
were found with embryos developing in their uteri. These re
suits give further evidence that TrichineUa normally feeds upon
host body fluids secured from the mucous membrane. Moreovei',
van Someren (1939) reported a functional buccal stylet in T.
spiralis and indicated that it is used to lacerate the host tissue
and release tissue fluids. From the examination of living
specimens immediately after recovery, van Someren believed
that the food, which is in a fluid state when ingested, consists
of tissue fluids, cell contents, or perhaps predigested tissue acted
on by a tissue lysate from the anterior esophageal glands.

Among other nematodes attached much of the time to the
enteric mucosa is Plnisaloptcra. Studies by Hocppli and Feng
(1931) showed that the mucosa about the anterior ends of these
attached worms was liquified or partially digested, presumably
from esophageal secretions from the nematodes. Studies of
sectioned mucosa showed definite excavation of tissue immedi-
ately around the anterior ends of the worms, presumably from
the taking of the liquified tissue as food.

UNATTACHED NEMATODES CLOSELY ASSOCIATED
WITH THE MUCOSA

Many nematodi's belonging to this grou]), while Iniving jioorly
developed buccal capsules, are able to puncture the mucous
membrane and draw blood. For example, Stadehnann (1891)
found blood corpuscles in the nearly nuiture Ostertagia oster-
tagi (Strongylu.i convolutiis) in nodules of the abomasum, and
Dikmans and Andrews (1933) found such stages of Ostertagia
circwmcincta in the mucosa and partly free in the abomasal
lumen of sheep. Unfortunately, however, much of the evi-
dence is circumstantial. Thus Ransom (1911), writing of
Haemonchus contortiis and Ostertagia ostertagi, stated that
they evidentl.v suck blood for the heavily infected liosts arc
anaemic. Other writers simply state that they suck blood.
Veglia's (191(5) observations on living worms demonstrated
that the oral lancet made definite cutting movements. Fallis
(1938) placed Nematodirus among the blood suckers on the
basis of a spectroscopical analysis of the body fluid which
showed the absorption bands for oxyhaemoglobin. In the same
year, Davey (1938), who studied the food of nematodes of the
alimentary tract of sheep, questioned the spectroscopic demon
stration of haemoglobin in nematodes as evidence of their being
blood suckers. He found that haemoglobin was present in tissues
other than the alimentary canal of Nematotlinis spathigrr and
that its absorption bands had different positions from those in
the blood of their hosts. These facts, together with his finding
of haemoglobin in species of Trichostrongylidae long after
any haemoglobin from the host would have decomposed, proved

Ihat these nematodes could synthesize haemoglobin. Davey 's
(1938) culture tests with serum, blood digests, and defibrinated
blood as food for Ostertagia, Cooperia, Nematodirus and Tri-
vliostrongi/lus were unsuccessful, as were also those on abo-
masum fluid for Ostertagia circumciiicta. These negative re-
sults led him to the conclusion that these nematodes with rudi-
mentary buccal capsules pjobably feed on tissue elements at oi
ill the mucosa.

Other evidence of intinuite association of trichostrongyles
with the mucosa of the alimentary tract is available from rab-
bit neumtodes. Alicata (1932) experimentally infected rabbits
with Olxliscoides ciinieiili by feeding infective larvae. Ex
amination about 2 months later showed nematodes free on the
mucous membrane of the stomach or under the membrane and
into the snbmncosa. That such trichostrongyles feed from the
enteric wall was the opinioTi of Wetzel and Enigk (1937) who,
on infecting raljbits with (irapliidiiim strigosum, found tlie
stonuich mucosa bloody. Enigk (1938) examined the intestinal
contents of several sexually mature G. strigosum and found a
colorless viscous mass containing nuclear remnants apparently
from white blood cells, granules and bacteria. Other tests such
as feeding the rabbits pulverized chaicoal. trypan blue and car
mine resulted in these substances being ingested by the nenm
todes. Also, injecting the hosts intravenously with trypan blue
for several days resulted in the worms taking up several blue
colored particles presumably desquamated mucosa cells. Enigk
concluded that G. strigosiim's food consists of gastric mucosa,
gastric juice and stonnxch contents.

Other unattached nematodes closely associated with the mn
cosa include lungworms which inhabit the bronchi and bron
chioles. Hung (1920) studying swine lungs infected with adult
Metastrongylus elongatus frequently found eosinophiles and red
blood corpuscles in the worms' intestines. The findings of Por-
ter (1930), who made similar studies, indicated that the mate-
rial in the worms ' intestines consisted of elements identical
with those found in the exudate surrounding the nematodes.
In cross sections of the worms. Porter recognized large uum
bers of eosinophilic and neutrophilic polymorphonuclear leuco-
cytes, lymphocytes and desquamated epithelial cells. Erythro-
cytes w^ere seen in some instances. These and some of the leuco-
cytes and epithelial cells appeared to have been digested in part
by the worms.

From the findings of the investigators cited, the food of
many of the unattached sti'ongyles appears to consist mainly
of substances derived from the mucosa, namely, leucocytes,
erythrocytes, lymphocytes, plasma, exudates and desquamated
mucosa cells, but also of some extra-mucosal material such as
stomach contents.

UNATTACHED NEMATODES NOT CLOSELY ASSOCI-
ATED WITH THE MUCOSA

Chief among the parasitic nematodes not closely associated
with the intestinal mucosa are members of the Oxyuroidea and
Asearidoidea. Among the early observations of the food of
such nematodes were those of Leuckart (1876) who found that
the intestine of Enterutiius vermicidaris usually contained yel-
low fluid which on microscopical examination proved to br
identical with the liquid host feces. Similar observations wi'rr
made by Leuckart on Oxyuris equi whose intestinal contents
contained small particles of vegetable material identical with
the contents of the horse intestine.

Early in the present century, Weinberg (1907) examined the
intestines of many Ascaris specimens but could not find red
blood corpuscles in them and expressed the opinion that the
horse Parascaris feeds on the contents of tlie host intestine.

To ascertain whether Ascaris feeds upon intestinal contents,
Vogel, cited by Hoeppli (1927), fed powdered animal charcoal
to a human patient infected with Ascaris. The results of the
first test were negative, but in a second test carried out simi-
larly, numerous charcoal particles w-ere found in the intestine
of the worm. On the other hand, a number of early workers
held to the view that the ascarids are blood suckers. This view
was derived, in part, from microscopical and chemical examina-
tions which showed evidence of blood in the intestines of
Ascaris and related forms. For example, Mueller (1929), on
studying specimens of Anisakis simplex from the sperm whale
stated that the intestine, in all cases, contained blood in con-
siderable quantities with occasional fragments of muscle and
other tis.sues. From the quantities of blood corpuscles pres-
ent, Mueller was of the opinion that the nematode had a blood-
sucking habit. Mueller was unable to determine the nature of
the intestinal contents of any other genus of the Anisakinae
that he studied.

If such ascarid forms are blood suckers some specimens
should be found in contact with the mucosa. Hoeppli (1927)
reported on the examination of 350 cadavers in which large
numbers of ascarids were found. No evidence was available
to show that anv of these nematodes were attached to the mu-

351

cosa. Hoeppli further stated that in Fiilleborn 's Laboratory no
cases had been found with the asearid, Toxocara canis, attached
to the dog intestine. Other workers on examining large num-
bers of horse intestines at slaughter houses always found
Parascaris equornm free in the lumen of the gut.

Standard textbooks carry the statement that Ascaris Iximhri-
coides feeds on intestinal contents but gnaws at the mucosa.
This statement doubtless is due to the occasional finding of
reddish spots in the intestinal epithelium in cases of asearid
infection. While such spots occur occasionally, those who have
examined hundreds of mammalian and avian intestines which
contained numerous ascarids can testify that in the great ma-
jority of eases, no evidences of the adult ascarids attaching
the mucosa are available.

As to certain Asearidoidea being attached to the intestinal
wall presumably for feeding, Guiart, cited by Hoeppli (1927),
found in the stomach of a dolphin the clear imprint of the
worms' lips in pit-like depressions of the mucous membrane.
Similar observations were made by Hoeppli (1927) on a Con-
tracaeciim sp. from a seal from northern waters. It is quite
possible that instead of being attached, the dying worms
pressed their anterior ends deeply into the mucous membrane
of the dead host.

As to the food of ascarids, Archer and Peterson (1930), by
giving patients infected with Ascaris liiinbricoides a barium-
cereal-meal, found that the enteric canals of the parasites
showed string like shadows, indicating that the nematodes in
the host intestine had swallowed the barium. These observa-
tions indicated that Ascaris lumbricoides feeds on the intes-
tinal contents of man.

Following this work, Li (1933a) fed to six dogs, positive for
ascarids, liquid Chinese ink or powdered charcoal twice a day
for several days. While most of the tests were negative, due
presumably to a vermicidal action of the charcoal, one dog
gave unquestioned positive evidence. The one female worm
from the dog 's intestine definitely showed charcoal and beef
particles in its enteric tract. In a subsequent series of tests,
Li (1933b) fed a mixture of powdered charcoal, clotted blood,
striated beef muscle and starch granules to experimental ani-
mals harboring ascarids as follows: Dog, Toxocara canis; cat,
Toxascaris leonina ; and chicken, Ascaridia (/alii. The re-
sults from the dogs gave no positive evidence ; that from the
cat showed that the worm intestine contained diarcoal, blood
cells, and beef particles. These findings were confirmed by
examination of paraffin sections of the worms. The results
from four chickens showed charcoal and beef particles in the
intestines of all worms including both male and female sjjeci-
mens. From similar experiments, in which starch granules
were substituted for powdered charcoal, all worms recovered
showed starch granules and some beef particles.

To ascertain the nature of food of the chicken cecal worm
SeteraMs gallinac, Li (1933b) fed infected chickens powdered
charcoal and beef as l)efore. On examination, most of the
worms showed charcoal in the entire intestine. In further
studies, Li opened tlic intestines of Ancaris lumbricoides from
man and mounted tlie intestinal contents on slides for micro-
scopic examination. Wliile most of these contents could not be
identified, Li found in one specimen two Ascaris eggs and a
piece of striated muscle. The results of Li 's experiments
(1933a, 1933b) indicate that the intestinal contents of the host
constitute part of the food of Ascaris lumbricoides, Toxocara
cauis, Toxascaris leonina, of mammals; and Ascaridia galli and
Jleteralcis gallinac of fowls.

The findings of Li and of other workers cited, while showing
tliat certain ascaroids take intestinal contents, do not pre-
clude the possibility that these nematodes may also feed upon
the intestinal epithelium. In a study of the food of the fowl
nematode, Ascaridia galli (Schneider), Ackert and Whitloek
(1935) deprived chickens infected with Ascaridia galli of food
by mouth; the experimental chickens were nourished by intra-
muscular injections of glucose. The results of the first series
of experiments on 141 chickens with worms of various ages indi-
dated that little growth occurred in the worms after the host
chickens were taken off the regular feed. In the second series
in which 96 additional chickens were used, Ackert, Whitloek
and Freeman (1940) used worm infections of one week's dura-
tion in the tests. Experimental and control chicks under com-
parison were of the same age and the developing worms were
from the same egg cultures. The results of this series of tests
were very uniform, namely, that in the chickens given only
water per os and intramuscular injections of glucose, the young
Ascaridia galli ceased growing whereas tlie worms in the regu-
larly fed control chickens made normal growth. These results
indicate that the large nematode of chickens wliose mouth parts
are very similar to those of mammalian ascarids, did not secure
nutriment from the intestinal epithelium of the host. These
nematodes may have fed to some extent on duodenal mucus
from the goblet cells but Ackert, Edgar and Friek (1939)
have shown recently tliat such mucus ninv contain an inhibitory

growth factor for young Ascaridia tliat have been grown in the
culture media developed by Ackert, Todd and Tanner (1938).
This last group of workers prepared a salt-dextrose solution in
which young Ascaridia galli will grow. On the introduction of
mucus from growing chickens into the nutrient solution, the
cultured Ascaridia ceased growing, whereas the control worms
in the nutrient solution continued to increase in length. In
the glucose-injected chickens, the duodenal mucus, while con-
taining an inhibitory growth factor, may have afforded the
Ascaridia galli food sufficient for maintaining life, but not for
growth.

The literature cites cases in which lilood has been found in
the digestive tracts of ascaroids. For example, Mueller (1929)
found blood in the intestine of Anisahis simplex and Guiart,
cited by Lievre (1934), saw some Ascaris whose digestive tracts
were full of blood. On the other liand, Lievre cited Brumpt
as having performed numerous autopsies to see if Ascaris
caused ecchj-motic spots on the mucosa. But Brumpt was un-
able to find such spots, and the intestinal contents of the worms
showed only chyme, never blood.

Indirect evidence of blood as a nutrient of ascarids is avail-
able from the finding of haemoglobin in the worms' bodies by
such tests as the Benzidine blood test and spectroscopic analy-
sis. That the former is an unreliable test for blood has been
shown recently by Davey (1938). Using spectroscopic analy-
sis, Lievre (1934) found traces of haemoglobin in the intestine
of the dog asearid, Toxocara canis. Even though the spectro-
scopic examination of blood was positive in 7.') percent of the
cases, the quantity of haemoglobin noticed was so small that
Lievre was led to think that the haemoglobin had come from
the flesh colored food of the animal. Lievre, on macerating the
intestines of Ascaris lumbricoides, Parascaris equorum and
Ascaris suum was unable to find any haemoglobin present in
these worms by spectroscopic analysis. He concluded that there
is no haemophagia in Ascaris and only in exceptional circum-
stances would there be ingestion of blood. Davey (1938) dem-
onstrated haemoglobin in the dermo-muscular tube of Toxocara
canis and in tissues other than the alimentary canal of Ascaris.
He found, further, that the absorption bands of the haemoglo-
bin in the tissues had different positions from those in the
blood of their hosts, indicating that these nematodes were able
to synthesize haemoglobin. Thus the presence of haemoglobin
in the tissues of nematodes is not necessarily evidence tliat tliey
feed on blood.

Further indicative evidence that ascarids may take blood is
available from the work of Schwartz (1921) who found that
the body fluid of Ascaris lumbricoides inhibited coagulation of
rabbit blood to a moderate extent. Extracts of Parascaris
equorum and of Toxocara sp. had a slight effect on the coagula-
tion of sheep's blood. Whether or not this property of the
asearid body is utilized by the living nematodes is unknown.
It is conceivable that asearid nematodes living with hookworms
which are known to draw l)lood in excess would swallow blood
from time to time. But as other writers have indicated, this
would be exceptional rather than normal.

In the light of our present knowledge, it appears that tlie
oxyuroids and ascaridoids feed normally on the intestinal con-
tents of the host including also any mucus, desquamated muco-
sa cells, and blood elements that may be free in the lumen of
the intestine.

Nematodes in the Physiological Interior of the Body

The nematodes that live in the physiological interior of the
liody are exemplified by Dirofilaria, Spirocerca and intra-mueo-
sal Strongyloides. In a recent study, Hsii (1938a) was led to
believe that Dirofilaria immitis feeds exclusively on red and
white blood cells. In the ease of Diplotrinena triciispis, Hsii
(1938b), after studying the intestinal contents of this parasite
of the crow, concluded that the worms ' food consisted of the
inflammatory exudate in the thoracic cavity. While there was
evidence of blood being ingested, Hsii believed that it is not
taken normally. As the adult Tt'uchereria bancrofti normally
lives in lymph vessels and nodes, it doubtless normally feeds
upon lymphocytes and other constitutents of lymph. When
such encapsulation as shown by Faust (1939) occurs, the en-
capsulated worm dies, apparently from lack of food.

In a further study of the food of nematodes, Hsii (1938a)
concluded that Spirocerca lupi feeds on inflammatory cells that
Iiass through the nodule walls.

Observations on the food of another nematode of this group,
Strongyloides stercoralis, were recorded by Askanazy (1900)
who concluded that the mother worms in the intestinal mucosa
fed on chyle; he found no indication that they take blood.
Faust (193.5), studying Strongyloides in the mucosa of the
jejunum, found evidence of lytic action by the female worms,
particularly around the head of the worm where disintegration
of the tissue was observed. Considering the facts that the adult
females spend much of their time in the intestinal mucosa and

352

tliMl Ilu'v liiivi- luit ln'i'ii (ilisiMvcd to take liUiod, it is iinilialilc
that they feed on t-liylo and tlio partially disintegrated tissues
ill their tunnels.

The Food of Larval Parasitic Nematodes

The nutrition of the larval parasitic nematodes is funda-
mentally like that of adult parasitie or free liviiiK iieiuatodcs
subject to the modifications imposed by the environment and
the structure of the larvae in question. For example, the re-
searches of McCoy (1<)2!)), Lepage (10.S3, in37) and Glaser and
StoU (lil.'iiS) on "the free-living stages of Strongylina have re-
vealed no essential differences between the mode of nutrition
of these immature forms and that of the free-living stages of
Rhabdiasidae (see Chu, l!)3(i) and Strongyloididae (see Faust.
lO.Si;'). Tlie feeding mechanisms (buccal capsule and rhabdi-
toid esophagus) and sources of food (bacteria or fluid organic
matter") are essentially the same. The method of feeding of
RhabdHix as described by Chitwood and Chitwood (1038, p. 7<i
of this series) is probably typical of this group.

Of the larvae of heteroxenous, parasitic nematodes in their
intermediate host, no complete study of the feeding habits is
available. But their locations in the intermediate hosts are
fundamentally similar to those of various adult forms in pri-
mary hosts. Since many of such larvae increase in size without
the presence of reserve food stuff, they must secure their niiur-
ishment from their lu>st. From the foregoing it would be logi-
cal to conclude that larval nematodes in secondary hosts feed as
do adult nematodes in analagous positions in primary hosts.
Inactive encysted forms are at such low levels of metabolic
activit.v in both types of host that simple diffusion is probably
more than adequate to maintain the parasite.

The nutrition of immature nematodes in a primary host is,
as far as known, like that of adult nematodes in similar posi
tions except for (a) larval nematodes carrying reserve food-
stuff and (b) larva! nematodes which may be nourished by dif-
fusion. For the rest it is possible to find a larval nematode
feeding habit identical with each ma.ior type of adult nematode
method of feeding.

Wetzel (1930) has shown fourth stage Oxyiiris equi to feed
like adult Strovgyliis sp. Ortlepp (lfl37) found the same true
of larval Gaipcria pachysceHs. According to Ackert (1931),
Ascaridia ffalli larvae penetrate the mucosa of the small intes
tine and feed much as do Physaloplcra sp. or StronqyJoidrs sn.

In a study of Cooperia curticei, Andrews (1939) noted the
third stage larvae feeding in the lumen of the gut. The fourth
stage larvae of this parasite had their anterior ends in the
crypts of Liebcrkiihn and grew while in this position indicating
the same type of nutrition as that observed in the adult
Triehostrongylidae.

Immature Probstmayria rivipara are found free in the gut
tube like ascarids indicating a similar mode of nutrition. Ac-
cording to Ransom (1911) immature Oesophapostonm colnm-
biaviim feed on the cheesy material in the nodule making their
mode of nutrition essentially similar to such forii's as Cnatlm-
stoma. Ascarid larvae in the blood stream ingest and digest
blood cells, according to Sminiov (193r>), hence resemliling adult
Dirofilaria. Wetzel (1931a) has reported a case of what he
considers to be extra-intestinal digestion by the fourth stage
larva of Dermatoxys veJtgera which attaches to the intestinal
mucosa by means of four cephalic hooks, a unique attachment
mechanism in nematodes.

The recent development of culturing techniques for parasitie
nematodes promises more information regarding their food.
However, to date only one parasitie nematode has been cul-
tured throughout its life cycle. This is Neopleciana glaseri
which is parasitic in the .Japanese beetle, PopiUia japonic'a
(Glaser, 1932). Attempts to grow Haemonchus contortiis of
sheep by Lapage (1933) and Glaser and Stoll (1938), and
Ascaridia galli of chickens by Ackert, Todd and Tanner (1938)
have been only partially successful. Hence, these are included
with the discussion of the nutrition of the larval forms. No
direct observations of the food of these parasitic nematodes
have been made, but the fact that the nematodes have grown
and developed in an artificial environment indicates that at
least part of the environment is a source of food. Table 1
lists these attempts at culturing parasitic nematodes.

From these considerations it appears that the food of lar-
val parasitic nematodes may include bacteria, enteric contents,
vascular fluids and elements, and mucosal cells and ti.ssnes.

Digestion in Parasitic Nematodes

Most of the parasitic nematodes are placed in intimate
contact with the host 's physiological fluids which carry nu-
trient materials to its cells. Since these nutrients are in their
simplest diffusable form it might be assumed that much of the
nourishment of parasitic nematodes is derived from this source
and that no true digestion is required. However, a number of

Author

Nematode

Glaser

N roplcctana

(1932)

glaseri

McCoy and

Neopleciana

Glaser

glaseri

(1936)

McCoy and

Neopleciana

Girth

glaseri

(1938)

Glaser and

Baemonchns

Stoll

conlorivs

(1938)

Ackert,

Ascaridia

Todd and

galli

Tanner

(1938)

Tahi,k 1. — Siiiiiiiiary of ulliiiipis Ui ciilliirc iiarasilic nematodes.

Successful
Degree of Culture Normal

Growth Media host

Complete Dextrose - veal .lapaneso
infusion agar beetle
with yeast
Complete Fomented po Japanese
tato medium hi \:

Complete Veal infusion & Japanese
preservatives beetle

L a s t Agar, liver ex- Sheep
part of tract, sheep
fourth blood and kid-
larval ney defibrinated
stage blood

Me asur Incubating Chicken
able. hens' eggs,
growth starch, dextrose,
commercial agar

workers have demonstrated the existence of a true digestion in
phylogenetically widely sejiarated parasitic nematodes; hence,
it is probable that they all carry on some form of digestion.
According to the location of the digestive processes, various
workers have distinguished between an intestinal and extra-
intestinal digestion. Much of the evidence of extra-intestinal
digestion rests upon the occurrence of necrotic or cytolyzed ma-
terial around the anterior attached end or within the buccal
capsule of parasitic worms. That such .-i i (i"fl>iiiM of the host
tissue is so often interpreted as extra-intestinal digestion is
somewhat questionable since the effect of parasite excretions,
simple trauma, mechanical pressure, and heterophilogenous
proteolytic enzymes upon the host tissue would produce many
of the conditions described as extra-intestinal digestion. This
form of digestion may be possible in some nematodes, how-
ever, since Hoeppli (1927) has discovered an epitheliolytic ma-
terial present in the anterior end but not in the posterior por-
tion of Stroiigyhis.

The intestinal digestion in nematod"s has been th? sub.ject
of work by a considerable number of investigators. Most of
the studies have been confined to the demonstrations of en-
zymes within extracts of the parasites. Because of the early
workers' limited knowledge of enzyme action, much of their
results need confirmation before they can be accepted. Flury
(1912), for example, made no attempt to crifically evaluate
the research of other workers. He simply listed the worker's
name and the enzymes which he reported. In little of this
early work was the action of bacterial enzymes adequately
controlled. The demonstration of a peptolytic enzyme in the
gut of Toxocara caiiis by Abderhalden and Heise (1909) is
questionable for this reason. Nor was any particular attempt
made in the early work to differentiate between intracellular
and extracellular enzymes. Most of it was done with extracts
of the parasite being studied, and peroxidases and proteases
were reported as though the question of their respective origins
was of little importance.

Recent researches have been more accurate. Enigk (1938)
showed that Graphidium strigosnm produces an amylase and a
protease which are active in the gut tube of the parasite. He
was unable to demonstrate a lipase. Chitwood (1938) demon-
strated in an extract of the esophagus of Asearis lumiricoides,
a proteolytic enzyme which was inactive at its isoelectric point
(ph 8.0) and most active in a weak acid solution. The fact
that such workers as Wetzel (1928) and Hoeppli and his co-
workers have demonstrated digested epithelial cells within the
alimentary tracts of certain parasitic nematodes, gives evidence
of the existence of ,jroteoIytie enzymes in parasitie nematodes.
Enigk 's (1938) finding of a varying reaction in the gut tube
of Graphidium strigosiim (pH 7.0 at the ends and 4.4-4.8 in
the middle), and Van Someren's (1939) report of an acid re-
action in the intestine and rectum of Trichinella spiralis are
additional confirmation of the presence of enzymes because al-
teration of the reaction of the digestive tract of animals is
universally coordinated w^ith the optimum pH for the enzymes
present.

Anticoagulants in blood sucking nematodes have been dem-
onstrated by a number of workers. While such products are
not primarily digestive, they doubtless prevent blocking of
the parasite's alimentary tract with clotted blood; hence, they
are an aid to digestion. Such products have been reported by
Schwartz (1921) and Hoeppli and Feng (1933).

Careful consideration of the relative values of the researches
demonstrating the presence of enzymes leads to the conclusion
that at least one and probably more proteolytic enzymes are

353

present in the intestine of many parasitic nematodes as well
as at least one amylytie enzyme. Demonstrations of lipases
have been impossible or questionable. Although little research
has been done on digestion in parasitic nematodes, the demon-
stration of these enzymes lends weight to the hypothesis that
digestion in parasitic nematodes is essentially like that of other
animals possessing a digestive tract.

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3S6-414.

Ernst, J. 1888. — Einige Fiille von .\nkylostomiasis, nebst
Sectionsbefundeii. Deutseh. Med. Wochenschr., v. 14:291-
294.

Fallis, a. Murray. 1938. — A study of the helminth parasites

of lambs in Ontario. Tr. Rov. Canad. Inst., v. 22, pt. 1
(47):81-128, figs. 1-30.

Faust, Ernest Carroll. 1932. — The symptomatology, diagno-
sis and treatment of Htronqyloidrs infection. J. Am. Med.
Assoc, v. 98:2276-2277.

1935. — Experimental studies on human and primate
species of Strongyloidcs. IV. The pathology of Strongy-
loides infection. Archiv. Path., v. 19:769-806.

1939. — Human helminthology Philadelphia. Lea &
Febiger. 780 pp.

Flury, Ferdinand. 1912. — Sur Chcmie und Toxokologie der
Ascariden. Arch. Exper. Path. & Pharmakol., v. 67:275-
392.

Garin, C. 1913. — Recherches physiologiqucs sur la fixation et le
mode de nutrition de quelques nematodes parasites du tube
digestif de I'homme et des animaux. Univ. Lyon, n.s., I.
Sc Med., V. 34:160 pp., figs. 1-55.

Glaser, R. W. 1932. — Studies on Neoaplcctana glaseri, a nem-
atode parasite of the Japanese beetle (Popillia japonica).
N. J. Dept. Agric. Circ. No. 211. 34 pp. pis. 1-3, - ' "

1-17.

Glaser, R. W. and Stoll, Norman R. 1938. — Sterile culture
of the free-living stages of the sheep stomach worm, Hae-
monchiis contortvs. Parasit., v. 30(3) :324-332, figs. 13.

(iuiART, J. 1908. — Le trichocephale vit aussi dans I'intestin
grele et se nourrit de sang. Lyon Med., v. 110(6) :325-
326.

Heller, M. 1933. — Entwiekelt sich die Trichinella spiralis in
der darmlichtung ihres wirtes? Ztschr. Parasitenk., v. 5:
370-392.

HoEPPLi, R. 1927. — Ueber Beziehungen zwischen dem biologi-
sehen Verhalten parasitischer Nematoden und histologi-
schen Reaktioncn des Wirbeltierkoerpers. Arch. Schi£fs-u.
Tropen-Hyg., v. 31 (3) :207-290.

1930. — Parasitic nematodes and the lesions they pro-
duce. Natl. Med. J. China., v. 16:103-110.

1933. — On histolytie changes and extra-intestinal di-
gestion in parasite infections. Lingnan Sc. J., v. 12
(Suppl.):l-ll, pi. 1, figs. 1-3.

HoEPPLi, R. and Feng, L. C. 1931. — On the action of esopha
geal glands of parasitic nematodes. Chinese Med. J., v.
17:589-598, pis. 1-3, figs. 1-6.

1933. — The presence of an anticoagulin in the esopha-
gus of Bunostomiim trigonocephalum from the intestine
of sheep. Arch. Schiffs u. Tropen-Hyg., v. 37(4) :176-182.

HoEPPLi, R. and Hsii, H. F. 1931. — Histological changes in the
digestive tract of vertebrates due to parasitic worms.
Chinese Med. J., v. 17:557-566, pis. 1-2, figs. 1-4.

Hsii, H. P. 1938a. — Studies on the food and the digestive
system of certain parasites. I. On the food of the dog
hookworm Ancylostoma caninnm. Bui. Fan Mem. Inst.
Biol., Zool., Ser., v. 8(2) :121-132, pis. 12 13, figs. 1 6.

1938b. — Idem. II. On the food of Schistosoma japoni-
cum, Paragonimiis ringeri, Dirofilaria iminitis, Sjrirocerca
sangiiinolenia, and Rhabdias sp. Ibid., v. S:.S47 3'i'>.

1938e. — Idem. IV. On the food of Viplotriaena tri-
citspvi (Nematoda). Ibid., v. 8:403-406.

Hung, Sbe-Lu. 1926. — The histological changes in lung tissue
of swine produced by Metastrongi/Uis clongatvs. N. Am.
Vet., V. 7(l):21-23, figs. 1-3.

Kauzal, G. 1936. — Further studies on the pathogenic impor-
tance of Chabertia ovina. Austral. Vet. J., v. 12:107-110.

Lapage, Geoffrey. 1933. — Cultivation of parasitic nematodes.
Nature, v. 131:583-584.

1937. — Nematodes parasitic in animals (Monograph).
London. Methuen and Co., Ltd. 172 pp.

Leichtenstern, O. 1886. — Weitere Beitriige zur Ankylostoma-
frage. Dent. Med. Wochenschr., v. 12:173-176.

Leuckart, R. 1870. — Die Menschlichen Parasiten. pp. 301,
345.

Li, H. C. 1933a. — Parasitic nematodes: Studies on their in-
testinal contents. I. The feeding of dog ascaris, Toxocara
cantis (Werner, 1782). II. The presence of bacteria.
Lingnan Sc J., v. 12 (Suppl., May):33-41, pi. 1, figs. 1-3.

1933b. — Feeding experiments on representatives of
Ascaroidea and Oxvuroidea. Chinese Med. .T., v. 47:1336
1342.

1933c. — On the mouth-spear of Tricliorrphahis tricJiit-

354

nis ami of a Trichoccpluiliin sp. from monkey, Macaciis
rhesus. Ibid., v. 47:13431346.

LlEVRB, H. 1S)34. — A propos <le rilcmatophngie des Ascaris.
Comp. Rend. Soc. Biol., Paris, v. ll(;:107!t.

Looss, A. ISlO.l. — The anatomy and life history of Agchylosto-
ma diiocloialc Dub. Rec. Egypt. Govt. Scli. Med., v. 3:1-
158, pis. 110, figs. 1-100, photos 1-6.

McCoy, E. E. and Girth, H. B. 1!)38.— The culture of Nco-
apUctaiia fflascri on veal pnlp. N. J. Dept. Agrie. Circ.
No. 28.3. i2 pp.

McCoy, E. E. and Glaseb, R. W. 1936. — Nematode culture
for Japanese beetle control. N. J. Pejit. Agrie. Circ. No.
265. 9 pp. figs. 1-5.

McCoy, Oi-ivek, R. 1920. — The suitability of various bacteria
as food for hookworm larvae. Am. J. Hyg., v. 10(1) :140-
156.

1934. — The development of adult trichinae iu chick
and rat embryos. J. Parasit., v. 20(6) :333.

Magatii, Thomas Byrd. 1919. — Camallauus americaiiiix. uov.
spec. Tr. Am. Micr. Soc, v. 38(2) :49170, pis. 7-16, figs.
1-133.

MtJELLER, Justus F. 1929. — Studies on the microscopical anat-
omy and physiology of Ascaris lumbricoides and Ascaris
megaloc>'plia}a. Ztschr. Zellforsch., v. 8(3)361-403, pis. 1-
18, figs. ISO.

Ortlepp, E. J. 1937. — Observations on the morphology and
life-history of Gaigeria jmchiiscclis Raill. and Henry,
1910: A hookworm parasite of sheep and goats. Onder-
stepoort J. Vet. Sc. & Auim. Indus., v. 8(1) :183-212, figs.
1-18.

Otto, G. F. 1935. — Blood studies on trichuris-iufestcd and
worm-free children in Louisiana. Am. J. Trop. Med., v.
15(6):693-704.

Porter, Dale A. 1936. — The ingestion of the inflammatory
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fig. 1.

Ransom, B. H. 1911. — The nematodes parasitic in the ali-
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Dept. Agrie, Bur. Anim. Indus. Bui. No. 127, 132 pp.,
figs. 1-152.

Schwartz, Benjamin. 1921. — Effects of secretions of certain
parasitic nematodes on coagulation of blood. J. Parasit.,
V. 7(3): 144-150.

Smirnov, G. G. 1935. — Nutrition of the Ascaris larvae in the
process of migration. Parazit., Perenosch. i ladovit.
Zhivotn. Slorn. Raliot. . . . Pavlovskii 1909-1935, pp. 298-
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1936. — On the question of hematophagia in thread-
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Inst. Exper. Med., v. 2:229-239. (Russian with English
summary.]

van Someren, \'erxon I). 1939.— On the presence of a buccal
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Stadelmann, H. 1891.— l'el)er dcii anatumischen Ban des
Strongylus coiirolutns Ostertag, nebst einigen Bemerkun-
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Veglia, Frank. 1916. — The anatomy and life history of the
Haemonchiis contortiis (Rud.). Dept. Agrie. Union S. Af-
rica, 3d & 4th Rpts. Director Vet. Res., pp. 347-500, figs.
1-60.

Weinberg, M. 1907.— Du Role des Ilelminthes. Ann. Inst. Pas-
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Weinland, Ernst. 1901. — Ucber den Glycogengehalt einiger
parasitischer wiirmer. Ztschr. Biol., v. 41 : 69-74.

Wells, Herbert S. 1931. — Observations on the blood sucking
activities of the hookworm, Ancylostoma caninum. J.
Parasit., v. 17(4): 167-182, fig. 1.

Wetzel, R. 1928. — Pathogenic effects of Strongylus equinus,
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Deutsch. Tieriirzte Wochenschr., v. 36: 719-722.

1930. — The biology of the fourth stage larvae of
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1931a. — On the biology of the fourth stage larva of
Bermaioxys veligcra (Rudolphi 1819) Schneider 1866, an
oxyurid parasitic of the hare. Ibid., v. 18:40-43.

1931b. — On the feeding habits and pathogenic action
of Chabertia ovina (Fabricius, 1788). N. Am. Vet., v.
12(9): 25-28, fig. 1.

Wetzel, R. and Enigk, K. 1937. — Zur Biologie von Graphidium
strigosum, dem Magenwurm der Hasen und Kaninchen.
Deutsch. Tierarzte. Wochenschr., v. 45(25): 401-405, figs.
1-3.

Whipple, G. H. 1909. — The presence of a weak hemolysin in
hookworm and its relation to the anemia of uncinariasis.
J. Exper. Med., v. 11: 331-343.

355

CHAPTER XI
CHEMICAL COMPOSITION AND METABOLISM OF NEMATODE PARASITES OF VERTEBRATES,

AND THE CHEMISTRY OF THEIR ENVIRONMENT

THEODOR VON BRAND, Department of Biology, Catholic University of America and
THEODORE LOUIS JAHN, Department of Zoology, State University of Iowa

The metabolic procLSses of nematode parasites comprise a
subject which has l)een under investigation for many years.
Progress in the field, however, has been particularly rapid dur-
ing the last decade, and it is the purpose of the present au-
thors to present a summary of the known facts of metabolism
together with the related subjects of the chemistry of the worms
and of their environment. Recent reviews which deal with
some of the subject matter here presented are those of Slater
(1928), McCoy (1935), Lapage (1S3S) and v. Brand (1934,
1938).

Peculiarities of Environment Which May Influence
Metabolism

The wide differences in the habitats of the various nematode
parasites of vertebrates are undoubtedly correlated with wide
differences in metabolic processes. The organisms which live in
the digestive tract, blood stream, lungs, kidneys, subcutaneous
tissue, etc., are subject to quite a variety of environmental
conditions. In those cases where open contact with the blood
stream or lymph is maintained the parasites are, of course,
subjected to an environment very similar to that of the cells of
the host body. Whenever a nematode is surrounded by a cyst
wall which reduces the availability of oxygen, or is located in
a region deprived of free blood circulation, metabolic jirocesses
are probably different from the processes in those species which
live in the blood stream. Species that live in the digestive tract
have an environment which is peculiar in many respects. The
chemistry of blood is adequately described elsewhere, and the
chemical environment within cysts and in chemically isolated
tissues is practically unknown (except for cestode cysts, Schop-
fer, 1932). Therefore, the present discussion of environment
is limited to the chemistry of the digestive tract.

From the viewpoint of nematology the chemistry of the in-
testinal contents is interesting for several reasons. A thor-
ough knowledge of the chemistry of the environment may allow
a better understanding of the physiology of the intestinal
parasites, it may aid in the formulation of culture media suit-
able for growth in vitru (cf. Glaser and Stoll, 1938), and it may
shed light on the problems of host specificity and on the possi-
bility that experimental modifications of intestinal contents
may be of use in controlling the activities of the nematodes.
The effect on nematodes of many of the substances found in
the intestine has not been studied. In the hope that the pres-
ent discussion might serve as a partial outline of substances to
be investigated, the authors have included a general discussion
of the chemical compounds present.

THE SEQUENCE OF CHEMICAL EVENTS IN THE
DIGESTIVE TRACT

In any discussion of the chemical composition of the contents
of the digestive tract it is necessary to keep in mind the se-
quence of events which occurs as the ingesta pass through the
alimentary canal. The chemical composition of the contents
of the gut varies with diet, with species, and with the state of
health. However, in any healthy animal on a constant diet
there is a definite sequence to the chemical changes which occur.

In man, the stomach leccives the mixture of food and saliva.
To this is added mucus, pepsin, and hydrochloric acid. The
material present in the duodenum is derived from four sources:
chyme from the stomach, bile, . pancreatic juice, and succus
entericus. The stomach contents when emptied into the duo-
denum consist, among other things, of proteoses and peptones,
starch, sugars, fat droplets, some fatty acids and glycerol,
hydrochloric acid, plant fragments containing cellulose and
undigested plant tissue, and water.

The bile contains mucin, the pigments biliverdin and bili-
rubin, the bile salts Na-taurocholate and Na glycocholate, cho-
lesterol, lecithin, fats, soaps, inorganic salts and water. The
relative amounts of taurocholate and glycocholate vary with
the species; the dog, for example, is entirely lacking in glyco-
cholate. The pancreatic secretion contains NasCOa and the
enzymes trypsin, lipase, and amylopsin. The succus entericus
contributes the enzymes erepsin, lipase, maltase, invertase, lac-
tase, and rennin, and a large amount of mucus and desqua-
mated epithelial cells. Due to partial sterilization of food, or
to the action of hydrochloric acid and bile salts, living bac-
teria are present only in small numbers in the duodenum and in

normal men may sometimes be absent (Kellogg, 1933). As
tliese materials pass through the duodenum and jejunum diges-
tion is completed, and tlie products of digestion and most of
the bile salts are absorbed. The bacteria increase in numbers,
utilize some of the products of digestion and decompose others.
As the material passes through the large intestine water is ab-
sorbed, and calcium, magnesium, iron, and phosphates are
secreted by the intestinal wall.

The feces of an animal on a carnivorous diet are composed
mostly of the intestinal secretions and bacteria. If vegetables
make up a considerable part of the diet, the bulk of the feces
is increased, and plant fragments appear in the feces, some-
times with the contained plant protoplasm only jiartially di-
gested. The large bulk of undigested cellulose stimulates
peristalsis, and consequently causes a more rapid passage of
ingesta through the intestine, which results in the absorption
of less water liy the colon and a more liquid feces.

The materials which are present in tlie digestive tract and
which may affect the metabolism of nemas are for convenience
discussed under the following headings: (1) Composition of
the intestinal gases, (2) Hydrogen ion concentration, (3) Dis-
solved materials (exclusive of gases), (4) Antienzymes. Nema-
todes, esi^eeially those which live in tissues, are known to secrete
digestive enzymes, but these are more properly discussed under
the subject of nutrition of the worms.

COMPOSITION OF THE INTESTINAL GASES

The composition of the gases in or in contact with the in-
gesta varies greatly in different parts of the digestive tract.
The gas tension of the stomach contents varies at different
periods following a meal and depends on the amount of air
ingested with food. The action of HCl causes a release of
bound COj, most of which is probably absorbed either in the
stomach or upper intestine. The oxygen ingested with the food
apparently undergoes a rapid decrease so that it is almost ab-
sent from the intestine below the duodenum. The analyses of
von Brand and Weise (1932) show that very little oxygen is
introduced into the intestine by the bile. These investigators
also studied the oxygen content of fluid intestinal matter and
of intestinal gases. They found that the oxygen content of the
fluid of both the large and small intestines of almost all ani-
mals examined was practically nil. The only exception was
one pig which contained quite appreciable amounts of oxygen.
This might have been caused by the swallowing of large
amounts of air, perhaps at the time of slaughtering. The
values for all animals except the pig correspond to about -5
percent saturation. The data of several investigators on the
oxygen content of intestinal fluids and gases are summarized
in Tables 13 and 14. The data in Table 14 demonstrate the ab-
sence of oxygen in the gaseous content of the intestine of all
animals except the pig. Long and Fenger (1917) found that
oxygen was present in appreciable quantities in the in-
testinal gases of the pig, and this was confirmed by v. Brand
and Weise. It has been assumed by Slater (1925) that the
intestinal walls give off oxygen to the intestinal contents during
digestion. This has not been proved experimentally, and Long
and Fenger (1917) found that the oxygen content was lowest
during active digestion. It seems probable (as indicated by
the data of Mclver, Redfield, and Benedict, 1926) that oxygen
may diffuse inward from the intestinal wall, but it is also very
likely that the bacteria present near the wall would consume
this immediately so that very little oxygen from this source
would ever reach the central portion of the lumen. The avail-
able evidence indicates that the environment of intestinal hel-
minths is not devoid of oxygen but contains oxygen in only
small quantities. Worms which live close to the intestinal wall
may have access to larger amounts. In the case of the hook-
worm it is apparent from the observations of Wells (1931) that
the blood sucking activities represent largely a respiratory
function.

Analyses of intestinal gases other than O: are not numerous.
The intestinal gases of man vary with diet. Ruge (1861) gives
the following data for percentage composition:

Diet CO. H= CH. N=

Vegetables 21-34 1.5-4.0 44-55 10.19

Meat 813 0.7-3.0 26-37 45-64

Milk -- 916 43-54 0.9 36-38

356

Tlio (lata of Fries (liHUi) slmw tliat tlif gasos of man iiu a
mixed diet are similar to tliose given above for a meat diet.
Further analyses are given hj Baseli (190S). The absorption
of intestinal gases is diseiissid liy Melver, Redfield, and Bene
diet (192(i), and the subjeet of human gastro intestinal gases
is reviewed bv Ziegler and Ilirseh U!l2r)) and Lloyd-Jones aiiil
Liljedahl (l!t"34).

The intestinal gases of the dog were analyzed by Planer
(ISlilO. His analyses demonstrated large amounts of CO2 and
N;, and a smaller amount of Hi; througluiut the digestive traet,
a small amount of 0» in the snuill intestine, and a small amount
of HaS in the large intestine when the dog was on bread or
meat diets. On a vegetable diet 11= largely replaced the N-,
while O2 and "US were absent. In these analyses methane is
conspicuously absent.

The intestinal gases of various herl)ivores have been ana-
lyzed by Tappeiner (18S3), and the literature is summarized
by Scheunert and Sehieblich (1!127). The data of Tappeiner
(1883) on the percentage composition of the gases in cattle,
sheep, and goats (all of which were quite similar) are as
follows :

Table 13. — Oxygen Content of Fluid Intestinal Maxxi

COa
Os -

CH.

Ha

Rumen

65

.5

30
0.6-4.7

1-40

Small Intestine
62-92

0

.04-6.6

0-37

1

Caecum

and Colon

about 30

0

38.r)3

2-6

23-34

Data for the horse (Tappeiner, 1883) are:

Small Caecum

Stomach Intestine and Colon Eectum

COi. 75 15-43 55-85 29

Os 0 0.57-76 0.14 0

CHi 0 0 11-33 57

H2 14 20-24 1.7-2.2 0.8

Na 10 37-60 .9-10.0 13

I>ata for the rabbit (Tappeiner, 1883) are:

Caecum

Stomach Small Intestine and Colon

CO2 32 75 6

O2 0 0 0.6

CH. 0 2 21.0

Hj 0 18 0.6

N2 ._ 68 6 72

Long and Fenger (1917) found a large amount of N2 (74 —
92'/i ) somewhat less CO2 (o — 28%), and about 5 percent Os,
but no methane or H2 present in the small intestine of hogs.

The production ot methane is probably caused mostly by bac-
terial decomposition of cellulose, althougli the data of Ruge
indicate that it can also be produced b.v bacterial action when
the animal is on a meat diet. The analyses of Tappeiner and
others also indicate the presence of H2S in some cases. H-S
and Xa must be formed by the action of bacteria on protein.
Ammonia is also formed by bacterial decomposition of protein,
Ijut it is usually bound by the acids of the intestine. Most of
the CO2 is probably of bacterial origin, although in the duo
denum it may also be formed by the NaX'Oa of the pancreatic
juice and the acid of the chyme. The NH., and the CO2 of the
succus entericus are discussed by Herrin (1937). Most of the
intestinal gases are eliminated from the body by the lungs.
Tacke (1H84) found that 10 to 20 times as much of the in-
testinal gases of rabbits escape by means cjf the blood and
lungs as by way of the anus.

The effect of the gases other than o-xygcn on intestinal nema-
todes is entirely unknown. Methane, H^, and N2 are probably
without either beneficial or harmful effects. The utilization of
o.xygen will be discussed in the part dealing with metabolism of
adult nematodes. The effect of CO2 is unknown. Since it is
incapable of further oxidation and since there is no evidence
of chemosynthesis in the nematodes, the only apparent effect
it could have would be the ad,justment of intracellular pH.
Since intestinal nematodes live in a medium usually saturated
with CO2 it is conceivable that they may depend on this sub-
stance as an intracellular buffer. Therefore, it may become
important to maintain a high CO2 content in in vitro cultures
(Cf. possible role in growth of intestinal protozoa, Jahn, 1934,
1936). It should be noted that Weinland (1901) found that
Ancarif: survived longer in vitro when the medium was satu-
rated with ('Oj.

Part of
.\nimal intestine

Oxygen in Number
volume per- of
cent mean deter-
and ( ) mina-
extremes tions

Horse Sm. intestine 0.024

(0.016 0.031)
Dog. ... Sm. intestine 0.028
Cattle Sm. intestine 0.013

(0.00 0.02.-,)
Sheep Sm. intestine 0.012

(0.00 0.025)
Pig .... Sm. intestine 0.083

(0.00-0.35,s)
Cattle Lg. intestine 0.010

(0.00 0.023)
Pig -. Lg. intestine 0,00

Investigator

2 Toryu (1934)

1 V. Brand & Weise (1932)

2 V. Brand & Weise (1932)

4 V, Brand & Weise (1932)

(i V. Brand & Weise (1932)

3 V. Brand & Weise (1932)
1 V. Brand & Weise (1932)

Table 14. — Oxygen Cont

Oxygen in

volume per

cent mean

Part of and ( )

Animal intestine extremes

Horse. .-Sm. intestine 0.67

(0.57-0.76)
Cattle..-Sm. intestine 0.00
Cattle -Sm. intestine *

Goat- Sm. intestine *

Sheep-...Sm. intestine *
Pig -Sm. intestine 5.5

(1.2 14.2)
Pig Sm. intestine 4.2

(0.4-8.2)
Dog Sm. intestine 0.2

(0.0-0.7)
Horse.- Lg. intestine 0.07

(0.000.14)
Cattle....Lg. intestine 0.00
Goat Lg. intestine 0.03

(0.00-0.07)
Sheep-— Lg. intestine 0.00
Rabbit -Lg. intestine 0.62
Dog -Lg. intestine 0.00

*Not enough gas for analysis.

ent of Intestinal Gases

iS' umber

of
deter-
mina-
tions Investigator

3 Tappeiner (1883)

1 Tappeiner (1883)

* V. Brand & Weise (1932)
» Tappeiner (1883)

* V. Brand & Weise (1932;
9 Long & Fenger (1917)

6 V. Brand & Weise (1932)

8 Planer (1860)

4 Tappeiner (1883)

1 Tappeiner (1883)

3 Tappeiner (1883)

1 Tappeiner (1883)

1 Tappeiner (1883)

6 Planer (1860)

HYDROGEN ION CONCENTRATION

The pH of the stomach and intestine has been measured for
a large number of animals, and some of the representative data
ai'e listed in Tables ]."j and 16. Contents of the stomach of car-
nivores, omnivores, and herbivores with a simple stomach, and
of the abomasum of ruminants are distinctly acid in character
due to the secretion of hydrochloric acid. The rumen and oma-
sum vary from neutral to distinctly alkaline. The pH of the
duodenum is extrenu^ly variable but is usually acid because of
the introduction of HCI from the stomach. The pH of the re
mainder of the small intestine is less acid than the duodenum,
and there is usually a progressive rise toward neutrality or to
a slight alkalinity; the pH seldom reaches a value higher than
8.0 or 8.2. The colon and caecum of most animals are neutral,
slightl.y acid, or slightly alkaline. Some of the recent litera-
ture is reviewed by Lenkeit (1933).

The pH of the intestine may be lowered b.v the administra-
tion of large quantities of lactose, especially if the diet is
low in protein. Robinson and Duncan (1931) found that the
pH of the rat intestine could be lowered about one pH unit by
the administration of 25 percent lactose with a low protein
diet (other literature is cited by these authors). In man it is
known that the acidity of the intestine may be considerably
decreased if large amounts of lactose accompanied by Lacto-
bacilltis aeidophiltis are ingested (literature cited by Kopeloff,
1926, and Frost and Hankinson, 1931). Comparable results
have been obtained with the domestic fowl (Ashcraft, 1933).
The direct addition of mineral salts such as NaCl, MgSO<, CaCU,
Ca(0H)2, CaSO., NaHCO:,, and NH.Cl to the diet may have no
effect on pH in experimental animals (McClendon et al, 1919;
Heller, Owens, and Portwood, 1935 ; Mussehl, Blish, and Ack-
erson, 1933). However, positive results with mineral salts have
been obtained by Robinson (1922), Shohl and Bing (1928) and
others. A deficiency of vitamin D is also known to cause tlie
intestinal contents to become alkaline due to lack of Ca ab-
sorption (Zucker and Matzner, 1923; Jephcott and Bacharach,

357

Table 15. — The pH of Stomach Contents

Animal

pH

Author

Man minimum pH

1.0 to 2..5
Eat _. 3.2-4.6

Eat

_1.8-5.6 (av. 3.6)

Bat

.,3.3-3.9

Horse - -

1.13-6.8 (507c

between 1.1

and 3.3)

Rabbit

..1.8

Cat

_3.34

Dog . —

_1.5-2.0

Dog -

..2.0-6.0

Dog

_1.37-5.7

(av. 3.47)

Chick, gizzard -

..3.39

Cliiclf. gizzard

.2.9-3.2

Chicken

proventriculus

.5.9

Chicken

proventriculus

.4.8-5.7

Cattle

abomasum

..2.0-4.1

Cattle

abomasum

.3.8

Sheep

abomasum

..3.15-0.25

(av. 4.0)

Cattle rumen „

..8.89 (8.61-9.68)

Cattle rumen --.

..7.5-8.0

Sheep rumen. ...

..7.0-7.6

McClendon and Medes (1925)
Kahn and Stokes (1926)
Sun, Blumenthal, Slifer, Ber-
ber and Wang (1932)
Eastman and Miller (1935)
Kofoid, McNeil and Cailleau

(1932)
Schwarz, Steinmetzer, and
Caithaml (1926)

McLaughlin (1931)
McLaughlin (1931)
Maun and Bollman (1930)
Schwarz and Danziger (1924)
Nagl (1928)

McLaughlin (1931)
Ashcraft (1933)

McLaughlin (1931)

Ashcraft (1933)

Schwarz and Kaplan (1926)

Mangold (1925)

Davey (1938)

Schwarz and Gabriel (1926)
Kreipe (1927)
Ferber (1928)

1926; Redman, Willimott, and Wokcs, 1927). The pH may be
appreciably lowered by addition of cod liver oil to a rachito-
genic diet. The effect of varying the proportions of protein,
fat, and carbohydrate has been reported to cause no marked
change in the pH of the intestine of rats (Redman, Willimott
and Wokes, 1927), dogs (Grayzel and Miller, 1928; Graham and
Emery, 1928), or man (Hume, Denis, Silverman, and Irwin,
1924). However, the data of Robinson and Duncan (1931)
show consistently higher pH values for rats fed on grain and
alfalfa than for rats on a high protein diet (Table 16). East
man and Miller (1935) studied the effect of a number of diets
on gastrointestinal pH in rats.

It has been suspected for some time that the pH of the cen-
tral portion of the lumen is not the same as that close to the
intestinal wall. Evidence for this is found in the feces in that

the surface of stools is more alkaline, apparently because of
secretion of alkaline salts by the intestinal wall. Kofoid, Mc-
Neil, and Cailleau (1932) reported ditterences in the pH of
contents and wall throughout the digestive tract of the rat. (Ta-
ble 16). Robinson (1935) studied the effect of placing various
salt solutions in the small intestine of dogs on the pH of the
solution and decided that each portion of the digestive tract
tended to produce a characteristic pH value in the solution, re-
gardless of the initial pH. He concluded that the pH of the
region close to the wall increases regularly from pH 6.5 to 7.5
or 8.0 throughout the length of the small intestine and pointed
out that the pH close to the wall is probably largely indepen-
dent of changes produced in the lumen by the action of bac-
teria. Ball (1939), by means of a capillary glass electrode, has
measured the pH of the wall (data given in Table 16).

The possibility that pH may be a limiting factor in the dis-
tribution of sheep nematodes was investigated by Davej' (1938).
He found that Ostertagia circumcincta was able to live between
pH 3.2 and pH 9.0. This range allows it to live in the aboma-
sum of sheep (pH 3.2-5.25) but apparently may be one rea-
son why it does not infest the stomach of the dog (pH 2 or
less) or horse (pH 1.1-6.8) or the abomasum of cattle (pH
2.0 to 4.1). Two duodenal species from sheep, Trichostrongylus
cohibriformis and T. vitrii-s. were alilc to stand a continuous
acidity as low as pH 3.6, but five other species {Nematodirus
fiUcoUis, N. spathiger, Cooperia oncophora, Cooperia curticei,
Strongyloides papillosus) from the middle and lower small in-
testine were killed at acidities of pH 3.9 to 4.6. Since the duo-
denum is more acid than the ileum, the low resistance to acidity
may be an important factor in preventing the five species from
the middle and lower intestine from infesting the duodenum.
It has been suggested by Lapage (1935a, 1938) that pH has an
influence on the second ecdysis of triehostrongylid larvae (out-
side of the host) and that this may be of importance in allow-
ing development of the parasite. The third ecdysis (in the
intestine) might be similarly affected.

It seems possible that the presence of nemas in the digestive
tract might cause a change in gastrointestinal pH, either
directly (perhaps because of lesions in the epithelium) or in-
directly through the systemic reactions of the host. In cases
of ancylostomiasis and intestinal schistosomiasis Eldin and
Hassan (1933) found evidence of gastric disturbance which
disappeared after removal of the worms. Fernandez (1934),
however, found no correlation between gastric acidity and hel-
minth parasites.

DISSOLVED SUBSTANCES (EXCLUSIVE OF GASES)

The dissolved materials of the digestive tract consist of the
ingesta and various secretions listed above, the products of
digestion, and the products of bacterial decomposition. Many
of these, especially the carbohydrates, may serve as food for
nematodes; many others may be toxic and may be effective in

Table 16. — The pH of the digest ive tract contents.

Animal and Diet Duodenum Jejunum

Ileum

Caecum

Colon

Investigator

Man

Man _

Man

Dog . —

Dog

Dog - —
Dog —
Cat

2.27-7.8
4.7 -6.5

4.5
2.0
6.2
5.9

-5.1
-7.6
-6.5

Rat

Eat — grain & alfalfa

Rat — high protein

Eat — high base

Rat

Eat — lumen of gut .
Rat — wall of gut...

Rat — wall of gut

Rabbit

Cattle

Cattle

Horse

6.5

6.5

6.75^

6.4>

6.4^

5 gi

(4.2 -6.9)

6.93
6.34
7.35
6.68

7.0

7.0-7.6
6.0-7.0
6.0-6.27

to

7.7'
6.8'
6.8'
6.6'
(5.0-7.3)

8.42

6.1-7.3
5.9-6.5

6.0-8.0
6.0-7.0
6.36

6.8
7.2
8.2'
7.3'
7.25'
6.9'

(5.6-7.7)
7.13
7.34
6.89
8.0
8.2

Hogs, calves, lambs ..

Fowl

Fowl — meat scrap

Fowl h 20% lactose

6.72 .... 7.09

Indefinitely variable 6.48 to 7.76.
More often acid than alk.
6.3 _. 6.22

5.96 ._ 7.1

6.51 .._ 7.16

6.0-6.5
6.57

6.5-7.2
7.0
7.3
7.0
6.4

(5.1-7.4)
7.13
7.34
7.06
6.26
8.2

8712

7.4

6.84
7.6 ■
5.25
6.4 ■
7.2
7.2
7.2
6.6
(5.4 ■
7.33
6.95
6.91

7.4-8.4

8.4
6.6

7.5)

Long and Fenger (1917)

Karr and Abbott (1935)

McClendon (1920)

Mann and Bollman (1930)

Graham and Emerv (1927-28)

Grayzel and Miller (1928)

Heupke (1931)

McLaughlin (1931)

Sun, Blumenthal, Slifer, Herber, and Wang ( 1932 )

Robinson and Duncan (1931)

Robinson and Duncan (1931)

Robinson and Duncan (1931)

Eastman and Miller (1935)

Kofoid, McNeil, and Cailleau (1932)

Kofoid, McNeil, and Cailleau (1932)

Ball (1939)

McLaughlin (1931)

Danniger, Pfragner, and Sehultes (1928)

Heupke (1931)

Danniger, Pfragner, and Sehultes (1928)

Long and Fenger (1917)

1.9=

McLaughlin (1931)

7.0

7.2

Ashcraft (1933)

5.1

6.3

Ashcraft (1933)

'Intestine divided into three approx. equal portions so that the measurements given may not correspond exactly to those
of the duodenum, jejunum, and ileum.

"Possibly a misprint in the original paper.

358

causing the localization of iKMuatodos in ccitain portions of the
(ligestivo tract.

The possibility that bile salts may affect the growth of in-
testinal parasites has been recognized for some time. Accord-
ing to Moorthy (l!t3.")) fresh bile from certain si)ecies of Barbiis
and from sheep and man is capable of killing Ci/clops and of
activating the enclosed larvae of linu-iinciihis mrilini iisix to es-
cape. De Waele (liHU) claimed that the eestode, Taenia kyda-
tigena {Cysticcrcun pixiformis), is able to infest dogs because
of the absence of Na-glycocholate in dog bile and that since
Na glycocholate is toxic to the organism it can not develo]i in
animals which secrete this substance.

Davoy (1938) has investigated the effect of bile salts ou
sheep nematodes. He found that the species which infest the
duodenum (Trichostrongylii.s colubriformis and T. vilriiius) of
sheep were much more resistant to Na-tauroeholate and Na-gly-
cocholate than other species {Ncmatodirim fillicoUis, A', spathi-
ger, Coopcria oncaphora, Coupcria curticci, and Ostcrtngia cir-
cumcxncta) from the lower small intestine and abomasum.
Cooperia curticci, which lives closer to the opening of the bile
duct than the other species except Tricliostrongj/lus colubrifor-
mis and T. vitrinus, has a resistance second only to Tricho-
Ktrongylus. Since the bile salts are introduced by the bile duct
and are largely reabsorbed in the snuill intestine, the concen-
tration of bile salts decreases along the intestine. The high
concentration in the upper small intestine probably prevents
species other than Tricliostrongylus from living in that region.
In these experiments glj'cocholate seemed to be somewhat more
toxic to Trichostrongylus than tauroeholate. Davey mentioned
the possibility that difi'erential susceptibility to the two bile
salts might be a factor in the determination of host specificity.

The products of bacterial decomposition are of several types:

1. Products of carbohydrate decomposition from:

a. Hydrolysis of cellulose to glucose in the rumen and
large intestine of herbivores.

b. Fermentation of simple sugars to lower fatty acids in
the small and large intestine of all vertebrates and in
the rumen of ruminants.

2. Products of protein decomposition from:

a. Hydrolysis of proteins to amino acids in the upper
small intestine.

b. Fermentation of amino acids to aporrhegmas and to
lower products in the lower small intestine and large
intestine of animals with simple stomachs and in the
rumeu of ruminants. Some of the products of fermen-
tation are indol, skatol, paraeresol, phenol, volatile fatty
acids, H=S, histamine, and tyramine. The relative
amounts of these products depend on the type of pro-
tein and on the species of bacteria present.

At present there is little evidence that these substances are
useful or harmful to intestinal nemas. Glucose is probably
absorbed by nemas, and on this assumi)tion changes in the diet
or in the bacterial flora which would affect the distribution of
glucose should affect the parasites. From the studies of Grove,
Olmstead, and Koenig (1929) on the low'er fatty acids in feces
it seems as if the quantity and perhaps the distribution of these
materials along the digestive tract is greatly affected by diet.
It is also probable that the products of protein putrefaction
may exert beneficial or harmful effects on the parasites. If
so, then experiments in which the amount of protein putrefac-
tion is controlled are in order. Such control is possible by the
administration of large amounts of lactose and bacteria which
ferment glucose to acid (review, Arnold, 1933). This treatment
results in the replacement of the protein putrefying organisms
of the coli-aerogenes group by those which ferment carbohy-
drate. The change in type of fermentation products is prob-
ably due to both the protein sparing action of carbohydrate and
the change in flora produced by increased acidity of the intes-
tine. Putrefaction could also be decreased by increasing the
rate of passage of ingesta. It is possible to increase protein
putrefaction at least in the large intestine by feeding such large
quantities of protein that some of it escapes complete digestion
and absorption in the small intestine. The putrefying organ-
isms also increase under conditions of achlorhydria which re-
sult in an alkalinization of the intestine, and if the achlorhydria
is severe they may even become implanted in the stomach. It
seems probable that experimental modification of the intestinal
contents through modification of the intestinal flora may bring
about changes in the distribution of nemas along the intestine,
and perhaps such experiments may result in methods of con-
trolling or eliminating certain species. Any changes which
may prevent eedysis of larval nematodes might be extremely
useful (Lapage, 193S).

It is known that HiS is highly toxic to vertebrates and that
it easily passes through most animal membranes. The studies
of Enigk (1936) on the lethal effects of H.S on the eggs of
Ascaris himbricoides and the studies of Lapage (193.5) on the

infective larvae of Triclionlroiigylus suggest that the outer cov-
ering of eggs and larvae may be permeable to H2S and other
sulfur compounds. Lapage (193.5b) obtained considerable evi-
dence that the permeability of the sheaths of larvae is changed
by sulfur compounds. In these experiments the effect of pH
was not carefully controlled, but the effect of 1 percent Na2S
on the eedysis of infective larvae was more pronounced than
that of 1 or 2 per cent NaOH. The sheaths became greatly
distended due to intake of water. If this effect is really due
to the sulfur compounds, this type of effect may give a chemi-
cal basis for the statements of Mudie (1934) and Johnston
(1934) that the eating of garlic will cause the disappearance
of threadworms from the human digestive tract. Lapage
(193.S) suggested that compounds which yield H:S when sub-
.iectod to the action of intestinal bacteria might eventually be
used as anthelmintics.

Some of the products of protein putrefaction, especially H2S,
rapidly combine with molecular oxygen and when in solution
produce very low oxidation-reduction potentials. Bergeim
(1924) devised a chemical method of obtaining an index of the
reducing power of intestinal contents, and he found that the
amount of reduction varied with diet. Preliminary electrical
measurements of the oxidation-reduction potential of the rat
digestive tract (Jahn, 1933) have shown that the Eh value may
be as low as — 200 mv. in the caecum and somewhat higher in
the lower small intestine. These measurements are well within
the "anaerobic" range and support the conclusions mentioned
above that oxygen is verj' scarce in the small intestine and ab-
sent in the caecum.

The osmotic pressure of the digestive tract is usually some-
what higher than that of the serum and tissues. Schopfer
(1932) gives the following freezing point depressions for va-
rious animals: sheep, 0.70-0.83° C; cow, 0.80° C. ; horse, 0.74-
0.77° C; hog, 0.9-1.0° C; and the elasmobranch Scylliorhini/s,
2.4° C. With the exception of the elasmobranch the serum of
the above animals has a molecular depression of about 0.55 to
0.65° G. Davey (1936b) gave a value of 0.55-0.63° C. for the
abomasal contents of sheep. The osmotic pressure of the in-
testinal contents probably varies considerably with salt intake,
but absorption and excretion are apparently rapid enough to
prevent the osmotic pressure from ever becoming more than
twice that of the blood. As will be discussed below (General
Chemical Composition) the osmotic pressure of the medium
determines that of the worms. However, the effect of this
change in osmotic pressure on worm metabolism is unknown.
Davey (1938) has shown that Ostertagia circumcincta is capable
of living in NaCl which varied from .4 percent to 1.3 percent
(0.9 percent is equivalent to a freezing point depression of
0.6° C). In balanced salt solutions the range would probably
be greater.

ANTIENZYMES

Since the nematodes of the vertebrate digestive tract live in
a medium high in the concentration of proteolytic enzymes, the
question of how they are able to resist digestion has often been
mentioned in the literature. The mechanism seems to be at
least dual: (1) the cuticle is relatively indigestible, and (2)
the worms contain or secrete antienzymes, i.e., substances which
inactivate the digestive enzymes. Evidence for this latter
mechanism was first described by Weinland (1903) who de-
scribed a substance with antitryptie powers in aqueous extracts
of Ascaris. Dastre and Stassano (1904) believed that the ac-
tion was antikinasic, but the experiments of Hamill (1906)
confirmed the original conclusions of Weinland (1903). Hamill
(1906) ascribed the following properties to the antienzyme:
highly soluble in water and weak alcohol; insoluble in 85 per-
cent alcohol ; thermostable in neutral or acid solutions ; ther-
molabile in weakly or strongly alkaline solutions ; readily dif-
fusible through membranes which retain colloids. Harned and
Nash (1932) described an improved method for preparing high
concentrations of antitrypsin by fractional precipitation with
alcohol. They claimed that by varying the concentration of
alcohol a preparation of antitrypsin could be obtained almost
free of Ascaris protease. These investigators were able to
demonstrate that their antitrypsin preparation also contained
a weak antipepsin. A powerful trypsin inhibiting fraction was
also recently isolated by Collier (1941) from Ascaris. An anti-
trypsin with chemical properties similar to those of Ascaris
antitrypsin has been prepared from egg white by Balls and
Swens'on (1934).

Sang (1938) investigated the mechanism of the action of
Ascaris antienzyme and confirmed the conclusion that the sub-
stance exerted both an antitryptie and an antipeptic activity.
However, he could not confirm the result of Harned and Nash
(1932) that the ratio of protease to antienzyme could be varied.
Sang concluded that Ascaris protease and Ascaris antitrypsin
and antipepsin are all one and the same substance, and he pro-

359

posed that this substance be called "asearase." His investiga-
tions showed that asearase was readily diffusible and that it
either is or is associated with a substance of the order of a
primary albumose. It was precipitated by ammonium sulphate
and 70 per cent alcohol, and was not destroyed by trypsin.
Asearase did not inhibit the action of papain. Von Bonsdorff
(1939) was unable to confirm the existence of antitrypsin or
antipepsin in Ascaris extracts, but he did find that the extracts
inhibited proteolysis of casein bv depepsinized gastric juiee at
pH 7.4.

Stewart and Shearer (1933) studied the digestion of pro-
tein by infected and noninfected sheep and concluded that the
nematodes of the stomach inhibited the normal digestive proc-
esses. They then obtained an extract from the worms which
was capable of producing a 40 to 7') per cent inhibition of the
peptic digestion of casein. For this sulistance and for similar
antienzymes of nematodes they siiggested the term ' ' nezyme. ' '
Andrews (1938) could not repeat the results of Stewart and
Shearer on the lowered digestive action of infected sheep. He
found that the digestibility coefficients were the same in infected
and noninfected animals. Infected sheep did not gain weight
as rapidly as controls, but Andrews concluded that this was
probably caused by intestinal irritation.

The existence of antienzymes has also been reported for
cestodes. However, de Waele (1933), on the basis of experi-
ments on Taenia sagiiiata, has questioned the existence of anti-
enzymes and has assumed that protection of the worms from
enzyme action is due entirely to the resistance of the cuticle.
One basis for this assumption is found in the fact that pieces
of worms but not whole worms may be digested by trypsin.
This conclusion is sub.iect to criticism in that when worm frag-
ments are placed in an enzyme solution considerable dilution
of any antienzyme may occur by diffusion and the antienzyme
may thereby be rendered ineffective. In view of the chemical
isolation of the antienzyme mentioned above (Hamill, 1906;
Nash and Harned. 1932; Collier, 1941) de Waele's conclusion
certainly can not Ije extended to the nematodes.

General Chemical Composition

DRY WEIGHT
There have been only a few determinations of the dry weight
of parasitic nematodes, and the values recorded are fairly high.
The average figures reported for Ascaris lumbricoidcs are 20.7
percent (Weinland, 1901) and 15 percent (Flury, 1912), for
Parascaris, 21 percent (Schimmelpfennig, 1903) and 14.8 per-
cent (Flury, 1912), and for a larval EiistrongtiUdes, 25 percent
(V. Brand", 1938). Flury (1912) measured the dry weight of
various parts of the body and obtained the following results:

Dry weight in percent of fresh weight
Ascaris fnmbricoidrs Parascaris equorum

Body wall ..- 23.5-25.0 25.0

Alimentary tract 27.5 24.9

Body fluid - 4.0- 6.7 5.0

Reproductive organs ... 25.0-33.3 24.0-27.4

It can be calculated from Flury 's figures that these values
represent the following fractions of the total dry weight: body
wall 65 percent, alimentary tract 3 percent, body fluid 10 per-
cent, and reproductive organs 20 per cent.

CARBOHYDRATE.S

Storage of carbohydrates in the form of polysaccharides
seems to be quite common among the parasitic nematodes. .W-
though chemical analyses have been made only for Ascaris, it
seems likely that in this respect other species are very similar.
Weinland (1901) and Flury (1912) found an optical rotation
of +183° to +193° for the polysaccharide of Ascaris. Since
these workers and Campbell (1936) identified the sugar result-
ing from hydrolysis as glucose, and since the solubility of the
polysaccharide and its color reaction with iodine are typical
of glycogen, it seems probable that the substance is true glyco-
gen. Campbell (1936), however, observed antigenic properties of
a polysaccharide fraction isolated from Ascaris. It does not seem
likely that pure glycogen would be capable of inducing the for-
mation of specific anti-bodies. One should therefore expect that
another polysaccharide is associated, perhaps in very small
amounts only, with the glycogen. However, in so far as meta-
bolic processes are concerned, it is justifiable to speak of
glycogen alone.

The occurrence of large amounts of glj'cogen in ascarids was
established in a qualitative or semi-quantitative wav by Claude
Bernard (1859) and Foster (1865), but Weinland "(1901) was
the first to undertake a large series of quantitative determina
tions. The more recent data on the glycogen content are sum
marized in the following table:

Glyco-
gen in

7o of
fresh
sub-

Species

Sex

stance

Country

Investigator

.-{.scans lumbricoidcs ...

?

5.4

Germany

Weinland, 1901

A.scaris lumbricoidcs ...

?

6.6

Germanv

Schulte, 1917

Ascaris lumbricoidcs ...

5

7.2

Denmark

V. Brand, 1934

Ascaris lumbricoidcs ..

9

8.7

Russia

Smorodincev
and

S

6.1

Russia

Bebesin, 1936

Ascaris lumbricoidcs ...

9

5.3

USA

V. Brand, 1937

Ascaris lumbricoicUs ...

$

5.8

USA

V. Brand, 1937

Dog Ascaris

?

4.5

Germany
Germany

Weinland 1901

Parascaris cqtiornm ....

t

2.1

Schimmelpfen-

nig, 1903

Parascaris equorum ....

9

3.8

Japan

Toryu, 1933

Parascaris equorum ...

S

2.9

Japan

Toryu, 1933

Ancylostoma caninum

mixed

1.6

USA

V. Brand and
Otto, 1938

Slrottpi/lus vulgaris ....

»

3.5

.Japan

Toryu, 1933

Filaria equina ..

?

2.2

6.9

Japan
USA

Torvu, 1933

Larval Eustrongylides

V. Brand, 1938

Apparently the glycogen content of parasitic nematodes is
always high. The lowest value amongst the intestinal nema-
todes was found in Ancylostoma. This may be related to the
fact that the hookworms have access to larger amounts of
oxygen than the other intestinal helminths. It is curious that
A.scaris lumbricoidcs analyzed in Denmark and Russia yielded
higher average glycogen values than those in USA and Ger
many. It is unknown whether this is caused by a different
diet of the host and therefore of the parasite in various couu
tries, or merely to different handling of the pigs before slaugh-
tering.

Sexual differences in glycogen content of parasitic nematodes
do not seem to be pronounced. Smorodincev and Bebesin (1936)
and Toryu (1933) found more glycogen in females than in
males of Ascaris and Parascaris. Von Brand (1937), on the
other hand, found slightlj' more polysaccharide in male as
carids.

So far, only adult nematodes of warm-blooded hosts have
been analyzed, and contrary to what is known about many
free-living invertebrates, no evidence of seasonal variation in
the amount of stored glycogen has been found. The obvious
explanation of this difl'erence lies in the uniform conditions
under which the parasitic organisms live throughout the year.
From this viewpoint, it should prove interesting to survey para-
sites from poikilothermic and heterothermic hosts, in which such
variations are more likely to occur.

The glycogen distribution in various organs and tissues has
been investigated both by quantitative chemical methods and
by differential staining. Toryu's (1933) analyses of various
organs of Parascaris equorum are summarized in the following
table:

Organ

Glycogen in percent of

fresh substance total glycogen

Body wall (cuticle + sub-
cuticle + muscles)

Intestine

Ovary

Uterus - -

Male reproductive system

9

s

9

s

5.8

4.9

66

96

0.6

0.6

2

0

fi.5

23

1.6

9

0.5

The body wall is obviously the most important storage place
for glycogen in worms of both sexes.

Differential glycogen staining has been used chiefly by v.
Kemnitz (1912) and ilartini (1916) working with Ascaris
and O.Tyuris, respectively. These workers extended the earlier
investigations of Brault and Loeper (1904) and Busch (1905).
It seems that in both cases the most intensive glycogen reac-
tions are found in the plasmatic bulbs of the muscle cells of
the body wall and in the hypodermis, cspeciall.v in the region
of the lateral chords, but it was also found in other organs,
for example, the intestine (compare also Hirsch and Bret-
schneider, 1937) and the reproductive organs. Glycogen, how-
ever, was never found in the cuticle, the phagocytic organs and
the nervous system. Additional data om the glycogen mor-
phology of other parasitic nematodes (Parascaris, Scleroslo-
mum, Helerakis and Ancylostoma) are found in the papers of
Busch (1905), V. Kemnitz (]912\ Faure Fremiet (1913), Tor-
yu (1933) and Giovaunola (1935). In these cases, the general

360

(lattoiii of glvcoKi'ii storagi' Sffiiis to Ix' similar to that of
Ascaris. In acuordaiu'e with the (luantitativc cliemical obsoiva
tions muoh U'ss glvcogon was fuuiul l)y morpliological inothods
ill hookworms than in ascarids. In the former, liowevcr, the
rays of the bursa are an important storage place, and prob-
ably represent an energy reserve for the male during the periods
of copulation when it is detached from the intestinal wall
(Giovannola, 193.')).

Not much is known about the occurrence of carbohydrates of
lower molecular weight in parasitic nematodes. Weinland
(1901) found 1.6 percent, and Schulte (I'UT) found 0.9 percent
glucose in Ascaris himbricoidt!!. It is, however, questionable
whether these figures are not too high, due to a partial break-
down of glycogen during the analyses. According to Foster
(lSG;i) and v. Brand (1934) only very small amounts of re-
ducing sugar occur in Ascaris. Faure-Fremiet (1913) found
0.15 percent glucose in the body fluid of Parascaris.

ETHER EXTRACTABLE MATERIAL

The parasitic nematodes seem to contain only small amounts
of material extractable with ether or petrol ether. The mean
values for Ascari.i Iinnhricoidcs vary from 1.2 to 1.6 percent
(Weinland, 1901: Flury, 1913; Schulte, 1917; v. Brand, 1934;
Smorodincev and Bebesin, 1936), and the value for a larval
EustrongyJides is 1.1 percent (v. Brand, 1S38).

The chemical compounds comprising the ether extract seem
to be quite similar in Ascaris and Parascaris (Flury, 1912;
Faure-Fremiet, 1913; Schulz and Becker, 1933). According to
Flury (1912) 100 gm of ether extractable material from As-
caris contains the following :

Volatile fatty acids _ 31.07 gm

Saturated fatty acids _. 30.89 gm

Unsaturated fatty acids 34.14 gm

Unsaponifiable matter 24.72 gm

Glycerol „ 2.40 gm

Lecithin 6.61 gm

The volatile fatty acids were represented chiefly by valeric
and butyric acids, with small amounts of formic, propionic and
acrylic acid. In Parascaris the whole series of volatile fatty
acids has been reported (Schimmelpfennig, 1903). The saturat-
ed fatty acids of higher molecular weight were recognized as
stearic acid with a small admixture of palmitic acid. Oleic
acid was the chief representative of the unsaturated fatty acids.
Flury 's value for glycerol is probably too low. Schulz and
Becker (1933), using newer methods, found glycerol values
ranging up to 8.8 percent. It is, therefore, unnecessary to as-
sume as seemed necessary to Flury (1912) that there is a com-
bination of part of the fatty acids with the unsaponifiable
matter. It is probable that all the fatty acids are present in
form of glyceryl esters. The unsaponifiable material is of
special interest because it contains a compound which so far
has been found in no other animal. This substance was found
independently by Flury (1912) and Faure-Fremiet (1913),
and it is known as ascaryl alcohol. It was recently reinvesti-
gated by Schulz and Becker (1933), who assigned it the for-
mula C33Hr»404. They state that its configuration is not yet
sufficiently known, but that it may be an ethereal combination
of glycerol with some higher alcohol. According to Faure-
Fremiet (1913) ascaryl alcohol occurs in the female repro
ductive cells only. Under these circumstances one wonders
why neither Flury (1912) nor Schulz and Becker (1933) men-
tion any other unsaponifiable substance, which should be ex-
pected in other parts of the body. Faure-Fremiet (1913)
found small amounts of cholesterol in the body fluid, the eggs,
and the testes of Ascaris, but Bondouy (1910) found no
cholesterol in Strongylus equinus. The ether extract of the lat-
ter species seems to be characterized by the presence of soaps.

Little is known about the distribution of the ether extract-
able material in different organs. Flury (1912) found it to
comprise 1.00 percent of the body wall of Ascaris and. 4.0 to
6.2."i percent of the reproductive organs. The latter figure
agrees with that given by Faure-Fremiet (1913) for the testes.
If allowances are made for the relative weights of body wall
and reproductive systems, it seems probalile that roughly the
same amount of ether extractable material is stored in both
these places. This is in marked contrast to the distribution of
glycogen.

Microscopical examinations (v. Kemnitz, 1912; Faure-Fre-
miet, 1913; Mueller, 1928/29; Hirsch and Bretschneider, 1937)
have shown that fat droplets are deposited in the plasma bulbs
of the muscles of Ascaris, in which the nuclei are usually
surrounded by an accumulation of fat, in the four chords, and

especially in the subcuticuhi. Stainable fat was also found in
ganglion cells, the intestinal cells, and the reproductive or-
gans. According to Mueller (1928/29) considerably more fat
can be demonstrated with osniic acid in Parascaris than in
Ascaris, although the pattern of fat deposition is the same in
both species.

NITROGEN CONTAINING SUBSTANCES

Flury (1912) found 8.1 percent proteins in Ascaris. This
is somewhat less than should be expected from Weinland 's
(1901) N figure of 1.80 percent. Flury (1912) ascertained
the presence of albumin, globulin, albumoses and peptones,
purinebascs, amines and ammonia, and he identified a series
of amino acids as degradation products of the worm i)rotein.
Recently Yoshimura (1930) performed a quantitative analysis
of the amino acids resulting from the hydrolysis of ascarids
with sulfuric and hydrochloric acid. His results are summarized
in the following table:

Amino acids in percent of dry substance upon hydrolysis with

hydrochloric
acid

sulfuric
acid

Leucine ._. 3.70

Alanine -- 1.4."

Valine 0.79

Proline 3.41

Isoleucine 1.45

Serine - 0.72

Glutaminie acid 3.93

Aspartic acid 0.36

Glycocoll 0.29

Phenylalanine 0.02

Leucine 15..54

Histidine 0.45

Arginine 1.28

Lysine ! 2.58

Tyrosine 2.09

The N containing substances constituting the cuticle have
already been discussed in another chapter (see page 32), and
that characteristic of the eggs (chitin) is mentioned on
page 177.

Faure-Fremiet (1913) described under the name of ascaridine
an intracellular protein of the spermatozoa of Ascaris. It con-
tains 17.5 percent N, but no phosphorus or sulfur. The chemi-
cal constitution of this interesting compound is not yet sufli-
ciently known. It is insoluble in cold distilled water," but dis-
solves rapidly in water of 50 to 51 °C. This critical temperature
varies greatly if the substance is dissolved in various salt
solutions (Faure-Fremiet and Filliol, 1937). According to
Champetier and Faure-Feimiet 's (1937) roentgenographie stud-
ies ascaridine seems to be a semi-crystalline substance, but it
can be changed experimentally into an amorphous state.

In recent years an increasing amount of attention has been
given to the occurrence of respiratory pigments in parasitic
nematodes. Haemoglobin seems to be widely distributed. It
has been found in Dioclophyma, Ascaris, Para.<icaris, To.tocara,
Nematodirns, species of Trichosirougyiits, Camallaniis, Spiro-
cerca, a larval Eustrongylides and larvae of Trichinella (Aduc-
co, 1889; Flury, 1912; Faure-Fremiet, 1913; Keilin, 1925;
Kriiger, 1936; v. Brand, 1937; Davey, 1938; Stannard, McCoy
and Latchford, 1638; Wharton, 1938, 1941; Hsii, 1938: Janicki,
1939). The best known case is that of Ascaris where it is
found both in the body fluid and the body wall. The absorption
bands of the haemoglobins occurring at these two places are
slightly different, and this indicates the presence of two kinds
of haemoglobin (Keilin, 1925). In all the above cases, where
haemoglobin has been found beyond the intestinal wall, one
can safely assume that it has been synthetized by the worm.
Parts of the host haemoglobin molecule may, of course, be
used in this process, but no definite data on this possibility have
been ob'oained. Obviously, haemoglobin found in the intestinal
tract of a worm will not fall in the same category, though in
some instances it may play a physiologically similar role (hook-
worm, for example).

Tlye only other respiratory pigments found so far are cyto-
chrome, which is known to occur in Ascaris, Parascaris and
Caviallanus where the highest concentration is found in the eggs
and sperm (Keilin, 1925; Wharton, 1941) and flavine found
In- .Goureviteh (1937) in Parascaris.

361

INORGANIC SUBSTANCES

Ascaris lumbricoUIes according to Flury (1912) contains 0.76
percent inorganic substances, and a larval Etistrongi/lides ac-
cording to V. Brand (1938) contains 1.1 percent.

A quantitative analysis of the inorganic substances of As-
caris by Flury (1912) gave the following results:

Na - - — 1.104% of the dry weight

K - 0.607

Ca -- 0.404

Mg 0.058

Al -- -- 0.131

Fe — 0.019

CI 1-272

PO4 -- 1-315

SO. . - - 0.114

SiO= 0.029

Neither copper nor manganese was found, and it can be said
that on the whole the composition of the ash of Ascaris seems
to be quite similar to that of free living organisms.

The osmotic pressure of the tissues of several Ascaris species
and that of the body fluid of Parascaris (Vialli, 1923, Schopfer,
1926, 1932) is similar, but not identical to that found in the
host intestine. The osmotic pressure of the worms always seems
to be a little lower, so that they live in a slightly hypertonic
environment. It is noteworthy that chlorides seem to play only
a minor role in producing the normal osmotic pressure of the
body fluid of Parascaris (Marcet, I86.1, Schopfer, 1932). The
total osmotic pressure corresponds to a freezing point depres-
sion (A) of — 0.62°C. wliercas the osmotic pressure due to the
chlorides is equivalent to a A value of — 0.12°C. The osmotic
pressure varies directly with that of the environment.' The
osmotic pressure of Frolcptiis obtusus living in the marine
elasmobranch ScuUiorhiiiiis is considerably higher than that
of the other parasites mentioned and is slightly higher than
that of Sci/lliorhiitiis blood (A = —2.40°, Schopfer, 1932).

iPanikkar and Sproston (1941) give data for Angusticneeum sp. from
the intestine of the tortoise. It is of interest that according to Stoll
(1940) the first parasitic ecdysis of Hiiemnnclius contortus is favored
by hypotonic solutions.

Metabolism of Adult Nematodes

METABOLISM UNDER ANAEROBIC CONDITIONS
Most of the experiments on nematodes under anaerobic con-
ditions have been performed with Ascaris Uimbricoides. Bunge
(1889) found that this species can be kept for several days
in the absence of oxygen and that it produces during this time
carbon dioxide and a volatile acid. Considerable progress was
made by Weinland (1901) who performed quantitative deter-
minations of the amounts of various substances consumed and
produced and who recognized that carbohydrates were pre-
dominantly used. In starvation experiments of several days'
duration he found that 100 gm of worms consumed 0.7 gm
glycogen and 0.1 gm glucose in 24 hours. He found among the
end products 0.4 gm carbon dioxide and 0.3 gm of a volatile
fatty acid which he identified as valeric acid. Later Weinland
(1904) found that caproic acid was also present in the ether
soluble excreta of Ascaris. A quantitative study of fat and
nitrogen in similar starvation experiments led Weinland (1901)
to the conviction that both carbon dioxide and fatty acids were
derived from the breakdown of glycogen, and he compared this
process to the fermentations produced by microorganisms. This
view concerning the anaerobic processes of Ascaris is still valid,
although subsequent investigations necessitated certain changes
in Weinland 's conclusions. In the first place it was found that
in addition to valeric and caproic acids, some formic, butyric
(Flury, 1912) and lactic acid (v. Brand, 1934a) were also
present in the excreta. At present it is certain that valeric
acid is the chief end product, but there is some uncertainty as
to the type of valeric acid excreted. It seems probable that it
is normal valeric acid (Waechter, 1934), although Flury (1912)
believed that he had identified isovaleric acid. Kriiger (193(5)
suggested the presence of methyl-cthyl-acetie acid, but Oesterlin
(1937) pointed out that this identification was insulflciently
supported by Kriiger 's data.

The second necessary modification of Weinland 's conclusions
concerns the intensity of the fermentation process. It was
found that with increasing length of starvation a deereising
daily amount of glycogen was used and that less carbon dia"ide
was produced (Weinland, 1901; Schulte, 1917; v. Brand, 19'i4a,
1937; Kriiger, 1936). In experiments conducted for only 24
hours' with fresh worms about 1.4 gm of glycogen was used.
This is twice as much as Weinland (1901) found for the av"n-

age daily glycogen consumption (11.7 gm ) in experiments whicli
lasted as long as (i days. It is, however, curious and not yet
sufficiently understood, tliat despite the different lengths of
their experimental periods, most of the above mentioned in-
vestigators found that between 0.2 and 0.3 gm of valeric acid
was produced per day. Kriiger (1936), however, found that
about 0..5 gm fatty acid was excreted during the first 24 hours.

The last complete biochemical balance under anaerobic condi-
tions was given by v. Brand (1934a) for females of Ascaris
hinihricoidcs. He found that 100 gm of worms consumed, dur-
ing 24 hours at 37°C., 1.39 gm glj'cogen and produced 0.71 gm
carbon dioxide, 0.22 gm valeric acid, and 0.02 gm of lactic
acid. No complete data are available for males. It has been
found, however, that the glycogen consumption is identical in
both sexes during the first 24 hours and that the more active
males later consume more glvcogen than the females (v. Brand,
1937a).

Parascaris equorum seems to have a (piite similar carbohy-
drate metabolism. Fischer (1924) ascertained the production
of small amounts of lactic acid. Toryu (1936a) found a small
amount of lactic and propionic acid and a large amount of
valeric acid, but no formic, acetic, butyric, caproic, malic, citric
or succinic acids. His glycogen/acid balance for the first 24
hours of anaerobiosis for 100 gm of worms was as follows:
Consumed: 1.39 gm glycogen. Produced: 0.6."i gm valeric acid
and 0.02 gm lactic acid. In addition carbon dioxide was pro-
duced and the amount of carbon dioxide differed markedly for
females and males (Toryu, 19361)). It is not clear what ani-
mals were used for the glycogen/acid experiments, and there-
fore it is impossible to introduce leliable carlioii dioxide values
into the above balance.

The above data indicate that the end jiroducts of the anaero-
bic carbohydrate metabolism are chiefly lower fatty acids and
therefore noticeably different from that of a vertebrate muscle.
This concept has been criticized chiefly by Fischer (1924) and
Slater (192-")). The former investigator concedes that living
Parascaris excrete only a small amount of lactic acid, and a
larger amount of an unidentified acid. He found, however, that
in minced material the i)roduction of lactic and the liberation
of phosphoric acid was sufficient to account for the whole
acidity oliscrved in aerobically conducted experiments. There-
fore, he concluded that there was no great difference between
the glycogen breakdown in Parascaris and in vertebrates. In
the opinion of the present writers, however, his observation in-
dicates merely that through changes in the experimental condi-
tions the course of the chemical reactions can be changed — a
phenomenon well known in e.xpcriments with yeast and other
lower plants. It should lie remembered that Weinland (1902)
found the same end products with extracts of Ascaris under
anaerobic conditions as he had found in experiments with
whole worms.

Slater (1925) demonstrated that bacteria capable of trans-
forming sugar into volatile fatty acids could be isolated from
a saline solution in which ascarids had been immersed. He
failed, however, to show that the^' were present in sufficient
numbers to account for all the organic acids produced in ex-
periments with worms, and, furthermore, he did not demon-
strate any substance which could have served as a substrate for
such bacterial fermentation.

Several lines of evidence have been brought forward which
seem to indicate a direct connection between nematodes and the
production of lower fattj' acids. The following two may be
mentioned. The volatile acids are found not only in saline in
which worms have been kept, but also in distillates of minced
worms (Weinland, 1901) and in the ether extract of whole
worms (Flury, 1912; Schimmelpfeunig, 1903). Valeric acid
has, furthermore, been found under both aerobic and anaerobic
conditions, although one should expect that such a difference in
the e.xternal conditions should have a deep influence on the
development of a bacterial flora in the surroundings. For fur-
ther information on this controversy compare the discussion of
Slater (1928) with those of Weinland (1901) and v. Brand
(1934b).

Several methods have been discussed in which valeric acid
may originate from carbohydrate. Weinland (1901) favored
the" following equation: 4G,Hi20,, = 9C0= + SC^HioOi + 9H=.
It must, however, be emphasized, that the postulated hydrogen
could not be found. Weinland (1901) had to assume that it
was used at once in other reactions. He also discussed an equa-
tion proposed by Koenigs:

13CoH,20„ = 12C=H,oO. + 18C0= + 18H:0.

Weinland rejected this equation because it did not predict
nearly as much carbon dioxide as he found to be present.
However, the excess might have originated either from bicar-
bonate or from protein decomposition. Jost (1928) has given
the following chain of reactions which leads to Koenigs' equa-

362

tion. These equatioiLs are piuely tliooretical, but the sorios is
interesting in that it sliowa a possible link between the prodne
tion of lactic and valeric acids.

Glucose

= 2 CjHoO;,

Lactic acid

CH3.CIIOH.COOH I
CH3.CHOH.COOH f
2 Lactic acid

Dismutation

and
dehydration

Pyruvic acid
( CHn.CO.COOH
( CHs.CHj.COOH

Propionic acid

+ H:0

CH..CH».COOH

t'Hn.CO.COOH + CHuCHo.COOH = CHa.COH.COOH
CH,a'HOH.CH=.CH2.COOH + CO:

-, Hydroxy-valeric aeid

CH3.CH0H.CHs.CH..C00H

= CH3.CH2.CH2.CH2.COOH 4-
Normal valeric acid

1 CoH„0„ = 1 CH..CH..CH0.CH2.COOH + HjO + CO2 + O
12 C«H,=Oe =12 CHr,.CHo.CH!.CH:.COOH + 12 H:0 +

1 C„H„Oo + 6 0=

12 CO. + 6 O2
6 CO2 + 6 H=0

13 CoH,.0„ = 12 CH::.CH...CH=.CH2.COOH + 18 CO2 + 18 H2O.

In effect, then, 12 molecules of sugar would be transformed
into 12 molecules of valeric aeid, carbon dioxide and water,
and the oxygen liberated during this process would be sufficient
to oxidize completely a thirteenth molecule of sugar.

Toryu (1936a) proposed the equation: 4C„Hi:08 = 400. +
4C.'iHio02 + H2O. This equation needs no further considera-
tion, since the O and H atoms on the two sides do not balance.
Correctly written it would read: 4CoHi-0,; = 400: + 4CgHio02
+ 4H;0 + 20=. This obviously corresponds closely to an inter-
mediate step of Koenigs' equation as formulated by Jost.

The amount of heat produced during the metabolism of
Ascaris lumbricoicles was first determined directly by Krum-
macher (1919). His experiments, however, were performed at
a time at which o.xygen was regarded as an inert gas for these
worms. Krummacher's experiments were neither clearly aerobic
nor anaerobic, and the data obtained are therefore difRcult to
interpret. Meier (1931), on Krummacher's suggestion, per-
formed similar experiments under anaerobic conditions. He
found a heat production of 0.300 gm cal per gm of worm per
hour. On the basis of Weinland 's chemical data and his own
heat determinations he calculated that the fermentation process
yields 22 percent of the energy obtainable by total oxidation
of the carbohydrate. This is considerabl.v more than usually
found in bacterial fermentations. Undoubtedly, however, Meier 's
figure of 22 percent is far too high. His experimental periods
lasted only from 4 to 12 hours, and he used presumably fresh
worms. Therefore, the carbohydrate consumption must have
been much higher than Weinland 's figure. Furthermore, Schulte
(1917) has demonstrated by direct comparisons of the heat of
combu.stion with the glycogen content of fresh and starving
ascarids that the carbohydrate metabolism accounts for only
80 percent of the total loss of calories from the body. Meier,
however, assumed that the total heat production was due to
carbohydrate fermentation. At present the data necessary for
an e.xact balance sheet of the energies involved seems to be
unavailable. A fair guess .would place the energy yield of the
fermentation between 6 and 12 percent. This is still more than
that usually found in bacterial fermentations. Lactic acid fer-
mentation, for example, yields only about 2.6 percent, and al-
coholic fermentation yields 4 percent.

Changes under anaerobic conditions in the material extract-
able with ether have been studied less thoroughly than the
changes in glycogen content. Weinland (1901) found that
there was no change in the fat content of ascarids during star-
vation, and V. Brand (1934a) reached the same conclusion.
Schulte (1917), on the other hand, observed a fat increase of
0.08 gm per 100 gm animals per day. He considered this fat
to be a product of carbohydrate fermentation. It seems cer-
tain, at least, that no fat is consumed under anaerobic condi-
tions. This is not astonishing, because it seems hardly possible
that an anaerobic process could yield energy from an oxygen
poor substance like fat (Weinland, 1901).

The nitrogen metabolism of Ascaris is not very great. For
100 gm of worms the amount of nitrogen excreted in 24 hours
was found by Weinland (1904b) to be 15 to 20 mgm and by
V. Brand f 1934a) to be 29 mgm. One third of the excreted N
is ammonia, and the greater part of the remainder can be
precipitated by phosjjhotungstic acid (Weinland, 1904b). Flury
(1912) found that the worms excreted not only ammonia but
small amounts of amine bases, substances which gave the

biuret reaction, hydrogen sulfide (also Kniger, 1936), and
mercai)tan. According to v. Brand (1934a) about one fourth of
the total excreted N is contained in discharged eggs. Chitwood
(1938) found urea in a concentration of about 0.02 percent in
the tiuid from the excretory pore of freshly collected worms.
.\ftcr 24 hours of starvation the tests for urea were negative,
and Chitwood doubts that the urea was formed by the worm.
It may have been obtained from the host.

METABOLISM UNDER AEROBIC CONDITIONS

Weinland (1901) believed that Ascaris did not consume oxy-
gen. However, he did observe that more carbon dioxide was
evolved under aerobic than under anaerobic conditions. He
explained this on the assumption that the extra carbon dioxide
was due eitlier to the metabolism of ;ierobically developing eggs
or to that of an aerobic bacterial flora. His view was generally
accepted until Adam (1932) proved that Ascaris was able to
consume oxygen. The observations of Adam were soon con-
firmed and extended to other forms. The following table sum-
marizes some of these data on oxygen consumption.

O2 consumption in
gm per 100 gm
worms in 24 hrs.

Species

Sex

at

body temp.

Investigator

Ascaris lumhricoides __

- S

0.38

Adam, 1932

Ascaris lumhricoides __

- 9

0.21

Adam, 1932

Ascaris lumbricoides .

. 2

0.21

V. Brand, 1934

Ascaris lumbricoides „

- 9

0.13

f Harwood and

Ascaris luvibricoides -

-S

0.21

\ Brown, 1934

Ascaris lumbricoides ..

?

0..1n*

Kruger, 1936

Ascaris lumbricoides ..

?

0.27*

Kruger, 1936

Parascaris equoruin ..

-9

0.08

Toryu, 1936

Parascaris equorum..

-S

0.35

Toryu, 1936

Setaria equiviim

?

0.89

Toryu, 1936

Ancyloslomn caninum

Lj

more than ten times

Harwood and

as

much

as female

Brown, 1934

Ascaris

The oxygen consumption of both Setaria and Ancylostoma is
considerably higher than that of Ascaris or Parascaris. The
former undoubtedly have easier access to oxygen and may
therefore be better adapted to aerobic metabolism.

The amount of oxygen consumed by Ascaris is influenced by
several factors. One factor is size, and small animals consume
relatively more than large ones. However, it is doubtful if the
difference in oxygen consumption of males and females can be
explained merely on the basis of size. Kruger (1936) gave a
formula which allows one to calculate approximately the in-
crease of oxygen consumption with increasing weight. The
formula is applicable only to worms which weigh over 1.4 gm.
In smaller worms the increase is more rapid. Kruger stated
nothing about the sex of his worms, but the deviation of his
data from the formula begins near the average weight of males.
In a recent paper Kruger (1940) shows that the 0= consump-
tion of ascarids of various sizes is fairly constant if referred
to surface rather than weight.

The oxygen consumption of starving ascarids kept for long
periods of time at the oxygen tension of air show a general
tendency to increase (v. Brand, 1934a; Kriiger, 1937). This
might be an indication of adaptation to the abnormally high
oxygen tension.

The oxygen consumption of Ascaris varies directly with the
oxygen tension, regardless of whether whole worms, parts of
worms or even minced material is used (Harnisch, 1933;
Kriiger, 1936). This is a striking contrast to what is known
from massively built free-living organisms, like aetiuians. In
these a similar dependence is observed in whole animals, but
it disappears if minced material is used. The diffusion rate
of oxygen is the limiting factor, and if the path through which
oxygen has to diffuse is shortened by using minced animals, the
oxygen consumption remains virtually unchanged over a wide
range of tensions. This explanation can not hold for Ascaris.
Harnisch, however, has found that the oxygen consumption of
planarians and Chironomus larvae, which is normally indepen-
dent of oxygen tension, may become dependent if the animals
are subjected to anaerobic conditions prior to the experiments.
In his opinion two kinds of aerobic processes must be dis-
tinguished: (1) a primary aerobic process which is considered
to be independent of the oxygen tension, and (2) a secondary
process which is considered to be dependent. In Ascaris only

'ICriiger (1936) gives data of various sized worms. Those for worms
of about the average size of males and females have been introduced in
the table, the higher figure being for worms of 1.5 gm. the lower for
worms of 4. .5 gm.

363

the secondary aerobic process is present. Harnisch (1937) of-
fered support of this view in the observation that washed
minced Ascaris material has only a negligible oxygen consump-
tion. The same material, suspended in Ascaris body fluid, has
a very high oxygen consumption and surpasses even that of
non-minced material. According to Harnisch this indicates the
presence of a powerful oxidizing mechanism outside of the cells
which may govern the entire aerobic processes of Ascaris.
This, he claims, is in accordance with his explanation of ex-
periments with artificially induced secondary aerobic processes
in Chlronomiis. The cellular agents which govern the primary
aerobic processes in Chironomns, however, could not be re-
moved from the cells by washing (Harnisch, 1936).

The data of Kempner (1937) show that in a variety of bio-
logical materials the effect of oxygen tension on oxygen con-
sumption varies with pH, CO2 tension, salt content, and tem-
perature. It is apparent that certain tissues heretofore con-
sidered to have a respiratory mechanism unaffected by oxygen
tension reallj' show an independence only in alkaline COa-free
media in a certain temperature range. These observations of
Kempner indicate that the whole question of oxygen tension
versus oxygen consumption should be reexamined, and that the
respiration of no material can be said to be completely de-
pendent or independent of O2 tension unless the effects of the
above factors have been investigated. It is possible that these
factors may have some effect on the nematode data discussed
above. A discussion of the theoretical relationship between
oxygen tension and oxvgen consumption is given by Marsh
(1935).

It seems that all the different organs of Ascaris are able
to consume oxygen. This has been shown for the body wall,
intestine, ovaries, uterus and even the body fluid (Harnisch,
1935, 1937; Kriiger, 1936). The largest absolute amount is
consumed by the body wall, although the intestine shows the
highest rate of oxygen consumption.

It is now generally believed that ascarids evolve larger
amounts of carbon dioxide under aerobic than under anaerobic
conditions (Weinland, 1901; v. Brand, in34a; Kriiger, 1936),
and Harnisch (1937) has abandoned his previous contention to
the contrary. The respiratory quotient in air is consistently
very high. In fresh worms it may be about 4 or even higher,
and in worms kept for several days in saline it is between 1.27
and 1.88 (Kruger, 1937). This indicates that the oxidation of
metabolites is not complete and that even in the presence of
oxygen the metabolism consists in part of anaerobic fermenta-
tions.

The excretion of organic acids under aerobic conditions, fiist
seen by Weinland (1901), is definite proof of the presence of
fermentations. The acids have been identified as small amounts
of lactic acid (v. Brand, 1934a), formic, acetic, and probably
butyric acid, a large amount of valeric acid and some unidenti-
fied higher acids (Oesterlin, 1937). Since these products are
similar to those formed under anaerobic conditions (see above),
it seems likely that the fermentations going on under aerobic
and anaerobic conditions are identical. The amounts of acids
excreted at the oxygen tension of air are definitely lower than
under strictly anaerobic conditions (v. Brand, 1934a; Kruger,
1936, 1937), but at low oxygen tensions even more acids are
excreted (Kruger. 1936).

It is customary in the nematode literature to refer to the
oxidations which involve oxygen consumption and which lead
to the production of carbon dioxide and water as oxidative
metabolism and to refer to the molecular rearrangements and
oxido-reductions which lead to the production of carbonic,
lactic, valeric, and other acids and in which oxygen is not con-
sumed as fermentative metabolism. Von Brand (1934a) and
Kruger (1937), by basing calculations on the ratio of anaero-
bically evolved carbon dioxide to anaerobically excreted acids
or similar data at low oxygen tensions, calculated the amounts
of aerobically evolved carbon dioxide which originated in fer-
mentative and in oxidative metabolism. This latter figure was
used, in connection with the oxygen consumption, to calculate
the true respiratory quotient which was found to be about 0.9
or 1.0. In some cases very low quotients were found, and these
data are difficult to explain at the present time. The opinion
of Harnisch (1933) that the aerobic processes do not lead to
the production of CO2 and that the respiratory quotient is
zero has been generally abandoned.

Kruger (1936) found that the uncorrected respiratory quo-
tient of ascarids kept in air instead of saline fell rapidly to
about 1.0 and remained at this level for some time. This would
indicate (Kriiger, 1937) either that the fermentations cease
altogether, or that the fermentations present do not lead to
carbon dioxide production (e.g., lactic acid formation).

The question of what substances are oxidized has received
some attention by v. Brand (1934a). He found that under
aerobic conditions somewhat less glycogen is consumed than

under anaerobic ones. On an assumption similar to that made
above for the carbon dioxide, he calculated the amounts of the
consumed glycogen which had apparently been decomposed by
fermentative and by oxidative metabolism. He arrived at the
following balances:

Uncorrected balance for 100 gm worms starving at 37° C.
under aerobic conditions:

Decomposed: 1.18 gm glycogen. Consumed: 0.21 gm oxy-
gen. End products: 0.84 gm carbon dioxide + 0.10 gm
valeric acid + 0.01 gm lactic acid.
Oxidative part of the metabolism:

Decomposed: 0.37 gm glycogen. Consumed: 0.21 gm oxy-
gen. End products: 0.34 gm carbon dioxide + ?.
Fermentative part of the metabolism:

Decomposed: 0.86 gm glycogen. End products: 0.48 gm
carbon dioxide + 0.16 gm valeric acid + 0.01 gm lactic
acid.
The amount of glycogen which disappeared was so great that
complete oxidation to carbon dioxide and water could not be
assumed for all of that which was calculated to undergo oxida-
tive metabolism. Probably only a partial oxidation takes place
(formation of aldehydes?).

Harnisch (1935) thought that possibly isovaleric acid would
be oxidized to aceto acetic acid or ^Q hydroxy-butyric acid which
in turn would lie decomposed to acetone and carbon dioxide.
However, chemical determinations on the excreta do not favor
this view. This statement applies also to v. Brand's (1934a, b)
original theory that fats may be changed into carbohydrate.

It seems as if Ascaris, in contrast to many free living ani-
mals, does not contract a noticeable oxygen debt during a pe-
riod of anaerobiosis (Adam, 1932; Harnisch, 1933). It was
found (v. Brand, 1937b), however, that ascarids sub.iected to
20 hours anaerobiosis and then brought for 2 to 6 hours into
aerobic conditions, resynthesized 1/20 to 1/10 of th" glycogen
consumed during the anaerobic period. This resynthesis is clear-
ly an aerobic process, and it is apparently much l"ss pronou"""d
in Ascaris than in similarly treated vertebrate muscles. This
may be due to the fact that in vertebrate muscle the end nrnd-
ucts accumulate, whereas in Ascaris they are excreted, and only
those present in the liody at the beginning of the aerobic period
are available for resynthesis. It is unknown whether lactic acid
or the lower fatty acids are resynthesized to glycogen.

There is still some controversy concerning the .significance of
the aerobic processes of Ascaris. Harnisch (1933) assumed that
the aerobic processes would yield no energy, and he still thinks
(Harnisch, 1935) that thev play no role in the normal energy
supply of the organism. This view is similar to that of Kriiger
(1937) who states that they are probably not linked to any
specific organ function and that any derived energy is prob-
ably wa.sted. The present writers are of the opinion that at
Hiis time no definite statements regarding the possible utiliza-
tion of this energy can be made.

The fact that the rate of the fermentative processes is re-
duced at the oxygen pres.sure of air, seems to indicate rather
clearly that fermentations and oxidations are not entirely inde-
pendent as Harnisch (1933) originally assumed. Whether Krii-
ger's (1937) view is correct that the oxidations follow essen-
tially the same course as in truly aerobic organisms, or whether
Harnisch (1937) is right in assuming that they correspond only
to the secondary aerobic processes occurring in free living ani-
mals only under sjiecial conditions, must be decided by future
investigations.

The aerobic metabolism of Parascaris eqvoriim has been
studied by Toryn (1934 to 1936b). He found an almost identi
cal glycogen consumption under aerobic and anaerobic condi-
tions, but since the worms excreted slightly less organic acids
under aerobic conditions, he concluded that a small amount of
glycogen was oxidized. Apparently the aerobic metabolism
of Parascaris follows the same pattern as that of Ascaris.

The question of whether or not parasitic nematodes use fat nn
der aerobic conditions is difficult to answer satisfactorily at the
present time. In v. Brand (1934a) aerobic experiments no fat
was used. In view, however, that his experiments lasted only 24
hours and that in general carbohydrate is consumed before the
fat reserves are attacked, these experiments can not be accepted
as conclusive evidence that no fat may be used during longer
periods of starvation. JIneller (1928/29) observed that in ex-
planted pieces of Ascaris a loss of morphologically demonstrable
fat occurred after several days, and Hirsch and Bretschneider
(1937) have shown that in starving ascarids much of the stain
able fat disappeared from the intestinal cells after 6 days.
These observations are suggestive that fat may be used, but
they should be confirmed by quantitative chemical methods.^
Bondony (1910) detected a lipase in Strongijlus eqitintis, and
the possible significance of its presence warrants further study.

iln a recent paper v. Brand (1914) showed that Ascnrin uses no fat
for production of energy during an aerobic starvation period of 5 day».

364

Tlic aoi'obio :iiul aiiat'roliii' iiitiogt'ii iiu'talMilism of Axcari.i
has been compaiod by v. Brand (l!i34a). The amounts of nitro-
gen excreted both in sohible exereta and in eggs were very
nearly identical in both cases. He assumed that at least a
large part of the X metabolism was involved in the transforma-
tion of the protoplasm of the body into that of eggs. He also
considered it likely that at least a large i)art of the nitrogen
metabolism was always anaerobic. This view is supported by
the fact that free-living animals, like tlie leeches, show, in
contrast to Ascarix, a marked dift'erence in the amount of nitro-
gen e.\creted under aerobic and under anaeroliic conditions.

DEDUCTIONS CONCERXIXG TIIK MKTABOLISM

IX riro

Deductions concerning the nature of the metaliolism of in-
ternal parasites can be drawn only from the chemical composi-
tion of their surroundings and their metabolism in vitro. Of
special interest is the question of whetlier the nematodes para-
sitizing the intestine lead an anaerobic or an aerobic life. On
the basis of the investigations of Bunge (LSSJ)) and Weinland
(1901) the first possibility was accepted for many years as an
undisputed fact. More recently certain investigators (Slater,
192.'); Mueller, 1928/29; Adam, 1932; Davey, 1938a and b)
have held the opposite view, i.e., that tlie worms can get enough
oxygen in the intestine to allow an oxidative metabolism. Re-
cently V. Brand (193S) has reviewed the question, and he be-
lieves that a general answer can not be given. Api)arently the
size or relative surface and the presence of respiratory pigments
will have a great influence on whether a worm can or can not
obtain sufficient oxygen at the low tensions prevailing in the
intestine. Large parasites, like Ascaris or Parascaris, must be
regarded as predominantly anaerobic organisms. As mentioned
above, the.v show a marked fermentative metabolism even in
air. Since their oxygen consumption is dependent on the oxygen
pressure, one can be reasonably sure that fermentative metabo-
lism will be relatively much greater in the intestine. Further
signs of their adaptation to an anaerobic life are that the.v
are remarkably resistant to the lack of oxygen in vitro and
that they are able to excrete the end products of anaerobic
metabolism. It seems, however, quite possible that the small
amounts of oxygen available in the intestine are not entirely
without significance. This may be indicated by the observations
that the worms contain some haemoglobin, that stimulated
Ascaris die much more rapidly in absence than in presence of
oxygen, and finally that they are able to perform under suitable
conditions such a clearly aerobic process as the resynthesis of
gl.veogen.

Small nematodes, on the other hand, offer better opportuni-
ties for the diffusion of oxygen because of their relatively
larger surface. This may explain why the sheep nematodes do
not show (Davey, 1937, 1938a and b) the same resistance
against lack of oxygen as Ascaris. The conclusion of Davey
that these worms lead an aerobic life under natural conditions
is, therefore, probably only in apparent contradiction with the
statement made above in regard to large helminths.

An entirel.y different way of getting oxygen may be realized
in worms sucking larger amounts of blood from their hosts.
According to Wells (1931) the blood sucking activities of hook-
worms seem to serve largely as a respiratory function. His data
allow the calculation that under optimal conditions 100 gm of
worms could obtain 20 gm of oxygen from this source in 24
hours. This would be about ten times as much as Harwood and
Brown (1934) found to be the actual oxygen consumption.

No data are known about the metabolism of adult parasitic
nematodes which normally live outside the intestine. It is there-
fore unnecessary to enter into a similar discussion concerning
their metabolism. On the whole one may assume that they will
have frequently, though probably not in every case, better op-
portunities to get larger amounts of oxygen than the intestinal
helminths.

SYNTHESIS OF RESERVE SUBSTANCES

There are only a few investigations which concern the ques-
tion of the synthesis of reserve substances in parasitic nema-
todes. Hoffman (1934) and Kriiger (1936) have shown that
the heat production and the o.xygen uptake of ascarids under
both anaerobic and aerobic conditions are increased if sugar is
present in the surrounding medium. Hirsch and Bretschneider
(1937) fed ascarids iron saccharate and concluded from their
histological investigation that it was absorbed as colloid and
broken down only in a certain part of the intestinal cells into
iron and sugar.

Quantitative determinations of the glycogen content of car-
bohydrate-fed ascarids have been performed by Weinland and
Ritter (1902). They found no increase in the glycogen con-
tent of animals kept in solutions containing various carbohy-

drates, altliough glucose caused a lowering of the rate of utili-
zation of body glycogen. More positive results were achieved
by injecting the sugar solutions into the animals. In these ex-
periments new glycogen was foJined after injection of glucose
and probably levulose. The consumption of body glycogen was
decreased by injections of maltose and perhaps galactose, but
not by injections of hictose.

Von Brand and Otto (1938) compared the glycogen content
of hookworms from dogs which had been starved for 48 to 72
hours before death with those from dogs which had been given
so much sugar during a similar 'period that the liver glycogen
rose from 0.06 percent to .").04 percent. No difference what-
ever in glycogen content of the worms was found. This may be
related to the fact that hookworms obtain their food from the
tissues rather than from tho lumen of the intestine and there-
fore can gain their maximal food requirements even from a
starving host.

So far no experiments have been performed on the deposition
of fat in parasitic nematodes except the above mentioned doubt-
ful results of Schulte (1917) concerning the fat increase in
ascarids under anaerobic conditions. The whole question of
synthesis should prove interesting for future investigations.

Metabolism of Eggs and Larvae

The eggs of many parasitic nematodes show, like the adults,
a surprising degree of resistance to lack of oxygen. The eggs
of such forms as Anci/lostoma, Parascaris, Trichoccphalus or
yematodiriis can be kept for days or even weeks in the absence
of oxygen, but they do not complete their development (Looss,
1911;"Bataillon, 19*10; Zawadowski, 1916; Faure-Fremiet, 1913;
Zawadowski and Orlow, 1927 ; Zviaginzev, 1934 ; Dinnik and
Dinnik, 1937). In Parascaris oxygen is unnecessary only during
the early stages, i.e., maturation, fertilization and perhaps the
first cleavage stages; for further development oxygen is indis-
pensable (Faure-Fremiet, 1913; Szweikowska, 1929; Dyrdow-
ska, 1931). The need of oxygen for completion of development
seems to be a general requirement, although the stage of de-
velopment at which oxygen becomes necessary seems to vary
somewhat with different species. Zawadowsky and Schalimow
(1S29), Schalimow (1931), and Wendt (1936) conclude that
the necessity for oxygen begins in Enterobius vermicularis
with the tadpole stage, and in Oxi/iiris eqni with the gastrula
stage. Relatively low oxygen pressures, however, are sufficient
to insure normal development in Ascaris and Ancylostoma
(Brown, 1928; McCoy, 1930).

The amount of oxygen consumed by one Ascaris egg in de-
veloping from the one-cell stage to the motile embryo is about
0.002.5 cmm with only slight variations whether the develop-
ment is completed in "21 days at 23°C or in 11 days at 30°C
(Brown, 1928). Huff (1936) obtained a value of 0.0041 cmm
for Ascaris, and Nolf (1932) obtained a value of 0.0027 for the
eggs of Trichuris. It is surprising that an Ancylostoma egg re-
quires for its development from the morula stage to the fully
developed larva almost exactly the same amount of oxygen
(0.0028 cmm at 23° C. according to McCoy, 1930) as an As-
caris egg, although development of Ancylostoma is completed
in about 24 hours. Since these eggs are about the same size,
it seems as if the difference in the rate of oxygen consumption
mentioned above for the adults of these species is also present
in the embryonic stages.

Huff (1936) observed that the o.xygen consumption of As-
caris eggs increased more than five times after removal of the
albuminous coating by antiformin. Friedheim (1933) found
that the oxygen consumption of Ascaris eggs is considerably
increased if they are immersed in a dilute solution of hallo-
chrome (a pigment which is a reversible oxidation-reduction
system isolated from the polychaete worm Halla parthenopea
and which has an aceelcrative eft'eet on respiration). The mech-
anism of the increase in respiration by either of these two
methods is not known. Friedheim (1933) apparently used mixed
stages of fertilized eggs, and there seems to be no reason for
assuming that hallochrome could penetrate the egg shell. There-
fore, one might expect the acceleration obtained to be due to
an increase in the effective oxygen tension or to an increase
of respiration in only those eggs on which an impermeable shell
had not yet been formed. The experiments of Huff might also
be explained as being caused by an increase in effective oxygen
tension because of slow diffusion of oxygen through the albumi-
nous coat, but no data concerning these possibilities are avail-
able. Since the R. Q. is always less than 1.0 (see below) the
possible effect of oxygen tension could not be merely to change
the ratio of oxidative and fermentative metabolism. The ac-
celerations produced by Friedheim (1933) and Huff (1936)
must, for the present, be accredited to changes in the rate of
oxidative metabolism, and the reasons for the changes re-
main obscure.

36S

The oxygen consumption of Ascaris or Farascaris eggs has
also been reduced experimentally by ultraeentrifuging and by
exposure to cyanide (Zawadowsky, 1926; Huff and Boell, 1936).
About 90 percent of the respiration was sensitive to cyanide,
and it seemed that ultraeentrifuging affected only the cyanide
sensitive respiratory mechanism.

The respiratory quotient of Farascaris and Ascaris eggs has
been found to be below 1, and this indicates that, in contrast
to results on tissues of the adult worm, no fermentative proc
esses are present in the eggs. The respiratory quotient deter-
mined at the beginning of development was about .80, and.
with some variations in the ease of Farascaris, it increased
during the later stages to .92.98 (Faure-Fremiet, 1913a, 1913;
Huff, 1936). The total energy liberated by one Farascaris dur-
ing its development was 50 x 10" cal. (Faure-Fremiet, 1913).
Nolf (1932) found that the R. Q. of Trichuris decreased from
a value of 1.0 for the first 5 days of development to a value of
0.73 for the 8th to ir)th days. "

In considering the chemical changes which occur in the eggs
of parasitic nematodes during their development, one must
distinguish clearly between processes which lead to the forma-
tion of the egg shells and ijrocesses which liberate energy.
The shells, as far as they are formed from the ovum, consist
essentially of the shell proper and the vitelline membrane. The
shell is composed of chitin in such species as Farascaris, Ascaris.
Dioctophyma and Enterobius (Faure-Fremiet, 1913; Szwejkow-
ska, 1929 ; Schmidt, 1936 ; Wottge, 1937 ; Chitwood, 1938 ; Jacobs
and Jones, 1939). The investigations of Faure-Fremiet (1913)
and Szwejkowska (1929) have demonstrated that in Ascaris
about half the glycogen stored in the oocytes was used to form
the glucosamine incorporated in the chitin. The latter has
shown in addition that 26 percent of the total nitrogen of the
egg was used during the chitin formation.

The vitelline membrane of the eggs of these and other species
is of a lipoid nature (Faure-Fremiet, 1913; Zawadowsky, 1928).
Faure Fremiet considered it to be mainly ascaryl alcohol,
Wottge (1937) obtained a positive reaction for cholesterol.
and Chitwood (1938) and Jacobs and Jones (1939) demon-
strated that it gave sterol reactions. During the secretion of
this layer certain changes in the chemical nature of the ether
soluble substances, perhaps a saponification, seemed to occur.
The necessity for further studies is indicated.

Chemical analyses of the egg indicate that both glycogen and
fat are oxidized, and these data are in accordance with the
above data on the respiratory quotient. Swejkowska (1929)
found in Farascaris eggs jnst after fertilization about 0.46
percent volatile fatty acid and 0..53 percent higher fatty acids.
After formation of the second polar body these suli-
stances had diminished to 0.34 and 0.36 percent re-
spectively. For the same period it was calculated that
in addition to the glycogen used in the formation of chitin an
amount of glycogen corresponding to about 2.7 percent of the
egg weight had disappeared. From Faure Fremiet 's (1912,
1913) experinients it would appear that both fat and glycogen
were used during the later developmental stages. All of these
experiments were conducted under aerobic conditions. Dyrdowska
(1931) found by the use of staining methods that the glycogen
content of Farascaris eggs kept under anaerobic conditions un-
derwent a slight diminution and that there was a marked de-
crease in the fat content. It seems desirable that this decrease
in fat content should be verified with quantitative chemical
methods since, as already stated above, it is difficult to under-
stand how processes which liberate energy from fat could
occur in the absence of oxygen. It should, furthermore, be
remembered that Faure-Fremiet (1913) gained the impression
that the amount of fat in anaerobically kept eggs tended to
increase.

With the exception of the above mentioned shifting of nitro
gen from the ovum to the chitin shell, nothing is known about
the nitrogen metabolism of eggs. Szwe.ikowska (1929) found
no change in the total nitrogen content during the time of
maturation, and Kosmin (1928) found the same nitrogen con
tent (1.78 percent) in undeveloped and developed eggs. She
points out that this may be caused by the impermeability of
the vitelline membrane for protein degradation products which
consequently might accumulate in the interior of the egg shells.

The fully developed embryo of Ascaris contains glycogen,
even in eggs which have been stored for 6 months (Stepanow-
Grigoriew and Hoeppli, 1926). This observation has a bearing
on Pintner's theory (1922) concerning the physiological reason
for the migration of parasitic worms through the host body
prior to life in the intestine. Pintner was of the opinion that the
chief function of the migration was to allow the worms to live
for a time under aerobic conditions. This would allow them
to accumulate a glycogen reserve which later on would enable
them to begin life in the anaerobic intestine. The above men-
tioned observation of Stepanow-Grigoriew and Hoeppli (1926)

is not what one might expect on the basis of this theory. How-
ever, StepanowGriegoriew and Hoeppli (1926) and Giovannola
(1936) found a definite accumulation of glycogen during the
migration.

The fact that glycogen is still present in old embryos also
indicates that the rate of metabolism in fully developed eggs
is probably very much lower than in the developing eggs, and
this problem seems worthy of quantitative consideration.

The young larvae of Ascaris, on the other hand, have a high
level of metabolism, as evidenced by the investigation of Fen-
wick (1938). He found a preliminary phase of about half an
hour during which the newly hatched larvae showed a low
oxygen consumption. This he explained on the assumption
that they had not yet become sufficiently adjusted to the new
environment. Then followed an intermediate phase, lasting
about an hour, in which 1,000 larvae consumed ]3er hour 9.3 cmm
oxygen at 37° C. After this the oxygen consumption decreased
to a third level (0.928 cmm per 1,000) which was about 1/10
that of the second level. This new rate of oxygen consumption
was maintained throughout the rest of the exjicriments. Fen-
wick explained the high rate of the intermediate stage on the
assumption that It was caused by the removal of an oxygen
debt which the larvae had contracted while living within the
egg shells. An investigation of the respiratory quotient of
eggs containing infective embryos should prove helpful in an-
swering this question.

The rate of metabolism of Trichinella larvae, according to
the data of Stannard, McCoy and Latchford (1938), was about
as high as that of Ascaris larvae in the third of Fenwick's
stages. At body temperature in T.vrode solution the Trichinella
larvae consumed 2.24 cmm oxygen per mgm dry weight per
hour. In saline the value was 1.70, and in Tyrode without
bicarbonate it was 1.78. The figures for 1,000 larvae in these
solutions can be calculated to be about 1.12, O.S,") and 0.88 cmm
oxygen per hour, respectively. The respiration was independent
of the oxygen tension in the range of 1 to 100 percent oxygen.
It was very sensitive to cyanide, but was stimulated by carbon
monoxide and paraphenylene diamine. The respiratory quotient
of the Trichinella larvae was always above 1, and the averages
were from 1.13 to 1.17. It seems probable that under aerobic
conditions some fermentations may take place, liut most of the
oxidative processes apparently proceed to completion. Fer-
mentation alone was sufficient to keep the worms alive under
anaerobic conditions, but apparently oxygen was necessary for
enabling them to move.

The fermentation processes of the Trichinella larvae are
very interesting, since they lead not only to the formation of
carbon dioxide but to the formation of other as yet unidentified
substances which are known to be non acidic. In this respect
they differ from all the other helminths. It is remarkable, fur-
thermore, that substances like iodoacetate and others, which
rapidlj' inhibit alcoholic fermentation or muscle glycolysis, were
quite slow in their action on the anaerobic carbon dioxide pro-
duction of these larvae (Stannard, McCoy and Latchford, 19,38).
McCoy, Downing and A'an Voorhis (1941) showed that radio-
active phosphorus fed to tlie host penetrates rapidly into the
larvae. This observation indicates that tlie larvae may have an
active metabolism inside the cyst.

The Trichinella larvae are clearly aerobic rather than an-
aerobic organisms. This is also true for the larvae of Enstron-
(/i/lidcs, investigated by v. Brand (1938). He found that these
worms survived much longer under aerobic than under anaero-
bic conditions. One hundred grams of worms in the presence
of oxygen consumed 0.3 gm of glycogen in 24 hours at 37° C,
and no organic acids could be found. ITnder anaerobic condi-
tions 0.9 gm glycogen was consumed and organic acids equiva-
lent to 30 ce n/10 acid were produced. The ratio between aero-
bically and anaerobically consumed glycogen was 1:3, a ratio
which places these worms intermediate between most free-
living worms which have ratios of about 1 :■" and Ascaris with
one of 1.0:1.3.

The experiments mentioned so far were performed with larvae
which had been living under natural conditions in a host. From
free-living stages of parasitic nematodes data are only avail-
able for Ancfilostonm caninnni. McCoy (1930) found that the
oxygen consumption of infective larvae varied greatly with
the temperature. At 7° C. it was imperceptible, but in the
range of 17° C. to 42° C. the oxygen consumption increased
about 9 percent for every degree rise in temperature, and fol-
lowed an exponential curve, the b constant, of which was
1.0879. The actual oxygen consumption at 37° C. corresponded
to 0.47 cmm per 1,000 larvae per hour, a figure somewhat
lower, but of the same order of magnitude as those mentioned
above for Ascaris and Trichinella larvae.

The free-living larvae of Xecator aniericanns, and Ancj/losio-
ma canininn seem to derive their energy primarily from fatty
substances stored in their body (Payne, 1923, Rogers, 1939),
and the amount of fat demonstrable seems to be

366

etiaractcristic of the physiological age of the larvae
(Payne, 1923; Cort, 1925). A decrease in the amount of fat
granules was also observed by Giovannola (1936) in the filari-
form larvae of several species, especially 'f" f'^J' were kept at
37° C.

It seems, however, that these larvae also consume glycogen.
Giovannola (1936) found small amounts of glycogen in young
rhabditiform larvae of Necator, Anci/lostoma and Nippostrongy-
lus, but none in the filariform stages. A comparable observa-
tion was made by Stepanow-Grigoricw and Hoeppli (1936) who
found glycogen in one- or two-day old filariform larvae of
Strongyloidcs, but never in three- to nine-day old larvae.

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metabolism. J. Cell. & Comp. Physiol., v. 10:339-364.

KrUgbb, r. 1936. — Untersuchungen zur Kenntnis des aeroben
und anaeroben Stoffwechsels des Schweinespulvpurmes {As-
caris siiilla) . Zool. Jahrb. Abt. Allg. Zool. & Physiol., v.
57:1.56.

1937. — Bestinimungen iiber den aeroben und anaero-
ben Stoffumsatz beim Schweinespulwurm mit einem neuen
Respirationsapparat. Ztsehr. Vergleich. Physiol., v. 24:
687-719.

1940. — Die Beziehuug des Sauerstoffverbrauches zur
Kbrperoberflaehe beim Schweinespulwurm (Ascaris Inmbri-
coides). Z. Zool., v. 152:547-570.

Krummacher, O. 1919. — Untersuchungen iiber die Warmeent-
wicklung der Spuhviirmer. Ztsehr. Biol., v. 09:293-321.

Marsh, G. 1935. — Kinetics of an intracellular system for res-
piration and bioelectric potential at flux equilibrium. Plant
Physiol., V. 10:681-697.

Meier, W. 1931. — Neuere Untersuchungen iiber die Warmeent-
wicklung der Spuhviirmer. Ztsehr. Biol., v. 91:459-474.

Mueller, J. F. 1928-29. — Studies on the microscopical anato-
my and physiology of Ascaris lumbricoides and Ascaris
megalocephala. Ztsehr. Zellforsch., v. 8:361-403.

Oesterlin, M. 1937. — Die von oxybiotisch gehaltenen Ascari
den ausgeschiedenen Fettsauren. Ztsehr. Vergleich. Physiol.,
v. 25:88-91.

SCHIMMELPPBNNIG, G. 1903. — Uber Ascaris megalocephala.
Beitrage zur Biologic uud physiologischen Cliemie dersel-
ben. Arch. Wiss. & Prakt. Tierheilk., v. 29:332-376.

ScHULTE, H. 1917. — Versuche iiber Stoffwechselvorgange bei
Ascaris lumbricoides. Pfliiger's Archiv., v. 166:1-44.

Slater, W. K. 1925. — The nature of the metabolic processes
in Ascaris lumbricoides. Biochem. J., v. 19:604-610.

1928. — Anaerobic life in animals. Biol. Rev., v. 3 :
303-328.

ToRTU, Y. 1934. — Contributions to the physiology of the As-
caris. II. The respiratory exchange in the Ascaris, As-
caris megalocephala Cloq. Sc. Rpt. Tohoku Imp. Univ.,
4th. Ser., v. 9:61-70.

1935. — Idem. III. Survival and glycogen content of
the Ascaris, Ascaris megalocephala Cloq. in presence and
absence of o.xygen. Ibid., v. 10:361-375.

1936a. — Idem. IV. Products from glycogen during
anaerobic and aerobic existence of the Ascaris, Ascai'is
megalocephala Cloq. Ibid., v. 10:687-696.

1936b. — Idem. V. Survival and respiratory exchange
of the Ascaris, Ascaris megalocephala Cloq. intercepted
from light in presence and absence of oxygen. Ibid., v.
11:1-17.

Waechter, J. 1934.— Uber die Natur der beim Stoffwechsel
der Spuhviirmer ausgeschiedenen Fettsauren. Ztsehr. Biol.,
V. 95:497-501.

Weinland, E. 1901. — tJber Kohlehydratzersetzung ohne Sauer-
stoffaufnahme bei Ascaris, einen tierischen Garungsprozess.
Ztsehr. Biol., v. 42:55-90.

1902. — Uber ausgepresste Extrakte von Ascaris lum-
bricoides und ihre Wirkung. Ibid., v. 43:86-111.

1904a. — Uber die von Ascaris lumbricoides ausgeschie-
denen Fettsauren. Ibid., v. 45:113-116.

1904b. — Uber die Zersetzung stickstoffhaltiger Sub-
stanz bei Ascaris. Ibid., v. 45:517-531.

Weinland, E. and Ritteb, A. 1902. — Uber die Bildung vou
Glykogen aus Kohlehydraten bei Ascaris. Ztsehr. Biol.,
V. 43:490-502.

Wells, H. S. 1931. — Observations on the blood sucking activi-
ties of the hookworm. Aiici/lostoma caninum.. J. Parasit.,
V. 17:167-182.

METABOLISM OF EGGS AND LARVAE

Bataillon, E. 1910. — Contribution a 1 'analyse experimentale
des phenomenes karyocinetiques chez Ascaris megaloce-
phala. Arch. Entwicklungsmeeh., v. 30(l):24-44.

von Brand, Th. 1938. — Physiological observations on a larval
Euslrongijlides (Nematoda). J. Parasit., v. 24:445-451.

Brown, H. W. 1928. — A quantitative study of the influence
of oxygen and temperature on the embryonic development
of the eggs of the pig ascarid (Ascaris suum Goeze). J.
Parasit., v. 14:141-160.

Chitwood, B. G. 1938. — Further studies on nemic skeletoids
and their significance in the chemical control of nemic
pests. Proc. Helm. Soc. Wash., v. 5:68-75.

CORT, W. W. 1925. — Investigations on the control of hookworm
disease. XXXIV. General summary of results. Am. J.
Hj'g., V. 5:49-89.

DiNNiK, J. A. and Dinnik, N. N. 1937. — Influence de la tem-
perature, de 1 'absence d 'oxygene et du desseehement sur
les oeufs de Trichoccphabis Irichiurtis (L.). Med. Para-
sit. & Parasitic Dis., v. 5:603-618. [Russian with French
summary. ]

Dtrdowska, M. 1931. — Recherehes sur le comportement du
glycogene et des graisses dans les oeufs i' Ascaris megalo-
cephala a I'etat normal et dans une atmosphere d 'azote.
Comp. Rend. Soc. Biol., Paris, v. 108:593-596.

Faure-Frbmiet, E. 1912. — Graisse et glycogene dans le de-
veloppement de I'oeuf de \' Ascaris megalocephala. Bull.
Soc. Zool. France, v. 37:233-234.

1913a. — Le cycle germinatif chez \' Ascaris megalo-
cephala. Arch. Anat. Micr., v. 15:435-757.

1913b. — La segmentation de I'oeuf A' Ascaris au point
de vue energetique. Comp. Rend. Soc. Biol., Paris, v.
75:90-92.

Fenwick, D. W. 1938. — The oxygen consumption of newly-
hatched larvae of Ascaris sutim. Proc. Zool. Soc. London,
Ser. A, V. 108, Part 1:85-100.

FaiEiDHEiM, E. A. H. 1933. — Das Pigment von Halla partheno-
pea, ein akzessorischer Atmungskatalysator. Biochem.
Ztsehr., V. 259:257-268.

Giovannola, a. 1936. — Energy and food reserve in the de-
velopment of nematodes. J. Parasit., v. 22:207-218.

Huff, G. C. 1936. — Experimental studies of factors influencing
the development of the eggs of pig ascarid (Ascaris suum
Goeze). J. Parasit., v. 22:455-463.

Huff, G. C. and Boell, E. J. 1936.— Effect of ultracentrifug-
ing on oxygen consumption of the eggs of Ascaris .suum,
Goeze. Proc. Soc. Exp. Biol. & Med., v. 34:626-628.

Jacobs, L. and Jones, M. F. 1939. — Studies on oxyuriasis.
XXI. The chemistry of the membranes of the pinworm
egg. Proc. Helm. Soc. Wash., v. 6:57-60.

KosMiN, N. 1928. — Zur Frage iiber den Stickstoffwechsel der
Eier von Ascaris megalocephala. Tr. Lab. Exper. Biol.
Zoopark, Moscow, v. 4:207-218. [Russian with German
summary.]

370

Looss, A. inil.— The aiiatoniy and life liistoiy of Anchylo-
stoma diiodcnalc Duj. Part II. The aevok)pment in the
free stage. Rec. Egypt. Govt. Sch. Med., v. 4:163 613.
[Not seen.l

MoCOT, O. R. 1930. — The iiitlueiice of teniiieiatuie, hydrogen-
ion eoncentration, and oxygen tension on tlie development
of the eggs and hirvae of the dog liookworm, Ancylostoina
canivtim. Am. J. Hyg., v. 11:413-448.

MoCoY, Q. E., Downing, V. F. and V.\N Voorhis, S. N. 1941. —
The penetration of radioactive phosjihorus into encysted
Trichiticlla larvae. J. Parasit., v. 27;."i3 ."iS.

NOLF, L. O. 1932. — Experimental studies on certain factors
influencing the development and vial)iUty of the ova of
the luiman Tricliuris as compared with those of the human
Ascari.f. Am. J. Hyg. v. 16:288-322.

Payne, F. K. 1923. — Investigations on the control of hook-
worm disease. XXX. Studies on factors involved in mi-
gration of hookworm larvae in soil. Am. .1. Hyg., v. 3:
547-583.

PiNTNER, Th. 1922. — Die vermutliehe Bedeutung der Hel-
minthenwanderungen. Sitzungsb. Akad. Wiss. Wien, Math.-
Naturw. Kl., Abt. I. v. 131:129-138.

Rogers, W. P. 1939. — The physiological ageing of Ancylostoina
larvae. J. Helm., v. 17:195-202.

ScHALiMOV, L. G. 1931. — A contribution to the biology of
Oxyuris equi. Tr. Dynamics Develop., v. 6:181-196. [Rus-
sian with English summary.]

Schmidt, W. J. 1937. — Doppelbrechung und Feinbau der
Eischale von Ascaris megalocephala. Ein Vergleich des
Feinbaues faserigen und filniartigen Chitins. Ztschr. Zell-
forseh., v. 25:181-203.

Stannard, J. N., McCoy, 0. R., and Latchpord, W. B. 1938.
— Studies on the metabolism of Trichinclla spiralis larvae.
Am. J. Hyg., t. 27:666-682.

STEPANOW-GBlGORlErvv, J. and HoKiM'Li, R. 1926. — Ober Bezie-
hungen zwischen Glykogengehalt parasitischer Nematoden-
larveii und ilirer Wanderung ini Wirtskiirper. Arcli. Schiffs-u
Tropen Hyg., v. 30:r)77-5S5.

SZWEJKOWSKA, G. 1929. — Recherehes sur la physiologic de la
maturation des oeufs d' Ascaris. Bull. Internatl. Acad.
Polon Sc. & Lett., Ser. B, 1928:489-519.

Wendt, H. 1936. — Beitrage zum Entwicklungszyklus bei Oxy-
uris vcrmicularis. Ztsclir. Kinderheilk., v. 58:375-387. [Not
seen.]

Wottge, K. 1937. — Die stofflichen Veranderungen in der
Eizelle von Ascaris megalocephala nach der Befruchtung.
Protoplasma, v. 29:31-59.

Zawadowsky, M. 1916. — Role de 1 'oxygene dans le processus
de segmentation des oeufs de \' Ascaris megalocephala.
(Note preliminaire.) Compt. Rend. Soe. Biol., Paris v
68:595-598.

1926. — Zum Mechanismus der Wirkung von Zyankalium
auf die lebende Zelle (Eier von A.<icaris megalocephala').
Biologia Generalis, v. 2:442-456.

1928. — The nature of the egg-shell of various species
of Ascaris eggs {Toxascaris limbata Reillet et Henry, Bel-
ascaris my.^tax Zeder, Belascaris marginata Rud., Ascaris
suilla Duj.). Tr. Lab. Exper. Biol. Zoopark, Moscow, v.
4:201-206. [Russian with English summary.]

Zawadowsky, M. and Schalimow, L. G. 1929. — Is autoin-
vasion possible given the presence of Enterobius (Oxyuris)
vermicularis in the intestine? Tr. Lab. Exper. Biol. Zoo-
park, Moscow, v. 5:1-42. [Russian with English summary.]

Zawadowsky, M. and Orlow, A. P. 1927. — Is there any pos-
sibility of autoinvasion during Ascariasis? Tr. Lab. E::;per.
Zoopark, Moscow, v. 3:99-116. [Russian with English sum-
mary.]

Zviaginzev, S. N. 1934. — Contribution to the history of devel-
opment of Nematodirus helwetianus. Tr. Dynamics De
velop., v. 8:186-202. [Russian with English summary.]

371

CORRECTIONS

We are indebted to Dr. G. L. Graham for his assistance in
compiling this table of errors:

Page Column Line

1 25 — Strongyles to read Strongiihm.

2 43 — adherants to read adherents.
2 oO — Hhabiiias spp. to read Shabditis.
1 11-12 — identifield to read identified.

1 under Adcnophori, line 4 — Knoploidrn to read Eno-
ploidea.

2 .■)! — Hagmeir to read Hagmeier.

1 bibliog. under Mueller 1927 — Anisakis to read
Anixakis.

1 8 — macramphidiiim to read macramphirlnm.

2 27-28 — Critical studies are due.

1 14 — Iciinl-eli to read l-iincl-eli.

2 1819 — infecta to read infeetnm.
1 7 — Comma between Chromaelora and Mono-

125
125
128
130
13-2

132
134

145
145
149
153
154

154
155
157

165
171
173

174
177
177
177
iGG

177

177
178
179

183
183

posHiia.
8 — Greeffiela to read Grirfficla
22 — Insert asterisk after parasitifcra.

I

1

2 under Schneider, A. 1858 — Gefass.vstem to read
Gefasssystem.

36 — Spinonoura to read Spironoitra.
14-1.) — postcriad to read posteriad.

1

1

1 under Josepli 1883a — Erkliirengen to read Erk-
larungen.

1 Acknowledgments — Mantoi' to read Manter.

1 ."4 — sculptored to read sculptured.

1 ."iSi — sculptoring to read sculpturing.

1 caption, Fig. 135 I. — Si/phaeea to read Sl/phacia.

1 caption Fig. IS.') R. — riirnrlonumtis to read Pscu-
rlnnymiis.

1 caption Fig. 135 HH. — fiUicolis to read filicollis;

Also 182, col. 2, line 4.

2 8 — sculptoring to read sculpturing.

2 44 — Trichostrongylidae.

2 4th line in next to last paragraph under Ovovivi-
parity — macrocera to read macrncerea.

1 17 — Thelostomatidae to read Thelastomatidae.

2 22-33 — Ascaricica to read Ascaridia.

183
186
187
187
188
189

189

189
190

191
192
193
203
204
204

205

214
221
223
229
229
231
231

232
235
239

240

240

2 36 — permiable to read permeable.

1 30 — Gonglonema to read Gongylonema.

1 1st line of 2nd paragraph — Dioctophymatoidea.

1 Bibliog. under Ackert — Ascaridea to read Ascaridia.

2 Bibliog. under Skinker — salmanoid to read salmoid.

1 Bibliog. under Steiner 1937 — Jubilcm to read Ju-
bileum.

1 Bibliog. under Zawadowsky and Shalimov — En-

twicklungsbedihungen.

2 Bibliog under Huff— Jour. Parasit., v. 36?

2 lender Annelid — Cliaetognath-Xemathelminth The-
ory.
II. Plathyhelminthes — etc.

1. Oblique cross fibers present

Treniatoda, etc.

2. Oblique cross fibers absent

Cestoidea, etc.

1 footnote — 3rd line between to read between.

2 12 — descendent to read descendant.

1 40 — cloace to read cloaca.

2 under Cholodowsky-Weiblichlen to read Wciblichen.

1 under Remane 1928 — Ostee to read Ostsee.

2 under Zeder-Naturgeseschichte to read Naturges

ehichte.

2 3rd line from bottom — intercallation to read in
tercalation.

2 under Held 1912 — Gesellecsh to read Gesellsch.

2 77-77 — descendents to read descendants.

2 footnote — line 3 — divison to read division.

1 21 — subsequal to read subequal.

2 18— Fig. 15SJ to read Fig. 157J.

1 6-7 — Delete Fig. 15()\V.

1 Captiou Fig. 158 — 4th line EH — Ancyelostoma to
read Ancylostoma.

1 12 — Esophagael to read Esophageal.

1 16-18 — caecae to read ceca.

2 under Pai 1928 — Beeintlussing to read Beeinflus-

sung.

1 under Schwartz and Alicata 1935 — Longistriati to

read Longistriata.

2 under Wehr 1935^superfamily Filarioidae to read

Filariodea.

372

ANNOUNCING SECTION II, PART III
AN INTRODUCTION TO NEMATOLOGY

J. R. CHRISTIE, EDITOR

Chapter } Title Authors

XII. Life History. Vagantia and Phytopara-

sitica J- R- Christie

XIII. Ecology, symptoms, control and treat-

ment for Vagantia and Phytopara-

sitica A. L. Taylor,

W. L. Courtney,
G. Thorne,
B. G. Chitwood
and J. L. Bassen

XIV. Feeding habits of nematodes. Vagantia

and Phytoparasitica J- R- Christie,

G. Thorne and
B. G. Chitwood

XV. Imnmnity due to nematodes Norman R. Stoll

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