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Are Vessels Infected with Yelow Fever 


SOME PERSONAL} OBSERVATIONS: 


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* GovEREMENT. PRINTING OREIOR. 
1902. 


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YELLOW FEVER INSTITUTE, BULLETIN No. 9. 
Treasury Department, Public Health and Marine-Hospital Service. 
WALTER WYMAN, Surgeon- General. 


Are Vessels Infected with Yellow Fever? 


SOME PERSONAL OBSERVATIONS. 


e By Surgeon H. BR, OARTER. 


SULT, 1.902. 


WASHINGTON: 
GOVERNMENT PRINTING OFFICE. 
1902. 


YELLOW FEVER INSTITUTE, 


“Treasury Department, Public Health and Marine-Hospital Service, 


WALTER WYMAN, Surgeon-Gieneral. 


BULLETIN No. 9. 


Section (.—TRANSMISSION. J. H. WHITE, Asst. Surg. General, Chairman of Section. 


ARE VESSELS INFECTED WITH YELLOW FEVER?—SOME PERSONAL 
OBSERVATIONS, 


By Surgeon H. R. CARTER. 


JULY, 1902. 


In a paper read before the American Public Health Association at 
Buffalo, September 18, 1901, Dr. Doty, the quarantine officer of New 
York, affirms the absence of secondary cases of yellow fever aboard ves- 
sels—i. e., that while cases of this disease contracted ashore develop 
aboard vessels, yet none are contracted aboard the vessel itself—that 
is, the vessel does not become ‘‘infected’’ with yellow fever. 

The experience of other quarantine officers has been different, and it 
may be of service then to group some cases already of record in which 
the contrary was observed. It is not proposed to collate a number of 
examples of vessels aboard which yellow fever was contracted, from the 
literature of the subject, but to give very briefly the history of some 
such vessels personally observed by the writer, from his own notes, 
during a four years’ service (1888 to 1891, inclusive) at the quarantine 
of the Gulf, Chandeleur and Ship islands. Here were received all ves- 
sels believed to be infected with yellow fever bound for all of the Gulf 
ports, except for New Orleans and from Tampa south. Consequently 
our clientele was considerable. The bulk of them, however, although 
certainly the worst class of vessels which entered the Gulf of Mexico, 
were not, in my opinion, ‘‘infected’’ when I received them—i. e., yel- 
low fever could not then have been contracted aboard them. 

I will premise here that I accept without reservation the conveyance 
of yellow fever by an infected mosquito of a certain kind, and that to 

2 SEC. Cc. 7 


Section C. 8 


me a vessel ‘‘infected’’ with yellow fever is simply one which is har- 
boring these infected mosquitoes. Whether they came aboard already 
infected or, being aboard, became infected by feeding on cases of yellow 
fever developing aboard ship but contracted ashore, can in general be 
determined from the history of the spread of the infection. Indeed, it 
was primarily the history of these and other ships which led to the 
(tentative) formulating of the laws of the ‘‘interval between the infect- 
ing and secondary”’ cases of yellow fever and the ‘‘period of extrinsic 
incubation of places’”’ of that diease, which, and much else, are so 
clearly explained by the conveyance by a mosquito host. 

The deductions as to the disease being contracted aboard the vessels, 
when such deduction is made, are, however, independent of the assump- 
tion of any theory of conveyance. I do assume, however, that the 
period of incubation of yellow fever, rarely, if ever, exceeds six or six 
and one-half days. 


1888.—SHIP ISLAND. 


I. Norwegian bark Magnolia, 946 tons, fifty-six days from Rio de 
Janeiro via Pensacola Bar, rock ballast. Left Rio de Janeiro May 20; 
left 2 men sick in hospital and had J aboard, considered yellow fever. 
Master sick third day out, May 22; died, May 27. All well till June1, 
then several (3) got sick at once. First mate sick, June 11; died, June 
17; black vomit. All were sick on the way up except 2; 21 on crew 
list including the 2 men left in Rio de Janeiro. One of these who 
escaped fever had had yellow fever, and the other was a lad from Dantzig 
on his first deep-sea voyage. In all 17 men were sick of fever en route, 
of whom 5 died. The last case, Elias Eliasen, developed June 14. 
Here, save the captain, all sickened not less than eleven days after 
leaving Rio de Janeiro, and the first mate and Eliasen on the twenty- 
third and twenty-sixth day, respectively. They then contracted yellow 
fever aboard ship. 

The picture is that of an infection introduced aboard the vessel by 
the men who sickened in Rio de Janeiro—i. e., there were uninfected 
stegomyize aboard which were infected from these cases and conveyed 
yellow fever to the remainder of the crew, except the captain, who con- 
tracted it ashore. I did not record the dates of the cases of the men 
left at Rio de Janeiro; it was shortly before clearing. The interval 
between an infecting and a secondary case is almost always fourteen 
days or over. 

II. Italian bark Riagino, Rio de Janeiro, for Pensacola, fifty-one days 
out ; rock ballast, 560 tons. No sickness in Rio de Janeiro until just 
before leaving, then sent 2 men to hospital. Left five days after. 
Log shows men were taken June 4 and June 6 and removed on June 6. 
Sailed on June 10. No one had been ashore save master and steward, 
using a harbor boat. 

First case reported sick en route June 21; 1 next day ; 6 sick en route ; 


‘ 


9 Section C 


3 deaths, June 28, June 29, and July 14, all with black vomit. Crew 
refused duty at second death. Last case well July 13. Sixteen on 
crew list; 2in Rio de Janeiro. Master had had yellow fever; steward 
sick just after leaving, not considered yellow fever. 

Six cases developed ten days after leaving Rio de Janeiro. Same 
remarks as were made of the Magnolia apply here. 

No record is made of where these 2 vessels lay in Rio de Janeiro, the 
writer not then appreciating the importance of this. 


1889. 


My notes for 1889 are lost, and indeed there may have been in 1888 
more than the 2 vessels given above, which should have been included 
in this paper; but my notes, taken at first solely with the view of 
determining the period of incubation of yellow fever, give data on only 
these two sufficiently definite to determine that they were infected— 
i. e., that yellow fever was contracted aboard. 


1890. 


ITI. British ship Avon, in rock ballast ; 22 in crew, 4immune to yellow 
fever. Sailed from Rio de Janeiro April 20. All well in port and en 
route until thirty-eight days out, when a boy in port watch sickened 
with yellow fever. Taken to hospital, Gulf Quarantine, on third day, 
and died on sixth day. Another case developed two weeks later in a 
quarantine attendant who helped me clean up the room, sail locker, in 
which the boy was sick aboard ship. 

It is remarkable that there should have been only 1 case of yellow 
fever among the crew aboard ‘this vessel. At the time it was ascribed 
to the fact that this boy, the only one on the port watch, helped a man, 
shipped in Rio de Janeiro and immune to yellow fever, overhaul his 
chest a few days before the boy was taken sick. Whether there was an 
infected mosquito in the chest which had survived this length of time, 
or whether there was any relation between the chest and the fever, may 
be a question. It in no wise affects the present question, that the dis- 
ease was, contracted aboard. It was the first case seen at this station 
that year. 

IV. British ship Curlew, from Rio de Janeiro, with rock ballast. 
No sickness was reported en route, in port, or on arrival. She was 
cleaned July 22 to July 23, 1890, and disinfection completed July 25, in 
the afternoon. One casé of yellow fever developod July 27, the sixty- 
fourth day out, in the early morning before day. 

V. British ship Chippewa, from Rio de Janeiro, with rock ballast. 
No sickness was reported in port, en route, or on arrival. She was 
cleaned July 26 and July 27, and disinfection completed July 28 One 
man, the quartermaster, developed yellow fever July 29, at night, sixty- 
eight days out from Rio de Janeiro. 


Section C. 10 


The Avon made no port after leaving Rio de Janeiro and communi- 
cated with no vessel en route. The other 2 made no port save Pensa- 
cola Bar, and communicated with no vessel save the pilot boats there 
and off Mobile Bar. The infection in these.3 vessels, then, must have 
been contracted aboard. They lay in open roadstead at my station, 13 
miles off shore and about + mile apart, and there was no visiting 
between them and none of their crews was ashore. ° 

VI. Spanish bark Castilla, fifteen days from Cienfuegos via Round 
Island Quarantine, in rock and earth ballast ; 14in crew. Hight days 
out from Cienfuegos to Round Island. All well in port, en route, 
and on arrival. Mate sickened fourth day after arrival at Round 
Island while discharging ballast. Vessel sent here in tow August 22. 
Mate had yellow fever; died on the sixth day of illness. Captain 
developed yellow fever day after mate’s death ; taken to hospital. No 
other cases of sickness aboard ; the remainder of the crew are, save 1, 
Manila men, and all probably immune to yellow fever, being mainly 
residents of Cuba for many years. 

Here 2 men developed yellow fever, 1 twelve and 1 seventeen days 
after leaving Cienfuegos. The infecting mosquitoes may well have been 
harbored in the hold, which the mate would probably not have visited 
until he anchored at Round Island and began discharging ballast, and 
in which the master would not be apt to go while the mate was on duty. 

VII. Spanish bark Grand Canaries, seven days out from Havana 
July 7. All well in port, en route, and on arrival and while in quar- 
antine. Crew probably all immune to yellow fever, being mainly 
Manila men and old residents of Havana. 

O. F., quarantine employe, went aboard as ballast master; next day 
developed yellow fever, July 11. This man had been exposed to no 
possible source of infection for the six months previous except this 
vessel. A case nearly similar to the above occurred in 1889, but I have 
no notes of it. 

VIII. Norwegian bark Queen of the Seas, in rock ballast, Rio de 
Janeiro for Pensacola, fifty-four days out. Left Rio de Janeiro with 17 
men ; 6deathsen route. All well in Rio de Janeiro. Lay at Mocanque, 
a healthful part of harbor. None save master allowed ashore, but’ he 
went in ship’s boat. Left 1 man at Rio de Janeiro—consumption. 
Shipped 1 man, a negro, in his place. Sailed April 23; master sick 
April 26; second nrate sick night of May 10; 2 men May 11; 1 man 
May 12; 2 men morning of 18th; 2 during day of 18th; 1 man sick and 
1 died 15th ; 1 man died 17th ; 2 sick 17th; 1 died 19th; 2 died 21st and 
22d; 1 sick 21st; 1 died 25th; 13 sick en route, 5 died. The man 
shipped in Rio de Janeiro (negro) and 1 of the others immune by: pre- 
vious attack. The picture is very clear of a clean ship, infected by the 
illness of the master contracted ashore—i. e., had uninfected mosquitoes 
aboard, which became infected from the master sick of yellow fever, 
and conveyed it to the crew. 


1 1 Section C. 


1891. 


IX. British ship Curlew, fifty-seven days from Rio de Janeiro for Pen- 
sacola. Lay in the Gamboa last eight days. Two men sick February 
27, taken to hospital that day ; sailed March 1. Master sick March 1; 
5 men besides him that night. Two men March 4, 1 March 5, and 2 
more during the day. Two men sick March 7. Two men died the 19th, 
sickening the 13th and 15th, respectively, both with black vomit. All 
aboard here, 19, were sick en route except 1, a Barbados negro; but 
don’t believe all had yellow fever, the crew having been badly fright- 
ened. The earlier cases and the 3 who died were undoubtedly yellow 
fever, as were the steward and mate. Here we have 2 cases, at least, 
developing thirteen and fifteen days after leaving Rio de Janeiro. 

_X. Swedish ship Condoren, seventy-nine days out from Rio de Janeiro 
via Pernambuco for Mobile. Rock and earth ballast; 18 in crew. 
All well in port. Lay in Gamboa last five days. No shore leave 
allowed, but took ship’s boat to go ashore. Sailed March 3; 3 men sick 
March 5; 16 men sick, all told, up to March 26, and 6 deaths. Last man 
got sick March 26, when she put into Pernambuco short-handed and 
sent 3 sick men to hospital. Two men sick March 20; 4 men sick March 
18; 1 man sick March 26 (really night of 25th). At Pernambuco she 
lay eleven days and was disinfected by sulphur. Shipped 8 new men, 
4, probably 5, of them immune to yellow fever. Developed no sickness 
on the rest of the way up. Here 4 men developed yellow fever fifteen 
days from Rio de Janeiro. 

XI. German ship Gustav and Oscar, Rio de Janeiro for Pensacola. 
Lay at Cobras, a healthful place. One case yellow fever at Rio de 
Janeiro, March 22, sent to hospital March 24. No shore leave allowed. 
Sailed from Rio de Janeiro April 1; first case sickness April 7, 2 men ; 
3 next day ; 1 next morning, and 2 during the day of the 9th. One 
death on the 10th, leaving 6 men sick. Captain sick on the 10th at 
night after supper. Lastcaseon14th. Two deaths on 11th ; 1 on 12th. 
Crew list shows 21 men left Rio de Janeiro; 14 sick and 4 deaths en 
route. It is reasonably certain that 4 of the remaining crew were 
immune to yellow fever by previous attack. 

XII. Norwegian bark Orown Prince, fifty-eight days out from Rio de 
Janeiro for Ship Island. Lay at Moncanque. No sickness aboard in 
Rio de Janeiro.. No shore leave granted, and did not use ship’s boat 
to go ashore. Sailed April 29. Master sick second day out (April 30). 
Next case May 16; 3 (2 aft and 1 forward) became sick. May 17, 2 
sick in morning, 1 in the day. May 18, 3 men in forecastle sick. May 
20, 2 sick, 1death. May 21, 1 death, 1 sick. May 23, 2 deaths. May 
24, 1 sick. May 28, 1 death last night. May 29, 1 sick this morning. 
M 0, 1 death. The 1 case on the 29th was the last case taken sick. 
There were 14 men aboard and every man had fever, 6 dying. She put 
into Barbados on June 10, disinfected and shipped (in quarantine) 4 


Section C. al 9 


new men, 1 probably unacclimated. No more sickness en route. All 
of these cases except the captain’s were not less than sixteen days from 
Rio de Janiero before developing. 

XIII. French ship Emily Postel, twelve days from Vera Cruz via 
Pensacola quarantine. Had ‘‘sickness’’ aboard just before leaving 
Vera Cruz, 1 man. Sailed from Vera Cruz July 28; no sickness since 
until crew went to discharge ballast, August 12. One man sick yellow 
fever August 15, 2 men the same, August 19, and 1 man August 20. 
Disinfection by sulphur was done on the appearance of the first case of 
yellow fever and no case occurred save the above. All were developed 
more than sixteen days after leaving Vera Cruz, hence from infection 
on board. The history points to infection (infected mosquitoes) in the 
hold. 

The picture given by the Curlew and Conderen are those of disease 
conveyed by mosquitoes coming aboard already infected just before 
they sailed. The infection was not introduced by the men who first 
sickened, the interval between them and the next cases was too short. 
Observe that they lay in the Gamboa, directly in the lee of a town 
badly infected. The other two give the usual history of a clean place 
(town or vessel) infected by some one developing yellow fever, con- 
tracted elsewhere, in it. 

XIV. Dr. G., assistant surgeon U. S. Marine-Hospital Service, 
developed yellow fever June 18 at the Gulf Quarantine Station, and 
died June 29. He wasimmediately from New York, where he had been 
on duty some months, and had been at the station but fourteen days 
when he was taken ill. There had been no case of yellow fever at the 
station that year. There were a number of vessels in quarantine, but 
the Gustav and Oscar (No. XI) was the only one I judged to be infected. 
On this vessel, as on the others, he had been with me inspecting, 
opening up drawers and boxes, and going into every compartment, etc., 
for the disinfection. I thought his infection was from this vessel. It 
was certainly from some vessel. 

I think it will be granted from the above that the ability of a vessel 
to carry the infection of yellow fever is no myth. Here are 13 vessels 
which did so carry ‘it collated from only three years’ observation at a 
single station. Such vessels are indeed rarer, much rarer, now than 
they were before 1894, yet they still come. Isaw 2 at Tortugas in 1894. 
Other cases are reported by Geddings and by Echemendia at the same 
place and at Port Tampa quarantine. Rosenau reports a case con- 
tracted aboard the steamship Vigilancia, from New York, plying between 
New York and Vera Cruz via Havana, in 1899. The steamship Bodo, 
last year (1900), from Bocas del Toro, for Mobile, developed 3 cases of 
yellow fever, seven, eight, and nine days out from Bocas del Toro. It 
would not be difficult, I think, to multiply instances of recent date. yet 
that they are rarer is without question. On the factors which have 
brought this about we can barely touch. 


1 B} Section C. 


Obviously there are two methods by which vessels can become 
infected. (a) A case of yellow fever contracted elsewhere may develop 
aboard a vessel already harboring stegomyia mosquitoes which become 
contaminated from it. (6) The stegomyia mosquitoes may come aboard 
already contaminated. In the first case, there being nearly always over 
two weeks between the infecting and the first secondary cases of yellow 
fever, it results that, if the first case occurs after leaving port, vessels, 
even sailing vessels, from Cuba and the Caribbean Sea will generally 
reach quarantine and (if at a southern station) be disinfected—i. e., 
mosquitoes killed, before it is time for the secondary cases to develop, 
or, indeed, to be contracted. This agrees with all observation. In 
vessels infected in the second way, cases of yellow fever may occur 
after a very short or no interval from leaving port.. The causes, then, 
which have lessened the number of infected vessels at United States 
ports, are— 

1. The very great falling off of vessels from Rio de Janeiro and 
Santos since the establishment of the Brazilian Republic. This does 
away with the bulk of the ‘‘long-trip vessels’? we used to have, which 
are the only ones developing secondary cases en route if infected by a 
case of yellow fever developing aboard. (Vide a.) 

2. The replacing of sailing craft by steamships. That steamers con- 
vey yellow fever less frequently than sailing vessels has long been known. 
This is because they lie a much less time in an infected port, and the 
discipline of their crews is better ; no shore leave means no man goes 
ashore. They also make quicker trips, and thus are not apt to develop 
secondary cases en route, even if yellow fever contracted elsewhere 
develops aboard and they have the stegomyia aboard. Itis also to be 
noted that the worst parts of the harbors of Havana and Rio de Janeiro, 
above San Jose wharf and the Gamboa, have never been berths for 
steamships. Note, too, that the sailing vessels displaced are the foreign 
sailing vessels; the American schooner was less often infected than 
foreign vessels. 

3. Especially since 1893, and to some extent before supervision had 
been kept by United States sanitary inspectors in the more dangerous 
yellow-fever ports over vessels bound for the United States, especially 
of passenger vessels. Certain anchorages have been recemmended as 
safe, others have been forbidden, notably the Gamboa at Rio de Janeiro 
and certain wharves and parts of the harbor at Havana. Passengers 
who it is believed will develop infection aboard have been barred ; ship- 
ment of new men in the infected port carefully supervised ; vessels in 
which yellow fever has occurred in port are disinfected before leaving, 
and many other measures taken to have the vessel leave port clean, or 
as nearly clean as commercial considerations allow. In general, the 
vessel owners, especially of the regular lines, have given hearty coopera- 
tion in these measures, as well as in keeping the crew aboard and in 
confining the visits of such officers as must go ashore to daylight. 

3 SEC. C. 


Section C. 1 4 


These restrictions, especially the last, have by no means been absolute 
for all classes of vessels, but are well observed, in Cuban and Mexican 
ports at least, by probably over five-sixths of the tonnage. The sani- 
tary measures to avoid infection (3) and the proportionate substitution 
of foreign sailing vessels by steamships (2) are without doubt the main 
factors acting in cooperation in lessening the infection of ships. No 
one can read Burgess’ list of infected vessels in Havana Harbor (Report, 
U.S. Marine-Hospital Service, 1896) without noting how great has been 
that decrease in recent years. 

We have said that if a case of yellow fever develops aboard a vessel 
harboring the stegomyia mosquito (proper conditions of temperature 
being premised) that they may become contaminated by feeding on him 
and infect others. A vessel which has no stegomyia aboard is like 
‘‘noninfectible territory’? and will not communicate infection, even if 
cases of yellow fever develop aboard. I think it fair to say that ves- 
sels plying to and from southern ports of the United States will, during 
the summer season, generally have the stegomyia aboard, independently 
of its berth in tropical harbors, and may at times breed them in their 
water supply. This mosquito, however, seems to be rare north of Vir- 
ginia Beach (its distribution has not been sufficiently investigated, 
however), and a vessel plying to and from a northern port of the United 
States would not harbor this mosquito unless it came aboard in the 
tropical port. Now how far this mosquito goes or is borne from shore 
has not, I think, been directly investigated, but we do know that the 
crews of vessels moored off from shore (say 200 or more fathoms) in 
that part of Havana harbor seaward from the line between the Sta. 
Catalina warehouses and the Machina wharf do not develop yellow 
fever (unless close to some vessel which is infected). This means that 
contaminated stegomyia, at least, do not go xo far from shore. Lying 
then at the anchorages accounted safe in Havana harbor, where the 
passenger vessels for the United States lie, one would think that the 
probability of any stegomyia coming aboard would be small. At Vera 
Cruz the vessels must lie nearer shore (although to windward of it), 
and experience shows that the crews of vessels lying there are not entirely 
safe, as I believe them to be in Havana, although infection in the part of 
the harbor picked out as safe is decidedly rare. The anchorages in both 
harbors regarded as safe are well to the windward of the town all sum- 
mer. A direct investigation of this matter—i. e., the presence of the 
stegomyia aboard vessels from northern ports in different parts of the 
harbor of Havana and other tropical harbors, should be made. 

To sum up— 

1. Vessels aboard which yellow fever had been contracted—i. e., 
vessels infected with yellow fever have not been rare, at least at south- 
ern quarantine stations. 

2. Such vessels are much rarer since 1893, and are not very common 
now. 


1 5 Section C 


3. That the diminution of the number of infected vessels reaching 
United States ports is due mainly to the sanitary measures for avoiding 
exposure to infection in the foreign port, and to the substitution of steam 
for sailing vessels. To some degree the falling off of the vessels from 
Brazilian ports is also a factor. 

4, That a case of yellow fever developing aboard a vessel plying 
between southern ports of the United States and the tropics will prob- 
ably infect the vessel so that other cases can, if time be given, be con- 
tracted aboard her. 

5. Such vessels, however, if short-trip vessels, not more than ten or 
twelve days en route after the occurrence of the case of yellow fever, 
will in general be disinfected at southern quarantine stations before any 
other cases have been contracted aboard, although harboring infected 
mosquitoes. 

6. That a case of yellow fever so occurring aboard a vessel from a 
northern port of the United States would be able to infect her or not 
according to whether she had acquired the mosquitoes stegomyia fas. 
in the tropical port. 

7. It is, in general, then necessary to disinfect all vessels running 
between southern ports of the United States aud tropical ports if a case 
of yellow fever occurs aboard, no matter where it be contracted ; while 
vessels running between northern ports and the tropics may, through 
precautions in tropical harbors, have no stegomyia aboard and are thus 
not infectable by cases of yellow fever occurring aboard. 

8. Some vessels giving no history of yellow fever in port, en route, 
or on arrival—even when many days en route—are nevertheless infected 
and communicate the yellow fever to those who go aboard, vide Nos. 
IV, V, VI, VI. Note, also, the first case aboard the Avon, No. II, was 
thirty-eight days out from Rio de Janeiro. This is probably due to the 
infection (infected mosquitoes) in parts of the vessels unfrequented by 
the crew while en route, or to the crew being all immune to yellow fever. 


YELLOW FEVER INSTITUTE, BULLETIN No. 11. 


Treasury Dipartnns ‘Prabilig Health and Marine- - Hospital Service. 
~ WALTER, WYMAN, Surgeon-General. 


SA HSSRTS AS CARRIERS OF 
- MOSQUITOES, 


BY 


Passed Asst. Surg. S. B. GRUBBS. 


MARCH, 1903. 


- WASHINGTON: 
: fomemnnpg PRINTING OFFICE. 
Si 1908. 


at 


"site | 


YELLOW FEVER.- INSTITUTE. 


Treasury Department, Bureau of Public Health and Marine-Hospital Service. 


WALTER WYMAN, Surgeon-General. 


Buiuetin No. 11. 


Section C.—TRANSMISSION. Asst. Surg. Gen. J. H. WHITE, Chairman of Section. 


VESSELS AS CARRIERS OF MOSQUITOES. 


By 8. B. Grupss, 
Passed Assistant Surgeon, United States Public Health and Marine-Hospital Service. 


At the present time, when evidence is pointing with more and more 
clearness to the mosquito as the sole means of transmitting yellow 
fever, nothing is of greater interest to the quarantine officer than to 

_ decide to what extent and under what circumstances these infecting 
insects may be carried by vessels. 

This subject may be approached in three different ways: First, by 
observations on the length of time after leaving infected ports vessels 
may develop yellow fever; second, by experiments with mosquitoes 
under artificial conditions made to simulate as much as possible those 
of nature; and third, by actual observation of vessels arriving from 
ports at the time infected or where the presence of the Stegomyia 
fasciata render them liable to infection. 

While it will require data obtained by all these means and extend- 
ing over along period to arrive at any conclusions sufficiently accurate 
to allow them to influence quarantine procedure, still I believe the 
last method of observation cited will throw more light on the subject 
than ‘the first two, 

It is for this reason that every vessel arriving at Gulf Quarantine 
Station from Stegomyia-infected ports has, since the 1st of July last, 
been carefully examined to ascertain if mosquitoes were present on 
board, and,’if present, their variety, where and when they came 
aboard, and under what conditions. 

Gulf Quarantine Station is an especially good point for these 
observations, from the fact that it is 10 miles from the mainland, and 
because vessels bound here do not pass near land, and so but rarely 
take on mosquitoes en route, and even these, as will be seen, are 


26 


26 


always the marsh-bred varieties of Culex. Besides, the examination 
of at least a thousand mosquitoes on Ship Island has convinced me 
that there are no Steyomyza here. 

Each vessel inspected was carefully searched, the inspector being 
armed with a cyanide killing bottle, and in addition the captain was 
asked the following questions: 

1. Were there any mosquitoes on board on your outward voyage, 
consisting of —— days? 

2. If so, did they come aboard before departure from home port or 
at sea, and under what circumstances? 

3. Were there any mosquitoes on board at your destination or on 
homeward voyage? 

4. If in port— 

(a2) How far were you from shore? 

(2) Prevailing wind and weather? 

5. Lf on homeward voyage (consisting of —— days)— 

(a) Were they from port? 

(b) Did they come aboard at sea, on what day, and how far were you 
from land ? 

(c) Were there wigglers in any of your tanks at any time? 

During the five months from June 1 to November 1 observations 
were made on 82 vessels, all arriving from ports where the Stegomyia 
is believed to exist in quantities. Of these 78 were sailing vessels 
and 4 were steamers. 

Of these 82 vessels 65 claimed to have had no mosquitoes aboard at 
any time during the voyage or at port of departure, and their absence 
having been confirmed by search, we can dismiss them from consider- 
ation and pass to the remaining 17. 

Five of these had mosquitoes on board at their ports of departure, 
2 being rid of them as soon as they were well at sea, while 3 others 
carried’ them two days and were then no more troubled, except one 
schooner on which they reappeared in quantities five days before she 
reached this port, when she was 20 miles from shore. 

Nine sailing vessels, having no mosquitoes on board before sailing, 
had them appear at sea, in one case from the water casks in which the 
captain found larve. But in the other cases they doubtless came from 
land which was at the time distant—20 miles in one case, 15 miles in 
three-cases, 10 miles in one case, and 2 miles in the last two instances. _ 
In all these vessels the mosquitoes found on board on arrival at this 
station were the common varieties of Culex, there being no Anopholes 
or Stegomyia among them. = : 

Stegomyia fasciata were found on board and were identified in the 
remaining three cases, as follows: ; 

The schooner Susie B. Dantzler arrived from Vera Cruz, Mexico, 
on July 16, 1902, after a voyage of fifteen days. The captain stated 


27 


that mosquitoes came aboard in large-quantities at Vera Cruz, although 
he lay a half mile from shore and there were variable winds with 
squalls and rain all the time. The number of the insects decreased on 
the voyage but were always in evidence, and we caught four or five of 
them here. No larve were found in any of the tanks, and as the cap- 
tain had repeatedly examined them without result in his efforts to be 
rid of the mosquitoes, I believe the insects found on board here came 
all the way from Vera Cruz. 

The schooner Eleanor arrived from Vera Cruz on July 17, 1902, 
thirteen days out. She had no mosquitoes on board before reaching 
Vera Cruz, but there quantities came on board. Her moorings were 
half a mile from shore and the winds were variable. The captain 
stated that he could not get rid of the insects after sailing, although 
the number decreased very much and there were no larve in any of 

_the tanks. At the time of her inspection here we caught and identi- 
’ fied a number of Stegomyta. 

The brigantine John H. Crandon arrived at the station J uly 27, 
1902, twenty-two days from Vera Cruz, where she had one case ee 
yellow fever on board. At that port she lay a half mile from the sea 
wall, three-eighths of a mile from an infected prison, and within 200 
yards of an infected vessel. Stegomyta fasctata were found on board 
by Acting Assistant Surgeon Hodgson before she sailed, as well as 
larve in the tanks. All during the trip there were mosquitoes in 
abundance, and a veritable plague of Stegomyia was found on board 
on her arrival here. There was a constant buzz in the forecastle, and 
anyone entering was sure to be attacked by several mosquitoes. Spec- 
imens were caught in almost every protected part of the vessel, and 
all were found to be the Stegomyta fasciata. The captain had emptied 
several water barrels because he found they were breeding mosqui- 
toes, but the water remaining had no live larve, although many old 
moults were seen. As breeding was surely going on in the tanks dur- 
ing a part of the voyage at least, it would be impossible to say how 
‘long any particular mosquito had been aboard or if any of them had 
been brought here from the infected port. 


SUMMARY. 


The above facts may be summed up as follows: 


Vesssels having no mosquitoes on board at any time ...-..--..----------------- 65 
Vessels having mosquitoes on board in port of departure ...--.-.--------------- 5 
Vessels on which mosquitoes (Culex) appeared en route......--..-------------- 9 
Vessels arriving with Stegomyia fasciata on board......-----------+-+--+-------+ 3 


Three and a half per cent, then, of all vessels brought Stegomyea 
on a voyage averaging Seventeen days. 


28 
CONCLUSIONS. 


From but one season’s observations ata single quarantine station 
we can not assume to draw any hard and fast conclusions regarding 
the probability of Stegomyia, infected or not, being carried by vessels. 
Nevertheless, I think we may conclude, first, that mosquitoes can come 
aboard vessels under favorable conditions when the vessel is not over 
15 miles from shore; second, that Stegomyia can be carried from 
Mexican or West Indian ports to those of our Gulf States; third, that 
they can board a vessel lying at anchor a half mile or less from shore, 
being conveyed by the open lighters used or flying aboard, and finally, 
that a vessel moored a short distance from land may become infected 
with yellow fever, our old beliefs to the contrary notwithstanding. 

I wish to acknowledge the aid of Assistant Surgeons Burkhalter 
and Ebersole in collecting data and specimens. 


YELLOW FEVER IN STITUTE, BULLETIN Bo, 12. 


Treasury Department, ‘Public Health and. “Marine. Hospital Services: 
WALTER WHMAM, Surgeon- -General, : 


/ 


Tae Earty History op Quarannit: 


ORIGIN OF SANITARY MEASURES DERBY 
YELLOW FEVER, 


PED AGAINST 


Passed Asst. Surg. J. M. EAGER. — 


WASHINGTON: 
: GOVERNMENT PRINTING OFFICE. 
c 1903. 


YELLOW FEVER INSTITUTE, BULLETIN No. 12. 


Treasury Department, Public Health and Marine-Hospital Service. 
WALTER WYMAN, Surgeon-General. 


THE EARLY History OF (UARANTINE: 


ORIGIN OF SANITARY MEASURES DIRECTED AGAINST 
YELLOW FEVER, 


BY 


Passed Asst. Surg. J. M. EAGER. 


MARCH, 1903. 


WASHINGTON: 
GOVERNMENT PRINTING OFFICE. 
19038. 


YELLOW FEVER INSTITUTE. 


Treasury Department, Public Health and Marine-Hospital Service. 


WALTER WYMAN, Surgeon-General. 


. Buiuerin No. 12. 


Section D.—QUARANTINE AND TREATMENT. Asst, Surg. Gen. W. J. PETTUS, Chairman of Section. 


THE EARLY HISTORY OF QUARANTINE—ORIGIN OF SANITARY MEASURES 
DIRECTED AGAINST. YELLOW FEVER. : 


By P. A. Surg. 7 . M. Eacur. 


FEBRUARY, 1903. 


The public sanitary measures included in the comprehensive term 
‘‘quarantine” have been more extensively applied in America against 
yellow fever than against any other disease. Most of these measures 
had their origin long before. yellow fever was known to the world. 
The way they came into existence and how they were later used as a 
protection against yellow fever is one of the most interesting topics 
in sanitary history—one without which no account of the prophylaxis 
of yellow fever would be complete. In the present writing the term 
‘‘quarantine” is not limited to its narrower sense, but is taken to mean 
any restraint, owing to contagious disease, of intercourse on land or 
by sea. It includes such incidental measures as disinfection. 

The history of quarantine is closely interwoven with that of medi- 
cine in general and of shipping. We read of these practices being 
applied against leprosy in biblical times, and Captain Cook, the Eng- 
lish navigator, telis us that the savages of the South Sea Islands, who 
had not advanced beyond the stone age at the time of his visit to those 
islands, resorted to rude sanitary precautions in the case of arrivals 


from neighboring places. 
3 


4 


The story of the beginnings of quarantine is associated particularly 
with the epidemiology of leprosy, pest, and syphilis. Cholera and 
yellow fever were later considerations. The first reported prevalence 
of yellow fever was at Bridgetown, Barbados, in 1647, the year before 
the great pest of Habana. At this time quarantine measures had been 
practiced against other malignant contagious diseases, a maritime quar- 
antine station having been in operation at Venice in 1403, nearly a 
century before the discovery of America. It was only necessary to 
include yellow fever in the category of contagious exotic diseases and 
apply against the malady the procedures already in vogue. The first 
appearance of yellow fever in Europe occurred at Lisbon in 1723, and 
is described in the article ‘‘ Yellow fever in Portugal” (Bulletin No. 
4, Yellow Fever Institute, United States Public Health and Marine- 
Hospital Service). It was not, however, until 1821, following an 
extensive epidemic in Spain, that quarantine was applied in Europe 
against yellow fever. The Spanish academies were interpellated as to 
the nature of the disease, and as a result of their replies yellow fever 
was declared quarantinable. Inquiry in England in 1823 and 1824 was 
followed by an act of Parliament directing quarantine against yellow 
fever in the same way as against plague. Quarantine theory and 
practice have from the beginning followed medical dogma. Religion, 
astrology, and crude or false doctrines of etiology extended their 
influence. Like most branches of practical medicine, the practice of 
quarantine passed from the hands of priests into those of empiricists. 
It took ages for public sanitation to establish itself on a scientific basis. 


LEPROSY AND LAND QUARANTINES. 


The first quarantines of which any mention is made in literature 
were land quarantines used as a protection against leprosy. The 
ancients regarded this disease as of African origin, and Lucretius 
states positively that it first came from Egypt. In the Old Testament 
the first indications are found of precautions taken against contagious 
maladies. Leviticus, Numbers, and the First Book of Samuel give 
directions for the sequestration of lepers, first in the desert, then out- 
side the camp, and afterwards without the walls of Jerusalem. In 
these books the inspection of persons for the detection of leprosy is 
detailed. Persons afflicted with skin diseases were directed to present 
themselves before the priests. An observation of each case was made, 
and, according to minutely described symptoms, isolation of the 
patients was ordered for a prescribed period. 

The crusaders on their arrival outside the walls of Jerusalem found 
lazarettoes still in existence, and after taking the city from the Mussul- 
mans sent all contagious maladies to these isolated places. The name 


Hospital of St. Lazarus was given to the place of sequestration. 
Returning to Europe, the members of the military expeditions brought 


5 


back with them not only numerous diseases, but also the word “‘laza- 
retto,” as applied to a place for the isolation of the victims of com- 
municable maladies. As a result lazarettoes were built outside the 
gates of nearly all the principal cities of Europe. Leprosy itself had, 
however, been introduced into Europe many centuries earlier. It is 
spoken of as a foreign disease by the earlier Greek and Latin writers. 
Pliny thinks that leprosy was introduced into Europe by Pompey 
returning to Rome from. Syria after his celebrated triumph over fif- 
teen nations in Asia. It is implied that leprosy walked with the three 
hundred princes before the triumphal car of the conqueror. These 
surmises give rise to the interesting query whether leprosy was not 
the first quarantinable disease introduced by sea. As a quarantinable 
disease leprosy takes precedence in several ways. For instance, it 
was the first quarantinable disease (quarantinable from the point of 
view of the United States quarantine regulations) of which’ the 
causative germ was discovered. 

During the epoch of the crusades leprosy became widespread in 
Europe and resulted in the extensive establishment of isolation sta- 
tions. Leper houses existed at Metz, Verdun, and Maestricht as 
early as the seventh century, for long before the crusades the disease 
had spread from Italy into the Roman colonies of Gaul, Britain, and 
Spain, and thence into the most remote countries. Mathew Paris 
estimates that at the time of the great epidemic of leprosy in western 
Europe succeeding the movement against the Mohammedans 19,000 
lazarettoes were in operation in Europe. Religious orders conducted 
the houses bearing the name of St. Lazarus, but in northern Europe 
many dedicated to St. George were under secular supervision. Not 
only were persons suffering from leprosy and other contagious dis- 
eases sent to such asylums, but the insane and individuals whose sep- 
aration from society was deemed an advantage to the populace or the 
ruling powers were also confined there. In these places of isolation 
quarantine measures, that afterwards had their application at maritime 
stations and ultimately were directed against yellow fever, developed 
primarily. Lepers were not strictly confined to the leper houses. 
They were, however, required to wear a special costume, to limit their 
walks to certain roads, to give warning of their approach by sounding 
a clapper, and to forbear communicating with healthy persons and 
drinking from or bathing in any running stream. 


PEST AND EARLY VIEWS OF ETIOLOGY. 


In connection with pest and later with syphilis the greatest advances 
of medizval times took place in public sanitary methods, leading to 
the establishment of maritime and land quarantines. During the 
Middle Ages more attention was given to the isolation of leprosy than 
of other diseases now known to be virulently contagious, for the reason 


6 


that the minds of medical men were hampered by accepted doctrines. . 
One of the first of these dogmas was founded on the fact that, while in 
the sacred Scriptures minute attention is given to precautions against 
leprosy and skin diseases, no measures are prescribed against pest. 
Yet most disastrous epidemics are recorded in the Old Testament. 

By the word pest is understood not only bubonic plague, but the 
different epidemic diseases, whatever they may have been, that were 
formerly included under that term. In their application to this group 
of maladies the various docrines of etiology had a most important 
bearing on etiology. The history is preserved in a great number of 
documents, many of them obscure and quaint, but all interesting as 
showing the gradual development of public sanitation. From an 
etiological standpoint the history of public hygiene in its relation to 
epidemiology is divided into four periods, during all of which widely 
diverse views of causation of epidemic disease were held, the state of 
knowledge in each successive epoch advancing nearer the truth. First 
came a chaotic period up to the time of Hippocrates, secondly the cen- 
turies that intervened from the time Hippocrates set forth his views 
of etiology to the middle of the sixteenth century, when Fracastoro, 
basing his observations on the epidemic prevalence of syphilis that 
extended throughout Europe, announced a theory of contagion. 
Then followed an interval lasting until the evidence of a living con- 
tagion gained credence. Lastly came the time when specific germs 
were found to be the cause of epidemic disease. The last era, how- 
ever, brings the history of quarantine to such a recent time as to be 
outside the scope of the present writing. 

The word plague aswell as pest was given by ancient medical writers 
to any epidemic disease that wrought an extensive destruction of life. 
Oalen, for example, used the word in this sense. History is replete 
with epidemics. Instances of ancient prevalences are the disastrous 
disease, recorded in II Kings, causing the destruction of the Assyrian 
army; the plague of Athens, described by Thucydides; the great 
pestilence in the reign of Marcus Aurelius, that extended over almost 
the whole of Europe, and the plague of Justinian, descriptions of 
which are given by Procopius and Evagrius. The plague of Justinian 
lasted for fifty years and has a decided interest in connection with the 
present subject, having been introduced in all probability largely by 
sea. It began at Pelusium,in Egypt, 542 A. D. After spreading 
through Egypt it appeared the next year at Constantinople. In sub- 
sequent years it advanced over the entire Roman world, making its 
initial appearance in seaboard towns and radiating inland. Frequent 
epidemics occurred in succeeding centuries, one of the most important 
of which was the great cycle of epidemics in the fourteenth century, 
which has been given the name of the ‘black death.” Throughoutall 


7 


this extensive period notions and practices relating to public sanita- 
tion were being evolved in accordance with the prevalent tenets of 
causation. In the earliest period religion, superstition, and stellar 
influence took the principal place in the confused ideas of etiology. 
Ill-ordered doctrines led to all sorts of irrational practices. Among 
the Greeks, in the rites of Msculapius, the sick were not permitted to 
enter the temples, where they underwent treatment, without first 
being purified by various baths, frictions, and fumigations. All this 
was accompanied by ceremonies similar to those practised within the 
temples, namely, magical performances and fervent prayers recited in 
a loud voice, often with musical accompaniment. As an accessory to - 
the purification preliminary to being admitted, the patient was 
required to pass the night stretched on the skin of a sheep that had 
been offered as a sacrifice. Here he was-‘ordered to compose his mind 
for sleep and await the arrival of the physician. Throughout these 
ages as well as in more recent times a fanciful association between 
the phenomena of the material world and the destinies of mankind 
closely linked the doctrine of etiology with astrology. The persistent 
belief of learned men in the relation of stellar conditions to epidemics 
is in part explained by the fact that astrologers who predicted epi- 
demics wrought charms against the impending pestilence, thus saving 
their credit, in event the disaster did not materialize, by claiming that 
it had been averted through their efforts. These primitive views of 
the origin of epidemics did not necessarily place the cause of the dis- 
ease outside the earth and its immediate surroundings. Winds, 
thunder and lightning, fogs, and other meteors were blamed for caus- 
ing pestilence, and the flight of birds and insects were supposed to be 
dependent phenomena. ‘Xanaphanes, five hundred or six hundred 
years before Christ, expounded an idea that the sun was a torch and 
the stars candles that were put out from time to time. According to 
his notion, which was seriously accepted, the stars were not heavenly 
bodies in the wider sense, but meteors thrown off from the earth. So 
a belief in stellar influence did not carry the mind outside worldly 
ranges. For this reason other practices than prayers and sacrifices 
were believed to be effective. They consisted chiefly in efforts to dis- 
sipate the meteors, such as huge and numerous fires, and to avoid 
meteoric influence by confinement in closed or otherwise protected 
places. 

During the period under consideration, the promptings of supersti- 
tion were paramount and the epidemiologists of the times confined 
themselves principally to interpreting the signs of the heavens. More 
advanced views came as the result of reasoning, but the path of dis- 
covery by experimental science was not entered upon until after many 
centuries. 


ETIOLOGY ACCORDING TO HIPPOCRATES. 


The doctrines of etiology took a more determinate form under the 
teachings of Hippocrates. According to Hippocrates, disease has its 
origin either in the régime of life or in the air that surrounds the 
living body and enters into it. He made therefore a twofold etiolog- 
ical division of diseases, those dependent on the personal régime, and 
those dependent on the quality of the air. Regarding the latter class, 
when many individuals are attacked by the same disease at the same 
time, he supposed the cause to be a common one, namely, the air 
breathed. Hippocrates believed that a régime of life, which differs 
with different persons, could not be the cause of a malady that attacks 
alike the young, the old, men and women. On the other hand, when 
diseases of different sorts occur, it was clear to him that the cause is 
individual. Epidemic disease, according to the Father of Medicine, 
is often promoted by a specific, unknown, and extraordinary condition 
of the air due to the presence of the guid divinuwm, which may also 
exist in miasms and certain other impure things. This guzd divinum 
has given much trouble to the followers and commentators of Hippoc- 
rates, and the judgment as to what he conceived it to be must be left 
to the fancy of the student of his writings. It seems probable, how- 
ever, that Hippocrates meant the scourge of divine wrath. It was 
this very idea that for centuries prevented the application of sanitary 
measures to epidemic disease. Men regarded pestilence as a punish- 
ment inflicted by the Almighty on delinquent humanity and an attempt 
to turn aside a weapon borne in the divine hand was considered vain 
and impious. 

The influence of Hippocrates’s views, with their bearing on sanita- 
tion, extended with slight abatement almost to the time when Fracas- 
toro announced his doctrine of contagion. Throughout all this period, 
moreover, the controlling power of Platonism held experimental 
inquiry in check. It was believed that the true nature of things could 
be discovered by the action of reason and not in any important degree 
by experience and observation. Thus, it will be seen, the measures 
directed against epidemic disease were often misguided, ineffective, 
and dependent on all sorts of false doctrines. 


GALEN’S VIEWS OF EPIDEMIOLOGY. 


Galen, not dissenting from the views of Hippocrates, was of the 
opinion that any disease that caused the almost simultaneous death of 
a large number of people should be regarded as of the nature of pest. 
He did not hold to any view of contagion in these maladies, that is, of 
their direct communication of man to man, though he evidently 
believed that the corruption of the air was more intense in the neigh- 
borhood of the sick than elsewhere. Pest, he declared, was born of a 


9 


pollution of the atmosphere and assailed man by way of respiration. 
This doctrine was ‘accepted by the pupils of Galen. In the commen- 
taries of the books of Hippocrates on epidemics, or popular diseases, 
as they were called, it is asserted that pestilential maladies proceed 
from a special condition of the heavens. These commentaries, at 
one time attributed to Galen, have since been demonstrated to be 
the production of his disciples. The long line of Greek, Latin, and 
Arabic medical writers down to the time of Avicenna, the Moham- 
medan physician, adhered to the teaching of Hippocrates and Galen, 
and when they speak of contagion the term must always be under- 
stood to mean contracting a disease by breathing altered air. The 
masters of medicine of the middle ages held similar opinions. Ber- 
nardo Gorgonio, professor of medicine at Montpellier, France, in 
1300, and Arnaldo da Villanova, who lived toward the end of the 
twelfth century, gave the name of pestilent fever to every deadly 
fever and maintained the cause to be a corruption of the air. Gug- 
lielmo Varignara, professor of medicine at Bologna in 1302, not only 
denied the contagious nature of measles and smallpox but declared 
that the buboes of plague were not contagious. Gentile, who died of 
pest at Foligno, Italy, in 1348, believed that the poison of pest existed 
in the air and was due toa putrefaction of this medium. John Godes- 
den, a leading English physician of the fourteenth century, announced 
the same views. De Chauliac, an eminent French physician of Avig- 
non, who observed the terrible epidemic of 1348-1361, recorded 
casually his idea that pest could be contracted by contact with the sick, 
but assigned as a primary cause decomposition of the air due to the con- 
junction of planets whereby a certain subtle substance is evolved capable 
of producing epidemics. Another famous physician of those times, 
Raimondo da Vinario, who was a spectator of the epidemics of pest in 
1348-1361 and 1373, says that it is a very dangerous thing to have to 
do with persons stricken with pest; that one person sick with pest 
may infect an entire city; that those employed in public hygiene in 
times of epidemic prevalence take the malady by contagion; that phy- 
sicians more than any other class are likely to catch the disease; and 
that monks are generally exempt from pest because they are isolated 
in monasteries and thus free from outside exposure. Still there is not 
room to believe that this master of medicine had any precise concep- 
tion of the nature of contagion. Like so many others, he put his 
faith in corruption of the air brought about by an influx of stars, 
planets, and constellations, and in poisonous exhalations emanating 
from the earth. The danger of contact with the sick he conceived to 
be due.to the air filled with pestilential poison that had been inspired 
and afterwards exhaled by the victims of the disease. Da Vinario 
held also that garments worn by the sick and other fabrics in close 
contact with them contained the infective principle, and hence should 


. 


10 


be transported with the sick to a distant and isolated place. Notwith- 
standing all this, he does not mention the necessity for purification of 
infected things nor ever suggest the caution of destroying fomites. 
There can be no stronger evidence than this of the tenacity with which 
the physicians of the middle ages adhered to the accepted doctrines of 
their predecessors. 


THE BEGINNINGS OF RATIONAL ETIOLOGY. 


1t took centuries of involuntary observation to shake the idea that 
epidemics are of celestial origin and to be combated by prayers, fast- 
ing, and processions. The first advances toward broader ideas were 
not made by medical men. The record of reformed views is found in 
works.on jurisprudence and in the narratives of travelers. In the 
books of jurisprudence of the emperors of the East it is noticed that 
care should be exercised in having relations with persons arriving 
from places where pest reigns. It was ordered, in consequence, that 
those so exposed should be separated from others for the purpose of 
observation. The term of forty days (whence the word quarantine) 
is named, this being the supposed maximum period of the duration of 
acute maladies. Whether this isolation was practiced in a particu- 
larly selected piace or in the houses of the suspects is not known. 

Merchants traveling in the East and detained at Alexandria or Cairo 
during the prevalence of pest observed that cloistered monks did not 
contract the disease. Many of these merchants, exiled by pestilence, 
staid constantly within the boundaries of their residences, transacting 
all business through barred windows and from terraces that crowned 
the house tops. The stubbornness with which medical men held to 
the doctrine of aerial corruption of celestial origin is shown by the 
report made to the Marseille government in 1720 by a body of dis- 
tinguished physicians, in which the condition of the air was pronounced 
to be the sole cause of pest, the idea of communicability from man to 
man being absolutely rejected. 

One of the most ancient edicts commanding the segregation of suf- 
ferers from pestilential maladies had for its authors two laymen, 
Sagacioand Pietro de Gazata, and is found in the chronicles of Reggio 
@Emilia. The document, dated 1374 and written in low Latin, orders 
that all persons sick with pest be taken outside the city, into the open 
country, a camp, or the woods, there to remain until dead or cured. 
The parish priests are required to promptly report all cases of pest 
under pain of death by fire. After registering these historical facts, 
the chronicler adds: 

And I saw in this same year that these orders were observed in Reggio, for which 


cause all were grieved and terrified more than by the fear of the illness which, when 
God permits, can not be averted. 


11 


ORIGIN OF THE DOCTRINE OF CONTAGION. 


The credit of having created the doctrine that pest is contagious by 
contact with the sick and their effects is chieffy due to Jacobo della 
Torre, known also by the name of Jacopo da Forli, from the ‘name of 
a city oa central Italy, where he was born in the ceeand half of the 
fourteenth century. Contagion had been referred to obscurely and 
timidly from Aristotle down, but now the idea took a practical form. 
The old notion was that fomites were a sort of tinder that caught from 
the air an infection existing independently of the sick. Many writers, 
including Galen, believed there was an extreme degree of atmospheric 
pollution in the vicinity of the sick, rendering such neighborhoods 
dangerous, but this was considered a primary cause of the illness rather 
than a direct emanation from the sick. 

Della Torre’s doctrines were not accepted by the various schools of 
medicine and were for a time absolutely forgotten. Fracastoro pro- 
claimed the same theories at a later period, when they were better 
received, and to him is generally given the honor of announcing the 
theory of contagion. Jacobo della Torre advised the magistrates of 
his native town to remove outside the city all persons affected with 
pest and to isolate them, as well as all persons who had -been with 
them. The authorities were warned against delay, for it was avowed 
that every precaution would be futile should the disease become dif- 
fuse throughout.the city. In his recommendations no mention is made 
of purification, but he asserted his disagreement from the accepted 
belief in the stellar origin of the infective principle. Della Torre’s 
disciple, Michele Savonarola, attained greater eminence than his mas- 
ter, and so far vindicated the honor of his school as to declare that even 
persons in good health may transport the pestilential virus to distant 
places, and that those who are not brought in association with the vic- 
tims of pest or with pest-bearing things escape the disease. But 
Savonarola did not fully indorse the teachings of his preceptor. He 
could not shake off a belief in astrology and admitted that the origin 
of pest resided in a disorder of the air generated in consequence of 
planetary contact. 

Giovanni da Concorrezzo, toward the second half.of the fourteenth 
century, was so profoundly convinced that pest came exclusively from 
universal aerial pollution that he denounced as useless every precaution 
to check the advances of the disease and affirmed that all measures 
designed to avert contagion are inefficacious. 

At this period, when the world had about decided that in epidemics 
sanitation was not worth while, three observing men lent their influ- 
ence to broader views and thus gave a potent stimulus to the doctrine 
of contagion. These writers were Alessandro Benedetti, Marsilio 
Ficino, and-Gerolamo Fracastoro. 


12 


BENEDETTI AND FICINO. 


Alessandro Benedetti, anatomist and military surgeon, wrote a 
treatise on pest, published in the last decade of the fifteenth century, 
in which is presented a résumé of his doctrine concerning pest. 
Pest, he declared, is not only catching by contact with the sick, but 
by fomites. The latter, he believed, are capable of receiving and pre- 
serving the contagion for long periods. Convalescents from pest, 
and the things that have been in relation with them, should, he said, 
be purified before being brought in touch with healthy persons. 

Marsilio Ficino was born in Florence in 1483, and passed his child- 
hood in the court of Cosmo de’ Medici. He was a priest as well as a 
physician. Pest had, in Ficino’s time, tormented Tuscany, and in 
1479 broke out in Florence. The Grand Duke Cosmo de’ Medici 
requested Ficino to prepare a book treating of the pest with the scope 
of instructing the people how to protect themselves from the scourge. 
The book, published about 1480, was written in Italian. In writing 
it, Ficino was associated with Tommaso del Garbo, Mengo da Faenza, 
and others, and the volume bore the title of Counsel Regarding the 
Pest. The book is a rare one in its original tongue, but fortunately 
was translated into Latin and is still preserved in different libraries. 
The list of the works of Ficino refers to this treatise by the title of 
Antidotus, and it is so cited in many medical books printed in later 
years. The theories given in this work as to the origin and nature of 
epidemic disease are the same fantastic stuff that antecedent writers 
dealt out, but the ideas as to how the disease may be imparted are of 
a much better sort. The view is advanced that pest can be communi- 
cated from man to swine, and that cats and dogs convey the disease. 
The reader is informed that pestilential poison may abide in the air 
for long periods and may infect food. Advice is given to boil all 
drinking water, or to impregnate it with iron rust; to dilute wine 
with water so prepared; to add an acid sauce to the food; to choose 
dry food and fruit grown in balsamic and elevated regions, and to 
dwell on hills or in the mountains. Treating of prophylaxis and die- 
tetics during times of pest, there is a long list of injunctions relative 
to exercises of the body and the quality of the food. For example, it 
is enjoined to shun the heat of the sun and of tires; to avoid sweating 
and the drying of sweat on the body; not to eat fish, or if needs be, 
to eat small fish from some clear running stream with a rocky bed, 
and to fry them in oil and treat them liberally with lemon juice, pep- 
per, and cinnamon; and, lastly, there is an enumeration of fruit and 
vegetables to be chosen or avoided, Overeating and overdrinking are 
admonished, and it is advised to cook all meat well and prepare it with 
aromatic condiments. To preserve the health of those in attendance 


18 


on the sick, it is directed to keep as far apart as may be from the bed- 
side; to ventilate the sick rooms; to fumigate the house with burning 
terebinth wood; to carry in the hand a firebrand, a pot of lighted 
charcoal, or a sprig of rue, mint, sage, or myrtle; and to bathe the 
body, morning and evening, with warm vinegar. Directions are 
given to sprinkle the house with preparations of terebinth, juniper, 
sandal, rose, rosemary, laurel, and similar herbs. The reader is 
informed that walls, partitions, and all structures made of wood are 
capable of preserving the contagion for more than a year, and that 
their disease-bearing qualities should be corrected by washing, fumi- 
gations, and fire; that garments of wool and similar stuffs, if not 
exposed to the air and sun, fumigated often, and well washed, may 
still contain contagion after three years. The statement is made that 
the morbid principle can diffuse itself through division walls and 
enter neighboring habitations. Caution is prescribed in moving ani- 
mals, money, furniture, and bundles from place to place because of 
the danger of conveying disease. 


FRACASTORO AND SYPHILIS. 


Gerolamo Fracastoro is generally credited with being the author of 
the theory of contagion, but, as has been seen from a review of the 
works of previous writers, it can only be claimed for him that he 
elaborated the theory, presented it in a popular form, and lent to the 
idea the influence of his high authority. 

An important event at this period of history was the extensive prev- 
alence of syphilis in Europe, a spread of the disease that gave it 
every likeness to a general pestilence. The chroniclers of this occur- 
rence were convinced that the disease could propagate itself at a dis- 
tance, and that it could be communicated by intercourse not more inti- 
mate than conversation and social commingling. The malady diffused 
itself through all classes of society, and history names a king and 
other potentates among the victims. In Italy the belief prevailed 
that the disease had gained access to the country with the invading 
army of Charles VIII, of France. The Italians called it the ‘“‘morbo 
Gallico.” In France it took the name of the Neapolitan disease. 
Wide credence was gained by another theory to the effect that the 
malady had come in by sea with the naked savages of America. In 
this case it must have spread and taken root very speedily, for it is 
said that when Columbus went to Barcelona on his way to pay homage 
to Ferdinand and Isabella, of Spain, syphilis flourished in that seaport; 
public prayers were being offered as in times of pest, and precautions 
were being taken against the disease as in case of leprosy. 

Laws were made in France for the regulation of syphilis. By an 
act of the Senate at Paris, dated March 6, 1496, persons affected with 


14 


the disease were forbidden under pain of the halter to have any deal- 
ings with well persons, and it was ordered that the sick should be seg- 
regated in places set aside for their reception in the Faubourg St. 
Germain. Notwithstanding the rigor of the ordinance, many stricken 
persons eluded the vigilance of the sanitary guards and moved about 
in the city of Paris, thereby spreading the disease. The provost then 
found it necessary to make public cry, warning all persons that there- 
after pretensions of ignorance would be disregarded by the authori- 
ties, and any individual, native or stranger, afflicted with syphilis and 
found witbin the city would be summarily cast into the river and left 
to his fate. 

Some years later there was similar trouble in the Italian part of the 
Tyrol, trouble which so interfered with one of the most important 
ecclesiastical gatherings of the times that Pope Paul III, by advice of 
Fracastoro, removed the Council of Trent to Bologna. Fracastoro 
had previously written a dignified and graceful medical poem, in 
Latin, entitled ‘‘Syphilidis sive Morbus Gallicus,” after whose hero, 
the shepherd Syphilus, the disease received its name. 

His interest in this prevalence of syphilis influenced Fracastoro to 
publish, in 1546, the work ‘‘De Contagionibus.” The great feature 
of this writing is the presentation of the subject in such a catching 
way that it took hold on the popular mind, and even had decided effect 
in loosening the deep-rooted medical opinion of the times. The lesson 
of contagion was taught by a number of clever similes. For example, 
Fracastoro divides contagious diseases into three classes, namely, dis- 
ease catching by contact, in which he compares the mode of com- 
municability to the way in which one decayed fruit spoils another 
perfect one; disease carried by fomites, a process likened to the per- 
sistence of soot on a smoky wall; and disease conveyed to a distance, 
in which manner the virus is carried just as the volatile essence of 
garlic or of an onion is borne through space, affecting the nostrils and 
causing the eyes to water. Fracastoro taught that the poison of dis- 
ease consists in corpuscles, and that it affects first the minute particles 
of the animal body. He says that this poison persists in the body, ia 
fomites, or in the air, in proportion to a kind of stickiness existing 
between the conveying medium and the poisonous corpuscles; and 
that woolen fabrics and the like absorb, retain, and transport con- 
tagion with ease, because they contain interspaces to lodge the cor- 
puscles, and are of a nature to protect the poison from the light, heat, 
cold, air, dampness, and other conditions injurious to it. 

So we see that, with the acceptance of the views of Della Torre, 
Benedetti, Ficino, and Fracastoro, things were fairly in the way for a 
beginning of quarantine on a practical basis. 


15 


MARITIME QUARANTINE. 


Maritime quarantine originated in connection with the Levantine 
trade. Its early history is associated with that of shipping in the 
Mediterranean, especially with that of the traffic of Venice, Genoa, 
and Marseille. Although commercial activity in these waters was 
initiated by the Pheenicians, the maritime pioneers, records of disease 
introduced by sea are not found bearing earlier date than the period 
when Roman navigation was well established. As has been seen, the 
practice of isolation was first applied against communicable disease by 
the Hebrews, but their lazarettoes, it appears, were little used in con- 
nection with foreign trade, leaving out of the question commerce by 
sea. In the exchange of commodities with foreign countries the 
Hebrews were largely dependent on the Phenicians and Arabs. Had 
the Jews been active in outside commerce, we should probably read in 
the Old Testament of sanitaiy laws applicable to caravans and vessels. 

As has been already mentioned, Pliny implies that leprosy was 
introduced into Europe by Pompey on his triumphal return from the 
_ East. It is altogether probable that the Roman ships, laden with spoil 
from Syria, and bringing many prisoners of war to Italy, carried in 
leprosy. 

In connection with the question of the first recorded introduction of 
disease by sea a curious error has entered into writings on the subject. 
J. Freind, adducing evidence in his History of Medicine that Procopius 
was a physician, quotes a translation of Procopius’s works by Dr. 
Howel, and says that the great Byzantine historian describes the pest 
at Constantinople (A. D. 584) as having originated at Pelusium, in 
Egypt. This is indeed what Procopius wrote. But it happens that 
later writers—evidently reading Freind’s history—say that Procopius 
states the epidemic in question was carried to Constantinople by ships 
and that this invasion of disease became later the foundation of the 
quarantine establishments on the Mediterranean coast. It is, how- 
ever, true that the Italian epidemics of the sixth century began in the 
maritime towns and thence spread inland; but it does not follow that 
the writers of the time considered the intervention of ships essential 
to the introduction of disease by sea. For example, Francesco Alfano, 
professor of medicine at the University of Salerno, which in those 
days was reputed to be the greatest medical school in the world, 
writing in 1577, says that the corrupt air capable of introducing pest 
may be blown over sea and land for long distances; otherwise how 
could it be explained, he asks, that pest was transported from Ethiopia 
to Athens and to all Attica? It was considered, moreover, that a ship 
might easily be pestridden. Even by going to sea a vessel with all 
well aboard at the time of departure could not always escape the 


16 


scourge. The infection extended over the water. Matteo Villani, of 
Florence, writing in 1581 of the epidemic of 1346, which spread from 
Asia into Turkey, Egypt, Russia, Greece, and Italy, says that in those 
evil days numbers of Italian galleys flying from the pest left the 
stricken ports for healthier harbors. Their crews perished miserably 
at sea. Some reached Sicily, Pisa, and Genoa, and the disease went 
with them. 
EARLY MARITIME SANITARY LAWS. ’ 


There is but little known of ancient laws relating to maritime com- 
merce, and even this little was lost to the world until 1147. The story 
is an interesting one. Justinian, during his reign, confided to ten juris- 
consults the task of collecting and adjusting the numerous Roman laws, 
together with the various sentences and rulings of judges and magis- 
trates. A compendium of these documents and of the laws promul- 
gated during the rule of Justinian was published. It is known by the 
name of the Codex of Justinian. The only part of this code that 
treats of ships is called the Dzgestwm, and it was lost for hundreds of 
years. Finally, in 1147, the papers were discovered at Amalfi and 
made public. The Digestwm treats of the reciprocal rights of the 
owners and renters of ships, but no mention is made of sanitary mat- 
ters. During the long period when this important legal instrument 
was lost, the Venetians, Genoese, and other Latin maritime nations 
supplied the deficiency in part from the initial sources of Roman law 
and in part by custom and agreement. Of this sort are two collec- 
tions, one known by the name of Recognoverunt Proceres and the other 
called the Consolato del Mare. Besides these, there is a great number 
of documents, such as constitutions, decrees, ordinances, sentences, and 
the like, which pertain to maritime rights. It is a remarkable fact 
that, notwithstanding the detailed attention given to most maxims 
relating to shipping, the PRecognoverunt and the Consolato del Mare 
are silent too on the subject of sanitation. Therefore, in the Middle 
Ages, in event of contagious prevalences, it rested with each individual 
city or country to make such provisions as were deemed opportune. 
Such an edict is the one, said to be the most ancient of its kind, already 
mentioned as having originated at Reggio d’Emelia, in 1374, and com- 
manding notification and segregation of cases of plague. 

The Venetians were, it is generally admitted, the first to make pro- 
vision for maritime sanitation. As far back as the year 1000 there 
were overseers of public health, but at first the office was not a per- 
manent one. The incumbents were appointed to serve during the 
prevalence of an epidemic only. The first information we have of this 
kind of public office is under date of 1348, when Nicolaus Venerio, 
Marinus Querino, and Paulus Belegno (their Christian names given in 
the Latin of the text) were appointed overseers of public health. 


17 


These officers were authorized to spend public money for the purpose 
of isolating infected ships, goods, and persons at an island of the lagoon. 
A medical man was stationed with the sick. As a later result of these 
arrangements, the first thoroughly constituted maritime quarantine 
station of which there is historical record was established in 1403 on 
the island of Santa Maria di Nazareth, at Venice. The island had pre- 
viously belonged to the hermit monks of the order of St. Agostino. 
The record of the foundation of the first maritime quarantine is found 
in a Venetian manuscript written by Giovanni Tiepolo, a patrician. 
The chronicle reads: 

1403. The pest began at Venice. A place for a lazaretto was seized from Friar 
Gabriel, of the order of Hermits, and Santo Spirito was given to him. 

Neighboring States engaged in commerce in the Mediterranean 
speedily followed the: example of Venice. The first maritime quar- 
antine station at Genoa was founded in 1467, and at Marseille in 1526. 
The Marseille quarantine, one of the most complete of its kind, occu- 
pied the island of Pomique. This establishment had, in former times, 
been a leper house, but, in 1476, was converted into a plague hospital, 
and later became a maritime quarantine station. 

It was not until 1459 that a public bureau of sanitation existed in 
the Republic of Venice. In that year officers, called conservators of 
sanitation, were regularly appointed. - This information was handed 
down by a contemporary seafarer, Ser Domenico Malipiero, a Vene- 
tian patrician, an expert in commerce and diplomacy, who, in 1488, 
commanded the men-of-war under Captain-General Ser Jacopo Mar- 
cello at the celebrated naval battle of Gallipoli. In the contest against 
the Ottoman fleet the captain-general was killed, and Malipiero (who 
had a grade relative to that of vice-admiral at the present time) took 
command and was victorious. Malipiero wrote certain annals of his 
life which he bequeathed to his son-in-law. This interesting diary, 
in Venetian dialect, remained secret until 1844, when it was published 
in the Italian Historical Archives. 

The city of Barletta became at one period of the Middle Ages the 
richest. commercial port, next to Venice, in the Adriatic. This was 
owing to certain concessions granted the city whereby the traffic of a 
large territory was compelled to enter and leave by her gates. The 
privilege was not without its drawbacks. Barletta underwent three 
pestilences of a particularly aggravating character. The first, in 1884, 
was a strange malady that caused the sufferers to lose their skins like 
a molting snake. The other two epidemics (1498 and 1656) were 
probably bubonic plague, and in the last 35,000 souls, almost the 
entire population of the city, perished. These afflictions gave rise to 
the practice at Barletta of absolutely refusing entry to any infected 
vessel until the expiration of a long period of observation at a place 
outside the entrance of the port. 


91526—No. 12—03——2 


18 


During all this period land quarantines were in operation at times of 
pest. Offenses against quarantine, both land and maritime, were 
severely punished. Pietro Follerio, a great Neapolitan jurisconsult 
of the sixteenth century, mentions whipping, the mill, exile, and death 
as penalties for infringement of sanitary regulations. A quarantine 
proclamation and command made by Don Carlo d’Aragona imposes 
rigorous punishment for surreptitiously entering the city of Palermo 
during a prevalence of pest. Torture, long service in the galleys, and 
work among the sick in a pest hospital are named among the penalties. 
Even the nobles were subject to heavy fines and Jong imprisonment in 
the castle. 

BILLS OF HEALTH. 


Sanitary bulletins were incident to quarantines and cordons. They 
were so called because they were stamped with the ‘‘ bollo” or seal of 
the authority issuing them. When the system of sanitary bulletins was 
fully developed these patients, in their connection with ships, were 
designated as clean, when beyond suspicion; touched, when from a 
noninfected place in active communication with infected places; sus- 
picious, without sickness aboard, but having received goods from 
places or from ships or caravans from places where ‘pest prevailed; and 
dirty, when from a place where disease existed. 

Professor Bo, a member of the council of health of Genoa, in mak- 
ing researches relative to ordinances of sanitation proclaimed in 
France in 1850, found an interesting document in the archives of the 
‘*Conservatori di Mare di Genoa,” a body of officials to whom in 
medizeval times was confided the vigilance over public health. This 
writing, dated 1300, makes mention of bulletins of health (budlettones 
swnitatis) with which ships from the littoral of Corsica and Sardinia 
were required to be provided. Prior to 1300 there is a record in a 
rubric of the statutes of the city of Urbino, Italy, in which, referring 
to precautions against pest, it is written that no person shall leave the 
gate of the city without a proper bulletin, and that, to this end, watch 
shall be kept day and night at the city gates and walls. During the 
pest at Naples, in the year 1557, citizens, usually merchants, were 
stationed at the gates of the city to examine bills of health. Cor- 
ruption and lack of diligence on the part of these persons were pun- 
ishable by death. Sentinels, some on foot and some on horseback, 
made a patrol about the city walls to prevent clandestine entrance. 
Bills of health to be acceptable had to be stamped with the seal of the 
university of the place from which the traveler came. They gave not 
only the day but the hour of departure, together with a description of 
the traveler. Sanitary bulletins were also issued to accompany mer- 
chandise, but in times of severe pest all articles except aromatics and 
medicaments were considered suspicious. The facts here given are 


19 


taken from the instructions written by Pietro Follerio, an eminent 
jurisconsult, who was assigned by the viceroy of Naples to superin- 
tend the province of Campania during the prevalence of pest with the 
special duty of indicating means for the betterment of public hygiene. 
It is worthy of notice that the provisions of public sanitation in those 
times are usually found, not in books of medicine, but in treaties on 
jurisprudence. This is explained by the fact that the medical pro- 
fession was looked to for scientific indications only, and that the appli- 
cation of sanitary measures founded thereon, limiting or compromising 
as they often did the rights of the public or the constitutional privi- 
leges of citizens, was a matter for legal consideration and action. 


AN EARLY SANITARY CONGRESS. 


The efforts of some of the pioneers of quarantine were at times ill- 
advised, did not always meet with general approval, and sometimes, 
indeed, occasioned strong outbursts of popular indignation. The 
experience of Girolamo Mercuriale (called the A%sculapius of -his 
time) and of his colleague Capodivacca is an instance. In the summer 
of 1576 the frequence of strange febrile diseases, often very mortal, 
was observed at Venice. The supreme magistrate of health of the 
Republic of Venice, suspecting pest, called a conference of great 
physicians, among others Girolamo Mercuriale, Capodivacca, and 
Nicola Massa. As for the verdict Massa wavered, and the other mem- 
bers were divided into two camps, one body for and the other against 
pest. Mercuriale and Capodivacca asserted decidedly that the malady 
was not pest, but an epidemic of fever, due to the excessive heat of the 
season. ‘This opinion carried the day, and no precautions were taken 
against the spread of the disease. Unfortunately for the optimistic 
diagnosticians, the illness increased, and speedily took on all the 
characters of pest. The populace uprose and made an effort to lynch 
Mercuriale and Capodivacca and burn their houses. Both the physi- 
cians, fortunately for them, escaped by flight, their property being 
saved by prompt action of the authorities. 


EARLY EFFORTS AT DISINFECTION. 


The armament of disinfection in early days was full of oddities. 
In the process of purification time was more trusted than anything 
else. Gian Filippo Ingrassia, appointed by Philip II of Spain to 
establish a public sanitary service in Sicily, begins his book on pest 
and contagious disease with the following distich by Martello: 


Lana, aura et linum captant contagia pestis; 
Ignis, furca, aurum sunt medicina mali. 


Before reviewing the different means besides fire, the gallows, and 
money used against contagion, it is interesting to make a survey of 


20 


the things, in addition to wool, the air, and garments, that were reck- 
oned infectible. Animals were considered capable of conveying dis- 
ease. During the pestilence at Palermo in the year 1575 Ingrassia 
caused all the dogs in the city to be brought together alive on a cer- 
tain day and cast into a common pit, where they were covered with 
quicklime and then with earth and stones. As to cats, they were 
allowed to live, so as ‘‘not to have worse war with rats,” says Ingras- 
sia, but all cats that had been near suspected houses were required to 
be kept closed up. There were similar restrictions for fowls and pig- 
eons. Elsewhere geese and cattle were banished from the cities dur- 
ing epidemics. Habitations, ships, and even the sails and cordage 
with which vessels were rigged belonged to the category of infectible 
things. Nicola Massa, a Venetian physician, who published in 1556 
a book on pestilential fevers, names the following as fomites: Wool, 
hair, cotton, linen, hemp, silk, thread, and all things made from these 
substances; skins, feathers, and the like; and all merchandise, as well 
as sacks, baskets, boxes, casks, and cords that cover them. Massa 
considered as noninfectible all metals and objects made of them, 
including arms and cooking utensils; precious stones and marble; 
grain, flour, and meal; vegetables, fruit—fresh and dried—and nuts, 
wine, oil, and vinegar; and all drugs and aromatics. In regard to 
metallic money he said that those who held it in suspicion might allay 
their fears by receiving it in a vessel of vinegar. : 

Exposure for many days to the air in selected places and to the dew 
was looked upon with great favor. The dew of the dead of night was 
supposed to be particularly efficacious. This practice originated in 
the more or less accurate observation that during the season when the 
mists of the Nile were thickest the pest in Lower Egypt began to 
diminish. : 

The vapors of volatilized aromatic substances, known technically as 
‘‘perfumes,” were credited with great virtues in correcting the alter- 
ation of the air generated by pest. Cloves, cinnamon, cedar bark, 
camphor, mints, resinous wood, and similar substances were kept boil- ’ 
ing in pots of vinegar and rosewater for long periods. One recipe 
containing garlic and known as the ‘‘vinegar of the four thieves” 
enjoyed high repute. Fumigations in summer differed from those in 
winter. Aromatic wine was added in fumigations for cold weather, 
being assumed to have a special property of correcting air at a iow 
temperature. It was also considered advisable to lengthen the period 
of isolation in winter because cold was thought to have a tendency to 
conserve the contagious principle. Sulphur fumigation was not 
regarded with favor in early days. The strong sulphurous fumes 
were said to alter the air unfavorably rather than rectify it; but sul- 


phur came more into vogue in the eighteenth century. The burning 
of gunpowder was also thought useful. 


21 


Huge fires, kept burning for weeks, were used from the most ancient 
times. The physician Acron is reputed to have rendered great service 
by the use of fires at Athens during the pest at the beginning of the 
Pelopennesian war. Fires made of shavings and chips were thought 
preferable, because they produce a clear flame, without smoke. Aro- 
matic wood was added to these fires, but special caution obtained 
against burning anything producing an offensive odor, such as the 
wood of certain nut trees, for fear of liberating vapors likely to add 
to the disturbed condition of the air. Not only were garments and 
similar articles burned, but sometimes houses and ships as well. Oppo- 
sition often existed against such measures on the ground of further 
deteriorating the atmosphere. 

Mixtures of lime were favorably regarded and whitewashing of 
infected apartments was habitually practiced. Acid fumigations are 
spoken of in the eighteenth century. Muriatic acid fumes, suggested 
as a disinfectant in 1774 by Guyton Morveau, of Paris, were used in 
1800 to disinfect rooms, garments, mattresses, and the like, after the 
epidemic of yellow fever in Spain (‘‘ Yellow fever in Spain,” Yellow 
Fever Institute, United States Public Health and Marine-Hospital 
Service, Bulletin No. 5). With all these measures, great stress was 
laid in cleaning up infected cities during and after epidemics, giving 
special attention to sewers, wells, cesspools, and disposing properly of 
dead bodies. In reading the chronicles of the middle ages the con- 
viction can not be avoided that, were it not for occasional epidemics, 
public sanitation would have fallen entirely into disuse. 


MEASURES ADOPTED IN A PEST-STRICKEN CITY. 


To gain a precise knowledge of what measures were usually prac- 
ticed in places afflicted with an epidemic in early days, it is instructive 
to examine specifically the provisions adopted in a particular city. A 
suitable instance is presented in the Treatise on Plague, by Alessandro 
Massaria, who was in charge of sanitary measures at Vicenza, Italy, 
during a prevalence of bubonic plague of one year’s duration in 1577. 
The first death was attributed to garments clandestinely introduced 
from Padua, where plague prevailed. After a necropsy establishing 
the diagnosis the furniture in the house was burned and every exposed 
person stripped, given new clothes, and removed outside the city. 
The house was purified by aromatic fumigations and painted with 
milk of lime. All infected vestments and bedding received a treat- 
ment with strong lye. The disease, however, spread, and in one year 
the city, with a population of 30,000, suffered 1,908 deaths from plague. 
As soon as the epidemic established itself the city was divided into 32 
sections and a daily house-to-house inspection made by 64 trustworthy 
citizens, two to each precinct. All cases of sickness were reported to 
one of four public physicians. These physicians served for periods of 


22 


fourteen days. Infected habitations received the same treatment as in 
the initial case, except that the furniture was not burned in all 
instances, but washed instead with lye and left in the sun and open air 
for thirty days. All garments were put in running water ‘for two 
days. Persons exposed or under suspicion went to the Campo di 
Marte, outside the city walls, where wooden houses had been built. 
A river separated the isolation camp from the lazaretto, where the sick 
were lodged and where physicians and nurses were in attendance. 
Suspects developing plague in the isolation camp were taken across the 
tiver to the lazaretto, and convalescents from the latter place were 
transferred to the former. Those who kept well in the Campo di 
Marte for twenty-two days returned to their disinfected homes in the 
city, there to remain under observation for an additional twenty-two 
days. Convalescents from the lazaretto passed twenty-two days in 
the isolation camp, and were afterwards confined to their houses in the 
city for another twenty-two days. At the height of the epidemic all 
the houses in the city were closed for forty days, and none but the 
guards were allowed in the streets. At this time 5,000 persons were 
fed from public funds, and there were about 400 persons in the lazaretto 
and 500 on the Campo di Marte. 


EARLY MARITIME QUARANTINE STATIONS. 


The maritime quarantine stations of the sixteenth century consisted 
of an anchorage, barracks for suspects and convalescents, and a place 
where purification could be applied. The practice, with obvious modi- 
fications, was the same as in the case of an infected city. The person- 
nel of these stations consisted in many places, at the earliest times, of 
surgeons and their assistants, for plague, being regarded as a surgical 
disease, did not fall clinically into the hands of physicians. Ata later 
period the physicians conducting the stations were aided by surgeons, 
barbers, and experts in aromatics, because, as Massa says, the physi- 
cians were so limited in their acquirements as not to know how to do 
manual operations or treat external maladies. 

With a view to learning how the various methods of disinfection 
were practically applied at early maritime quarantine stations, it will 
be interesting to relate what was done to a Catalan ship that arrived 
at Palermo from Barcelona on the way to Naples at the time Ingrassia 
was chief of sanitation in Sicily. The account at least shows that the 
sanitarians of the sixteenth century were thoroughgoing. This vessel 
had 97 persons aboard, 18 of them passengers. Three seamen and 
two passengers had died of a disease suspected of being pest. The 
deaths occurred while the vessel was taking on cargo in the harbor 
where she lay at anchor. The cargo consisted of barrels of salted fish, 
cases of sugar (destined for Palermo, and already disembarked and in 


23 


store), salted cheese, salt in bulk, a.quantity of sumac, and merchan- 
dise, including many bales of cloth from Barcelona, a port not under 
suspicion. The master of the vessel was at once required to give 
20,000 scudi security not to leave the harbor until given pratique. To 
make assurance doubly sure, the rudder was taken away from the ship 
anda watch set. All persons, except the sick and a sufficient number 
of seamen to guard the ship, were sent ashore to a place known as the 
Borgo, where all garments were taken from them and they themselves 
exposed to the fumes of boiling pitch and afterwards washed with 
vinegar. Some of the clothing was burned and some washed, aired, 
and perfumed for fifty days. 

The sick were sent to a lazaretto, the Cuba, a huge stone building, 
which still stands at Palermo as a monument of early quarantine. 

The treatment given the cargo was as follows: Barrels of salted 
fish, washed outside, first with sea water and then with vinegar; cases 
of sugar, salted cheese, and sumac, coverings removed and burned 
and the commodities without further treatment delivered to the owners; 
salt, no treatment, not being considered infectible; merchandise, aired 
and perfumed ashore for 50 days, and the cloth unrolled and hung 
from the rigging of the ship for 50 days. The sails and cordage of 
the ship were taken down, submerged in the sea for a week, and then 
hung from the masts, yards, and booms in the air, sun, and dew, by 
day and night, as long as the ship remained in quarantine. Fumiga- 
tion was made in the interior of the ship by boiling pitch in caldrons 
between decks. Fifty days were set as the period of detention, 
instead of forty, because the season was winter. 


FURTHER HISTORY OF QUARANTINE. 


Without touching on quarantine in America, which is another and 
interesting story, it is profitable to take a view of the further history 
of quarantine in Europe. Following the discovery by Anthony van 
Leeuwenhoek, in 1675, of bacteria, called by him ‘‘animalcules,” there 
was a wide belief in the casual connection of microscopic creatures 
with disease, a belief supported by the doctrine of living contagion 
enunciated by Marcus Antonius Plenciz, of Vienna, in 1762, but it 
was without marked effect on quarantine procedure. The theory, in 
fact, lost hold on the public and medical minds to such an extent that 
in the early part of the nineteenth century the doctrine of a living 
contagion was looked upon as an absurd assumption. It was not until 
the middle of the last century, following the investigations of Pasteur, 
Pollender, and Bavaine, that quarantine practice became established 
on its modern scientific basis. ; 

English quarantine procedure prior to 1800 did not differ much 
from that of the Mediterranean ports. English vessels, which did 


24 


not begin to enter the Mediterranean until the time of the Crusades, 
were usually, in early years when engaged in the Levantine trade and 
from infected ports, sent to Mediterranean quarantines for treatment. 
In 1710, under the reign of Queen Anne, a rigorous quarantine act 
was passed in England, and in 1721 two ships with cargoes of cotton 
goods from Cyprus, where plague prevailed, were burned by the san- 
itary authorities in English waters. A quarantine station was estab- 
lished in 1741 in Stangate Creek, on the Medway. Here vessels, not 
treated at Mediterranean quarantines, were submitted to practically 
the same procedures as were in vogue at French and Italian ports. 
Floating hulks were also used as quarantine stations in England from 
about the middle of the eighteenth century. The act of Queen Anne’s 
reign was qualified by later enactments, and during the pest in Poland, 
in 1780, vessels bound for England from the Baltic were compelled to 
undergo a typical old-fashioned quarantine. A few years later there 
was an order in effect directing all vessels on the way to England and 
liable to quarantine to show a yellow flag at the mainmast head when 
in sight of other vessels at sea during the day and a distinctive light 
at night. From the beginning of the nineteenth century quarantine 
restrictions were, by changes in the laws and their application, materi- 
ally relaxed in Great Britain, and as a substitute for former practice 
it has not been the custom in modern times to detain any vessel unless 
there has been communicable disease aboard during the voyage, or 
such exists on arrival. Following the decision of the Spanish Govern- 
ment in 1821, that yellow fever was to be considered quarantinable, 
an inquiry on the subject was made in England in 1823 and 1824, 
which resulted in the passage of a law directing the same procedures 
to be applied against yellow fever as against plague. 

In France, until the year 1821, vessels from the Levant were not 
allowed to enter at any ports except Marseille and Toulon. The 
sanitary regulations of these ports were fortified by royal edicts. 
With the appearance of yellow fever on the frontier of Catalonia in 
1821, an appalling epidemic that spread from Barcelona and killed 
25,000 people in five months, a law was passed by the French Cham- 
bers, March 5, 1822, making a uniform sanitary code for all France, 
which, with certain subsequent modifications, formed the basis of 
French maritime sanitary practice. 

Quarantine in the different continental European maritime countries 
during the eighteenth century was practically on a uniform basis, and 
during the first halt of the succeeding century quarantine was prac- 
ticed on the same lines in all European countries engaged in Eastern, 
American, and African trade, England excepted. . 

The international sanitary conferences at Paris in 1851 and 1852, in 
which participated the different European powers having interests in 
the Mediterranean, marked the close of the old régime of quarantine. 


25 


Delegates were present from Frange, Austria, the two Sicilies, Spain, 
the Roman States, Greece, Portugal, and Turkey. ‘England was not 
signatory. Regulations were adopted much less restrictive than former 
ones, it being admitted that the efficacy of many measures formerly 
practiced was doubtful or negative, science having proclaimed that, for 
the most part, pestilential maladies are not contagious. This surpris- 
ing declaration was followed by a revolution in quarantine methods on 
the Continent and resulted in the general adoption of practices based 
on the limited communicability of epidemic diseases. These changes, 
with which the early history of quarantine closes, were brought into 
effect at the beginning of the new era, during which the doctrine of 
specific living causes of epidemic diseases have been built up on the 
substantial basis of experimental medicine. 


ACKNOWLEDGMENTS. 


For assistance in collecting data for the early history of quarantine, 
acknowledgments are due to Dr. Enrico Buonocore, of Naples, and 
to the librarians of the public libraries of Naples and Palermo. 


BIBLIOGRAPHY. 


[The whole title-page of many of the works consulted and some subtitles are given because of the 
interest attaching to the writings as documents in which the early history of quarantine is pre- 
served.] 

Historiz Ecclesiasticee Scriptores Greci. Colonize Allobrogrum. Petrus de la 
Rouviére. MVCXII. BookIII. Chap., XXVIII. Evagrii Scholastici Epipha- 
niensis et ex preefectis oriundi. Historise Ecclesiasticee. De pestilente morbo. 

Jacobi Foroliviensis, medici singularis. Expositio et questiones in primum cano- 
nem Avicenne & Venetiis, 1547. I Can: Fen: 2. Doctr. I. Chap. 8. 

Ovid. Metamorfosi. Lib: VII. 

Procopii (Cesariensis). De bello Persico. Raphzelem Volaterranum conversus. 
Rome apud Jacobum Mazochium. Romanze Academie Bibliopolam. Anno 
MDXVI. Die XXIX, mensis Februari. Triumphante Divo Leone X Ponti- 
fice Massimo. Anno ejus tertia. Lib: II. De novo genere pestilentic 
(an: 534). 

Muratori, Rerum Italicarum Scriptores. Vol. 18. Milan, 1731. The edict of Reg- 
gio d’ Emilio is found on page 82, letter D, year 1374. 

Tractatus singularis doctissimi viri Marsilii Ficini de epidemize morbo, ex italico in 
latinum versus. Cum privilegio imperial. Auguste Vindelicorum in Sigis- 
mundi Grim Medici et Marci Vuyrsung officina excusoria. Anno virgine 
partus MDX VIII. : 

Joannis Baptista Van Helmont. Ortus Medicine id est Initia Physice inaudita. 
Progressus Medicine novus. In morborum ultionem ad vitam longam: Lug- 
duni. Sumptibus Joannis Baptistee Devenet. In Vico Mercatorio. Sub signo 
Crucis aurese. 1640. Tumulus pestis. 

Honorati Fabri, 8. J. Tractus duo. Quorum prior est de Plantis et de generatione 
animalium. Posterior de Homine. Parisiis. Apud Franciscum Muget, Regio 
ac Illustriss: Archiepiscopi Parisiensis Typographum, ad insigne Adorationis 
trium Regum. 1666. Cum privilegio et permissu. De Homine. Liber VI. 
Propositio XII. Page 38. Explicantur ea que pertinent ad febres. 


26 


Ioannis Fernellii, Ambiani. De abditis rerum causis. Libri duo postremo ab ipso 
auctore recogniti, compluribusque in locis aucti, ad Henricum Francise Christ- 
ianissimum. Lagduni, apud Bartholomeeum Vincentium. 1605. 

Hieronymi Fracastorii. De contagionibus et contagiosis morbi, et eorum cura. Libri 
tres. Ad Alexandrum Farnesium Cardinalem Amplissimum. 

Ioannis Francisci a Ripa, papiensis. Comentaria ad jus canonicum. Item Tractus 
de Peste et Responsa: summo studio et labore, collatis manuscriptis exemplaribus 
&. Augustae Taurinorum. Apud haeredes Nicolai Bevilaquae. 1574. 

Nicolai Massa, Veneti, Artium et Medicinae Doctoris. Liber de febri pestilentiali, 
ac de Pestichiis, Morbillis, Variolis et Apostematibus pestilentialibus, aeorumdem 
curatione, necnon de modo quo corpora a peste praeserveri debeant. Opus sane 
utilissimum, cui nuperrime auctor tum pleraque alia, tum praecipue doctrinam 
addidit de rebus quae pestilentem contagionem suscipere, vel non suscipere 
possint &  Venetiis, apud Andream Arrivabenum. Adsignum Putei. 1556. 

Ad Instructiones Urbanas et Regias pro custodia pestis. Brevis apparatus, praefectis 
sanitatis non inutilis. Auctore Petro Follerio, I. C. Ad admodum Illustrem D. 
Regentem Salazar, Praefectissimum sanitatis. Romae, apud baeredes Antonii 
Bladii impressores camerales. 1577. Cum licentia superiorum. 

Hieronymi Mercurialis Poroliviensis, medici praeclarissimi. De pestilentia. Lec- 
tiones habitae Patavii, 1577, mense Januarii. In quibus de peste in universum, 
praesertim vero de Veneta et Patavina, singulari erudictione tractatur &. 
Patavii, apud Paulum Meietum. 1560. 

Francisci Alphani, philosophi ac medici Academiae Salernitanae. Opus de Peste, 
Febre pestilenti et Febri maligna, nec non de variolis et morbillis, quatenus 
nondum pestilentes sunt. Neapolis, apud Horatium Salvianum. 1577. 

Danielis Sennerti uratislaviensis, Doctoris et Medicinae Professoris in Accademia 
Vittembergensi. Operum in Quinque Tomos Divisorum. Lugduni, sumptibus 
Joannis Antonii Huguetan et Marci Antonii Ravaud. MDCLXVI. _Institu- 
tionum Medicinae. Liber II. Pars II. De causis morborum. Caput XII. 
De causis morborum tortius substantiae. Vol. I. ; 

Archivio Storico Italiano. 1844. 

Statuta Civitatis Urbini. Impressa Pisauri per Bartholomaeum Caesanum. Anno 
Incarnationis Domini nostri Jesu Christi 1559. 

Opera Ambrosii Parei. Regis Primarii et Parisiensis chirurgi, a docto viro plerisque 
locis recognita, et Latinatate donata. Jacobi Guillemeau, Kegii et Parisiensis 
chirurgi labore et diligentia. Ad clarissimum virum Marcum Mironem, Regis 
Archiatrum dignissimum. Parisis apud Jacobum Du Puys, sub signo Samari- 
tanae, MDLXXXII. De Peste. Liber Vigesimusprimus. 

Informatione del Pestifero et Contagioso morbo. I quale affligge et have afflitto 
questa cittd di Palermo, et molte altre cittA e Terre, di questo Regno di Sicilia, 
nell Anno 1575 et 1576. Data allo invittissimo et Potentissimo Re Filippo Re di 
Spagna & Col regimento preservativo et curativo. Da Giovan Filippo Ingrassia, 
Protofisico per Sua Maesta in Questo Regno. Cum privilegiodecennium. __ 

Alexandri Massariae, Vicentini, Antiq: et celebri gymnasii Patavini Doctoris primarii 
Opera Medica & Lugduni, Sumptibus Joannis Amati Candy. 1534. 

Bando et Comandamento da parte dello Illustrissimo & Eccellentissimo Sig. D. Carlo 
d’Aragona, Principe di Castelvetrano, Duca di Terra Nuova & Luogotenente & 


Capitan Generale per Sua Maesta in questo Regno di Sicilia. Promulgated in 
Palermo, November 28, 1575. 


Istorie di Matteo Villani, cittadino fiorentino, che continua cuella di Gi 
fratello. In Firenze nella stamperia de’Giunti, 1581. 


Thucydides. De bello Peloponnesiaco. Translation in Italian by Peyron. Turin, 
1861. 


ovanni suo 


27 


Grand Dictionnaire Universe du XIXme Siécle, par Pierre Larousse. Encyclope- 
dia Brittanica. 

J. Freind. Histoire de la Medicine dupuis Calien jusq’ au 16me Siécle. Trad. de 
l Anglais par Etienne Coulet, A. Leide, J. A. Langerak, 1727. 

Joannis Astruc. De morbis Venereis & Venetiis. 1740. Vol. I. Lib. I. Cap. 15. 

La Grande Encyclopedie. Vol. 27me. Police sanitaire. Quarantaines. 

Dictionnaire des Science Médicales. Par une Société de Médecins et de Chirurgiens. 
Paris. C. L. F. Panckoucke. Edit. 1818. 

Gauthier, L. R. A. Recherches historique sur l’exercise de la médicine dans les 
temples chez les peuples de l’antiquité. Paris. 1844. 

Ferdinando Gregorovius. Storia della Citta di Roma nel medio evo dal Secolo V al 
XVI. Prima traduzione Italiana sulla secunda edizione Tedesca dell’ Avv. 
Renato Manzato. Venezia, 1875. 

Loffredo, Savino. Storia della citta di Barletta. Napoli, 1895. 

Delle Instituzione di Sanita Marittima del Bacino-del Mediterraneo. Studio Com- 
parativo di Giovanni Bussolin, Birettore dell’ I. R. Lazzaretto Marittimo in 
Valle San Bartolomeo, Segretario di Governo. Edito dall’ I. R. Governo Marit- 
timo. Trieste, 1881. 


O 


YELLOW VEVER INSTITUTE, BULLETIN No. 14. 
_ Tradiy Department, U. 8. Public Health ‘and Marine. Hospital Service. 
. WALTER WYMAN; "Surgeon General, 


get 


REPORT 


“WORKING PARTY No. 2, 


¥ 


YELLOW FEVER INSTITUTE. 


EXPERIMENTAL STUDIES IN YELLOW FEVER AND MALARIA 
. ‘AT VERA CRUZ, MEXICO. 


BY b> 


M. J. ROSENAU, “Passmp ASSISTANT: ‘hrataea. ‘= 

HERMAN B. PARKER, Passep Assistant SURGEON, 

EDWARD FRANCIS, Assisranr SURGEON. © o 
. GEORGE E. BEYER, Acrine ASSISTANT SURGEON. 


MAY, 1904. 


™~ 


WASHINGTON: | 
“GovERNAEENT PRINTING ‘OFFICE. 
ae 1905. 


fg ia 


YELLOW FEVER INSTITUTE, BULLETIN No. 14. 
Treasury Department, U. S. Public Health and Marine-Hospital Service. 
WALTER WYMAN, Surgeon- General. 


REPORT 


OF 


io WORKING PARTY NO. 2, 


YELLOW FEVER INSTITUTE. 


EXPERIMENTAL STUDIES IN YELLOW FEVER AND MALARIA 
AT VERA CRUZ, MEXICO. 


BY 


M. J. ROSENAU, Passep Assistant SURGEON. 
HERMAN B. PARKER, Passep Assistant SURGEON, 
EDWARD FRANCIS, Assistant SURGEON. 
GEORGE E, BEYER, Active Assistant SURGEON, 


MAY, 1904. 


WASHINGTON: 
GOVERNMENT PRINTING OFFICE. 
1905. 


CONTENTS. 


eface and acknowledgments -____..____.----2 22-2222 enn eee eee 
\e cause of yellow fever......:......-----.---.-- ideesereustaniy aya mmeceeeeeee 


Resulting from mosquito bites (Table 1).._._..__-...-.-.--.------- eee 
Resulting from blood inoculations (Table 2)_.........-.-..----------- 
ie filtration of yellow fever blood._._...___..-..---. 2-2-2 -2 eee ee eee 
Yellow fever produced by the bites of mosquitoes _...__......-. 1 --.-- 
Yellow fever produced by the inoculation of blood serum ___.________- 
marks on filtration experiments with yellow fever blood..........-_-_-. 
sting of filters with objects of ‘‘ ultramicroscopic ”’ size -___.._.-.-_----- 
.e filtration of certain virtises_.____...-.---.---------------- 22 eee 
MITES! 6 Seen toposes ee eee ease sa eaeeee as eae e uae eee ees 
.e filtration of malarial blood___ ._._-.-.-.---.-------------------+-----. 
Estivo-autumnal fever -_-__..-_.---.- Be ae spac tala dear oe tats 


Longevity 3:5 25.8 seee seek cess ee ee oe ee ete 
OVIPOSItING 2555. sah cscs Becers az kdemaeece eee se ee ener 
Size" Of SCYCONING =. adc ds ose tess csce ghowisnease ase cas seegasiiedeses 
sinf6CtiOn. 6XPeTIMCNts = a..co scence semecadamaraensen dene sesesmecciaeeece 
mmary and conclusions--..--..------------------------------ eae oe 


LIST OF ILLUSTRATIONS. 


Puater 1. Wild yeasts in pure culture. __.__..._..- 2-22-22 e ee eee eetaesee 
2. Character of the malarial parasites in the blood of Filomena Mar- 

tinez at the time it was filtered __.-....._...------------------ 

3. Character of the malarial parasites in the blood of Andres Mendez 

at the time it was filtered.............-...------------- ---+--- 


FiaurE 1. Rosenau’s spreader for making blood smears --__-.-.-.-.-------- : 


2. The arrangement used for filtering through a Pasteur-Chamber- 

laid DOUBIEZB 2 accgcceo set isc once ccceer sree tceemeseaicee sees 

8. Showing the method of filtering through a Berkefeld filter by 

means of a hand vacuum pump .----- .-.--------------------- 

4. Showing screen containing 16 strands or 15 meshes to the inch. 

Allows male and female stegomyia fasciata to pass. -.-------- 

5. Showing screen containing 20 strands or 19 meshes to the inch, 
through which stegomyia fasciata can not pass -.---------.-- 

TEMPERATURE CHARTS OF— 

Mar COS O00 2 tatters nr pep retype ae arene ted RS 


German Ramos -__-_..-_-._.-._- 2 Bot ee Oe a acess asic earl edie pag 
Guadalupe Gomez --_--...-222 00 ee eee eee eee 
Filomena Martinez _._.__...-_2 22-2 eee eee eee 
Wndres Mendez ana ce 2iscn domenenmieee asc a eminent odeion 
EALIS POLED 0 isig 5 als ciacis ecemrat nee tare eee ete dee aan 
ONOIOI CINE A = 2) sure ehcmmamecdae etait) Aes icee cine a om cinciaaiatateiee 


PREFACE AND ACKNOWLEDGMENTS. 


Working Party No. 2, Yellow Fever Institute, consisting of Passed 
sst. Surg. Herman B. Parker, Asst. Surg. Edward Francis and Act- 
z Asst. Surg. George E. Beyer, was detailed by the Surgeon- 
meral U. S. Public Health and Marine-Hospital Service, with the 
iproval of the Secretary of the Treasury, to Vera Cruz, Mexico, 
oril 27, 1903, for the purpose of making further studies upon the 
use and methods of transmission of yellow fever. 

Doctor Parker returned to Washington upon official business June 
1903, and on September 13, 1903, returned to Vera Cruz with Passed 
sst. Surg. M. J. Rosenau, Director of the Hygienic Laboratory, who 
d in the meantime been appointed chairman of the commission, 
th instructions to repeat that part of the work of Working Party 
9. 1 relating to the Mywxococcidium stegomyie. 

Professor Beyer left for New Orleans on October 4 to resume his 
tties at the Tulane University of Louisiana. 

The remaining three members of the working party continued work 
Vera Cruz until November 28, 1903, when, on account of the sub- 
lence of the yellow fever epidemic and scarcity of material, they 
turned to Washington. : 

The commission made a brief report to the Surgeon-General, signed 
r all of its members and published in the Public Health Reports 
r January 15, 1904, as follows: 


ndings of Working Party No. 1, Yellow Fever Institute, not all corroborated 
by Working Party No. 2. 


WASHINGTON, December 18, 1903." 
IRGEON-GENERAL. 
Sir: We have the honor to report that, as a result of our studies at Vera 
uz, Mexico, this summer, we have not been able to corroborate all the findings 
Working Party No. 1, Yellow Fever Institute, Public Health and Marine- 
yspital Service, having found phases of the organism described by them as 
yeococcidium stegomyie in normal mosquitoes. 
Respectfully, M. J. Rosenav, 
Chairman Working Party No. 2. 
H. B. Parker, 
EXpwarp FRANCIS, 
Gro. E. BEYER. 


The commission was now, January 18, 1904, dissolved, and its 

embers permitted to publish individually any further matter bear- 

g on the summer’s work. 

This bulletin, therefore, has been prepared by two members of the 

mmission, Doctors Rosenau and Francis, who have continued cer- 

in phases of the work, but who here wish to make full acknowledg- 
(v) 


VI 


meht of the services rendered by their colleagues. Especial mention 
should be made of the fact that the mosquitoes which fed on yellow- 
fever cases and subsequently were used to produce the initial case of 
experimental yellow fever (Marcos Cruz) were handled by Professor 
Beyer. 

Credit is also due to Professor Beyer for the scheme of experi- 
mentation which was partly carried out. This plan was published by 
him in full in the New Orleans Medical and Surgical Journal for 
May, 1904, entitled “The mouth parts and salivary glands, normal 
and otherwise, of the yellow-fever mosquito.” Professor Beyer was 
a member of Working Party No. 2 from May 5, 1903, to January 
18, 1904, and-was in charge of the laboratory at Vera Cruz from June 
8 to September 17, 1903, during the absence of Doctor Parker. 

Asst. Surg. Joseph Goldberger was associated with us throughout 
the entire summer, having been detailed to Vera Cruz to supervise the 
sanitation of vessels leaving for the United States. He helped us find 
suitable cases of yellow fever and malaria in the hospitals from which 
he infected a large collection of mosquitoes, and he also made many 
of the observations which we have embodied under “ Miscellaneous 
observations on mosquitoes.” 

The plans of the commission were laid before Governor Dehesa, of 
the State of Vera Cruz, who was always most zealous in furthering 
the scientific investigation of yellow fever, and offered us many 
facilities. 

To Mr. Alexander M. Gaw, of Jalapa, Mexico, we desire to express 
our particular appreciation of many thoughtful kindnesses and mate- 
rial assistance. 

To Dr. Eduardo Licéaga, president of the superior board of health 
of Mexico, and to his representatives in Vera Cruz, Doctors del Rio, 
Iglesias, and Garcia, we wish to express our thanks for their interest 
in the work and for many courtesies, thoughtful kindnesses, and mate- 
rial assistance, 

The United States consul, Mr. W. W. Canada, and Acting Asst. 
Surg. S. H. Hodgson, U. S. Public Health and Marine-Hospital Serv- 
ice, were always ready to assist us in every way possible. 

. Finally, we wish to express our appreciation to the Surgeon-Gen- 
eral of the Public Health and Marine-Hospital Service for his con- 
tinued interest and support which made the work possible. 
M. J. Rosenav, ; 
Passed Assistant Surgeon, Chairman. —: 
Herman B. Parker, _ 
Passed Assistant Surgeon. © 
Epwarp Francis, dl 
Assistant Surgeon. 
Gro. E. Bryer, 
Acting Assistant Surgeon. 


YELLOW FEVER INSTITUTE. 


Treasury Department, Bureau of Public Health and Marine-Hospital Service. 


WALTER WYMAN, Surgeon-General. 


BULLETIN No. 14. 


Section B.— ETIOLOGY. P, A, Surg. M. J. ROSENAU, Chairman of Section. 


EXPERIMENTAL STUDIES IN YELLOW FEVER AND 
MALARIA. 


By M. J. Rosenau, Passed Assistant, Surgeon, 
Herman B. Parker, Passed Assistant Surgeon, 
Epwarp Francis, Assistant Surgeon, 

GEoRGE E. Bryer, Acting Assistant Surgeon. 


THE CAUSE OF YELLOW FEVER. 


The cause of yellow fever is not known, but we have to consider 
the. Myxococcidium stegomyiw of Parker, Beyer, and Pothier. 
These authors described in some detail the life cycle of a supposed 
animal parasite in infected mosquitoes closely resembling coccidia. 

It was our first duty to investigate the merits of this announcement. 

We therefore first sectioned about one hundred normal mosqui- 
toes, Stegomyia and Culex, both male and female. A study of these 
slides soon convinced us that bodies resembling Myxococcidium stego- 
myiae may be found in normal mosquitoes and that for the most part 
these bodies were yeast cells in various stages of reproduction. Car- 
roll had called our attention to this in a conversation and subsequently 
discussed it in an article published in the Journal of the American 
Medical Association for November 28, 1903. 

Since then the French commission, working at Rio de Janeiro,? 
has come to the same conclusion. 


« Marchoux, Salimbeni, and Simond: La fiévre jaune; rapport de la mission 
francaise. Ann. de Inst. Pasteur, tome XVII, November, 1903. 


(49) 


EXPLANATION OF PLATE 1. 


Wild yeasts in pure culture isolated from banana at Vera Cruz, Mexico, in the 
summer of 1903. Stained with hematoxylin and eosin. 

All the specimens show deeply stained granules. 

1. Shows the lemon-shaped budding forms of Saccharomyces apiculatus. 

2 and 4. Other budding forms. 

3. Well marked granules. 

5. Ovoid forms with granules. 

6. Filamentous yeast. 


J 


Plate 1. 


WILD YEAST IN PURE CULTURE ISOLATED FROM BANANA AT VERA CRUZ, MEXICO, 
IN THE SUMMER OF 1903. STAINED WITH HEMATOXYLIN AND EOSIN. 
ALL THE SPECIMENS SHOW DEEPLY STAINED GRANULES. 


51 


shaudinn? considers yeasts as normal commensals of all mosquitoes 
believes they play an important part in the physiology of the 
ct, generating the gas that is almost always found in the eso- 
zeal diverticulum and also producing an enzyme or other irritat- 
substance which, when injected under the skin of man, causes the 
immation resulting from mosquito bites. Schaudinn considers 
e yeast cells to play a very important part in the economy of the 
ct and believes them to be hereditarily passed from the adult 
ugh the egg to the larve and pupe. 
osquitoes fed upon fruits have many more yeast cells in their 
es than those fed upon blood or other material. This we were 
to confirm. We also fed mosquitoes upon pure cultures of 
| yeasts growing upon banana, and found that the insects fed on 
1 a fermenting diet would soon be so swelled up with gas that 
r bodies looked like transparent air bubbles. Insects so fed do 
t badly and it is difficult to keep them alive over a week in trop- 
temperatures. 
ome of these wild yeasts are very interesting; one in particular— 
Saccharomyces apiculatus, which is found widely spread through- 
nature especially on fruit. This particular yeast assumes at times 
racteristic spindle or lemon shapes, with a bud at the pointed 
, somewhat resembling one of the conjugating forms of protozoan 
inisms with which it has been confused. 
7e were enabled to isolate this yeast in pure culture from the 
anas at Vera Cruz only after some difficulty. The ordinary plate 
hods failed because the other saccharoniyces overgrew the small 
nies of S. apiculatus. The following expedient finally succeeded : 
overripe and fermenting piece of banana containing the mor- 
logic forms desired is planted into orange juice. This culture 
ium was made by simply squeezing the. oranges, taking care not 
et any of the oil of the peel, then filtering until clear, and steriliz- 
by heat in test tubes. As the Saccharomyces apiculatus is a bot- 
yeast, the growth which appears ¢ at the bottom of the test tube in 
lve to eighteen hours is examined under the microscope and, if the 
ser forms are found, transferred to another tube containing 
= juice. This is repeated until a number of subcultures are 
le, and as the Saccharomyces apiculatus grows better in the orange 
e than the other yeasts, the latter are quickly left behind until 
ire culture is obtained. 
Te have noted in stained preparations of these wild yeasts that 
+ sometimes show red chromatin (?) granules in a blue protoplasm 


schaudinn, Fritz 1904, Generations- und W: irtswechsel bei Trypanosoma und 
ochaete (vorliufige Mitteilung.). Arb. a. d. k. ee Berl., 4°. 


13046—05 m——2 


52 


when stained with polychrome methylene blue, such as Goldhorn’s. 
We call atention to this, for isolated yeast bodies of this character 
stained thus might lead to errors of interpretation. 


THE BLOOD IN YELLOW FEVER. 


We are fully justified in concluding that in the blood of yellow- 
fever cases there is a living entity floating free in the plasma and 
capable of reproducing the ‘disease. The positive results obtained in 
the filtration and inoculation experiments done by Reed and Carroll, 
corroborated by the French commission and ourselves, is sufficient 
proof of that statement. 

We carefully examined many blood smears stained with poly- 
chrome methylene blue of Wright and Goldhorn, and failed to see the 
presence of any body which could be considered to stand in any causal 
relation to the disease. 

The smears were taken from 17 cases at periods of five hours to six 
days after the onset of the disease. In every case blood was taken 
within the first three days of sickness. In several cases the blood was 
taken daily or on alternate days. The corpuscles and plasma were 
carefully searched. The red cells often showed minute blue bodies, 
usually round and sometimes slightly irregular, which resemble those 
ascribed to cell degeneration or nuclear rests in anemia. 

The mononuclear leucocytes and polymorphonuclear neutrophiles 
often showed in their protoplasm small, round, clear spaces having a 
punched-out appearance. These spaces could not be made to take up 
any one of several stains employed. They were also found in mala- 
rial and normal blood. 

In making our blood preparations we used a method devised by one 
of us (Rosenau) about four years ago, which has been in constant use 
in the Hygienic Laboratory since, and as it has proven so satisfactory 
in our hands we will describe it. The technique was suggested by the 
glass slides commonly used for this purpese. The instrument consists 
of a little glass apparatus we call the “spreader,” made by simply 
welding two pieces of solid glass rods together, as shown in fig. 1. 
The short arm should be true, so as to lie flat when applied to the 
slide, and should be severai millimeters shorter than the width of the 
slide. A drop of blood is taken from the ear or finger tip and placed 
upon one end of the slide in the usual manner. The spreader is then 
applied to the drop, and if the glass is clean the blood will at once be 
drawn by capillary attraction across its whole length; it is then 
spread by a gentle, even stroke, without undue pressure, along the 


53 


le. Very beautiful préparations, with the corpuscles lying singly, 
: thus obtained. 


Chis little apparatus can readily be made at the blowpipe. 


Fia. 1.—Rosenau's spreader for making blood smears. 


THE PERIOD OF INCUBATION OF YELLOW FEVER. 


[he exact period of the incubation of yellow fever is a matter of 
xat importance in quarantine and public-health work. For years 
: quarantine regulations of the Marine-Hospital Service required 
letention of five days, which was considered amply safe to cover 
: period of incubation of the disease. The regulations of the Pub- 
Health and Marine-Hospital Service, promulgated August 10, 
)8, lengthened the time of observation in special cases to six days, 
sing this action upon the recent experimental work which has made 
sossible to determine the period of incubation of yellow fever with 
at exactness. 


54 


We have collected from the literature all the cases in which the 
period of incubation may be stated with precision. These are of 
course for the most part experimental cases in which the exact time 
of the mosquito bite is known, and in which the onset of the disease 
has been carefully observed. 

The disease usually begins sharply with a chill, pains, and rise of 
temperature. In such cases the precise hour of onset may be stated, 
but sometimes the attack begins vaguely or at night. Then the period 
of incubation can be stated only approximately. In the following 
table the onset of the disease is considered from the time the temper- 
ature rises, thus omitting the prodromal symptoms of lassitude, 
headache, etc, which sometimes send a patient to bed twenty-four 
hours before the fever sets in. 

Of course from a practical standpoint in public health work only 
those cases infected in a “natural” way—that is, by the bites of 
mosquitoes, can be considered. -Subjoined is a table of 40 such cases. 


TaBLE 1.—Period of incubation in yellow fever, resulting from bites of infected 
mosquitoes. 


[Carter: ‘‘The period of incubation of yellow fever,” Med. Rec., Mar. 9, 1901: also, private cor- 
respondence. Observations of the disease following one short exposure in the infected region 
at Orwood, Miss., during the epidemic of 1898.] 


Case No.— Bitten. ~ Attack. Incubation. 


WS cet preed oes mie avensay Uelnedcrcicinnen [omen emmomeainmnesawentes 3 days. 
nee 10. ; 
.| Between 3 and 4 days. 
Do. 


In these observations, which were of a clinical nature, no attempt : 
was made to determine the period of incubation within hours, any- 
thing less than one-fourth of a day being disregarded. 


[Reed, Carroll, Agramonte, and Lazear: ‘The etiology of yellow fever; a preliminary note,” 
Phila. Med. Journ., Oct. 27, 1900.] 


Case No.— Bitten. Attack. Incubation. 
6 |) eee Aug. 27,2 p.m-_-_.... Aug. 31 (?) a.m... 3 days 17-22 hours (about). 
14 (11) ----- 2-2. Aug. 31, lla. m_.__.. Sept. 6 (?) p.m._..... 6 etn (about). According to the 
. authors, 6 days 2 hours. 


55 


TaBLe 1.—Period of incubation in yellow fever, etc—Continued. 


sed, Carroll, and Agramonte: ‘The etiology of yellow fever; an additional note,” Journ. Am. 
Med. Assoc.,.Feb. 16, 1901.] 


4 ? 2 
sase No.— Bitten. Attack. Incubation. 
Gl aeree eee Dec. 5,2 p.m-_..-...- Dec. 8, 11.30 p. m 3 days 9 hours. 
(B)eusctececed Dec. 8,4 p.m _..._.-. Dec. 14,9 a,m__.._-.. 4 days 20 hours, took to bed; 5 days 
. 17 hours, onset of fever. 
Dec. 12, 9.80 p.m. __._ 3 days.11 hours (about). 
Dec. 15, noon... -| 3 days 194 hours (bed). 
t Dec. 25, noon. -...__.- 2 days 19} hours since shortest, and 
times—Dec. 21, 4 days since Jongest exposure. 


noon, and Dec. 22, 


4.30 p.m. 
(6) .---.-----| Dec. 30, ll a.m ......| Jan. 3, 10.30 a. m__...| 8 days 22} hours. 


[Reed: ‘‘ Experimental yellow fever,” Am. Med., July 6, 1901.] 


Jase No.— Bitten. Attack. Incubation. 
Jan. 19, 3.30 p.m -.... 3 days 23} hours. 
Jan. 31, 9.30 a. m_ 3 days 2} hours. 
-| Jan.6, ll a.m _- 3 days 6 hours. 
Jan.7, 2p.m-___.._... 2 days 22 hours. 


eed and Carroll: “‘ Etiology of yellow fever; a supplemental note,’’ Am. Med., Feb. 22, 1902.] 


Jase No.— Bitten. Attack. Incubation. 
(GL) eee Sept. 16, 4p. m__.....| Sept.19, 4.30 p. m_...| days 4 hour. 
(2) eocusmence Oct.9, 4p. m-_..------ Oct. 13, midnight ....| 3 days 8 hours (about). 


(Guitéras: Revista de Med. Trop., vol. 2, No. 10, 1900-1901.] 


Case No.— |° Bitten. Attack. Incubation. 
(2) p.m-.-.... 3 days 10 hours (about). 
, (2) P.M... 4 days 5 hours. 
> (7) p.m... 3 days 3 hours. 
, (2) &, TY aca, 5 days 3 hours. 
6 Ms .45p.m..| 3 days 19 hours. 
. (?7)6a.m _...| 3 days 21 hours. 
, forenoon.-_-__| 5 days 21 hours (about). 
, (7) 4.30p, m-__| 3 days. 


arker, Beyer, and Pothier: ‘“‘A study of the etiology of yellow fever,” Yellow Fever Institute, 
Bull. No. 13, March, 1903.] : 


Case No.— Bitten. Attack. Incubation. 


Sept. 4, 9.30 a,m -.--- Sept. 7, (?) a. m--.... 3 days 2 hours (about). 


hi Salimibeni, and Simond: ‘La fievre jaune,” Rapport de la Mission Francaise, Institut 
snail ; Pasteur,. Annales, November, 1903.] 


Yase No. — Bitten. Attack. Incubation. 


3 days 18 hours. 
3 days 22 hours. 
5 days 22 hours. 
7 days 5 hours. 


y i i by infected mosquitoes patient had received injections of blood from 

ae Ba ee adios immunity: B cc. blood twelve days old; followed fifteen days later 
ity eight days old. 3 

eae baal been given 20cc.serum taken on the eighth day and passed through a 

rkefeld filter; six days later 20 cc. of same serum not filtered ; subsequently bitten by infected 

»squitoes. The serum injections may have induced a partial immunity, which delayed the 

set and modified the disease, for he had a mild attack. 


56 


TaBLy 1.—Period of incubation in yellow fever, etc.—Continued. 


[Francis and Beyer.] 


Case No, — Bitten. Attack. Incubation. 
AOS acpeprerse etter Sept. 11, 9a. m.,and | Sept. 14, 3.30 p. m_...| 3 days 7 hours, or 2 days 1 hour. 
Seat. 12, 2.30 p. m. ei 


A study of the 40 cases in this table discloses the fact that yellow 
fever usually begins about three days after the mosquito bites. 

The period of incubation resulting from this natural method of 
conveying the disease is rarely under three days. We have but one 
such authentic instance, namely, two days twenty-four hours (case 
No. 24). 

The longest period observed was seven days five hours, but it must 
be noted that the man who had this unusually long period of 
incubation had previously been treated with injections of immunizing 
sera, which may have delayed the onset and modified the disease, 
for he had a mild attack. 

Leaving this case (No. 39) out of consideration, the longest period 
of incubation resulting from the bites of mosquitoes is the case (No. 
14) of Reed. Carroll, Argamonte, and Lazear, in which an incubation 
period of six days two hours was observed. This corresponds strik- 
ingly to Carter’s clinical observations in which he reports a case with 
an incubation period of five and three-fourths days. See case No. 12 
in Table 1. 

The French, commission, working in Rio de Janeiro, came to the 
concluson that the period of incubation of the disease may be much 
longer than this; but we find on analyzing their work that they drew 
their inferences largely from the disease produced by such artificial 
means as the inoculation of modified blood serum. 

One of the conclusions of this commission was that yellow fever 
may not infrequently incubate for twelve days before symptoms 
declare themselves. 

They state that “this incubation of twelve days is not absolutely 
rare. We have had occasion to see that the natural infection may 
also present an incubation equally léng.” 

With this statement we must take issue, for the long experience 
of the Public Health and Marine-Hospital Service in the many 
wars it has waged against yellow fever has amply demonstrated 
that for practical purposes five days is sufficient to cover the period 
of incubation of the great majority of cases. An analysis of all the 
cases reported in Table 1 supports this view. / 

The French Commission reports several cases in support of their 
contention. One, a young man 18 years old, who took yellow fever 
ten days after having arrived in Petropolis from Rio de Janeiro. 
Petropolis is a village free from yellow fever. Another instance 


57 


was a girl 12 years old, who was taken with yellow fever ten days 
after returning from Rio, her father having sent her to Petropolis 
because his wife and three other children had the fever. 

We do not doubt that Petropolis is “ indemne,” free of Stegomyia 
fasciata, and that the disease has never been known to spread there; 
but the communication with Rio is close, and if yellow fever cases are 
brought to’ Petropolis it is conceivable that infected mosquitoes may 
also be carried. There are many other “loopholes” which weaken 
observations of this kind, and we have therefore refrained from 
placing them in our table. 

The last case cited by the French commission is as follows: 

On board the vessel Messageries, returning to Burope, having taken passengers 


from Rio de Janeiro, an isolated case of yellow fever declared itself among the 
latter passengers between Dakar and Lisbonne; that is, nine to fourteen days. 


It was our experience that some cases of yellow fever are so mild 
that they are detected with difficulty, especially under such unfavor- 
able conditions as on board ship: ‘“ The isolated case” on board the 
Messageries may have been the second case, especially as the fourteen 
days is sufficient to cover the “ extrinsic incubation ” of the. disease. 
The literature has several instances of such cases. They should be 
carefully considered before drawing definite conclusions. 

It is interesting to compare the period of incubation resulting from 
exposure to infection in the “ natural” way with the period of incuba- 
tion resulting from experimental yellow fever, produced by the inocu- 
lation of blood or blood serum. The following table shows 17 such 
cases: 

TABLE 2.—Period. of incubation in Eien Sever, resulting from the injection of 
ood. 


(Reed, Carroll, and Agramonte: ‘‘ Experimental yellow fever,” Am. Med., July 6, 1901.] 


Case No.— Inoculated. Attack. Incubation. 
Jan. 4, lla,m-_._......| Jan. 8,9 a.,m__....... 3 days 22 hours. 
Jan. 8,9 a.m_-_- e -| 2 days 12 hours. 
Jan. 22,1 p.m__--....- » 9, M_...-.-- 1 day 19 hours. 
Jan. 25, 12.45 p. m_,-.| Jan. 28, 1.15 p. m_--... 3 days 1 hour. 


No. 1 received subcutaneously 2 cc. blood taken on second day. 

No. 2 received subcutaneously 1.5 cc. blood taken 12 hours after beginning of attack. 

No. 3 received subcutaneously 0.5 cc. blool taken on second day. : 

No. 4 received subcutaneously 1 cc. blood taken 27+ hours after commencement of disease. 


[Reed and Carroll; ‘The etiology of yellow fever; a supplemental note,” Am. Med., Feb. 22, 1902.] 


Case No.— Inoculated. Attack. Incubation. 


WB) cewensconce Oct. 15, 4p. m__.----- Oct. 20, 6 p. Me. .veoee 5 days 2 hours. 


Case 5 received subcutaneously 0.75 cc. partially defibrinated blood 15} hours old. 


58 


Taste 2.—Period of incubation in yellow fever, etc.—Continued. 


{Reed and Carroll: ‘The etiology of yellow fever; a supplemental note,” Am. Med., Feb. 22, 1902.] 


Case No.— Inoculated. : Attack. Incubation. 
GAD) ate aac cic dere Oct. 15, lla.m-..-.-- Oct. 19, 3p. m-_ 4 days 4 hours. 
ui (8 epee eens | Oct. 15, 11.05 a. m....| Oct. 19, noon... . -| 4 days 1 hour. 


Cases 6 and 7 were inoculated subcutaneously with 3 cc. of an equal volume of water and 
serum filtered through a Berkefeld filter. 


(Marchoux, Salimbeni, and Simond: “La fievre jaune,” Rapport de la mission frangaise, Insti- 
tute Pasteur, Annales, November, 1903.] 


Case No.— . Incubation. 
C16) eee DCG SOTWIMN a4 one dies ov eorseiecd oon acinncies seca cuaennnsecceictindsace ns 5 days 5 hours. 
9 6 saEsseeawem 5 cc. serum heated to55° for ten minutes; five days later, 10cc. | 12 days 12 hours. 


heated to 55° for ten minutes; seven days later, 1 cc. blood. 

This was a ‘‘remarkably benign case,” and as the man had 
been injected previously with heated yellow fever serum. 
the immunity produced probably explains the long perio 
of incubation as well as the mildness of the attack. 

MO 4 )iccinsiccsi'es- 5 cc. serum heated to 55° for twenty minutes; seven days | § days 5 hours. 
later, 10 cc. serum heated to 55° for ten minutes; eight days 
later, 1 cc. serum heated to 55° for five minutes. Then 1 cc. 
serum. . 

The same explanation for this unusually long period of incu- 
bation as above, especially as a parallel case similarly 
treated showed an immunity. 


lec. serum filtered through a chambediand F filter... 5 days 18 hours. 


12 days 18 hours. 
of si 4 days 18 hours. 
WS Oldenrercccesices wae oo ee ee 2 days 21 hours. 


[Francis and Beyer.] 


Case No.— — Inoculated. Attack. Incubation. 
15 (2)a_. ~.| Sept. 15,4 p.m___.... 17, (?) a, m_.--- “ 
16 @) b i a : ban fk hemo cs | cag ih ra iil 
DCAM GL esas eeee|ae weet rn a. an 1 day, 17 hours. 


aIntravenous injection of 1.75 cc. serum diluted with a 1 f salt solution and 
filtered through a Chamberland B filter. i echidna iciaicle ligienciccnson 


b Intravenous injection of 2.5 cc. serum diluted with an e 1 vol f salt solution and 
filtered through a Chamberland B filter. : SS eau eka ES 


eIntravenous injection of 2.5 cc. s di i i 
aes onsale fai omer Seale iluted with an equal volume of salt solution and 


It will be noted from these 17 cases that the period of incubation of 
yellow fever produced by the inoculation of blood or blood serum is 
not so constant a factor as in Table 1, in which the disease was in- 
duced by the bites of mosquitoes. 

The shortest time in this table is one day fifteen hours, and the long- 
est twelve days eighteen hours. 

Surg. H. R. Carter, Public Health and Marine-Hospital Service, 


has given special attention to this phase of the subj ect, and we are in- 
debted to him for valuable suggestions. 


THE FILTRATION OF YELLOW-FEVER BLOOD. 


Reed and Carroll (Am. Med., Feb. 22, 1902) were the first to filter 
yellow-fever blood and prove the infectiousness of the filtrate. They 
passed it through a Berkefeld filter, which on testing held back the 
Staphylococcus pyogenes aureus. 


59 


The filtrate showed no growth in bouillon, and yet when injected 
Into nonimmunes produced yellow fever. The blood from the latter 
was also shown to be capable of producing yellow fever when injected 
into a third subject. 

That the men inoculated with the filtrate suffered from yellow fever 
induced by a morphologic entity which passed the filter, and not from 
a toxemia, was shown not only by their rather long periods of incu- 
bation, but was conclusively shown by carrying their experiment to 
the third degree. 

The following experiments were planned in order to determine 
among other things whether the organism of yellow fever, as it exists 
in the blood serum, is capable of passing the pores of the Pasteur- 
Chamberland B filter: 

An investigation of the literature of the other filterable viruses 
shows that the South African horse sickness is the only one which has 
yet been reported as having passed the Chamberland B filter. 

In the filters of the Pasteur-Chamberland system those marked 
“B” are finer, more compact, with thicker walls, and consequently 
less porous than those marked F. We have been informed by 
Assistant Surgeon-General H. D. Geddings, who has recently inquired. 
about this in Paris, that only two grades—B and F—are now being 
made. 

The subjects used for our experimentation were all volunteers, non- 
immunes, and carefully selected from among the native Mexicans at 
Jalapa and the adjacent mountainous country, taken by train to Vera 
Cruz, and immediately placed within the screened wards of our hos- 
pital. All cases recovered. 

Jalapa is a town having an elevation of about 4,000 feet, where yel- 
low fever has never been known to spread and has not existed, except 
for the cases occasionally imported from the coast (tierra caliente). 

In order that the case from which we drew the blood for filtration’, 
should be one in which there was the highest degree of confidence as 
to the diagnosis of yellow fever, we decided to produce the disease 
through the bites of infected mosquitoes rather than to select a case 
by clinical evidence alone from the yellow-fever wards. 

Mosquitos which had been allowed to feed upon typical cases of 
yéllow fever in San Sebastian Hospital, Vera Cruz, were applied in 
succession to the hands of four persons whom we had selected as 
being nonimmunes. The first three failed to become infected, but 
the fourth took sick with what proved typical yellow fever. The 
histories of the three negative cases are here given in brief: 

G. M., age 22, Mexican.—On August 18 he was taken to Vera Cruz 
and placed in our screened ward. August 15, at 3.20 p. m., he was 
bitten by two mosquitoes which had fed twelve days previously, at 
9.30 a. m., on J. R., a fatal case of yellow fever. Nothing unusual 

18046—05 M——3 


60 


was noticed in the patient during the period of observation, which 
continued until August 28. 

J. O., age 18, Mexican—He was taken to Vera Cruz August 15 
and aval in the mosquito-proof ward. On August 28, at 9.30 a. m., 
he was bitten by four mosquitoes, two of which had fed sixteen days 
previously, at 4 p. m., on A. L., a fatal case of yellow fever, forty 
hours after the onset of the disease, and the other two had fed fif- 
teen days previously, at 10.30.a. m., on the same case fifty-eight hours 
after the onset of the disease. The patient remained perfectly well 
throughout the following month while under observation in the 
screened room. 

M. R., age 21, Mexican.—He was brought to Vera Cruz August 28 
and kept in the screened ward. ‘On September 1, at 6.30 p. m., he 
was bitten by two mosquitoes which had fed nineteen days before, at 
10.30 a. m., on A. L., a fatal case of yellow fever, fifty-eight hours 
after the onset of the disease. The patient continued in his usual 
health during Sepember 2 and 3. On September 4, at 2 p. m., on 
going into the ward the patient was found wrapped in his blanket 
and said he felt chilly and complained of slight temporal headache. 
There was no elevation of temperature. 

_ The next case succeeded: 


Yevtow Fever Propucep sy tHe Brres or Mosquitors. 


Marcos Cruz (case XLII), age 21, born in Perote, a mountain 
town free from yellow fever, where he has always lived. States that 
he never had fever of any kind. He was physically sound on exami- 
nation, and brought to Vera Cruz, where he was immediately placed 
in a mosquito-proof room and kept under observation for fourteen 
days, when he was bitten by 11 mosquitoes, as follows: 

On September 11, at 9 o’clock a. m., 3 mosquitoes which had fed 
fifteen days previously, at 9.30 a. m., upon Trinidad Martinez, a fatal 
case, fifty-one hours after the onset. At the same time, 3 other mos- 
quitoes, which had fed fourteen days previously, at 2.30 p. m., upon 
Hipolito Vasquez, a fatal case, sixty-nine hours after the onset of the 
disease. At 2p. m. of the same day he was bitten by 2 more mosqui- 
toes, which had fed fourteen days previously, at 2.30 p. m., on Hipo- 
lito Vasquez, sixty-nine hours after the onset.. 

The next day, September 12, at 2.30 p. m., he was bitten by 3 
mosquitoes, 2 of which had fed Abeer days pee at 2.30 p. m., 
on Hipolito Vasquez, sixty-nine hours after the onset of the disease, 
and the other had fed sixteen days previously, at 9.30 a. m., on Trini- 
dad Martinez, fifty-one hours after the onset of his disease. 

On September 12 and 13 the patient had no symptoms, and his 
temperature remained normal. 


‘ZI SOoTePL JO JUV oanyereduray, 


61 


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62 


September 14, at 4 p. m., Cruz complained of feeling chilly and 
had frontal headache. The chilly sensation lasted for several hours 
and the headache became so severe that he was given ice caps to his 
forehead for the relief of this symptom. The conjunctive became 
injected; the gums turgid and red. 

The case continued clinically with typical symptoms of yellow 
fever. 

‘On September 15, at 8 a. m., there was a slight icterus of the 
eyes; at 10 a.m. there was marked vomiting; at 7 p.m. the gums were 
very much swollen. Urine contained no albumin. 

September 16: Eyes injected and yellowish, skin jaundiced; no 
albumin. 

On September 17, the third day of the disease, albumin first 
appeared in the urine and was found daily until September 25, after 
which examination was discontinued. 

On September 15, at 8 a. m., 16 hours after the onset of the disease 
80 cc. of blood were drawn into a sterile flask by means of an aspirat- 
ing needle from the median basilic vein of his left arm. 

The flask was set aside in the lower part of the ice chest, at a tem- 
perature of from 16° to 19° C., for five hours in order to allow the 
blood to coagulate. ~ 

Thirty-five cubic centimeters of the clear serum were then drawn 
off, and to it was added an equal volume of physiological salt solu- 
tion. 

The mixture was transferred with all due precautions to the inside 
of a Pasteur-Chamberland B bougie and filtered from within out- 
ward by means of vacuum, which was applied to the outer surface 
of the filter in a reverse manner to that shown in fig. 2, omitting 
the paraffin cup. 

It required one hour to obtain 18.5 ce. of filtrate, which was used 
for the injection of three nonimmunes, Bonifacio Orea, German 
Ramos, and Guadalupe Gomez. 

Orea and Ramos each received 5 cc. of the filtrate, injected intra- 
venously into one of the veins of the arm. As the same was diluted 
with an equal volume of salt solution, each man received 2.5 cc. of 
the original blood serum. 


Gomez received 3.5 cc. of the mixture, representing 1.75 cc. of the 
original serum. 

These injections were made at 4 p. m. September 15, which was 
just eight hours after the blood had been drawn “frora Cruz, the 


blood aeving kept five hours at a temperature of 16° to 19° ©. and 
three hours at room ‘temperature. 


63 


‘ 


Yettow Fever Propucep sy tHe LNocunation or Buoop Srrum. 


Bonifacio Orea (case LXV), aged 33, single; born in the mountains 
near Puebla; said that he had never been on the coast and never had 
any sickness of any kind. He was physically sound on examination; 
blood and urine negative. 

He was brought to Vera Cruz August 28 and kept in a mosquito- 
proof room under observation for eighteen days. 


ExperimentaL Yettow Fever. 


ASE. Bontracio EA 
Cee ele “Oh INTRAVENOUS INJECTION. 


Morth\ SEPTEMBER 


Day of 
Wen th. 15 \76 77 78 19 20 2/ 22 | 23 124|25 
Qay of 
Disease’ g 2 3 4 a C6 7 1819 
a]ic} Js a8 
AM | Noe agy t>{s01 0) wis nds NN | ian IN fo 
iS ky IQ 9 iS) LIS} iS) 
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4) an 


ery 


40 LTS a8 K 


ace 


+ 
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4 TiN bd A 
: i f 
ses FAHY , 
nN K "4 
ST OREOS TH \v 
37 ca 
[) 
: im 
36 
Pulse. | See AEGORDEABUELOBGUN SIAN BW WAI 


Temperature chart of Bonifacio Orea. 


On September 15, at 4 p. m., he was given an intravenous injection 
into one of his arm veins of 5 cc. of Marcos Cruz’s diluted serum fil- 
tered through a Chamberland B bougie. As the serum had been 
diluted with an equal quantity of physiological salt solution Orea 


64 


actually received 2.5 cc. of the blood serum of Cruz. (For details of 
this filtration, see p. 62.) 

On September 16 there were no symptoms. , 

September 17, at 7 a. m., he was found with a temperature of 39.5° 
C., with marked frontal headache, pains in the loins and calves of the 
legs. His gums were slightly swollen and he had injection of the 
ocular conjunctive. The patient said that at 1 o’clock in the morning 
he felt like stretching and hada chill.. The blood showed no malarial 
parasites. Urine showed a trace of albumin. 

September 18: Eyes and body jaundiced. 

The patient made a rapid recovery after a mild but definite attack 
of yellow fever. 

German Ramos (case L), aged 22, single; has always lived in the 
mountains near Puebla. He was given a careful physical examina- 
tion August 26. Blood and urine negative. He was brought to Vera 
Cruz August 28 and immediately placed in a mosquito-proof room, 
where he was kept under observation eighteen days, when he was 
given an injection of filtered serum, as follows: 

On September 15, at 4 p. m., he was given an injection into the 
right median basilic. vein of 5 cc. of diluted serum of Marcos Cruz, 
filtered through a Pasteur-Chamberland filter B. This serum having 
been diluted with an equal volume of physiological salt solution, 
Ramos received 2.5 cc. of the serum of Cruz. (For details of this 
filtration, see the records of Marcos Cruz, page 62.) 

September 16, no change. 

September 17, at 7 a. m., his temperature was 37.8° C., and he did 
not feel at all unusual; but at 9.15 a. m. his temperature was 39.4°. 
He had frontal headache, pains in the back and calves of the legs. 
The blood was negative for malaria. 

September 18, the eyes were injected and the body jaundiced. 
Patient vomited twice. He exhibited a typical clinical picture of 
yellow fever. 

His temperature on the third day was higher than at the onset of 
the disease, which is rather unusual, and in Vera Cruz is considered 
a grave sign. It will also be noted that his febrile period, which 
lasted seven days, did not show the characteristic remission. Albu- 
min first appeared on the 21st and continued until the 25th, when 
examination was discontinued. 

Patient recovered. 

Guadalupe Gomez (case LI); born in Jalapa, aged 17, had never 
been on the coast, and-states that he never had any kind of fever. He 
was physically sound when examined; blood and urine negative. He 
was brought to Vera Cruz August 28 and placed in a mosquito-proot 
room, where he was kept under observation eighteen days. 


26 
70 


OEL 


2s 


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24 


Ww 


23 


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rd 


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INJECTION. 


al 


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INTRAVENOUS 


oy] \ 


EXPERIMENTAL YeLLow Fever. 


79 


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78 


17 


GERMAN Ramos. 


IS \76 


Case. 
Monrh. 
Day of 
Month. 
Day of 

Disease, 


A.M. 
P.M. 


Pr 


Temperature chart of German Ramos. 


Eo 


a ws 


EL 


41 
40 
39 
38 
37 
36 
False. 


66 


On September 15 at 4 p. m. he was given an injection of 3.5 cc. of 
diluted blood serum from Marcos Cruz, filtered through a Pasteur- 
Chamberland B filter. As this serum had been diluted with an, equal 
quantity of physiological salt solution, he actually receved 1.75 ce. 
of Cruz’s serum. The injection was given into one of the superficial 
veins of the arm. 

September 16, no symptoms. 


EXPERIMENTAL YELLOW Fever. 
Case. GUADALUPE Gomez. INTRAVENOUS INJECTION. 
Month (SEPTEMBER. 
oye | 15 ie] 17 18 19 20 21 | 22 | 23 |24)25 
(on 
Day of v/ 2 3 4 S 647 [819 
Disease. E Js ae J 
: ar as 
AM. Noi alas | | felole aN alas) | INS {ds IN es 
fs) iy 19 Ss 9} RAS 8 
P.M. | lel fotos WB lo: a: joy eules Qf iss} fol iS 
4\ Ke 
a 
LSS 
40_ T 1 
i Bd f = 
R re! S LS BR 
39 nN 
a nl jad 
SECT LENE Sed 
38 B 1 
J 
Bri 
az7_ He 
B | 
] Vas 
[To i bs hell 
SS 
36 J 
Pulse. bbb bb RARERS SS ass see 8 


Temperature chart of Guadalupe Gomez. 


September 17, 7 a. m., had a temperature of 38.1° C., frontal head- 
ache and pains in the back and in the calves of the legs. Says he 
first felt.chilly at 10 o’clock of the previous night Vomited yellow- 
ish fluid. No malaria, no albumin. 

September 18, no albumin, no malaria, gums swollen. Bleeding — 
from right nostril. 

September 19 and 20, urine shows albumin, but none subsequently. 

Patient made a rapid and uneventful recovery. . 


67 


REMARKS ON FILTRATION EXPERIMENTS WITH YELLOW-FEVER BLOOD. 


We have been careful to give with some minuteness all the details 
of the manner in which the blood was filtered in these experiments. 
We know that the filtration of micro-organisms or other small parti- 
cles through porcelain or diatomaceous earth is influenced very much 
by the length of time the filtration is continued, the pressure used, by 
the character of the fluid in which the particles are suspended, the 
temperature, and other factors which are perhaps less known. 

Our review of the literature on the filtration of blood and body 
juices containing the infectious material of diseases, the causes of 
which are unknown and which are believed to be ultramicroscopic, 
disclosed reports of successful and unsuccessful filtration with such 
meager details that it is difficult to draw proper conclusions. Those 
factors which control the power of a given filter to allow an organism 
to pass or to hold it back also account for the different results which 
various experimenters have obtained in certain cases. 

For instance, we succeeded in passing diluted yellow-fever serum 
through the closest-grained Pasteur-Chamberland B filter that we 
could obtain, whereas the French commission—Marchoux, Salinibeni, 
and Simond—working at Rio de Janeiro, failed to pass the infective 
agent of yellow fever through a Chamberland B filter, though they 
found that it did pass through the Chamberland F filter, As the 
French commission used undiluted blood and we used diluted serum, 
the apparent discrepancy in results is accounted for; for it is a well- 
known fact that particles suspended in an albuminous medium filter 
with more difficulty than particles suspended in water, alcohol, or 
other limpid menstra of this character. 

Nocard, Roux, and Dujardin-Beaumetz, in 1899, endeavored to 
repeat Liffler’s experiment with aphthous fever. They first failed to 
pass the infective agent contained in the lymph of this disease through 
a Berkefeld filter because they used an albuminous fluid, viz, “ Mar- 
tin’s serum-bouillon,” in order to dilute the lymph with a nutrient 
medium, thus hoping to obtain cultures without the danger of con- 
tamination in the filtrate. They found, however, that the albuminous 
matter contained in the diluting fluid clogged the pores of the filter, 
so that the filtrate was not virulent. 

They repeated the experiment, using water to dilute the lymph in 
the proportion of 1 to 50, when they found the organisms causing 
aphthous fever readily passed through a Berkefeld filter, and gave the 
disease.by intravenous injection to young and old cattle. 

It is also a well-known fact that filters which successfully hold 
back certain bacteria will permit them to pass if the filtration is con- 


13046—05 m——_4 


68 


tinued long enough. In this case the organisms are believed to grow 
through the pores of the filter. 

It is also evident that the passage of small particles through the 
pores of a filter depends directly upon the pressure used, and in all 
filtration experiments the exact pressure, whether positive or negative, 
should be stated. 

It is further necessary to call attention to the very great discrep- 
ancy in filters. We have made a careful study of various filters found 
upon the market and find that there is no satisfactory method by 
which they can be accurately graded, although we find in certain 
makes an attempt to graduate the power of the filter. Filters of 
course should always be tested under water with air pressure for pin 
holes and cracks, and also with small bacteria for permeability. It is 
‘only in this way that we may determine approximately what a par- 
ticular filter is capable of doing. 

The Berkefeld filters, made of diatomaceous earth, are more porous 
and variable than the Pasteur-Chamberland bougies, made of 
unglazed porcelain, which have finer pores and are more constant in 
their ability to filter micro-organisms. 

After filters have been tested they must be dried and sterilized with 
the greatest care in order to prevent cracking, and should always be 
tested for porosity with microbes after filtration in order to insure 
this point. 

We have found in testing various filters that the weakest part is apt 
to be the joint, and that in any mechanical arrangement of the filter 
and flask there is the greatest danger of contamination and untrust- 
worthy results if either the liquid that is being filtered or any other 
fluid comes in contact with a joint. 

It will be noted that in the arrangement which we had for filtration 
by pressure (fig. 2), the fluid was simply passed into the Pasteur- 
Chamberland candle and withdrawn by means of a pipette in such a 
manner that contact between the two fluids was eliminated, and that 
no dependence was placed upon the security of any joints except those 
necessary to retain the air pressure. In the case of the small Berke- 
feld filter (fig. 3), in which the filtration was done by the pressure 
of the atmosphere produced by a vacuum, the joint between the filter- 
ing candle and the metal top was kept well out of the liquid, so that 
here again was avoided the possibility of error from this source’ 


TESTING OF FILTERS WITH OBJECTS OF “ULTRAMIOROSOOPIO” SIZE. 


Four filters of the Pasteur-Chamberland system, letter B, were 
tested to determine whether they would allow particles of micro- 
scopic size to pass into the filtrate. 


At the outset we were confronted with the difficulty of finding a 


69 


. Substance suitable for such a purpose. The substance should be in 
a very fine state of division, composed of particles grading gradually 
in size from the ultramicroscopic to those of definite microscopic size 
The substance should be insoluble in the menstrum, so that a particle 
recognized in the filtrate would not represent a precipitate formed 
after passing the filter. 

We finally selected carbon on account of its insolubility, the very 
fine state of division into which it can be ‘brought, and the ease 
with which the small particles may be recognized because of their 
black color and violent Brownian movement. 

To 60 ce. of distilled water we added 40 drops of Higgins’s Amer- 
ican india ink, bought on the market, and this suspension was placed 
into each of the four Chamberland B filters and drawn through the 
walls from within outward by a vaccuum in a reverse manner to fig. 2. 
The first water to come through was pale, but gradually it became 
slightly brown and later the surface of the filter took on a distinctly 
dark color. About one and a quarter hours was required for the 
60 cc. to pass through each filter. 

The filtrates of the four filters were examined with Zeiss micro- 
scopes, using objectives of 1.5 and 2 mm. and oculars 4 to 12, and there 
was not the slightest difficulty to see in the hanging drops small parti- 
cles of carbon in active Brownian movement. Dried specimens of 
the filtrate showed small particles plainly visible. 

These filters were new and were tested under pressure beneath the 
surface of water and found free from cracks and pin holes. Before 
testing with the india ink they were washed with distilled water, 
about 200 cc. being put through each one. 

The filters first became black in disseminated points on the surface. 
The black areas were of irregular shape, having a diameter of one- 
eighth to one-fourth inch. As the filtration continued these areas 
became larger. At the end of the filtration the filter had a distinctly 
mottled appearance, showing streaks of white, small circumscribed 
areas of deep black, and larger areas less deeply stained. That these 
areas of black are carbon may be demonstrated by burning them in 
the flame. 

This shows a lack of uniformity in the structure of each individual 
filter, which only confirms what may be seen after breaking a filter 
into pieces. At places air spaces may be seen which may extend 
through almost the entire thickness of the wall, thus reducing the real 
thickness of the filter to a mere shell. 

Two new Berkefeld filters, 24 by % inches, were tested with the 
dilute ink solution. Neither pressure nor vacuum was used. The 
filtrate came in drops in rapid succession and was as black as the test 
fluid and showed the particles of carbon under the microscope. 


70 


These same filters were tested with a bouillon culture of Staphylo- 
coccus pyogenes aureus in a reverse manner to fig. 2. From three to 
four hours were taken in passing 150 cc. of the bouillon culture 
through ‘each filter. The filtrates remained sterile after twelve days 
in the incubator. 

The Berkefeld filters were rigged with the glass cylinders which 
come with them and a vacuum was used. About four hours were 
required to run 150 cc. of the bouillon culture through each filter. 


THE FILTRATION OF CERTAIN VIRUSES. 


Peripneumonia of cattle, rinderpest, foot-and-mouth disease, South 
African horse sickness, exudative typhus of chickens, mosaic disease 
of the tobacco leaf, yellow fever, epithelioma contagiosum of fowls, 
hydrophobia, clavelee, and hog cholera have each been shown to be 
due to a virus which passes the pores of certain porcelain and diato- 
maceous filters which hold back the ordinary bacteria. 

With the exception of peripneumonia we know nothing of the 
character of the infective agent in these filtrates, which by direct 
microscopic examination and by cultural methods have yielded no 
morphological entity. . 

The outlook for finding in the body fluids, the specific cause of any 
one of these diseases, by the microscopes in present use is encouraging 
as long as we can say that we have a filter which will not allow the 
virus of the disease to pass, but which does allow the particles of 
some test substance to be plainly seen in the filtrate. 

It is far more important to know what particular filter a certain 
virus can not pass through than it is to know what brands of filter 
it does pass through. Given a filter that will not permit the virus 
of a disease to pass through its pores, and if on testing that filter 
we find that we can put through it visible particles of some test sub- 
stance, there is plenty of hope that the infective agent of that virus 
may be visible with our present oil-immersion systems. 

On the other hand, if we can find a filter which will not transmit 
particles of microscopic size and yet will allow the virus of a certain 
disease to pass into the filtrate, we can not expect to see the individual 
entities in the virus. 

Several factors influence the filterability of a virus, namely, the 
kind of filter used, the character of the menstruum in which the 
virus is suspended, the degree of pressure or vacuum used, the amount 
of time allowed to the process, the temperature, the motility of the 
particles, and other factors. Unfortunately, in the study of the 


literature of the various filterable viruses we sometimes fail to find 
exact data on all these points. 


71 


_Peripneumonia.—Peripneumonia * of cattle is the only filterable 
virus which has so far given a visible growth on artificial media. 
Collodion sacs were filled with Martin’s peptone bouillon, to which 
was added a little serum of the rabbit or cow in the proportion of 1:20. 
The’ sac was then inoculated with peripneumonia and placed in the 
peritoneal cavity of rabbits and cows for fifteen to twenty days. 
The fluid became turbid and in it, under a magnification of 2,000 
diameters, could be seen the most extremely small, moving, strongly 
refractile points. In a series of subcultures made from such a growth 
the last of the series was virulent. 

The colonies on agar mixed with bouillon-serum, were transpar- 
ent, small, and made up of exceedingly fine particles whose form it 
was impossible to determine. The microbe of this disease was made 
to pass the Berkefeld and Chamberland F filters, but when an 
albuminous diluting liquid was used, it could not be made to pass 
either.? 


Foot-and-mouth disease—Loeffler and Frosch state that lymph 
was taken from the blebs of calves suffering with this affection, 
diluted with 35 parts of water, and then passed through a filter 
candle. The filtrate, in amounts which correspond to one-tenth to 
one-fortieth cuhic centimeter of the original lymph, when injected 
into calves caused them to sicken in two days, the same as the con- 
trol animals into which were injected equal amounts of unfiltered 
fluid. 

McFadyean says that foot-and-mouth disease passes the Berkefeld 
filter when in watery suspension, but is arrested when in an albumi- 
nous fluid. 

Nocard ¢ says that aphthous fever passes through Berkefield, Cham- 


berland, and Kitasato filters. 


South African horse sickness——Nocard* succeeded in passing the 
virus of this disease through a Berkefeld filter only. 

McFadyean © reports that pure blood taken from an animal sick 
with the disease was passed through the Berkefeld filter under a 
pressure of 26 inches of mercury and the filtrate, when inoculated 
into a horse, produced the disease. — . 

When the blood serum was diluted with four parts of water and 


@Nocard, Roux, Borrel, Salimbeni et Dujardin-Beaumetz: Le microbe de la 
peripneumonie. Ann. de l’Inst. Pasteur, vol. 12, 1898, p. 240, ete. 

+ Nocard, Roux, and Dujardin-Beaumetz: Etudes sur la peripneumonie. Re- 
cuil de med. vet., 1899, 8e. serie, Oct. 26, 1899, p. 441. 

eLoeffier and Frosch: Bericht der kommission zur erforschung der maul 
und klauenseucHe bei dem Inst. f. Infek.-krank. in Berlin. Centbl. f. bakt. 
u. infek., 1898, bd. 23. 

@Nocard: La ‘horse sickness” ou “ maladie des chevaux de ]’Afrique du 
Sud. Bull. de le soc. centr. de med. vet., n. s., vol. 19, 1901, p. 37. 

éJourn. comp. path. and therap., 1900, XIII. . 


72 


filtered through a Chamberland B filter for two hours under a pres- 
sure of 29 inches of mercury, the filtrate was infective to a horse 
into which it was injected. After an incubation of three days and 
a clinical course of six days the horse died. 

Exudative typhus of chickens—Magiora and Valenti? made 
experiments with the emulsions of the blood, lungs, liver, spleen, 
kidneys, and heart. They used the Berkefeld filter and Chamberland 
F. Dilutions were made with 40 and 60 parts of physiological salt 

-solution and a pressure of 14 atmospheres was employed. 

Bacteriological examination of the filtrate proved negative, but 
chickens injected with 5 cc. of the filtrate died in about two days, 
presenting the same clinical and pathological picture as the naturally 
infected ones. 

Another set of chickens injected with the blood of the ones which 
had received the filtrate developed typical symptoms and post-mortem 
changes of the disease. 

An exposure of five minutes at 65° C. sterilizes the virus. 

These investigators found that the filtrates had very much less 
virulence than the unaltered blood. Four cubic centimeters were 
found to represent the minimum fatal dose of a filtrate from a mix- 
ture of blood and water in the proportion of 1: 160, whereas 4 cc. 
represented the minimum fatal dose of an unfiltered mixture of 
blood and water in the proportion of 1: 1,500,000. 

It is interesting to note how the filtration experiments cleared up 
an error which former students had made in regard to the loss of vir- 
ulence in pure cultures of organisms which they had isolated in this 
disease. They had found a cocco bacillus in the internal organs. The 
culture tubes inoculated from the body fluids showed growths of this 
organism. Inoculations into chickens from colonies on the first set 
of cultures caused the disease, but subcultures from the first set of 
cultures were not virulent. Into the first set of cultures there had 
evidently been carried some of the invisible virus along with the 
cocco bacillus. 


Mosaic disease of the tobacco leaf—Beijerinck® pressed the sap 
out of diseased plants and passed it through very thick porcelain 
filters, and the filtrate was free from bacteria, but virulent for the 
tobacco leaf. 


LE pithelioma contagiosum of fowls—It was found by Marx and 
Sticker ¢ that the infective agent suspended in sodium chlorid solution 
passed through a Berkefeld filter, but not through a porcelain filter. 
The filtrate gave no growth on media; it was carried through a series 


4 Magiora and Valenti: Ueber eine seuche von exsudativen typhus bei hiihnern. 
Zeit. fiir hyg. und infekkr., vol. 42, 1903, p. 198. 

> Centrbl. ftir bakt., Abt. 2. bd. 5. 1899. p. 27. 

¢ Deut. med. wochenschr., bd. 28, 1902, p. $92. 


73 


of 16 generations in fowls; it resisted 60° C. for three hours, and 
after one hour in a vacuum tube at 100° C. it was virulent. 


Hydrophobia.—Remlinger and Riffat-Bey « ground up a rabbit’s 
brain in water together with a bouillon culture of chicken cholera 
and filtered it by aspiration through a Berkefeld V filter. The fil- 
trate inoculated into rabbits caused rabies. 

Celli and de Blasi ® ground the brain and spinal cord in sand under 
300 atmospheres pressure. A suspension in distilled water, when sub- 
jected to a small Berkefeld filter under a vaccuum of 570 mm. for 
half an hour, gave an infective filtrate. 

Remlinger (Ann. de I’Institut Pasteur, v. 17, No. 12, 1903, p. 834) 
confirmed his earlier work with Riffat-Bey mentioned above. He 
showed that the virus of hydrophobia can not be made: to pass 
through a Chamberland filter nor through a Berkefeld N or W. 
It can only be forced through a Berkefeld V, which filter is the most 
porous of the Berkefeld system. 


Hog cholera —De Schweinitz,’ in a preliminary note, mentions a 
disease peculiar to hogs, indistinguishable clinically and at post- 
mortem from hog cholera, but which can be transferred from hog to 
hog by inoculation with certain body fluids which have been rendered 
free from bacteria by filtration through the finest porcelain filters. 
This filtrate was shown to contain no organisms of hog cholera or 
swine plague, because when inoculated into rabbits and guinea pigs 
the animals remained healthy. 

Rinderpest-—Nicolle and Adil-Bey passed the virus of this dis- 
ease through a Berkefeld filter, but not through a Chamberland F. 


Clavelee (sheep pox).—Borrel ¢ filtered a suspension of the pus- 
tules in water. The filtrate from the Berkefeld filter was infective, 
but that from the Chamberland F was not. 


Nonjilterability of vaccine and smallpox.—Parke ‘ crushed vaccine 
virus with fine sand, using 25 tons of pressure to the square inch. 
One portion of the suspension of crushed virus was passed through a 
Berkefeld filter and another portion through a Chamberland filter. 
Both filtrates were evaporated over sulphuric acid in a vacuum. 

Calves and rabbits inoculated with the filtrate before and after 


@Remlinger and Riffat-Bey: Le virus rabique traverse la bougie Berkefeld. 
Compt. rend. heb. des Sec. de la Soc. de Biol., vol. 55, 1903, p. 730. 

b Deut. med. wochenschr., vol. 29, p. 945. 

eU. S. Dept. of Agriculture, Bur. Animal Industry, Circular No, 41, Sept., 1903. 

4 Nicolle et Adil-Bey: Htudes sur ia peste bovine. Ann. de I’Inst. Pasteur, 
vol. 16, 1902, p. 56. 

eBorrel: Experience sur la filtration du virus claveleux. Compt. rend., Soc. 
de Biol., vol. 54, 1902. 

f Assn. Am. Physicians: Trans., vol. 17, 1902. 


74 


evaporation ‘failed to show any reaction. Control animals inoculated 
with the crushed material before filtration always had successful 
vaccinations. The object of the crushing was to liberate the organ- 
‘isms from epithelial cells or other tissues which might retain them. 
Smallpox virus from three fatal cases failed after crushing to 
pass into the filtrate, as determined by the inoculation of monkeys. 


Filterable bacteria.—Von Esmarch * sought to determine whether 
there are such things as ultramicroscopic organisms among the 
saprophytes. i 

We readily believe that the virus of a filterable infectious disease 
is made of very small organisms, possibly ultramicroscopic, and that 
if these organisms could be made to multiply the resulting mass 
would have an appreciable size. If there are ultramicroscopic sapro- 
phytes he thought that all conditions were in the highest degree 
favorable for their multiplication, and that on the ordinary labora- 
tory media they ought to find their most suitable conditions of 
growth and give an appreciable evidence of their existence. 

He used 40 different kinds of fluids, including sewage, rich vege- 
table infusions, decomposing urine, emulsions of sputum, cavaders, 
and feces. The clear filtrates from these suspensions were planted 
on all the laboratory media and these plants kept under different 
conditions showed no growth. 

During the first week’s observations of the original filtrate no 
growth was noted; but after ten days this fluid showed a turbidity 
which was due to a very fine motile organism (Spirillum parvum), 
which grew as vibrios and spirilla, which were recognized only 
by the greatest magnification. It passed the Berkefeld, Chamber- 
land F, Reischel, and Pukall filters and appeared in the first 200-300 
cc. of filtrates. No other bacteria were found in the filtrates. Its 
size is about the same as that of the influenza bacillus, being 1 to 3 
micra in length and 0.1 to 0.8 micra in width. 

Von Esmarch grew bacteria through filters which hold them back 


in ordinary filtration work. He used Berkefeld, Kitasato, and 
Maassen filters. 


These filters were filled with plain bouillon and were placed in a 
vessel containing bouillon inoculated with an organism, and the whole 
was kept at 37°, or room temperature. 

Typhoid grew through the Kitasato filter at 87° in twenty-four 
hours, and at room temperature in two days. 

Cholera went through a Maassen filter at 37° in two days, but a 
control kept at room temperature did not grow through after thir- 
teen days. 


A small Berkefeld filter allowed Bacillus prodigiosus to pass in 


@Centbl. fur bakt., bd. 32, 1902, p. 561. 


75 


from one to three days, and a large Berkefeld allowed pyocyaneus 
and prodigiosus to pass in seven days. 

Wherry ¢ states that the bacillus producing pneumonia in guinea 
pigs (0.5 micron wide and 0.7 micron in length) passed the small . 
Berkefeld No. 5, but was not found in the filtrate from the thicker 
walled Berkefeld No. 8, nor in the filtrate from the Chamberland F. 
It, however, grew through the walls of all three. 


FOMITES. 


While we made no experiments directly designed to determine the 
part played by fomites in transmitting the infection of yellow fever, 
still our work strongly bears on this point, and we can fully corrobo- 
rate the conclusions of Reed and Carroll that fomites or inanimate - 
objects are not dangerous in this respect. , 

Nonimmunes whom we kept for weeks under observation in our’ 
mosquito-proof rooms slept on the same beds, used the same clothing, 
washed from the same bowl, ate the same food, drank the same water, 
and breathed the same air as those sick with yellow fever; neverthe- 
less they remained free of all-fever except that which was purposely 
given them by mosquito bites or blood inoculations. 

As these experiments were done in the summer time at Vera Cruz, a 
badly infected city where the disease prevailed at the time in epidemic 
form, it removes some of the objections which were made at the time 
to the work of the Army Commission, which for the most part was 
done during the winter months in an otherwise healthful locality— 
Camp Lazear. 


THE FILTRATION OF MALARIAL BLOOD. 


The filtration experiments with malaria were undertaken with the 
hope that they would throw light upon yellow fever, which bears so 
many analogies to malaria. Both diseases are transmitted by mos- 
quitoes, and it is therefore natural to suppose that yellow fever is due 
to an animal parasite, perhaps similar to the well-known plasmodium 
of Laveran. However, as the one disease is filterable and the other 
is not; and as the parasite of the one is visible and the other can not 
be seen with the highest powers of the microscope at present at our 
command, either in the mosquito or in man; and as the one produces 
an immunity and the other does not, we find the analogy is not after 
all so very striking and that it does not seem helpful in solving our 
problem. 

The malarial rosette breaks and liberates spores (merozoites) which 
are exceedingly minute, and in order to carry out the analogy in an 


«Journ. med. research, vol. 8, 1902, p. 322. 


76 


experimental way we filtered malarial blood in order to determine 
whether there might be forms of the malarial parasite which are even 
smaller than this spore. 

We know from the work of Novy that a trypanosome (7rypano- 
soma Lewisi), which is a colossal organism when compared with a 
malarial spore, has forms which are so minute that they pass a 
Berkefeld filter, for he has succeeded not only in artificially culti- 
vating the adult trypanosome parasite, but in infecting animals with 
the filtrate from these cultures. We also know from the recent work 
of Schaudinn® that some of the animal parasites (Spirochaeta), 
multiply by reducing division; that is, each time cleavage takes 
place the organism is reduced in size, and this process continues until 
the divided forms become too small to be seen as individuals and can 
be made out only as clusters. 

We therefore reasoned that if the malarial parasite has an ultra- 
microscopic form minute enough to pass the pores of a filter, it 
would encourage us very much to look for a visible form of the 
yellow fever organism in the blood and tissues of man and the mos- 
quito by the aid of technique that had not previously been employed. 

Our filtration experiments with malarial blood resulted negatively 
so far as demonstrating the presence of a minute or ultramicroscopic 
form of this parasite was concerned, but there developed unexpectedly 
what appears to be a demonstration of the malarial toxin. We pro- 
duced a definite paroxysm by the inoculation of blood serum freed 
of the malarial parasites by filtration; and it is reasonable to 
suppose that the same substance circulating in the blood, which caused 
the chill, fever, and sweat in one man, caused a precisely similar chain 
of symptoms in the other two into whom this serum was transferred. 

We found that if the blood is drawn after the height of the parox- 
ysm and while the fever is declining this poison is not manifest; but 
if the blood is taken during the chill and while the temperature is 
rising, it is present. 

If this poison is the toxin causing a malarial paroxysm it is remark- 
able that it should be present in the blood serum in such a considerable 
quantity and disappear so very rapidly. Still, the clinical symptoms 
of the disease would indicate the sudden production of a large quan- 
tity of toxin and its rapid elimination, neutralization, or destruction. 
So far as we know, this is the first time that a poison has been demon- 
strated which is capable of reproducing the symptoms of a disease 
due to an animal parasite of microscopic size. 

It would be folly from a few observations to claim that we have dis- 
covered the malarial toxin. The only conclusion justified is that we 
have demonstrated the existence of some poison in the blood which is 


¢ Loe. cit. 


77 


capable of reproducing the symptoms of the disease when injected 
into the veins of other men. 

We are not unmindful of the fact that chemical substances derived 
from the hemoglobulin or other proteids in the blood may be toxic, 
and we are of course familiar with the work of Gauldi, Montesano, 
Mannaberg, Celli, and others, who failed to demonstrate a pyrogenic 
toxin in malarial blood from similar experiments. The length of 
time the blood was exposed to the air between the time it was drawn 
-from the malarial patient until it was injected into the person experi- 
mented upon may account for the discrepancies in results. The time 
the blood is drawn in relation to the paroxysm and many other factors 
should also be taken into account. 

Mannaberg? drew blood during the attack in a case of ordinary 
tertian malaria. He centrifugalized it and injected the clear serum 
subcutaneously into two healthy people. 

One received 1 cc. of serum at 4 p. m., when his temperature was 
36.7° C. The temperature at 4.30 p. m. was 87° and at 6 o’clock 36°. 

The other patient was given 0.7 cc. of the serum and his temper- 
ature rose within fifteen minutes after the injection from 36.5° to 
87.6° C. ; 

Celli ® took during the cold stage a small quantity of blood from 
each of many malarial patients. 

Young children were inoculated with 50 cc. of the serum sub- 
cutaneously and 50 cc. intravenously. 

Another child was given the concentrated serum remaining after 
treating 260 cc. of serum in a vacuum apparatus at low temperature. 
The child was injected intravenously and subcutaneously. 

From a hemorrhage in a case of severe comatose pernicious malaria 
25 cc. of serum were obtained and injected into another patient. 

None of the patients into whom the serum was injected showed 
pyrexia. There was in several instances, however, a slight rise of 
temperature which the experimenter says may occur after the injec- 
tion of normal serum. 

Rievel and Behrens ¢ studied a sarcosporidium of the llama. They. 
removed ten of the sacks and ground them up with physiological salt 
solution in a mortar, and injected 2 cc. of the fluid subcutaneously 
into a rabbit. After seven hours the rabbit died. The autopsy 
revealed nothing unusual. 


@Mannaberg, Julius: Die malaria krankheiten. Nothnagel’s Specielle Path- 
ologie und Therapie, Bd. 2, 1899. 

bCelli, Angelo: Malaria. Transl. by J. J. Eyre. Longmans, Green & Co., 
New York and London, 1900. 

¢ Rievel and Behrens: Beitriige zur Kenntnis der Sarcosporidien und deren 
Enzyme. Centralblatt fiir bakt. u. parasit. (orig.). Bd. 35, no. 3, s. 341. 


78 


Another rabbit received by mouth the contents of several sacks 
rubbed up in salt solution. This rabbit was given at the same time 
‘a subcutaneous injection of 1 cc. of the fluid. The animal died after 
eight hours. From a gross examination of his internal organs and 
a bacteriologic examination of the same, nothing abnormal was found. 

Blood from the spleens of the above-mentioned rabbits, ‘when 
injected into three other rabbits, caused no abnormal symptoms. 

' Pieces of the flesh of the llama were cut up in salt solution and 
the fluid part was injected into two rabbits subcutaneously. Both 
remained sound. 

A rabbit inoculated subcutaneously with a suspension of the con- 
tents of sarcosporidia sacks in salt solution died after seven hours. 
The post-mortem was negative. 

Two other rabbits treated in the same way remained alive six 
hours. Another died after seven hours. 

A suspension was subjected to dialysis and it was found that the 
dialysat, when injected into a rabbit, caused death within twenty- 
four hours. The cooked dialysat was inactive. 

Our experimental cases in malaria follow: 


Fiurration Experiments wits Esrivo-AuTuMNAL FEver. 


Filomena Martinez (case LXIIT), 35 years old, born in Mexico 
City, lived in Vera Cruz about one year. 

The patient was admitted to the hospital of Working Party No. 2 
October 27, at 10 a. m. He had been under observation the previous 
day and early that same morning at San Sebastian Hospital. 

As he showed a heavy infection with malarial parasites he was 
transferred to our laboratory. 

He gives a history of having had yellow fever about six months ago. 
His present illness, according to his statement, began some two weeks 
ago with fever, but he says he did not have chills. The patient’s 
mental condition when seen was below par, and he was unable to give 
consistent answers. He seemed somnolent and was evidently begin- 
ning to show the effects of his infection upon the brain. 

An examination of his blood, taken at 4.15 p. m., October 26, 
showed very many young ring forms, some of. them with active 
amceboid shapes. None appeared pigmented in the smears stained 
with Goldhorn’s polychrome methylene blue. Crescents and ovoids 
also present. 

At 12 o’clock noon, October 27, a trifling incision was made through 
the skin over the median cephalic vein on the right side. A needle 
was introduced into the vein and 100 cc. of blood were quickly drawn 
into a sterile flask. The wound was covered with a sterile dressing 
and healed without complications. 7 


79 


The blood was immediately put into the ice chest, the temperature 
of which registered between 16° and 19° ©. Clotting took place 
rapidly. The red cells settled to the bottom of the flask, the upper 
part of the clot being composed of a firm yellowish buffy coat. The 
serum separated well and was very clear. 

The blood serum was drawn off and diluted with an equal volume 
of an isotonic salt solution and then divided into two portions. 


CASE. FILOMENA MARTINEZ. 
Estivo-AUTUMNAL MALARIA. 
Month [OCTOBER. 
we | ee | BB 29 —=—«| a0 
Day of 
disease. 
SS 
A.M. a CuolO! | kul fold 
Ley js) 
P.M. aay oul? es 
41. i 1s 
SP 
PDs mS bs 
NTS Se 
40_ Frac 
_ S 
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BS 
SCS 
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SS Te 


Temperature chart of Filomena Martinez. 


One portion was passed through a Chamberland B filter and in- 
jected into José Ojeira. 

The other portion was passed through a Berkefeld filter and 
injected into Luis Peredo. 

Blood smears made from the blood which was drawn from the vein 
showed in stained specimens crescents and the young small ring forms 
of estivo-autumnal malaria. Some of the stained parasites showed 
one chromatin point, others two. A few were irregular in outline, 


80 


EXPLANATION OF PLATE 2. 


Estivo-autumnal malaria. 

The character of the malarial parasites in the blood of Filomena Martinez at 
the time it was filtered. 

Stained with Goldhorn’s polychrome methylene blue. 

1. Small ring forms. 

2. Young ameboid forms. 

3, 4, 5, and 6. Ovoids. 


Plate 2. 


CHARACTER OF THE MALARIAL PARASITES IN THE BLOOD OF FILOMENA MARTINEZ 
AT THE TIME IT WAS FILTERED. 


81 


indicating older parasites with ameboid motion. These latter were 
two or three times the size of the small ring forms. (See plate 2.) 

These irregularly shaped parasites had two and some three chro- 
matin points. In the blood taken at subsequent periods similar forms 
were seen, the older or younger forms predominating, depending upon 
the time of day the blood was examined. 

The details of diluting and filtering the blood serum of Filomena 
Martinez follow: 

At 5.30 p. m. the blood was taken from the ice chest, having been 
there just five and one-half hours, and 27 cc. of the clear serum were 
pipetted off. This serum contained a few flakes and very few red 
blood cells. , 

To this serum was added an equal amount (27 cc.) of physiological 
salt solution (0.6 per cent). 

The mixture was transferred to a filter flask and a Chamberland B 
filter was carefully lowered into the fluid and securely fastened in 
position. This was a new filter marked as follows: “B. filtre Cham- 
berland systéme Pasteur H. B. Cie., Choisy-le-Roi. BTE S. 6.0.G. 
Contrélé.” 

The filter was tested before using with an air pressure of 30 pounds, 
after which it was lowered into water. When first lowered into the 
water the air came from every part of the surface of the filter in very 
fine bubbles, but nowhere was there evidence of a crack or pinhole. 
As goon as the filter became wet no air could be forced through it 
with a pressure of 30 pounds. This particular candle was consid- 
ered to be tighter than the other Chamberland-Pasteur filters which 
we had similarly tested. 

The filter was then thoroughly washed by allowing 200 cc. of water 
to pass through it under 20 pounds pressure. It was sterilized in the 
hot air sterilizer for one hour on the day before the blood was filtered, 
at a temperature of 150° C. for one hour. © 

The filtration was begun at 6 p. m., October 27, and was conducted 
in accordance with the diagram (fig. 2) by means of pressure from 
an air pump. This air pump was worked by hand and the diluted 
blood serum filtered under a pressure of 15 pounds. The pressure was 
controlled by the gauge, as shown in the sketch. 

Very slight variations occurred both above and below 15 pounds, 
owing to the difficulty of exact control with hand power. 

The pressure was kept up for one hour, and the filtrate was drawn 
from the inside of the bougie with a long sterilized pipette. In this 
manner it will be noticed that there was no possible chance of contact 
between the filtrate and the blood serum, and throughout the process 
the greatest care was taken in order to prevent such a contamination. 
The filtrate as it came through the filter was clear and of amber 


color. 


82 


At 7.20 p. m. 20 cc. of the filtrate were injected by means of an 
appropriate syringe with hypodermic needle into the left median 
cephalic vein of José Ojeira with entirely negative results. 

A second portion of the blood serum of Filomena Martinez was 


_G 
PP 


ugie B. PP, pressure pump. G, pressure 
held in place by a rubber stopper. P, a 
‘face of the filter. B, the blood serum. 


stopped with cotton and sterilized; 


keep the small quantity of blood in contact with the sur 


Fig. 2—The arrangement used for filtering through a Pasteur-Chamberland bo’ 


gauge. D, Pasteur-Chamberland bougie, 


a | | | 

ry wale al fabs S AGS : 4 
ek) RG a 
t Ke 1S : NS y < EX 5 . 
Eo) eee i 

<<a TT 

itl : 

3 

4 


pipetted off and diluted with an equal quantity of physiological salt 
solution, and filtered through a small Berkefeld filter, as follows: 
-A new Berkefeld filter was prepared by thoroughly washing by 


allowing water to pass through it for several hours, and then ster- 
ilized in dry heat. 


83 


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84 


This filtration was also done from without inwards, as may be seen 
by reference. to the sketch (fig. 3), but by using vacuum instead of 
direct air pressure, as in the case of the filtration a the Pastenr- 
Chamberland bougie. The filtrate was carried over to a sterile bottle, 
as shown in the sketch, and drawn out with a pipette, so that, care 
being taken, there could be no chance of contamination. It reaived 
about twenty minutes to filter 46.5 cc. of diluted serum, and at 
8.15 p. m., viz, eight and one-fourth hours after the blood was drawn, 
twenty cubic centimeters of this filtrate, which represented 10 cc. of 
the original serum, were injected into the left median basilic vein of 
Luis Peredo with entirely negative results. 

This filter was then thoroughly washed with water which ran 
through in drops under atmospheric pressure, and was preserved 
for further testing, with the following results: 

On March 1, 1904, this filter was tested with a bouillon culture of Staphylo- 
coccus pyogenes aureus. The filtrate remained sterile after ten days in the 
incubator. . 

At 10 p. m. Martinez was given 1 gram of bimuriate of quinine 
directly into one of the veins of his arm. This was repeated at noon 
on October 28, and again at 11 p. m. on the same day. 

On the 29th he received another gram into the vein, with marked 
improvement in his symptoms and a notable reduction in the number 
of intracorpuscular forms in the blood, as will be seen by the following 

_ notes of the case: 

October 27,10 p.m.—One gram bimuriate of quinine intravenously. 
Blood examination, 3 crescents in one field; some fields have as many 
as half a dozen small ring forms. 

October 28, 2 a. m.—Blood examination. Some fields have 5 and 6 
small ring fans some irregular amoeboid shapes, also ovoids. 

6 a. m.—Blood examination. One or two ring forms to each field; 
also, crescents. 

10 a. m.—Blood examination. About 1 organism to each field; 
some young ring forms; some amceboid shapes ; also ovoids. 

12 noon.—One gram bhouriate of quinine intravenously. 

2 p. m.—Blood examination. About 1 intracorpuscular form to 
each field. 

11 p. m.—One gram bimuriate of quinine intravenously. 

October 29, 2 a. m.—Ten-minute search of a slide stained with 
polychrome methylene blue showed no intracorpuscular forms; cres- 
cents not diminished in numbers. 


6 a. m.—Only 2 intracorpuscular rings seen; crescents in moderate 
numbers. 
10 a. m—Given 1 gram bimuriate of quinine into a vein. Five- 


minute search of a stained blood smear shows 5 ovoids and only 1 
intracorpuscular ring form. 


85 


2 p. m.—No intracorpuscular forms. 

10 p. m.—No intracorpuscular forms. 

October 30, 6 a. m.—Blood examination shows no intracorpuscular 
forms. A large mononuclear leucocyte has much brown pigment. 
Ovoids still present in apparently undiminished numbers. Patient 
has very much improved in his general condition. His mind is 
better, appetite has returned, and he was returned to San Sebastian 
Hospital. 


FintraTion EXperimEents with Tertran Fever. 


Andrez Mendez (case LXVT), 39 years old; born in La Luz, Estado 
de Guanajuato; never had fever in his native place. In 1878 had yel- 


Case. | Anores Menpez. DousLe TERTIAN MALARIA. 
Month. NOVEM BER 
Day of ‘ 
oe 7 8 2 
Day of | q 
Disease. tk 
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Li) Lb) 
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SF eT: NLS] OPA] Ato 
Pulse ra FFX SPSS PSR Bs sSxXsBlqS Ses S/o) oe 
: URES 


Temperature chart of Andres Mendez. 


low fever (?) in San Antonio, Estado de Guanajuato, with which he 
says he was sick about one month. He came to Vera Cruz three 
years ago and has had fevers five or six times since. 


86 


_ Present illness dates from about November 3, but states that he 
has been troubled with mild attacks of fever for a month, which he 
describes as coming on alternate days, but not sufficiently severe to 
keep him from his work. 

The fever which initiated his present sickness began with a severe 
chill, and was followed by fever and sweat, and was associated with 
some nausea and vomiting. He states that these paroxysms were 
repeated daily until his admission to San Sebastian Hospital, Novem- 
ber 6, 1908. 

‘ Blood examination showed that he had a heavy infection with 
tertian parasites, and he was immediately transferred to the labora- 
tory of Working Party No. 2, Yellow Fever Institute. 

The man was physically saalusl but very anemic, mucous mem- 
branes particularly pale, skin cold antl damp. 

At about noon on this date (November 6), the patient was seized 
with a chill. 

By 12.30, half an hour later, the rigor was very marked; he lay in 

‘bed with a blanket drawn over his head, and was shaking violently ; 
he could not hold a thermometer in his mouth, and the pulse was 
taken with difficulty. During this time the temperature was rapidly 
rising, it being now 39.1° C. 

At 12.40 blood was drawn from one of the superficial veins at the 
bend of the elbow. On account of the rigor there was some difficulty 
in introducing the needle. The blood flowed freely; 125 cc. were 
quickly drawn. It was permitted to flow into a porcelain dish and 
immediately defibrinated by whipping with sterilized forks. Clotting 
took place very quickly, so that the fibrin was readily and quickly 
separated from the fluid. 

Judging from the size of the clot and color the fibrin had enmeshed 
a number of corpuscles. The defibrinated fluid showed no further. 
tendency to clot, and on microscopical examination looked like fresh 
blood containing a normal number of corpuscles. 

To 25 ec. of defibrinated blood was added 25 cc. of physiological 
salt solution, and this diluted blood was filtered through the same 
Berkefeld filter in the same manner as was done with the blood of 
Filomena Martinez (see p. 84). This filter, when tested later, March 
1, 1904, held back Staphylococcus pyogenes aureus. 

Nine ce. of the filtrate were injected into the right basilic vein of 
Luis Peredo as soon as this amount could be obtained. This injection 
took place at 1.40 p.m. It only took about forty minutes to defibrin- 
ate and filter the blood, which process was done as rapidly as possible. 

Stained smears of the filtrate showed no morphologic elements. 
The filtrate had a distinct red color. For the method by which this 
filtration was done, see fig. 3. 

As a control, José Ojeira, at 2 p. m., was given an injection into 


Plate 3. 


CHARACTER OF THE MALARIAL PARASITES IN THE BLOOD OF ANDRES MENDES 
AT THE TIME IT WAS FILTERED. 


EXPLANATION OF PLATE 3. 


Double tertian malaria. 

The character of the malarial parasites in the blood of Andres Mendez at the 
time it was filtered. 

Stained with Goldhorn’s polychrome methylene blue. 

1. Young ameboid forms. : 

2. Older pigmented parasite. 

8. Young and old forms in the same field. 

4, 5, and 6. Segmenting forms. 


88 


his left basilic vein of 4 cc. of the unfiltered mixture. As the blood 
was diluted with equal parts of salt solution, he therefore received 2 
cc. of Mendez’s blood. 

The unfiltered mixture of defibrinated blood and salt solution, upon 
microscopic examination shortly after Ojeira received his injection, 
showed amoeboid tertain organisms with dancing pigment. For the 
character of the malarial parasites infecting the blood of Mendez, see 
illustration, plate 3. 

After drawing the blood from Mendez he continued to have a 
chill, with severe rigor and chattering of the teeth, accompanied by 
nausea and vomiting. His temperature continued to rise after the 
blood was drawn until it reached 40.2° C. The febrile period was 
followed by drowsiness and moisture of the skin. 

As will be seen by reference to the temperature chart, Mendez was 
kept under observation without quinine, and had another typical 
malarial paroxysm the next day. All the evidence in his peripheral 
blood, which was examined frequently, pointed to a severe double 
infection with the tertian parasite. 

He was then given quinine, which entirely controlled the disease, 
and caused the complete disappearance of the parasites from his 
peripheral blood. 

The results caused by the injection of the blood of Andres: Mendez 
into Peredo and Ojeira follow: 

Luis Peredo (case LXIV), a volunteer, aged 25, born in Jalapa, 
State of Vera Cruz, where he has always lived. When examined at 
Jalapa, August 26, he was found to be physically sound; urine con- 
tained no albumin; peripheral blood showed no plasmodium. 

He was brought to Vera Cruz August 28 and taken from the station 
directly to the laboratory, from which time he was kept constantly 
within a mosquito-proof room. 

On October 27, after -having been under daily observation two 
months, during which time he remained in normal health, he was 
injected with the filtered blood of Filomena Martinez (page 84), who 
at the time was suffering with a paroxysm of malarial fever of the 
estivo-autumnal type, his blood containing many young ring-forms 
and crescents. 

It will be noted by reference to the records of Filomena Martinez 
that the blood was drawn during the decline of the paroxysm. It was 
then allowed to clot in the ice chest; the clear serum was pipetted off 
and diluted with an equal quantity of isotonic salt solution, and this 
filtered through a new Berkefeld filter. 

Twenty cubic centimeters of the filtrate, which on account of the 
dilution represented 10 cc. of the blood serum, were injected into the 
left median basilic vein of Peredo. 


89 


For further details of the manner in which the blood serum was 
obtained and the filtration performed, see the above records of Filo- 
mena Martinez. 

Peredo was carefully watched from the hour he was injected, but 
he remained in good health, and no deviation from the normal was 
detected. 

His temperature was taken every four hours during the night and 
day, both before and following the injection, as will be seen by the 
temperature chart. No symptoms developed. 

‘His blood was examined daily for plasmodium, but none was found. 
The result of this injection must therefore be considered negative. 

Ten days later he was again injected with filtered malarial blood 
under different circumstances, and with positive results. 

At 1.40 p. m., November 6, he was given an intravenous injection 
of the blood of Andres Mendez, passed through the same Berkefeld 
filter as before. Mendez was suffering with a double tertian in- 
fection; his blood was drawn during his chill and before the height 
of the paroxysm, as will be seen by reference to the temperature chart 
(page 85), 

Thinking that allowing the blood to clot four or five hours in the 
ice chest in order to obtain a clear serum for filtration might be too 
severe a tax upon the vitality of the malarial parasite, we this time 
defibrinated the blood as quickly as possible, diluted it as before with 
an equal volume of physiological salt solution, and filtered it through 
the same Berkefeld filter in the same manner as was done with blood 
of Filomena Martinez. 

As soon as 9 cc. of the filtrate could be obtained it was inj jected into 
the basilic vein of the right arm of Louis Peredo. This injection took 
place at 1.40 p. m. 

About thirty-five minutes after receiving the injection he began 
having chilly sensations and headaches, and presently went to bed 
covering himself with his blanket (2.25 p. m.). Five minutes later 
(2.30) he was having a violent chill, his teeth chattering so that we 
could not trust the thermometer in his mouth. The rigor of the entire 
body was so marked that there was difficulty in taking the radial 
pulse. The face was pale, and at this time he vomited most of the 
dinner he had eaten a short time before receiving the injection. 

The patient complained of headache, which he localized at the fore- 
head and occiput; says he felt cold and had pains in the knees. At 
this time the skin was diy. The chill lasted somewhat over half an 
hour. 

At 3 p. m. the patient had transient chilly creeps, very slight rigor. 

| At 3.15 p. m. le said he felt “ warm inside,” and all sense of chilli- 
ness had disappeared; still has headache. 

At 3.25 p. m. he complained of marked pain in the legs. 


90° 


At 3.80 p. m. vomited the remainder of his dinner. 

It will be seen from the temperature chart that during this time 
his temperature was rapidly. rising and reached its highest point 
(38.7° C.) at 4 o’clock p. m., just two hours and twenty minutes after 
receiving the injection. . 

The pains in the knees and back continued, and nausea and vomit- 
ing now became a distressing feature of the paroxysms for the patient. 

The fever gradually subsided, and reached normal at 4.30 a. m. that 
same night. (See temperature chart.) 

As the fever subsided the skin became moist, the nausea and pains 
gradually disappeared, so that by 6 o’clock p. m. the patient was quiet 
and dozing. The entire paroxysm, therefore, according to the tem- 
perature record, lasted about eight hours, although the patient was 
sleeping quietly five hours after receiving the injection. 

It is interesting to note that this man Peredo had what seemed to 
be a typical malarial paroxysm beginning with a distinct rigor asso- 
ciated with a rise of temperature and followed by slight sweating. It 
is of particular interest to note that his paroxysm, so far as symptoms 
were concerned, was very much like the paroxysm from which Andres 
Mendez suffered, especially the nausea and vomiting. 

Peredo was kept under very close scrutiny until November 24, 
eighteen days following the injection, during which time he remained 
entirely normal and no plasmodium appeared in his peripheral blood, 
which was frequently examined, as follows: 


Blood examination.—Goldhorn’s stain. 


November 6.—4.30 p. m., 8 p.m. No malaria. 

November 7.—4.30 a. m., 8.30 a. m., 12.30 p. m., 5p. m.,11 p.m. No malaria. 
November 8.—7 a. m., 1 p. m., 6 p. m., 9.30 p. m. No malaria. 

November 9.—7.30 a. m., 1.30 p. m. No malaria. 

November 10.—2 a. m., 3.30 p. m., 8. p. m., five minutes each. No malaria. 
November 11.—4, 7, 10 a, m., 2, 6, 11 p. m., five minutes each. No malaria. 
November 12.—1.30, 6.25 a. m,, five minutes each. No malaria. 

‘November 13.—7 a. m., 9.30 p. m., five minutes each. No malaria. 
November 14.—8 a. m., 8 p. m., five minutes each. No malaria. 

November 15.—8 a. m., 8.30 p. m., five minutes each. No malaria. 
November 16.—7 a. m., 9.30 p. m., five minutes each. No malaria. 
November 17.—8 a. m., 8 p. m., five minutes each. No malaria. 


_ José Ojetra (case XXIII), a volunteer from Jalapa, 18 years old; 
had never lived on the coast, and says he never had fever of any kind. 
On examination in Jalapa, August 11, he was found to be physically 
sound, of robust physique; urine showed no albumin, and blood exam- 
ination for malaria was negative. 

He was taken to Vera Cruz August 13, and immediately trans- 
ferred to a mosquito-proof room in the laboratory, where he was 
kept under close observation. 


Case 


Month 
Day of 


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91 


On August 28, at 9.30 a. m. , he was bitten by four mosquitoes, two of 
which had bitten Antonio Leal (case XX XV), a yellow-fever patient 
fifteen days seventeen hours previously; and ie other two had bitten 
the same case fourteen days twenty-three hours previously. 

The man was kept under close observation in a mosquito-proof 
room, but showed no reaction. There was no rise of temperature, nor 
did he present any untoward symptoms. 

On October 27, 7.20 p. m., he received intravenously 20 ce. of diluted 
blood serum of Filomena Martinez (estivo-autumnal infection), 
passed through a Pasteur-Chamberland filter B. This represented 
10 ce. of blood serum. For detals of this filtration see Filomena 
Martinez (p. 81). 

Ojeira showed no reaction whatever as a result of this injection. 

It will be noted that the blood of Martinez was drawn after the 
height of the paroxysm, and while the temperature was on the decline. 
Martinez was suffering with a very severe wstivo-autumnal infection 
at the time the blood was taken. 

Ojeira’s blood was carefully examined several times daily, both be- 
fore and following this experiment, and at no time was anything 
resembling a malarial parasite seen in his peripheral blood. 

On November 6, the patient having continued in good health since 
the last experiment, was used as a control for the experiment made on 
Peredo. 

On this date, at 2 p. m., he was given an intravenous injection of 
4 ce. of the unfiltered, diluted, and defibrinated blood of Andres 
Mendez. At the time the blood was drawn from Mendez it contained 
a heavy infection of a double tertian malaria, and the blood was taken 
from him during a chill and before the height of his paroxysm. It 
was at once defibrinated, diluted with an equal volume of physiolog- 
ical salt solution, and filtered through a Berkefeld filter. Nine cc. of 
the filtrate were given intravenously to Peredo, causing a malarial 
paroxysm without, however, the presence of the malarial parasite, 
and due, as we believe, to the toxin (?) in the blood of Mendez. 

Ojeira, who received 2 cc. of unfiltered blood (4 cc. dilution), reacted 
within an hour, with a slight rise of temperature and nausea, and 
four days following developed a typical malarial paroxysm, with 
many tertian parasites in his peripheral blood. 

There can be no doubt that the reaction to the 2 cc. of defibrinated 
blood injected into the vein of Ojeira caused a slight paroxysm, 
which it is reasonable to suppose was due to the same poison present in 
the blood of Mendez, and which also caused the reaction in Peredo. 

It will be noticed that 2 cc. of this blood caused but a slight reac- . 
tion in the case of Ojeira, while 4.5 cc. caused a more marked reac- 
tion, with a rise of temperature to 38.7° C., in the case of Peredo, 


92 


indicating in a very definite manner that the severity of the symp- 
toms were directly due to the quantity of poison introduced. Ojeira 
did not, have a chill or other manifestations of a malarial paroxysm, 
other than a rise of temperature and nausea. He vomited gastric 
mucus several times. _ 

On November 10, the fourth day following the injection, Ojeira 
had a typical malarial paroxysm, with tertian parasites in his periph- 
eral blood. He suffered with a double infection, having a chill 
every day, as will be noticed by reference to the temperature chart. 

The character of the parasites in his blood and the clinical course 
of the disease resembled in all respects those of Mendez, from whom 
the blood was taken. Both cases were entirely controlled by quinine. 


MISCELLANEOUS OBSERVATIONS ON MOSQUITOES. 


In association with Doctor Goldberger we made some miscellaneous 
observations upon the life history and biology of the Stegomyta 
fasciata and Culex pipiens, some of which were of sufficient interest 
to record. 

We found that the female Stegomyia does not always lay her eggs 
at one time. More often she deposits them in groups at intervals of 
several days. The maximum number laid by any one insect observed 
by us was 101. The female Stegomyia sometimes dies, apparently 
from exhaustion, after laying her eggs, but we noted several instances 
in which this was not the case. The insect which laid 101 eggs was 
alive and vigorous until killed by us five days later. 

The manner in which the female Stegomyia lays her eggs is of 
some interest. She bends her abdomen ventrally, and as the genital 
orifice comes in contact with the sides of the vessel or with the water 
or other object the egg is deposited. The insect moves along and 
repeats the performance. 

The eggs are sometimes laid on the water, sometimes on the side 
of the vessel above the water line, and sometimes on a leaf floating on 
the water. 

In accordance with the few observations which we made on this 
particular point, Stegomyia fasciata females that are fed solely on 
banana or sugar do not lay eggs. They seem to require a feeding of 
blood for ovipositing. Unconjugated females also do not lay eggs. 

The longest life that we observed was in a female Stegomyia, 
which we kept for sixty-four days, and then killed for sectioning. _ 

We found, as has been often noted by other observers, that the 
greatest activity of the Stegomyia fasciata is during the daytime, 
but we have observed them flying at night. We have also observed 
them feeding on us at night by artificial light. We have noticed on 
several occasions that they are especially voracious early in the morn- 


93 


ing, about sunrise. On several occasions a number of noninfected 
insects were let loose in the laboratory and we observed that upon ris- 
ing at sunrise they attacked us viciously. 

It may be noted that this fact apparently explains the danger to 
persons sleeping in an infected house and the comparative freedom 
from danger in daylight communication with an infected town, 
especially if the person remains in the open air and sunlight and 
avoids houses, and confines his visits to the streets and parts of the 
town free from the disease. 

. A number of experiments were made with the female Culex pun- 
gens, but they could not, under any circumstances, be induced to feed 
upon blood while in confinement. It was found that they preferred 


death. 
* MOSQUITOES MAY BITE CADAVERS. 


The female Stegomyia fasciata will bite a cadaver, and, if on a 
dependent portion, can draw blood. We havé two observations on 
this point. 

Narciso Nadal (case XX). A number of Stegomyie were applied twelve 
hours after death, only one of which apparently obtained blood. 

Trinidad Martinez (case XXII). A number of female Stegomyiv fasciate 
were applied one-half hour after death, and three insects succeeded in feeding 
with blood. 


As it has been shown by the work of the French commission that 
the blood of yellow fever is not infective after the third day, the 
danger of conveying the infection by means of mosquitoes feeding 
upon cadavers must be exceedingly remote. 


LonGEVITY. 


Several experiments were undertaken to determine the fact whether 
the male Stegomyia fasciata, as has been stated, has a brief life his- 
tory. We have one experiment showing that the male mosquito may 
live and thrive over a month. 

Observation —A number of male mosquitoes were placed in a cage October 
10 and subsequently fed on sirup. They were all alive and in good condition 
on November 15, when they were killed and used for experimental purposes, 
having lived thirty-six days. 

Ovirosrrinc. 


Sometimes the female Stegomyia fasciata will lay a considerable 
number of eggs at one time and then die. 


Observation.— (Mosquito XLIII. Francis, Re. No. 4.) This female Stego- 
myia fasciata was taken from the breeding jar on- October 8, fed on normal 
blood October 4, 6, 7, 8, and 10, then placed in a jar with water to tempt ovi- 
positing, and banana feeding begun. On October 19 four males were added to 
the jar. On October 23 the female was given another blood feed. On the 26th 


94 


she laid 54 eggs and was found exhausted and dying on the surface of the 
water. 


More often the female Stegomyia lays groups of eggs at intervals 
of several days, and sometimes lives after the last laying. 


Observations.—-(Mosquito XLIII-38. Francis, Re. No. 1.) This female Steg- 
omyia was taken from the breeding jar October 3; fed on normal blood on 
October 4, 6, 7, 8, and 10; then placed in a jar to tempt ovipositing and given 
banana; laid eggs on October 10 and 11; given another blood feed October 16; 
found apparently dying on the surface of the water on October 18. 


(Mosquito XLIII-68. Francis, Re. No. 3.) This female Stegomyia was taken 
from the breeding jar on October 3 and fed on normal blood October 4, 6, 7, §, 
and 10. It was then placed in a jar to tempt ovipositing and given banana. On 
October 11 she laid a considerable number of eggs. On October 19 again given 
blood feed and three males placed in the jar. October 25 she laid 29 eggs. On 
October 26 laid 12 more eggs. On the 30th the insect was removed in a dying 
condition. 

(Mosquito XLIII-67. Francis, Re. No. 5.) This female Stegomyia was taken 
from the breeding jar October 3. Fed on normal blood October 4, 6, 7, 8, and 
10. Then placed in a separate jar with water to tempt ovipositing and given 
banana. On October 13 she laid some eggs. On the 19th given a blood feed 
and three males added. She‘laid 11 more eggs on October 23, 16 on the 25th, 
and 37 on the 28th, when she was found dying on the surface of the water. 

(Mosquito XLIII-69. Francis, Re.) This female Stegomyia was taken from 
the breeding jar when less than forty-eight hours old and fed upon normal 
blood October 4, 6, 7, 8, and 10, and subsequently at intervals of one or two 
days up to October 23, when she was placed in a cage by herself with a 
beaker of water to tempt ovipositing. At the same time given banana to feed 
upon. October 25 two males were added to the cage. October 25 she laid 
51 eggs; November 7, 24 eggs; November 8, laid 26 eggs; total, 101 eggs. 

She was given another feed of blood November 10. 

Was killed November 13 while apparently vigorous. 


Female Stegomyia fasciata that have fed on the blood of yellow- 
fever patients on the second, fourth, and sixth days of the disease may 
subsequently lay eggs that hatch in a normal manner, and the larve 
develop into pupz and imagoes. 

Observations.—(Mosquito XLVII-36. Marcial Lujan, Rx. a.) This insect 
was separated from the breeding jar October 8 and fed on Marcial Lujan, a 
typical case of yellow fever on the sixth day of his illness. She was subse- 
quently fed on normal blood October 11, 13, 16, 17, and 19. On October 22 a 
beaker of water was placed in the cage in order to tempt ovipositing, and banana 
feeding begun. She laid 15 eggs on October 25 and 15 more on October 26. 
Both sets hatched. o 

(Mosquito XLYII-87. Marcial Lujan, Rx.b.) This female Stegomyia taken 
from the breeding jar October 8. Fed on blood of Marcial Lujan on the sixth 
day of his illness, October 9, and subsequently on normal blood October 11, 13, 
16, 17, and 19. On October 22 given a beaker of water to tempt ovipositing 
and banana feeding begun. She laid 31 eggs on October 26, 9 on the 27th, and 
12 on the 30th. The eggs laid on the 26th and 27th hatched on the 29th. 

(Mosquito XLII-122. Marcos Cruz, Rn. 1.) This insect was separated from 
the breeding jar Octo>er 14 and allowed to feed on Marcos Cruz, one of our 
experimental cases of yellow fever October 15, that is, on the second day of his 


95 


illness. She was subsequently fed on sirup. On November 1, placed in a cage 
with a beaker of water and two males. She laid 12 eggs on November 4, which 
subsequently hatched. 

(Mosquito LVIII-32. -Sesoleda Martinez, Rx. b.) This female Stegomyia... 
was separated from the breeding jar October 19. ed upon the blood of Sesoleda = 
Martinez, a fatal case of yellow fever October 20, the fourth day of his illness... 
Subsequently this insect was given banana. October 28 a normal blood feed. 
On November 5 a beaker of water was placed in the cage to tempt ovipositing. 
Four days later, November 9, she Jaid 26 eggs, which subsequently hatched. 


The statement has been made that the female Stegomyia fasciata, 
and mosquitoes generally, require a feeding on blood in order to lay 
eggs. In three experiments tried by us we are able to confirm this 
statement so far as the Stegomyia fasciata is concerned. The insects 
were fed on sirup and banana, but could not be tempted to lay eggs. 

Observations.—Banana feeding. A large number of male and female Stego- 
myia fasciata that had been fed on banana for fourteen days were given a 
beaker of water to tempt ovipositing. They were Jeft nine days. No eggs laid. 
'They were then killed for section. ‘ 

Sirup feeding. A large number of male and female Stegomyie that had been 
fed on sirup for fourteen days were given a beaker of water to tempt ovipositing. 
They were observed twenty-one days later. No eggs were laid. 

Banana and sirup feeding. A large number of male and female Stegomyia 
were given alternate feedings of banana and sirup for thirty-two days, at which 
time a beaker of water was placed in their cage to tempt ovipositing. They 
were observed nine days later. No eggs were laid. 


Unconjugated females do not lay eggs. 


Observations.—Stegomyie pup were isolated and placed in separate small 
bottles so that the imagoes could not be kept in strict quarantine. Six of these 
unconjugated females were given a feeding of blood twenty-four hours after 
birth, and were subsequently fed on banana. They were kept in a cage with a 
beaker of water to tempt ovipositing. Five days subsequently they were given 
a second feeding on blood. Twenty-five days later they were killed, not having 
laid eggs. 


Size oF SCREENING. 


4 


It is of considerable practical importance in quarantine and public 
health work to know the size of screening that will keep out the 
Stegomyia fasciata, and as no accurate observations upon this subject 
had been made, with which we were familiar, we conducted a few 
experiments to determine this point. 

Screens with a varying number of meshes to the inch were placed 
over breeding jars, and banana, sirup, and other food placed on the 
other side so as to tempt the hungry insects to pass through. These 
experiments were arranged by placing the fruit and food in a jar 
which was inverted over the breeding jar. <A piece of gauze or net- 
ting was inserted between the two jars so that the Stegomyte would 
have to pass through its meshes in order to apear in the upper jar. 

We found that both male and female Stegomyiw may pass a wire 


96 


. 


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proper protection, and that. 


eugnus 
g must also be of a finer wire than is sometimes 


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a 


inch, through which stegomyia fasciata can not pass. 


inch. Allows male and female stegomyia fasciata to pass. 


gauze containing 16 strands or 15 meshes to the inch, but could not 


pass 20 strands or 19 meshes to the inch. 


It is therefore evident that the large-meshed mosquito bars ordi- 


Fia. 4.—Showing screen containing 16 strands or 15 meshes to the 


Fia.5.—Showing screen containing 20 strands or 19 meshes to the 


narily used in this latitude would not offer 


window screenin 
employed. 


97 


DISINFECTION EXPERIMENTS. 


A few tests were made to determine the relative efficiency of sul- 
phur dioxid, tobacco smoke, and pyrethrum as insecticides with par- 
ticular reference to the Stegomyia fasciata. 

A small room and hallway containing 1,200 cubic feet of air space 
were used in these experiments. The room contained a large window 
and one door, which were made reasonably tight to prevent the escape 
of the fumes, and the mosquitoes were exposed in cages in various 
parts of the room. 

Experiment No. 1—Tobacco—One pound of tobacco per 1,000 
cubic feet; exposure, one hour; result, some mosquitoes survived. 

Six hundred and twenty-five grams of tobacco, which is about the 
proportion of 1 pound.per 1,000 cubic feet, were burned in a pan in the 
center of the room. The cages containing the mosquitoes were placed 
on the floor, near the ceiling, and on a chair. 

The room was opened one hour after the tobacco was lighted, 
which was done by means of alcohol. The mosquito cages were 
immediately removed and placed in a current of fresh air in order to 
give the mosquitoes a favorable opportunity to revive. 

All the mosquitoes in the cage which was near the ceiling were dead. 
Of those in the cage on the chair, one female was flying actively 
about; the other females and another male were all dead. Those in 
the cage that stood on the floor were stupefied, but none was killed, 
most of them flying actively about. 

The tobacco was completely consumed in this process, and the 
fumes upon opening the door were very strong. The unpleasant odor 
was very persistent and disagreeable. 

Experiment No. 2—Tobacco—Two pounds per 1,000 cubic feet; 
exposure, two hours; result, all mosquitoes killed. 

The mosquito cages were immediately removed after two hours had 
elapsed, at which time none of the insects showed apparent signs of 
life; but after remaining in the fresh air for three hours a few of 
them moved their wings and tarsi. None, however, revived. 

. Eaperiment No. 3—Pyrethrum.—Two pounds per 1,000 cubic feet ; 
exposure, 2 hours; result, all mosquitoes killed. 

The pyrethrum was burned in a brazier placed upon some sand on 
the floor. 

Three cages containing many mosquitoes were distributed, one on 
the floor, one near the ceiling, and one in an open box on the tabie. 
The cages had a piece of crumpled gauze upon the bottom and a 
folded handkerchief hanging in the cage, in order to give the insects 
retreats in which to hide from the effects of the fumes and to test 
the penetrating action of the gas. 
"All of the mosquitoes were killed. 


98 


Experiment No. 4—Pyrethrum.—Two pounds per 1,000 cubic feet; 
exposure, two hours; result, all mosquitoes killed. 

Mosquito cages were placed in several parts of the room. At the 
end of the experiment some of the insects showed signs of life, but 
none revived. : 

Experiment No. 6—Pyrethrum.—One pound per 1,000 cubic LOGS 
exposure, two hours; result, all mosquitoes killed. 

The pyrethrum was burned in an open brazier upon the floor in 
the same room used for the preceding experiments. The mosquitoes 
were freely exposed to the effects of the fumes in appropriate cages, 
which were placed upon the floor, near the ceiling, and one inside a 
box laid upon a table. 

At the end of the experiment the cages were immediately taken to 
the fresh air and many of the Stegomyia showed signs of life, but 
none revived. 

Exwperiment No..6—Sulphur.—Three and one-fourth pounds per 
1,000 cubic feet; exposure, two hours; result, all mosquitoes killed. 

In this experiment four large rooms and the hallway of our lab- 
oratory building were fumigated to destroy some mosquitoes that had 
escaped. The rooms communicated with each other and with the 
hallway through large openings. No attempt was made to seal the 
doors and windows or to paste cracks. ; 

Three pots of sulphur were distributed at points of vantage, each 
pot containing 20 pounds, the total space to be fumigated being 
12,280 cubic feet. 

Two hours after the sulphur was lighted the house was opened and 
it was found that only about two-thirds of the sulphur had burned; 
that is, about 34 pounds per 1,000 cubic feet. In this experiment the 
pots containing the sulphur were not placed in water, the object being 
to obtain a diye gas and thereby minimize the destructive action of the 
fumes upon the fabrics and pigments. 

Four cages containing mosquitoes were placed in different parts 
of these rooms and all were killed. 

As a result of these disinfection experiments we conclude that: 
While we found tobacco smoke efficacious in destroying the insects, 
we also found that the method is exceedingly objectionable on account 
of the persistent and disagreeable odor that it leaves, as well as on 
account of the yellow stains which remain. Tobacco smoke in con- 
centrated form stains fabrics, paint work, and other surfaces, but 
the stains may be removed by washing; still, this forbids its use in 
parlors and the rooms of fine houses. 

We found that the burning of 1 pound of tobacco per 1,000 cubic 
feet, with an exposure of one hour, was only sufficient to stupety the 
insects. All Stegomyia fasciata were killed by an exposure of two 


99 


hours to the fumes of tobacco burned in a proportion of 2 pounds 
per 1,000 cubic feet. 

We found 1 pound of pyrethrum per 1,000 cubic feet, with an 
exposure of two hours, sufficient to kill ees yia fosmid, and, 
although many of them still showed signs of life after this exposure, 
none revived. Two pounds per 1,000 cubic feet, with an exposure 
of two hours, was sufficient to kill them outright. 

We made only one experiment with sulphur dioxid in order to 
kill some Stegomyia fasciata, which had escaped in the laboratory. 
We selected sulphur on account of our confidence in the insecticidal 
value of this substance. In this experiment we used about 3 per cent 
of the gas, generated by burning in open pots, with an exposure 
of two hours. The previous work of one of us¢ showed that 1 per 
cent, with an exposure of one hour, is quite sufficient in a small inclo- 
sure, but we used the excess on account of the peculiar construction 
of the house. 

’ When burning sulphur for its insecticidal effects care should be 
taken to keep the gas as dry as possible, while the contrary is neces- 
sary in order to obtain its germicidal action. 

The small percentages of sulphur dioxid kept dry are not sufficient 
during short exposures to bleach pigments or injure fabrics; and 
this, in our opinion, is the best of the poisonous gases to insure the 
destruction of such vermin in houses. Formaldehyde gas is utterly 
untrustworthy in this connection. It is not an insecticide. 

We made no experiments with hydrocyanic-acid gas. While rec- 
ognizing its great insecticidal power, we considered it entirely too 
poisonous a substance to use in the household or other inhabited 
places. In our opinion the use of this gas should be limited to green- 
houses, railroad cars, granaries, and other isolated and uninhabited 
places. 


SUMMARY AND CONCLUSIONS, 


The cause of yellow fever is not known. 

The Myxococcidium stegomyiae is not an animal parasite. Yeast 
cells sometimes simulate the coccidia in form and staining reaction. 

The infection of yellow fever is in the blood serum early in the dis- 
ease. No abnormal elements that bear a causal relation to the disease 
can be detected in the serum or in the corpuscles with the best lenses 
at our command. 


«Disinfection against mosquitoes with formaldehyde and sulphur dioxid, M. J. 
Rosenau. Bull. No, 6, Hys. Lab., U. 8. Pub. Health & Mar.-Hosp. Serv., Wash., 
Sept. 1901, 


100 


The infective principle of yellow fever may pass the pores of a 
Pasteur-Chamberland B filter. : 

Particles of carbon visible with Zeiss lenses pass through both the 
Berkefeld and Pasteur-Chamberland B filters. 

Because the virus of an infectious disease passes a Berkefeld or 
Pasteur-Chamberland B filter it does not necessarily follow that the 
parasite which passed the filter is “ ultramicroscopic,” or that it may 
not have elsewhere another phase in its life cycle of large size. 

The filtration of viruses may succeed or fail, depending upon the 
character of the filter, the diluting fluid, the pressure, time, tempera- 
ture, motility of the particles, and other factors. 

The period of incubation of yellow fever caused by the bites of 
infected mosquitoes is usually three days, sometimes five days, and in 
one authentic instance six days and two hours; but when the disease 
is transmitted by such artificial means as the inoculation of blood or 
blood serum the period of incubation shows less regularity. 

Yellow fever may be conveyed to a nonimmune by the bite of an 
infected Stegomyia fasciata; but the bites of Stegomyia which have 
previously (over twelve days) bitten cases of yellow fever do not 
always convey the disease. 

Fomites play no part in the transmission of the disease. 

The tertian and estivo-autumnal malarial parasites will not pass 
the pores of a Berkefeld filter. 

We have demonstrated a poison in the blood during the chill of ter- 
tian infection which, when injected into another man, caused chill, 
fever, and sweating. This poison, while present in a case of tertian 
during the rise of temperature, could not be demonstrated in the blood 
of a case of estivo-autumnal fever during the decline of the paroxysm. 
While this poison reproduced the symptoms of the disease, still the 
data are too limited to consider it the malarial toxin. 

Stegomyia fasciata is a domestic insect. It is most active dur- 
ing the day, but will bite at night under artificial light. The female 
lays eggs at intervals; the maximum number of eggs laid by one 
insect observed by us was 101. The mosquito does not always die 
directly after ovipositing. ; 

Stegomyia fasciata may bite and draw blood from cadavers, 
although the danger from spreading the infection from this source is 
remote. 

Male and female Stegomyia fasciata may pass a screen containing 
i6 strands, or 15 meshes to the inch, but not one of 20 strands, or 19 
meshes to the inch. 

Tobacco smoke produced by burning two pounds per 1,000 cubic 
feet with an exposure of two hours is sufficient to kill Stegomyia 


2 


101 


fasciata. This method is objectionable‘on account of the yellow stains 
and disagreeable odor. 

Pyrethrum burned in the proportion of 1 pound per 1,000 cubic 
feet with an exposure of two hours will stupefy Stegomyia fasciata; 
it requires 2 pounds to kill them outright. 

From the limited number of experiments made and from previous 
experiments we consider sulphur dioxid the best of the gaseous insec- 
ticides for this purpose. 

_ Formaldehyd gas is not an insecticide, and therefore not applicable. 


O 


YELLOW FEVER INSTITUTE, BULLETIN No. 15. 
Treasury Department, U.S. Public\ Health and Marine-Hospital Service. 
i WALTER WYMAN, - Surgeon- General. 


REPORT 


OF 


WORKING PARTY NO. 38,. 


YELLOW: FEVER INSTITUTE. 


ATTEMPTS TO GROW THE YELLOW FEVER PARASITE, 


THE HEREDITARY TRANSMISSION OF THE YELLOW FEVER 
PARASITE IN THE MOSQUITO. 


BY 
M. J. ROSENAU 


AND 
JOSEPH GOLDBERGER. 


« TFTANVUVARY, 1906. 


WASHINGTON: 
GOVERNMENT PRINTING OFFICE. 
1906. 


LETTER OF TRANSMITTAL. 


PuBLiIc HeattH anp Marine-Hospitat SERVICE, 
Washington, January 8, 1906. 


SURGEON-GENERAL 
Pusric HesLtH anp Marine-Hosritat SERVICE, 
Washington, D. C. 

Str: We have the honor, in compliance with your instructions, to 
submit herewith a report of part of the work done by us in New 
Orleans during the latter part of the epidemic of 1905 in the study of 
some problems connected with yellow fever. 

This report covers two points, namely, an attempt to grow the yel- 
low fever parasite and some experiments on its hereditary transmis- 
sion in the mosquito. 

In a future report we hope to cover the results of our study of the 
mosquito material collected by us. This material consists of mosqui- 
toes (Stegomyia fasciata) some of which were permitted to feed on 
yellow fever cases in the first three days of the disease and others 
(controls) which stung a series of healthy subjects or such as were 
suffering from some affection clearly not yellow fever. 

‘We desire here to express our appreciation of the invaluable assist- 
ance rendered us by Surgeon J. H. White. 

To Surgeon A. C. Smith we are indebted for the loan of apparatus 
and for placing at our disposal the hospital laboratory. Passed 
Assistant Surgeon T. F. Richardson rendered us valuable help in many 
ways. To Passed Assistant Surgeons ‘Rupert Blue and Thomas D. 
Berry and Assistant Surgeon Wm. C. Rucker our thanks are due for 
collections of mosquito larve. To Dr. H. P. Jones, Dr. Birney Guthrie, 
and Prof. P. E. Archinard, of New Orleans, our thanks are due for 
numerous courtesies at the Emergency Hospital. Finally, we desire 
to acknowledge our indebtedness to many of the other officers of the 
Service on duty at New Orleans for material assistance on numerous 
occasions. 


Respectfully, fae tae 
. J. ROSENAU, 


Passed Assistant Surgeon. 
Jos. GOLDBERGER, 


Passed Assistant Surgeon. 
(111) 


YELLOW FEVER INSTITUTE. 


Treasury Department, Bureau of Public Health and Marine-Hospital Service, 


WALTER WYMAN, Surgeon-General. 


Buuretin No. 15. 


Section B.X—ETIOLOGY. P, A. Surg. M. J. ROSENAU, Chairman of Section. 


s ‘ 


ATTEMPTS TO GROW THE YELLOW FEVER PARASITE, 


THE HEREDITARY TRANSMISSION OF THE YELLOW FEVER PARASITE IN 
THE MOSQUITO. 


By M. J. Rossnau, Passed Assistant Surgeon, 
and 
JosEPH GOLDBERGER, Passed Assistant Surgeon, 
U. S. Public Health and Marine-Hospital Service. 


ATTEMPTS TO GROW THE YELLOW FEVER PARASITE, 


In view of the fact that the infective principle causing yellow fever 
may pass through the close-grained pores of a Pasteur-Chamberland 
B filter, it seemed to us hopeless, with the limitations of the present 
microscope, to expect to see the causative agent of this disease by 
direct examination of the blood. 

Novy’s work with trypanosomes, both his success in their artificial 
cultivation and his filtration experiments indicating the possibility of 
an ‘‘ultramicroscopic” phase in their developmental cycle, suggested 
to us the possibility of cultivating by similar methods the yellow fever 
parasite and thus perhaps developing a stage in its life cycle which 
might readily be visible. We attempted, therefore, to grow the para- 
site of yellow fever in the ‘‘water of condensation” of blood-agar 
tubes. 

The culture tubes were prepared in several different ways; both human 
blood (nonimmune) and rabbit’s blood were used. Some tubes were 


prepared with the whole, and some with the defibrinated blood. When 
(103) 


104 


the whole blood was used it was quickly added while fresh to melted 
agar, at 42° C.,in the proportion of about 2 parts of blood to 1 of agar. 
After mixing, the tubes were slanted and allowed to set. The defibri- 
nated blood was prepared by whipping in the usual way, and then it 
was added to the melted agar in about the same proportions as above 
stated. After standing a short while the blood-agar slants, thus pre- 
pared, developed from several drops to about 1 ce. of ‘‘ water of con-' 
densation.” 

A drop or two of blood from typical cases of yellow fever taken from 
the arm vein during the early stages of the disease was planted into this 
‘water of condensation.” 

Other cultures were prepared with much larger quantities of the 
yellow fever blood, using the yellow fever blood itself as a part of the 
culture medium. To tubes containing about 2.cc. of melted agar, about 
4 cc. of fresh yellow fever blood was added as quickly as possible after 
its withdrawal from the vein. Other tubes were similarly prepared 
with the defibrinated yellow fever blood. 

Some of the cultures were kept in the incubator at 37° C., and others 
at room temperature. Of the latter, some were kept in the dark and 
others exposed to the light in order to simulate the conditions as they 
appear to occur in the mosquito. 

The, water of condensation was examined from time to time both in 
hanging drop and in stained smears. It was found to contain large 
numbers of bodies of various sizes and shapes, some of them exhibiting 
curious and exaggerated Brownian motion. All of the particles were 
interpreted as degeneration products, mostly from the cellular ele- 
ments of the blood. 


HEREDITARY TRANSMISSION OF THE YELLOW FEVER PARASITE IN 
THE MOSQUITO. 


The question of the herditary transmission of the yellow fever para- 
site from the Stegomyia fasciata to its progeny is of interest both bio- 
logically and practically. 

Reasoning by analogy such transmission can not be regarded as. 
impossible, as it is known to occur in some, probably closely allied 
diseases, namely through the tick in Texas fever® and canine piro- 
plasmosis’. Schaudinn¢ has satisfied himself that hereditary transmis- 
sion of the tertian malarial parasite (Plasmodium vivax) occurs in 
Anopheles, and recently Dutton and Todd? have shown that the 
spirochaete of the tick fever of the Congo is passed from tick to tick 
through the egg. 

To the sanitarian the question is of interest in its bearing on the 
problem of the recrudescence of yellow fever. 

The recrudescence of epidemics of yellow fever has heretofore been 
explained in one of two ways: (1) Either a Stegomyia fasciata that had 
become directly infected by feeding on a case of the disease had sur- 
vived (as they are experimentally known to be able to do), or (2) the 
infection had in the interval between the epidemics been continued by 
unrecognized cases and on the recurrence of favorable conditions the. 
disease would reassume epidemic proportions. 

From time to time a third explanation has been advanced, namely, 
the transmission of ‘the infection from the mother mosquito through 
the eggs to its progeny’ which, under favorable circumstances, were. 


@Smith and Kilborne, 1893, U. 8. Department of Agriculture, Bureau of Animal 
Industry, Bulletin No. 1., 

bLounsbury, C. P., Transmission of Malignant Jaundice of the Dog by a Species 
of Tick. Reprint Cape of Good Hope Agricultural Journal, November 21, 1901. 

¢Schaudinn, Fritz, Generations und Wirtswechsel bei Trypanosoma and Spiro- 
chaete. Arbeiten aus dem Kaiserlichen Gesundheitsamte, Berlin, Band XX, Heft. 
8, 1904, p. 428. 

@ Dutton and Todd, Liverpool School of Tropical Medicine, Memoir xvii, 1905. 

¢Finlay (Medical Record, N. Y., May 27, 1899, p. 738), inspired by the discovery 
of Smith and Kilborne of the hereditary transmission of the parasite of Texas fever 
in the tick, was the first to suggest the hereditary transmission of the yellow fever 
parasite in the mosquito. In 1901 Reed, Carroll, and Agramonte (American Medi- 
cine, Phila., July 6, 1901, p. 19) reported the negative results of an inoculation 
experiment with 14 mosquitoes hatched from the ova of a Stegomyia fasciata that had 
already shown itself capable of conveying the disease, and Guiteras (American Med- 
icine, Phila., Nov. 23, 1901, p. 810) reports two experiments. In both the mother 


(105) 


106 


capable without themselves directly having had access to a case 

yellow fever, of giving the disease to a susceptible individual. Tt 
explanation has now received the support of an experimental case 
yellow fever induced by the sting of a Stegomyza Jasciata apparent 
hereditarily infected. This case is reported by Marchoux and Simon 
in a paper on ‘‘The hereditary transmission of the yellow fever vir 
in the Stegomyia fasciata,” a translation of which we give in appendi 
_p. 114. 

: Against this one positive case we submit the negative results « 
inoculations attempted in 13 nonimmunes. 

In an endeavor to account to ourselves for the divergence of o1 
results from that of the French workers we have considered sever 
factors in the problem, failure to comply with any of which mig 
readily be productive of negative results. We believe, howeve 
that our work, so far as we can judge from the details in the 
paper, closely parallels the work of Marchoux and Simond. Natu 
ally the first factor which arises for consideration is whether tl 
mothers of the Stegomyia fasciata used by us for the inoculation | 
our nonimmunes were infected. Marchoux and Simond state that tl 
mother of the insect whose sting produced the positive case . 
fever hud been made to feed on severad (number not stated) of the 


mosquitoes were experimentally proved to be infected. In the first the progeny 
one mother were tried without results upon three nonimmunes; in the other a lar 
brood from several mosquitoes was kept in a breeding jar and was fed upon noni: 
munes with impunity. 

«During the progress of this bulletin through the press the second report of t 
French Commission to Rio de Janerio (Marchoux and Simond, Annales de I’ Instii 
Pasteur, Paris, XX, 2, Jan. 25, 1906, p. 16) came to our hands, giving full details 
the positive experimental case of yellow fever produced by the sting of a Stegom 
fasciaia apparently hereditarily infected, as follows: 

“Experiment.—A female Stegomyia fasciata born in the laboratory and arriving 

, the adult stage January 19 (probably means January 9), 1905, was paired from the £ 
to the 11th. Itstunga yellow-fever patient presenting a severe attack in the seco 
day of the disease, on the 11th of January, and laid the first batch of eggs Janua 
17. On the 25th of January it stung another patient in thasecond day of the disea 
who presented an attack of moderate severity, and laid the second batch of eg 
January 28. This latter batch hatched out from the 8rd to the 4th of February, a 
the larvee cared for in the laboratory produced perfect insects February 16. 

‘‘Two females from this batch were isolated in tubes and fed with sirup up 
March 2. At this date—that is to say, 14 days after completing their metamorphos 
these mosquitoes were made to sting subject A. This subject, a Portuguese, h 
arrived in Brazil only a few days before and had never had yellow fever. Heshow 
no reaction to this inoculation. After an interval of eight days, March 10, the sa: 
subject was stung a second time by one of the two mosquitoes, the other having ac 
dentally died. Four days later, March 14, he presented symptoms of yellow feve: 

It will be noted, therefore, that the eggs giving rise to the progeny that apparen 
caused an attack of yellow fever were laid by the mother mosquito 17 days af 
the first and 3 days after the second feed of yellow-fever blood. (Compare « 
mosquitoes Nos. 3 and 4, Group II, of Set 1, p. 107.) 


107 


cases of yellow fever in order to determine a heavy infection. In our 
work mother mosquito of Set 1 had three feedings of yellow fever 
blood from two severe cases. 

Mother mosquito of Set 2 and that of Set 3 each had one feed of 
yellow fever blood early in the disease. 

That the interval between the infecting feed and oviposition must 
enter as an important element in the transmission of the infection 
through the eggs to the progeny—if such transmission ever takes 
place in yellow fever--must be evident. Marchoux and Simond do 
not report clearly on this point; they state simply that their mosquito 
was 20 days old at the time of oviposition and that some time prior to 
the laying it had been made to sting several cases of yellow fever. 

In our experiments the intervals were as follows: 


Ser 1. 


Group I, mosquitoes Nos. 1 and 2.—The eggs producing these mos- 
quitoes were laid 13 days from the first, 114 days from the second, 
and about 24 days after the third feed of yellow fever blood. 

Group II, mosquitoes Nos. 3 and 4. —The eggs giving rise to this 
group were "Waid 16 days from the first, 14 days from the second, and 
about 5 days from the third feed of yellow fever blood. (Compare 
footnote (*), page 106.) ‘ 

Ser 2. 


Group I, mosquito No. 5.—The eggs giving rise to this group were 
laid 15 days after one feed of yellow fever blood. 


/ Ser 3. 


Group I, mosquito No. 6.—The eggs giving rise to this group were 
laid 14 days after one feed of yellow fever blood. 

Groups IT, LIT, and IV, mosquitoes Nos. 7, 8, 9, 10,.11, 12, 13, and 
1j.—The eggs giving rise to these groups were laid 15 days after one 
feed of yellow fever blood. 

Another important factor in the problem,.and one to which Mar- 
choux'and Simond call attention, is the time needed by the hereditarily 
infected mosquito to become infective. In their case this was twenty- : 
two days. In our work the inoculations were carried up to and 
including at least the forty-ninth day, as shown in Table 1. 


@See note ¢ on page, 106. 
19294—06—_2 


108 


Taste 1.—Summary of inoculations of nonimmunes by hereditarily infected (?) mosq 
toes—subjects kept under observation at least seven days after each inoculation. 


[The mosquitoes are designated by numbers from 1 to 14; nonimmunes by capital letters.] 


Age of Age of 
Stun, : Stung i 
Mosquito. ent mosquito Remarks. Mosquito. nonim- eee - Remarks 
attime of mune—|2ttime o: 
mune—| stinging. stinging. 
Days. Days. i 
No B 21 No reaction. |; Nos. 6 and 10... G 26 | No reactic 
No: B 3 Do. NO 14 ecceumnees aL 26 Do. 
No A 6 Do. Nos. 5and 9.... F 27 Do. 
No.1 B 9° Do. NO26 cescavaeeex H 28 Do. 
No. 2 Cc 10. Do. Nos. 3 and 4.... G 29 Do. 
No. 2 A 12 Do. Nos.12,18,and14| bM 30 Do. 
Nos, 1 and 2 Cc 13 Do. ING: 6cemeccezcues J 31 Do. 
Nos. 8 and 4 B 13 Do. Nos. 1,11, and 12. B 32 Do. 
Nos. Land 2. B 20 Do NORD asiceacasm J 33 Do. 
No. 3 E 21 Do NOG 10s es ste cescrercicne M 34 Do. 
Nos. 11 and 12... H 22 Do Nos.12,18,and 14 G 84 Do. 

(ee Seen B crascturata E 28 Do. INO. Dc stesesernssccpetre H 35 Do. 
Nos. 13 and 14... J 23 Do. Nos. 12 and 13 .. J 36 Do. 
Nos. 1 and 2. D 24 Do. NO. 3 sscsececees oL 37 Do. 
No. 6 F 24 Do. NOs cccnepeenscaa K 39 Do. 
Nos. 5 and 9. F 25 Do. Nos. 13 and 14... N 39 Do. 
Nos. 11 and 1 J 25 Do. NO} 12 cacesicnoe N 40 Do. 
No. 18 G 25 Do. NG. 8 ceiscienameas G 45 Do. 
No. 3 F 26 Do NOUS scaswecwe os N 49 Do 


aSubject passed from observation after 6 days. 
>Subject passed from observation after 5 days. 

A factor in the problem which is of prime importancé and whic 
must always be reckoned with in estimating the value of negativ 
results is the susceptibility to the disease of the subject used for th 
inoculations. We were careful to select only those who we were sa’ 
isfied never had had the disease. 

Another factor which must be considered is temperature. No mer 
tion is made in the paper of Marchoux and Simond at what tempers 
ture their mosquitoes were kept. Our mosquitoes were kept unde 
artificial conditions at a temperature of between 80° and 90° F. (Se 
p- 109.) : 

Many other factors which we shall not discuss undoubtedly ente 
into and affect this problem. 


DETAILS OF EXPERIMENTS, 


In our study we used three sets of Stegomyia fasciata, comprisiny 
fourteen insects, the progeny of three mothers that had fed on yellov 
fever. The history of these mosquitoes is as follows: 


Set 1, Groups I and 11, mosquitoes Nos. 1, 2, 3. and 4. 


Mother mosquito.—The mother mosquito of this set was one of : 
number raised from the larval stage in our laboratory, and, withou 
any prior feeding, was made to sting, on October 3, at 5.20 p. m., : 
patient (Melancon) with a severe case of yellow fever, 144 hours afte: 

_ the initial chill; about 42 hours later this mosquito was again mad 


109 


to sting the same patient, now about 56 hours after the onset. On 
October 14, at 3.55 p. m., this insect was made to sting a second yel- 
low fever patient (Kippers), suffering from a severe attack of the 
disease, about 48 hours after the onset of the first symptoms.? In all, 
then, this mosquito had three feedings of yellow fever blood from two 
severe cases in the early stages of the disease. This, as well as all 
our mosquitoes, was kept in a room in which the temperature was 
artificially kept between 80° F.and 90° F. Four or five times through- 
out the course of these experiments the temperature in this room fet 
to 70° for six or eight hours at a time. 

Group I.—On October 17, at 8.30 a. m. (134 days from the first, 114 
days from the second, and ahont 24 days from the third feed of yellow 
fever blood), this mosquito deposited eggs from which there were 
hatched between November 4 (4 p. m.) and November 5 (8.30 a. m.) 
two? adult female Stegomyia fasciata, he comprise our Group I of 
Set 1, and were numbered 1 and 2. 

Group IT.—On October 19, at 4.30 p. m. (16 days from the first, 14 
days from the second, and gion 5 days from the third feed of yellow 
fever blood), this same mother insect laid a second batch of eggs from 
which were hatched between November 7 (8 a. m.) and November 8 
(8.30 a. m.) two adult female Stegomyza fasciata, which comprise our 
Group II of Set 1, and were given the numbers 3 and 4. 


eo 
Set 2, Group I, mosquito No. 6 


Mother mosquito.—The mother mosquito of this set was one of a 
number raised from larve and for some time fed on immune blood. 

On October 4, at 9 a. m., this insect was made to sting a severe case 
(Melancon) of yellow fever 30 hours after the initial chill.¢ 

Group I.—October 19, at 4.30 p. m. (15 days after the feed of yellow 
fever blood), this insect laid a batch of eggs from which there was 
hatched between November 7 (8.30 a. m.) and November 9 (8.30 a. m.) 
one adult Stegomyia fasciata, which was given the number 5 and was 
the only one comprised in this set. 


Set 3, Groups I, II, III, and IV, mosquitoes Nos. 7, 8, 9, 10, 11, 12, 
13, and 14. 


Mother mosquito.—The mother mosqhito of this set was one of a 
number of Stegomyia ponent raised from larve in our laboratory 


@On Oct. 8, 10, and 12, it was permitted to fill itself by stinging an immune. 
After Oct. 16, fed with sirup. 

>We mention only the mosquitoes that survived and were used for inoculation; 
others, including males, are ignored in this report. 


: ¢On Oct. 6, 8, 10, 12, and 15, fed by stinging an immune. After Oct. 16, fed with 
sirup. 


110 


and, without any prior feeding, was made to sting on October 4, at 
9 a. m., a severe case of yellow fever (Melancon) 30 hours after the 
initial chill.¢ 

Group [I.—October 18, at 4.20 p. m. (14 days after the feed of yel- 
low fever blood), this insect deposited some eggs, from which there 
was hatched November 12, at 9 a. m., an adult female Stegomyia 
fusciata, which formed Group I of this set and was given the num- 
ber.6. 

Group I[.—October 19, at 4.30 p. m. (15 days after the feed of vel- 
low fever blood), this mother mosquito laid another batch of eggs, 
from which there were hatched between November 7 (8.30 a. m.) and 
November 9 (8.30 a. m.) three female Stegomyia fasciata, numbered 
7, 8, and 9, which form Group II of this set. 

Group [[].—November 12, at 9 a. m., there was hatched an addi- 
tional adult female Stegomyia fasciata, which was numbered 10 and 
forms Group III of this set. - 

Group IV.—Between November 13 (8.30 a. m.) and November 18 
(8.30 a. m.) there were hatched four additional females, numbered 
11, 12, 13, and 14, which comprise Group IV of this set. 

At stated intervals these fourteen Stegomyia fasciata, the progeny of 
mothers (Sets 1, 2, and 3) that had fed on cases of yellow fever as 
above indicated, were made to sting nonimmune subjects, and during 
the intervals fed upon sirup. 

Mosquitoes Nos. 1 and 2 (Set 1, Group I) were applied to and stung 
seven nonimmunes (A, B, C, D, G, H, K) at various invtervals 
between the sixth and thirty-ninth day after completing their meta- 
morphoses, as shown in Table 2. 


TaBLE 2.—Inoculation with mosquitoes Nos. 1 and 2. 


{Nonimmunes are designated by capital letters.] 


stung Age of Stung Age of 


Mosquito. nonim- | Mosquito Mosquito. nonim- | Mosquito 
muue. | #t time of d mune. | at time of 


stinging. stinging. 


OPamy 
AMAow 
or) 
nf 
eo 


Of these inoculations, four were made after the twenty-second day 
(the mosquito incubation period in the successful case reported by 
Marchoux and Simond), namely, at age periods of 24, 32, 35, and 39 
days.. 


4On Oct. 6, 8, 10, 12, and 14, fed by stinging immune. After Oct. 15, fed with 
sirup. 


111 


- Mosquitoes Nos. 3 and 4 (Set 1, Group II) were made to sting eight 
nonimmune subjects (B, E, F, G, J, L, M, and N) ten times at inter- 
vals between the thirteenth and forty-ninth day after emergence as 
adult insects, as shown in Table 3. 


TaBeE 3.— Inoculation with mosquitoes Nos. 3 and 4. 


[Nonimmunes are designated by capital letters.] 


‘| Age of Age of 
Stung . Stung * 
Mosquito. nonim- | Mosquito Mosquito. nonim- | Mosquito , 
mune— | 2t time of mune— | 2t,time of 
stinging. || . stinging. 
Days. Days. 
B 13-14 5 34 
Ez 21-22 37-38 
E 23-24 42-43 
F 26-27 45-46 
oo 29-30 49-50 


aSubject. passed from observation at the end of 5 days, 


Mosquito No. 5 (Set 2) was made to sting subject F on two separate 
days; the first time 25 and the second 27 days after reaching the adult 
stage, 3 and 5 days, respectively, later than in the positive case reported 
by the French workers as shown in Table 4. 


TaBLe 4.—IJnoculations with mosquito No. 5. 


[Nonimmune is designated by a capital letter.] 


Age of Age of 
Stung i Stung ; 
Mosquito. nonim- aay Mosquito. nonim- se rae 
mune— JMS mune— | #t,timeo 
stinging. stinging. 
Days. || ; Days. 
F 25-27 || NOB icressce oe tow seice weasel F 27-29 


Mosquito No. 6 (Set 8, Group I) was made to sting at age periods of 
2, 4, 6, 9, and 12 days lancer than in the successful case reported by 
‘Marchoux and Simond. In all, five subjects were used. 


TABLE 5.—Inoculation with mosquito No. 6. ° 


[Nonimmunes are designated by capital letters.] 


Age of Age of 

Stung Stung 

Mosquito. nonim- | Mosquito” Mosquito. nonim- | mosquito 

mune— | #t.time o: mune— | & time o 
stinging. stinging. 
Days. « Days. 

F 24 || NOs Geccseexssecemseemeesees J 31 
G 2G || INO: Gn wicininininiSinin ate pialeeenae se M 34 
H 28 


Mosquitoes Nos. 7, 8, and 9 (Set 3, Group IT) were made to sting 
subjects Band F. Subject B was stung by all three insects 3 (to 5) 
days after completing their metamorphoses. Subject F was stung by 

e 


112 


insect No. 9 on the twenty-fifth (to twenty-seventh) and again on the 
twenty-seventh (to twenty-ninth) day after its metamorphosis. 


Taste 6.—Inoculation with mosquitoes Nos. 7, 8, and 9. 


({Nonimmunes are designated by capital letters.] 


Age of . Age of 
Stun * Stung . 
Mosquito. mon mosquito Mosquito. nonim- POs. 
: at time of mune— | #t,time o: 
mune stinging. r stinging. 

Days. Days. 
Nos. 7, 8, and 9............. B 85). MIN Gs Diaseerernacpclerlneianeet ote F 27-29 
NOs 9 pereeieectedanateietens F 25-27 


Mosquito No. 10 (Set 3, Group II) stung subjects B and G, 2 and 
26 days respectively after emergence from the pupal shell, the latter 
inoculation being 4 days after the 22-day period. 


TaBLe 7.—Inoculation with mosquito No. 10. 


[Nonimmunes are designated by capital letters.] 


Age of Age of 
Stung * i Stung * 
Mosquito. nonim- mosaUiLo, Mosquito. nonim- eatin 
mune— | 8t.¥me o mune— | #t time o 
stinging. stinging. 
Days. Days. 
NOn1Otcaess ones sew eceeades B 2 NOD0s cccsasworasicactcwceee G 26 


With mosquitoes Nos. 11, 12, 18, and 14 we made one inoculation at 
least 22 days after completing their metamorphoses, and nine inocula- 
tions of seven subjects (B, F, G, J, L, M, and N) at varying intervals, 
after this period up to and including the fortieth day after attaining 
the adult stage, as shown in Table 8. 


TaBLE 8.—Inoculation with mosquitoes Nos. 11, 12, 18, and 14. 


[Nonimmunes are designated by capital letters.] 


Age of Age of 
Stung Stun és 
Mosquito. nonim- Boel Mosquito. nonitn- presi 
mune— | ‘stinging. mune— | ‘stinging. 
Days. Days. 
Nos. 11 and 12 H 22-27 || NOD eeeecten seas ssreceseeess FE 82-37 
Nos. 13 and 14 J 23-28) || NONI aeerciarasinnaas ser B 82-37 
Nos, 11 and 12.. J 25-30 || Nos, 12, 13,and14 G 34-39 
No.13 G 25-80 ||?Nos, 12 and 13......... J 36-41 
INO STB asc ssicscraicaarorcimarnss(artieeieecres aL 26-31 || Nos. 13 and 14......... Be N 39-44 
Nos. 12, 18, and 14.......... bM 80-85; ||. NO. Iie. .cccccesesemencesme N 40-45 


aSubject passed from observation after 6 days. 
bSubject passed from observation after 5 days. 
We have recorded above our work with particular reference to the 
mosquitoes. Below (Table 9) we tabulate it with reference to the non- 
immunes who were the subjects of the inoculations. 


118 


TaBLe 9.—Nonimmunes and inoculations to which they were subjected. 


Age of mos- 
Subject, age, and nationality. Stung by mosquito— we a 
loculation.a 

; Days. 
A, nonimmune, 23 years, Canadian........ eg dokececemawerans a 
B, nonimmune, 44 years, Dalmatian..................0ese seer eee Nos. 6 and 10.....-... 2 
4 : Nos. AD 8, and 9....... 3 
e NOG 1. aie aivsinene siicisoare's 9 
Nos. 8 and 4.......... 13 
Nos. land 2.........-. 20 
NOP? sicescsnpaeweeces 32 
C, nonimmune, 16 years, Austrian..........2.-..ceeeeeee eee eee INO) 2 sees Sesiietarceien anise 10 
. Nos. 1 and Dito teats! 18 
D, nonimmune, 26 years, Norwegian.......---......+..22eee eee Nos. land 2.......... 24 
gE nonimmune, 21 years, American... 21 
F nonimmune, 23 years, American Be 
26 
27 
32 
G, nonimmune, 23 years, American Ee 
29 
No. 32 
Nos. 12, 18, and 14 34 
H, nonimmune, 34 years, American..........--2---+e-ee eee eee ee or ll'and 12... A 

*, 0.0.....----- 

NO 52 scissoretorciziere 85 
J, nonimmune, 45 years, Irish... .......2-0.s- eee e cece senna eee eee Nos. 13 and 14 23 
: : 3 Nos. 1l.and 12 ........ 25 
mene Senet eee esemaet ees 31 
is wielareisninigeesisibia ates 33 
Nos. 12and 13....-... 36 
K, nonimmune, 27 years, Norwegian............-.-----e--eeeee eee NOs 2) ecieis cesisciaqsccteccrs, 39 
L, nonimmune, 38 years, American No. 14 Ee 
M, nonimmune, 20 years, American a 
N, nonimmune, 31 years, Irish.........-.. Diwan ewe dues eeasawiexe 39 
No. 12 o 


7 : 
a Ages given in this table are minimal. For further details consult previous tables. 


In all, thirteen subjects were used. After each inoculation they 
were kept under observation for at least 7 days, except in three 
instances, in two of which the observation period was 5 and in the 
third 6 days. 

Our results were uniformly negative, no reaction of any kind being 
observed in any of the subjects of our inoculations. . 


CONCLUSION. 


In view of the negative results recorded by us in our efforts to con- 
firm the positive work of Marchoux and Simond, we feel that addi- 
tional work will be necessary to settle the question of the hereditary 
transmission of the parasite of yellow fever in the Stegomyia fasciata. 
Nevertheless, the sanitarian will do well to continue his measures of 
mosquito destruction after the suppression of an epidemic. 


& 


APPENDIX.? 


THE HEREDITARY TRANSMISSION OF THE VIRUS OF 
YELLOW FEVER IN THE STEGOMYIA FASCIATA. 


By E. Marcnovux and P. L. Srionp. 


‘Among the new facts concerning yellow fever which we gathered in 
Brazil there is one the importance of which obliges us to publish at 
once. It concerns the question of the possibility of the hereditary 
transmission of the yellow fever virus from mosquito to mosquito. 

. Since 1903 our attention has been turned to the fact that in certain 
foci of an epidemic zone it is at times difficult to find a case of yellow 
fever of recent date as the origin of the new cases which spring up at 
a given time. There being no doubt that the lighting up of these foci 
was due to the presence of infected Stegomyia fasciata, we were forced 
to conclude that one or several of these mosquitoes had in some way 
been imported from a distant point where the disease existed from 
which they had drawn the virus. This undoubtedly occurs frequently. 
We, nevertheless, were led to ask ourselves if, under certain circum- 
stances, eggs derived from a Stegomyia infected in the course of an 
epidemic some months prior to the one observed could not have given 
birth to Stegomyias hereditarily infected. 

Several experiments were made in 1903 to confirm this hypothesis. 
We had some Stegomyias lay eggs that had stung some cases early in 
the disease. -The eggs were hatched into larve, and the adult insect 
raised from these was made to sting a human subject. 

These experiments did not give us positive results at that time, 
although the subjects that had been bitten by these mosquitoes were 
not immune to the disease, for subsequently it was possible to give it 
to them by injections of fresh virulent serum. 

We resumed these experiments in February, 1905. We collected a 
number of eggs of one laying from a Stegomyia 20 days old which 
had stung several of our cases in order to determine a heavy infection, 
and the larvee which were hatched the 4th of February were placed in 
a jar to be reared. The adult insects began to emerge February 16. 
These, isolated in tubes from the time of emergence, were fed with 


«Translated from Comptes Rendus, Société Biologie, Paris, Vol. LIX, No. 27. 


August 4, 1905, p. 259. 
(114) 


71 SRNL "PRISER 


115 


sirup until March 2. At this date, 14 days after the metaniorphosis, 
two of these Stegomyia stung subject A, a Portuguese, who had arrived 
in Brazil a few days before, and had up to that time never had yellow 
fever. The subject showed no reaction following this inoculation. 

He was stung again by one of these two mosquitoes (the second 
having died in the meantime) on the 10th of March, 8 days after the 
first inoculation. Four days later, March 14, he developed a typical 
though mild attack of yellow fever. The character of the period of 
invasion, the vomiting, the pains, the course of the temperature, the 
icterus, and the progress of convalescence permitted no doubt as to 
the nature of the disease. 

We deemed it a duty, nevertheless, to confirm our diagnosis experi- 
mentally. After recovering, this subject was twice submitted to the 
stings of several Stegomyia infected by a case of yellow fever. He 
showed himself absolutely refractory to these inoculations, as do all 
individuals recently immunized by a first attack. 

Let us add that the conditions under which he was observed by us 


- from the time of his arrival in Brazil do not permit that any source 


of contamination, other than the’ hereditarily infected mosquito by 
which he had been stung, could have brought on the attack of yellow 
fever which he had presented. 

It may be concluded from this experiment that under conditions. 
which can not as yet be precisely defined the Stegomyza fasciata, the. 
progeny of a mother directly infected by a case of yellow fever, are 


‘themselves infected hereditarily. It follows from the various experi- 


ments done on this subject that the time needed by the mosquito hered- 
itarily infected to become capable of discharging the virus with its 
salivary secretion is longer than in the case of the mosquito which has, 
drawn the virus directly from the blood of a patient. This period. 
was 22 days in the positive case. 

It follows likewise, both from experiments and from epidemiologic 
facts, that this hereditary transmission can not be considered as the. 
general rule but rather as an exceptional occurrence. 

The mildness of the attack suffered by A warrants the belief that the 
passage of the virus from one generation of Stegomyia to another is 
accompanied by a certain amount of attenuation. This may bea new 
field open to research with reference to vaccination against yellow 
fever. 

The knowledge of this mode of propagation explains one of the 
most obscure points in the history of yellow fever, that of the recur- 
rence of certain epidemics under conditions where a primary case can 
not be found that is sufficiently recent to explain the infection of the 
Stegomyia. 

Finally, its importance can not be disregarded from the point of 
view of prophylaxis. 

O 


YELLOW FEYER, INSTITUTE, BULLETIN No, 16 
0 iblid. Health and Marine Hospital Service 


Surgeon General 


YELLOW 


_ETIQ sacsigte SYMPTOMS 


‘JOSEPH GOLDBERGER 


JULY, 1007 


WASHINGTON — 
GOVERNMENT PE ive 
ao al 9 


YELLOW FEVER INSTITUTE, BULLETIN No. 16 
Treasury Department, U. 8. Public Health and Marine-Hospital Service 
WALTER WYMAN, Surgeon-General 


e 


YELLOW FEVER 


ETIOLOGY, SYMPTOMS 
AND DIAGNOSIS 


BY 


JOSEPH GOLDBERGER 


JULY, 1907 


WASHINGTON 
GOVERNMENT PRINTING OFFICE 


1907 


YELLOW FEVER AINSTITUTE. 


Treasury Department, Bureau of Public Health and Marine-Hospital Service. 


WALTER WYMAN, Surgeon-General. 


Buiwuetin No. 16. 


YELLOW FEVER. 


ETIOLOGY, SYMPTOMS AND DIAGNOSIS. 


By JoszrH GotpBercER, Passed Assistant Surgeon, 
U. S. Public Health and Marine-Hospital Service. 


_ ETIOLOGY. 


The claims, by various authors up to 1890, of having discovered the 
specific cause of yellow fever, were all effectually disposed of by the 
investigations of Sternberg. Since that time several investigators 
-have reported finding the specific causative agent; but it is notable 
that no two of the micro-organisms for which this claim was made 
were identical, and since only one could be the specific organism, it is 
evident that the others could have no real claim to specificity. 

Of the organisms referred to, that described by Sanarelli (1897) as 
the Bacillus icteroides attracted most attention and, indeed, was at 
first: hailed as the long-looked-for germ. 

A series“ of epoch-making investigations and discoveries by a com- 
mission composed of Walter Reed, James Carroll, Aristides Agra- 
monte, and Jesse W. Lazear, medical officers of the United States 
Army, which have been fully confirmed and in some respects amplified 
by independent workers—Cuban?, Brazilian’, American’, French®, 
German /—have resulted in establishing: 

1. That yellow fever is transmitted, under natural conditions, only 
by the bite of a mosquito (Stegomyia calopus) that at least 12 days 


.4Reed, Carroll, Agramonte, and Lazear, 1900; Reed, Carroll, and Agramonte, 
1901a, and 1901b; Reed and Carroll, 1902. 

> Guiteras, 1901. ¢ Barreto, de Barros, and Rodrigues, 1903. 4 Ross, 1902; Parker, 
Beyer, and Pothier, 1903; Rosenau, Parker, Francis, and Beyer, 1904; Rosenau and 
Goldberger, 1906. ¢Marchoux, Salimbeni, and Simond, 1903; Marchoux and 
Simond, 1906a, 1906b, 1906c. Otto and Neumann, 1905. 


(3) 


4 


before has fed on the blood of a person sick with this disease during 
the first 3 days of his illness. » 

2. That yellow fever can be produced under artificial conditions by 
the subcutaneous injection of blood taken from the general circu- 
lation of a person sick with this disease during the first 3 days of his 
illness. 

_ 8. That yellow fever is not conveyed by fomites. 

4, That the Bacillus icteroides Sanarelli stands in no causative 
relation to yellow fever. 

As all preventive measures are based on the foregoing fundamental 
propositions, a somewhat more detailed consideration of each is 
desirable. 


A.— Yellow fever is transmitted, under natural conditions, only by the 
bite of a mosquito (Stegomyia calopus) that at least 12 days before 
has fed on the blood of a person sick with this disease during the first 
three days of his illness. 


The unusual prevalence of insects during some epidemics of yellow 
fever was noted more than a century ago. It was not until 1848, 
however, that any suggestion was made as to their etiological con- 
nection. In that year Josiah C. Nott of Mobile, Ala., reasoning from 
certain epidemic peculiarities of the disease, expressed it as ‘‘ probable 
that yellow fever is caused by an insect or animalcule bred on the 
ground,” and mentioned “‘‘mosquitoes, flying ants, many of the 
aphides” as illustrations of insects whose general habits were such as 
to fulfill the requirements as transmitters of the diseage. At about 
this time there appears to have prevailed a fairly widespread belief in 
the existence of some relation between mosquitoes and yellow fever, 
for Dowler, writing in 1855, states that many persons regarded ‘‘any 
increase in the number of mosquitoes as a‘certain prelude or precursor 
to a yellow-fever epidemic.” 

The first to definitely assert that the mosquito is the medium of trans- 
mission and to specifically indicate the mosquito concerned was Carlos 
J. Finlay. In 1881, at a meeting of the Royal Academy of Medical 
and Physical Sciences of Habana, he stated that three conditions were 
necessary for the propagation of yellow fever, namely: ‘‘(1) The 
existence of a yellow fever patient into whose capillaries the mosquito 
is able to drive its sting and to impregnate it with the virulent parti- 
cles, at an appropriate stage of the disease. (2) That the life of the 
mosquito be spared after its bite upon the patient until it has a chance 
of biting the person in whom the disease is to be reproduced. (3) The 
coincidence that some of the persons whom the same mosquito hap- 
pens to bite thereafter shall be susceptible of contracting the disease.” 
During the succeeding twenty years Finlay continued, tenaciously, to 


5 


maintain his theory which, in collaboration with Delgado, he attempted, 
though unsuccessfully, to prove. . 

To Reed, Carroll, Agramonte, and Lazear is due the credit for the 
masterly experiments which converted a discredited hypothesis into 
an established doctrine. 

The transmission of the disease by the mosquito is not, as Finlay 
thought, a simple mechanical transfer from one individual to another, 
such as occurs at times in plague through the instrumentality of fleas 
or in surra through biting flies. In these diseases neither the flea nor 
the fly is necessary, but in yellow fever not only is the mosquito nec- 
essary, but it is essential that the mosquito be of a particular species 
or at least of a particular genus. Thus, attempts to transmit the disease 
by means of mosquitoes of other than the genus Stegomyia® have not 
been successful. 

It has been found, furthermore, that in yellow fever, unlike either 
surra or sleeping sickness, a certain period must elapse after the infect- 
ing feed before the mosquito is capable of communicating the disease.? 
Experimentally this interval appears to be not less than 12¢ days, so . 
that a susceptible individual may expose himself with impunity. to 
repeated stings within the first 10 or (?) 11 days @ after the mosquito 
has fed on a person sick with the disease. This is the period of 
‘extrinsic incubation” of Carter, whose painstaking observations at 
Orwood and Taylor, Miss., in 1898, resulted in his tentatively fixing 
this interval as ‘“‘usually in excess of 10 days” and served, in the 
light of the then recent discovery of the mosquito transmission of 
malaria, to direct the attention of the Army Commission to Finlay’s 
mosquito as a possible ‘‘ intermediary host” for this disease. 

The duration of this period of ‘‘ extrinsic incubation” is decidedly 
influenced by the temperature of the air. It is at its minimum at 
temperatures above 26° C (80° F), but becomes progressively longer 
as the temperature declines below this point. 

The period of the disease at which the mosquito bites is another 
essential factor in the latter’s power to transmit the disease. Thus 
all attempts to produce an attack by means of the bites of mosqui- 
toes that had previously fed on cases after the third day of the 


4 No experiments have as yet been recorded with any species of this genus other 
than S. calopus. 

6In surra and sleeping sickness for example, no such interval exists. On the 
contrary, it is only during the two days immediately following the infecting feed 
that the tsetse flies concerned can transmit these diseases. After the third day their 
bite is perfectly harmless. In dengue this interval appears likewise to be absent. 

¢I say ‘‘appears to be,’’ because the recorded experimental evidence,is not suffi- 
cient to prove that it may not under favorable conditions be a (very) little shorter 
than 12 days. 

@Nor do such bites during this period confer, as Finlay believed; an immunity 
from subsequent attack. 


6 ‘ 


disease have failed,* whereas all successful attempts have been with 
such mosquitoes as had been allowed to feed on cases during the first 
three days. 

There are some who, while granting that the mosquito is capable of 
transmitting the disease directly by biting, maintain that the disease 
may also be acquired by ingesting water in which the body of an 
infected mosquito has disintegrated. Again, there are others who, 
while admitting that the mosquito is the sole medium of transmission, 
hold, nevertheless, that there may be sources other than the one men- 
tioned from which this insect may acquire its infection, and suggest 
black vomit or articles soiled by yellow-fever patients as pertinent illus- 
trations. But neither the results of experiments especially designed 
to test these hypotheses nor the indirect evidence furnished by a large 
mass of observations give the slightest support to these assumptions. 
After the mosquito has become infective it probably remains so for 
life. 


B.— Yellow fever can be produced under artificial conditions by the 
* subcutaneous injection of blood taken from the general circulation 
of a person sick with this disease during the first 3 days of his illness. 


The subcutaneous injection of a drop? (0.1 cc.) of yellow fever blood 
serum from a case in the first day of illness has produced an attack of 
yellow fever, whereas five times this amount from a case in the fourth 
day of the disease produced no symptoms. 


C.— Yellow fever is not conveyed by fomites. 


Before the demonstration by the Army Commission of the trans- 
mission of yellow fever through the mosquito it was very generally 
believed, notwithstanding a large mass of evidence to the contrary, 
that the disease was communicated by the exhalations of. the sick, by 
contact with their excretions, or with articles that had been exposed 
to or been soiled by them. 

In order to put this almost universal belief in fomites to a rigorous 
test, the Army Commission exposed each of a series of seven non- 
immunes to clothing and bedding which had been used by cases of 
yellow fever and which had become soiled with blood, urine, feces, 
and black vomit. The house in which the experiment was carried 
out was especially constructed for the purpose in an isolated place 
near Habana. In order to prevent access of mosquitos and to simu- 


@The recorded experimental evidence is not sufficient to show that this infective 
period may.not at times extend into the fourth day. This is of considerable prac- 
tical importance. A case of yellow fever should be protected from mosquitoes during 
four full days at least. 

bParker, Beyer, and Pothier (1903) induced an attack of yellow fever by the sub- 
cutaneous injection of 0.033 cc. of filtered serum from a case in the third day. 


7 


late the conditions thought most favorable to infection by fomites, the 
windows and doors were screened and so placed as to prevent free 
ventilation, special pains were taken to exclude sunlight, and pro- 
vision was made for heating during the day so that an average 
temperature of 72.6° F. was maintained throughout the entire period. 
The men were exposed in squads for periods averaging 21 nights each. 
Each ‘squad ‘entered the house at night, removed the soiled articles 
from the boxes in which they were packed, shook them out, hung 
some about the room, and used some for making up the beds in 
which they slept. In the morning the various garments and articles 
of bedding were repacked and the men left the room to occupy a 
near-by tent during the day. The result of this experiment was 
entirely negative; the men remained in perfect health. Subsequently 
some of them submitted to mosquito inoculation and promptly 
sickened with the disease, showing conclusively that they were not. 
immune. 

It may be of interest to observe that the first experiments to deter- 
mine the infective power of fomites were made over a century ago. 
In 1800 Cathrall reported having repeatedly applied black vomit to 
his tongue and lips and to the skin of various parts of the body with- 
out experiencing any ill effects. In company with a friend he had, 
besides, exposed himself to the fumes of heated black vomit, both in 
the open air and in a confined space, likewise without harm. In 1804 
Ffirth, imitating Cathrall’s example, went so far as to repeatedly swal- 
low several ounces of fresh black vomit; he rubbed some into incisions 
in his arms and dropped some into his eye without experiencing any 
but momentary disagreeable effects. 

In view of the foregoing, one can not but admire the acute reason- 
ing of La Roche,* who, half a century ago, in discussing the evidence 
in. support of transmission through the agency of clothes, bedding, 
merchandise, etc., concluded that “‘we may well infer” that in the 
record of such instances ‘‘some error has crept"in—something has been 
omitted or overlooked—and that the production. of the disease was 
really due to some other agency than the one contended for,” a con- 
clusion which will be concurred in by anyone who will take the pains 
to critically examine the recorded instances of alleged transmission by 
such means. 


D.—LEaperiments to show that the Bacillus icteroides Sanarelli stands 
in no causative relation to yellow fever. 


The fact that the Army Commission was able to produce three cases 
of yellow fever by the subcutaneous injection of blood which was 
shown to be sterile by the culture method is sufficient to eliminate 


Vol. 2, p. 522, 


8 


B. icteroides from consideration. That the attacks of fever so 
produced were not simply such as might be caused by the injection of 
a soluble toxine circulating in the blood is shown by the following 
chain of experiments: . 

The first link in the chain was a fatal nonexperimental case of 
yellow fever which furnished the Army Commission® with blood that 
culturally showed the absence of B. zcterocdes, but 0.5 ce. of which 
injected subcutaneously into a nonimmune (W. F.)¢ induced an attack 
of fever having all the characters of yellow fever. From the latter 
case blood was drawn and 1 cc. injected into a second nonimmune 
(J. H. A.)¢; culturally this blood was sterile, but nevertheless it 
caused an attack in all respects similar to yellow fever. ight hours 
after the onset of this man’s illness some mosquitoes were allowed 
to bite him, one of which, 26 days later, was applied to a nonimmune 
(Vergara) °, who developed an attack of yellow fever 3 days, 10 hours 
later (see diagram). 


Diagram. 

Non- First. * Second. Third. 
experimental Experimental Experimental Experimental 
case. a case. case. case. 

Induced by injection of Induced by injection Induced by bite 
0.5 ec. blood from No.1. of 1 ec. blood from No. of a‘ mosquito that 
Cultures from blood, no 2. Blood cultures ster- had fed on No. 3, 
B. icteroides. ile. 26 days before. 


The only possible explanation of this chain of events is that there 
was present in the blood used for the subcutaneous injections an 
organism that can not be cultivated on ordinary media—B. icteroides 
grows readily on all ordinary media—and that the mosquito that bit 
the second of the experimental cases became infected with this organ- 
ism and 26 days later transmitted this infection to a nonimmune. It 
is inconceivable that a toxine alone could infect a mosquito in such a 
way as to enable the latter, 26 days later, to reproduce the disease by 
biting a nonimmune. ‘It may be observed in this connection that a 
person who has suffered from an attack of the disease, acquired natu- 
rally or experimentally through the bite of a mosquito, is immune to 
injections of virulent yellow fever blood serum and, vice versa, 
an attack of the disease induced by the injection of yellow fever 
blood protects against subsequent inoculation by means of infected 
mosquitoes. 

The parasite.—W hile the organism of yellow fever has not yet been 
discovered, we are, nevertheless, in possession of some facts which 
enable us to form some idea of its character. The disease has been 
found to occur in nature only in man and the mosquito, so that it is 


@ Reed, Carroll, and Agramonte, 1901b, p. 16. 
bGuiteras, 1901, p. 812. 


9 


inferred that the parasite is one of those that requires for the complete 
evolution of its life cycle a mammalian and an arthropod host. We 
have familiar analogies in Piroplasma bigeminum of Texas fever and 
the Plasmodium of malaria. Because of these analogies it is inferred 
that biologically it may be grouped with them as a protozoon. On 
the basis of these and other analogies, both Schaudinn (1904) and Novy 
& Knapp (1906) have suggested that it may be a Spirocheta. Stim- 
son’s recent discovery of a spirocheete-like organism in the tubules 
of a yellow fever kidney is, therefore, exceedingly interesting and 
suggestive. 

The cycle in man is represented clinically by a stage of incubation 
and by a stage of fever. Some attempts to infect mosquitoes by allow- 
ing them to bite subjects during the stage of incubation, in one instance 
as late as 6 hours before the onset of the stage of fever, have been 
unsuccessful; whereas a mosquito that bit a case of the disease 8 
hours after the onset became infected and conveyed the disease to a 
nonimmune 26 days later. This would indicate that the parasite does 
not appear in the circulating blood until the onset of the disease. We 
already know that it remains in the blood only during the first three 
days of the disease or, at least, it is only during those three days that 
it exists in a form capable of continuing its life cycle in the mosquito 
or in a fresh nonimmune. : 

In the circulation it exists in a form so minute as to be capable of 
passing through the finest grained porcelain filters, such as the Cham- 
berland B and the Chamberland F. 

Its resistance to deleterious influences is feeble when withdrawn 
from the circulation. When kept in a test tube exposed to the air in 
the dark, at a temperature of 24° C. (75° F.) to 30° C. (80° F.), it 
loses its virulence in 48 hours. Under the same conditions, but pro- 
tected from the air by keeping under oil, it retains its vitality some- 
what longer—up to between 5 and 8 days. Heating for 5 minutes 
at 55° C. (182° F.) apparently suffices to kill it. The etfect of low 
temperatures has not been studied. 

The cycle in the mosquito requires at least 12 (?) days* for its com- 
pletion. As to the changes which it undergoes during this period we 
are in complete ignorance. 

The French commission has recorded one experiment which would 
indicate that the parasite may, under certain circumstances, be trans- 
mitted to the progeny of an infected mosquito through the egg. An 
attempt by Rosenau and Goldberger to confirm this resulted negatively. 
The same commission attempted, but without success, to transmit the 
parasite from one mosquito to another by feeding larve with cadavers 
of infected adults; they appear, however, to have sueseded in trans- 


«See page 5, footnote ¢, 
2742—No, 16—07——2 


10 


mitting the parasite to a mosquito by feeding it with sirup in which 
the body of an infected insect had been crushed. 

Judging from the variations in the virulence of different epidemics 
it is fair to infer that there is a corresponding variation in the viru- 
lence of the parasite. The variation in severity of individual cases 
appears, however, to be largely influenced by the susceptibility or 
resistance of the subject, for the bite of the same mosquito or mos- 
quitoes will be followed in one instance by a severe and in another by 
a mild attack. Nor does there appear to be any appreciable difference 
in severity between attacks induced by the bite of a single as com- 
pared with those induced by the bites of several insects. 

Susceptibility.—Attempts to induce the disease in the ordinary lab- 
oratory animals have been unsuccessful. Marchoux and Simond (1906a) 
caused a mild febrile attack in one orang-outang and in one chimpan- 
zee by bites of infected mosquitoes. Thomas (1907) induced a mild 
febrile attack with albuminuria in a chimpanzee sellowing an inocula- 
tion by infected mosquitoes. 

All persons are naturally susceptible, but there is a difference in the 
degree of this susceptibility in different races. Thus the mortality in 
the negro is less than in the Caucasian. Age has a distinct influence 
on susceptibility, as is shown by the mildness of attack and relatively 
low mortality in children. Nativity and long-continued residence in 
an endemic focus were supposed at one time to ‘‘acclimatize” and thus 
protect against the disease, but it is now believed that this protection 
was obtained not by the occult influence of climate but by having 
had during childhood or at some other age a mild and unrecognized 
attack of the disease. 


THE YELLOW FEVER MOSQUITO. 


This insect has been known by a variety of names of which Culex 
mosquito, Culex teniatus, and Culex fasciatus were in most common 
use up to 1901. In that year Theobald, having observed that some 
sixteen species of Culex, while agreeing amongst themselves, differed 
from the others of this genus in certain peculiarities of scale arrange- 
ment, separated these into a group to which he applied the name 
Stegomyia. In this group was included the yellow-fever mosquito 
whose name thereupon became Stegomyia fasciata. Blanchard (1905), 
however, has pointed out that the specific designation fusciata is not 
applicable to this insect, as it had first been applied to another, so that 
calopus, suggested by Meigen in 1818, has the right of priority. There- 
fore, under the rules of zoological nomenclature, the correct name is 
Stegomyia calopus (Meigen, 1818) Blanchard, 1905. 

Adult.—The Stegomyia calopus (figs. 1 and 2) is readily recognized. 
It isa handsome insect—a study in black and white. The distinction 


MESONOTUM, 


SCUTBLLUM, mae 
METATHORAY 0... essen : 


HALTERE ------- 


prrioct or 4 supmanoimac ceut 


i “ <> 
TTT 


ABDOMINAL 
SEGMENTS 


Fie. 1.—External anatomy of Stegomyia calopus. 


Fic. 2.—Stegomyia calopus (female). 


11 


tween the male and the female is readily discernible in the characters 
the antennx; in the former (fig. 3) these organs are prominent and 
ithery— decidedly hirsute. Another prominent point of difference 
ists in the length of the palpi; in the male they are long—almost as 
ig as the proboscis, but in the female they are short—less than one- 
ird the length of the proboscis. 

The palpi in both sexes are black, but are ornamented with white 
iles which, in the male, are arranged as four narrow bands, while in 
2 female they are collected into a white tuft at the tip. 

The proboscis is black and is devoid of ornamentation, differing in 
is respect from both Culex twniorhynchus and Culex sollicitans, 
ch of which has the proboscis marked by a pale band in the middle. 
1ese two insects bear a superficial resemblance to S. calopus, for 
uich they are not inffequently 
istaken by the uninformed. 

The head is clothed by the broad 
it scales characteristic of the 
mus. These scales are black, ex- 
pt for a line of white down the 
iddle extending to the neck and 
narrow white border to the eyes. 
The thorax is dark brown, almost 
ack, ornamented with silvery 
hite patches and lines of which 
ie following are peculiar to and 
stinctive of this species, and en- 
yle one to recognize it at a glance: 
_well marked, easily recognizable, 
ure white curved line on either yg. 3 appendages of head of Stegomyia 
de of the back (mesonotum) be- ___ calopus (male). 
veen which, but less obvious to the naked eye, are two delicate 
tedian parallel lines; a prominent transverse white line of scales 
o the scutellum. 

The abdomen is clothed with black and white scales, the latter col- 
ted in bands at the bases of the abdominal segments, and in distinct 
atches at the sides. . 

The legs are black scaled, except for white bands which are arranged 
; follows: A basal band on the first joint of the fore, on the first and 
xcond of the mid, and on all of the hind tarsi except the last, which 
as a rule, all white. Each leg is provided with a pair of claws 
hich are equal in size in the female but unequal in the male. They 
iffer in other respects in the two sexes; in the female those of the fore 
ad of the mid legs are provided with one tooth, those of the hind 
gs are simple; in the male all the claws are simple except the larger 


ne of the forefoot. 


12 


The veins of the wings are clothed with dark brown scales. The 
first submarginal cell is longer than the second posterior cell and the 
base of the former is nearer the root of the wing. 

Biting.—The male insect does not bite; it lives almost exclusively 
on vegetable and fruit juices. In the females, however, a feed of 
blood is a necessary condition precedent to egg laying. At summer 
temperatures this insect will digest a full meal of blood in about 48 
hours. If disturbed in the act of feeding it will fly away, but will 
return and attempt to finish its interrupted meal. In this way one 
infected mosquito in its efforts to obtain one full meal may bite several 
individuals, and so may, almost simultaneously, produce more than 
one case of yellow fever. 

It. has long been observed that communication with an infected 
town is distinctly safer during the day than after dark. In an effort 
to explain this phenomenon the French yellow fever commission first 
suggested, then made some experiments which appear to show that 
under natural conditions the yellow fever mosquito, after the first 
week, ceases to bite during the day and bites only at night—that is, 
between 5 p.m.and 7a. m. These results are not, however, alto- 
gether in harmony with the observations of others, and there are 
cases recorded showing that yellow fever may be contracted by visit- 
ing an infected house during theday.?_ We must conclude, therefore, 
that the Stegomyia calopus, young or old, may bite at any time dur- 
ing the 24 hours, though probably it is most vicious about dusk and 
about dawn. The female is impregnated almost immediately after her 
birth, and then proceeds to seek a blood feed; 3 or 4 days after this 
she is ready to lay her eggs. 

Breeding places.—The Stegomyza calopus appears to be strictly a 
house mosquito—a domestic though not domesticated animal. Her 
breeding places, therefore, may be expected, and actually have been 
found to be any collections of water in and about habitations, such 
as cisterns, wells, water barrels, tubs or jars with or without water 
plants, sagging roof gutters, more or less broken and discarded 
crockery, bottles and tins, fountains (not containing fish), cemetery 
vases, baptismal’ and other fonts in churches, chicken or horse 
troughs, grindstone troughs, and tubs or barrels containing water 
which has been softened and made more or less alkaline by the use of 
ashes. The larve have been found in tin cans containing fecal matter, 
in cesspools, and in some natural collections of water formed by leaves 
of certain tropical plants, such as the palm and century plant. Ordi- 
narily, she does not seek street puddles or gutters, favorite breeding 
places for Culex teniorhynchus and Culex pipiens (=pungens), though 
her larve have been found in these situations. 


4 Carter, 1901b, p. 936. 


13 


Lgg.—The female lays her eggs (fig. 4) on the surface of the water 
or on the sides of the container at or just above the water line. The 
eggs do not adhere one to the other to form the compact boat-shaped 
masses characteristic of Culex (fig. 5), but lie on their sides more or 
less isolated, though frequently grouped into clumps. At the moment 
of laying the eggs are of a cream color but rapidly become jet black; 
they are somewhat cigar shaped with one end slightly broader and 
more bluntly rounded than the 
other. They measure on an aver- gf 
age about 0.55 mm. in length and «~ ad | 
0.16 mm. in width at the broadest &! 
part. Under the microscope the g 
apparently cylindrical egg is seen to 
be slightly flattened” on one side. 
The eggs are most commonly laid 
during the night or early morning, 
but they may be laid at any time during the 24 hours. The total 
number of eggs laid varies, the average being about 65 to 70; the 
maximum recorded is 144.¥ 

The act of ovipositing appears to greatly exhaust the mosquito, so 
that it may fall on the surface of the water and die immediately after 
even the first egg laying. There are numerous exceptions, however, 
andthe act may: be re- 
peated several times and 
the mosquito survive for 
some time after. 

If laid on the surface of 
the water the egg floats, 
being supported by the 

Fig, 5.—Eggraft and eggs of Culex (after Stephens & surface film. Disturbance 

Christopher, 1904). 

of the water surface may 
cause the egg to become wet and sink to the bottom, but this does not 
prevent its hatching out into the larva. The egg shows marked powers 
of resistance to unfavorable influences. Thus it may be kept dry for 
from two or three to six and one-half months? and still retain its 
° vitality and hatch out when put back into the water. Reed and 
Carroll ¢ have shown that freezing does not destroy its vitality. The 
egg probably plays the leading réle in the hibernation of this mosquito. 

Under the most favorable conditions as to temperature (30° C. 
(86° F.) and over) eggs hatch out in about 36 hours after they are laid, 
but with a lowering of the temperature this period becomes progress- 
ively longer until 20° C. (68° F.) is reached, below which they will 
not hatch at all. 


@Marchoux and Simond, 1906b. %Francis, 1907. ¢ Reed and Carroll, 1901. 


Fia. 4.—Eggs of Stegomyia calopus (after 
Stephens & Christopher, 1904); 


14 


Larva.—The egg hatches into the larva (‘‘ wiggle-tail”) (fig. 6), 
which can be distinguished readily from the larva of Culex pipiens 


Dy M5 


ye 
ns 


pu oyNe 


Fia. 6.—Larva of Stegomyia calopus (after 
ei Howard, 1901). 


surface for air. It thrusts its breath- 


(fig. 7), its most common messmate, by 
the color and proportions of the breath- 
ing siphon (air tube). Inthe S. calopus 
the respiratory siphon is black and 
somewhat barrel-shaped, with its great- 
est transverse diameter equal to about 
one-half of the length; whereas in Culex 
pipiens the air tube is brown, longer, 
more slender, and with the greatest 
transverse diameter less than one-third 
of the length of the tube. The larva, 
though it lives in the water, is strictly 
an air breather and must come to the 


ing tube up into the surface film and 
remains suspended head down, at an 
angle somewhat less than 45°, for a 
variable time. A film of oil on the sur- 


face of the water is sufficient to obstruct- 


the air tube, and thus cause the death 
of the larva by suffocation. The larva 
is very timid, so that a very slight jar 
or a sudden shadow will cause it to 
move rapidly to the bottom of the 


container where, indeed, it may very 


commonly be observed to feed. 


Fic. 7—Larva of Culex pungens (after 
Howard, 1901). 


The duration of the larval stage is influenced by food supply and 
temperature. With an abundant supply of food and under favorable 


15 


conditions of temperature this stage lasts not less than 6 or 7 days; 
under conditions where the supply of food is scanty or the tempera- 
ture reduced the duration of this stage may become very much pro- 
longed (weeks) or development may altogether cease. In the latter 
case the larva may die without completing its metamorphosis or, with 
the return of favorable conditions, it resumes its development. Freez- 
ing for short periods does not appear to injure it. 

Pupa.—After several moults the larva changes into the pupa (fig. 8). 
The pupa is not provided with a mouth and does not feed. It spends 
its time at the surface of the water for, like the larva, it is an air 
breather, and is provided with two trumpet-shaped breathing tubes 
which spring, not from the tail as in the larva, but from the dorsum 
of the thorax. It moves only when disturbed, and then rather rapidly. 
and jerkily downwards into the depths. The pupal stage lasts at least - 
36 hours, during which time important changes take place in its inter- 
nal organization preparatory to the _ 
emergence of the perfect insect or 
imago. The pupal, like the larval 
stage, is normally passed in the water. 
Berry has shown, however, that the 
pupa may be spilled on the ground 
without its metamorphosis being in- 
terfered with. Under the most favor- 
able conditions it takes at least 9 
days from the time the egg is laid to 
the appearance of the imago. 

Longevity.—The length of life of Fic. 8—Pupa of Stegomyia calopus (after 
the adult, female under natural con- risiennaeaeignice 
ditions probably varies greatly. Experimentally, Guiteras (1904a) 
succeeded in keeping a presumably infected one alive for 154 days at 
the fall and winter temperatures of Habana. At summer tempera- 
tures, deprived of water, it does not usually survive longer than 3} to 
4 days, and only very exceptionally 5 days. This fact has a bearing 
on the possibility of transporting the mosquito in bandboxes or trunks. 

Its activity, which is greatest at about 30° C. (86° F.), distinctly 
diminishes as the temperature declines and approaches 20° C. (68° F.). 
Below the latter point and as the temperature of 15° C. (59° F.) is 
approximated the insect seeks obscure corners for protection, becomes 
very sluggish, and can only exceptionally be induced to bite. In a 
refrigerator at 8° to 10° C. (46.5° to 50° F.) Guiteras (1904a) was able 
to keep some mosquitoes alive without food or water for 87 days. 
How much longer they mave have lived it is impossible to say, because 
the experiment was terminated at the end of this time by some ants 
that gained access to and destroyed the mosquitoes. A freezing tem- 
perature kills the mosquito rather quickly. 


16 


In the influence of variations in temperature on the rate of multi- 
plication, on the activity and on the duration of life of the mosquito 
we have a satisfactory explanation of the peculiarities of seasonal 
prevalence of the disease in endemic foci, of the decline of epidemics 
with the advent of cool weather, and of their abrupt cessation on the 
occurrence of a severe frost. The occurrence of cases even after a 
killing frost is explained by the fact, already mentioned, that the 
S. calopus is peculiarly a house mosquito, and it is for this reason 
occasionally able to escape the full rigors of the climate. 

Aérial conveyance.—On this subject I can do no better than quote 
Carter (1904), who has given it a great deal of attention. 

Although direct observations on this problem are few, yet there are certain indi- 
rect ones bearing, however, entirely on the aérial conveyance of the Stegomyia 
‘infected with yellow fever. It is notorious that yellow fever is usually conveyed but 
a short ways aérially ‘‘across the street’’ or more often ‘‘to the house in the rear,”’ 
which is about as far as it was expected to be thus conveyed. This represents a 
distance of about 75 yards. The two longest distances recorded in recent times of 
aérial conveyance, one of 225 meters (Melier) and one of 76 fathoms—456 feet (the 
writer )—are entirely exceptional. So much for the distance which the ‘‘infected”’ 
Stegomyia is conveyed—or, rather, usually conveyed—aérially. 

On the other hand, it is known that vessels moored in certain districts of the 
Habana harbor did not develop yellow fever aboard except in those who had been 
ashore or unless they lay close to other vessels which were infected.. This experi- 
ment has been made on s0 large a scale, with so many vessels, and for so many years 
that we must accept as a fact that an infected Stegomyia was not conveyed aérially 
from the Habana shore to those vessels, or, allowing for errors, was very rarely so 
conveyed. The distance which had been found safe was something over 200 
fathoms—1,200 feet. The prevailing wind was generally slightly on shore, but was 
not constantly blowing. Whether there is any difference in the distance to which 
infected or noninfected mosquitoes are conveyed is, of course, entirely a matter of sur- 
mise. There is no apparent reason why there should be. Yet the infected Stegomyiz 
have almost certainly become so in a house, and with their very domestic habits must 
be found out of doors, where they would be subject to conveyance by the wind in 
much smaller numbers than the uninfected insects, and consequently a lesser number 
of them would be conveyed aérially. Observation is needed on this subject—the 
distance (across water) that Stegomyiz are aérially conveyed. 


Conveyance by railroads and vessels.—The yellow fever mosquito 
may be conveyed from one place to another in the railway car. I cap- 
tured one in a day coach en route between Donalsonville and Bain- 
bridge, Ga., in August, 1905. My experience in traveling by rail, 
both in Mexico and in the southern part of the United States, leads me 
to believe that the number thus conveyed is very small, so that the 
chance of conveying one that is infected is probably very slight. 

Distribution by vessels may not infrequently be observed. They 
have been found on steam vessels, but much more commonly and in 
greater numbers on sailing vessels, because the latter are more likely 
to present easily accessible breeding places. It can hardly be doubted 
that the outbreaks of yellow fever in such northern cities as Balti- 
more, Philadelphia, New York, Boston, and Quebec were due to the 


17 


importation on sailing vessels of infected mosquitoes. These in pro- 
portion as they found conditions favorable, multiplied more or less 
rapidly and abundantly and produced epidemics which were more or 
less closely confined to, or in the neighborhood of, the shipping. 

Geographic distribution.—The Stegomyia calopus has been found to 
be one of the most widely distributed of mosquitoes. It is primarily 
a tropical insect, but has extended north and south along lines of 
travel, establishing itself permanently wherever the conditions of 
temperature and moisture are favorable. Speaking broadly, it belts 
the globe between 38° north and 38° south latitude. 

Within the United States the points at which it has been found, with 
few exceptions, ‘‘fall within the limits of what are known as the 
tropical and lower austral zones. These life zones include practically 
all of the southern United States which border on the Atlantic Ocean 
and the Gulf of Mexico, with the exception of those portions of 
Virginia, North and South Carolina, Georgia, and Alabama which 
constitute practically the foothills of the Appalachian chain; in other 
words, western Virginia and North Carolina, the extreme northwest- 
ern corner of South Carolina, the northern part of Georgia, and the 
extreme northeastern corner of Alabama. Further than this, the 
lower austral zone includes the western half of Tennessee, the western 
corner of Kentucky, the extreme southern tip of Illinois, the south- 
eastern corner of Missouri, and all of Arkansas except the northern 
portion. It also includes the southern portion of Indian Territory, 
southern Arizona, and some of northern Arizona, and southern strips 
in Utah, Nevada, and California. 

“In the greater part of the territory thus indicated, and where the 
climate'is not too dry, Stegomyia fasciata will, with little doubt, upon 
close search, be found. 

“<A]l the rest of the lower austral territory just indicated, and where 
the climate is not too dry, will constitute a region where the yellow- 
fever mosquito, if once introduced, will undoubtedly flourish. Even 
in the dryer portions of western Texas, southern New Mexico, south- 
ern Arizona, southern California, and southern Nevada, where the 
climate is exceptionally dry, there is a possibility that this species, if 
once introduced, will breed in the water supply of ranches, except, 
possibly, where the water is impregnated with alkali.” 4 


INCUBATION, 


In 29° cases of experimental yellow fever, recorded in the literature, 
produced by mosquitoes in nonimmunes that had not been subjected to 


a Howard, 1903. . ; 

% bThis does not include one case apparently induced by mosquitoes, that had 
*- acquired their infection by feeding on sirup in which the bodies of infected mosqui- 
toes had.been erushed. In this case the incubation period would appear to have 


been not less than 9 nor more than 12 days. 


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19 


Pains.—Pain in some form is one of the earliest and one of the 
most constant symptoms. It is usually marked, but at times, in 
children, and occasionally: in mild cases in adults, it may be slight, 
and in the former sometimes altogether absent. Frequently marking 
the onset or, if not, appearing soon after, are headache, pain in the 
‘back and limba. After two or three days, with the decline in the 
‘ fever, the severity of these usually diminishes. The headache is 
usually frontal, but it is sometimes temporal or occipital; there is 
usually associated with it more or less aching of the eyes. The pain 
in the back is sometimes described as if it had been produced by 
blows with a rod, on which account the French in the West Indies 
have called it the coup de barre; in some instances it is not unlike the 
lumbar pain of smallpox. The aching in the limbs has its seat in the 
muscles, and affects more particularly the muscles of the thighs and 
calves of the legs. 

Facies.—With the onset of the disease the face usually becomes 
flushed and somewhat swollen. The flushing may be slight or occa- 
sionally altogether absent, or it may be so marked as to suggest the 
initial rash of dengue, especially if it extends, as it sometimes does, 
down the neck to the upper part of the chest. The amount of swell-- 
ing varies; it may be inappreciable or it may be sufficient to smooth 
out somewhat the lines of expression. Coincident with the flushing 
of the face the eyes become congested and red and sensitive to light. 
In mild cases the injection of the conjunctiva may be shown only as an 
abnormally prominent capillary mesh; in the severe cases the con- 
junctiva may appear as if inflamed, and in rare instances it may become 
raised around the cornea from infiltration of serum and blood. The 
flushing of the face and the injection of the eyes usually diminish as 
the temperature begins to decline. 

In certain grave cases, coincident with the appearance of black 
vomit, the face becomes pale, the lips cyanosed, the eyes sunken, and 
the redness of the conjunctive becomes replaced by a more or less 

distinct tinge of yellow. 

~~ .“Skin.—At first the skin is warm to the fuel and usually, but by 
no means always, dry; sometimes, indeed, it is covered with perspira- 
tion which may persist throughout the disease. Later, in some 
cases, with the occurrence of black vomit, the skin becomes cool and 
clammy. Jaundice occurs in all but some mild cases; it usually 
_ appears first about the third day as a slight tinging of the ocular con- 
junctiva. At almost’ the same time, or very soon after, it may be 
noticed that the skin also has acquired a pale yellow tint. Its early 
detection may be facilitated by pinching up a fold of skin and causing 
a momentary local anzemia. 

As the case progresses the icteric tint, which at first is faint, grad- 
ually becomes more pronounced. The depth of color attained varies 


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Yellow fever, continued type; very severe. Experimental by bites of Stegomyia catepus. (Parker, Beyer, and Pothier. } 


21 


reason that there may be observed in many cases a progressive lower- 
ing of the temperature with the approach of a fatal termination, so that 
at the end the temperature may be little if any above normal. In some 
fatal cases, however, the temperature remains elevated to the end; or, 
if it has fallen, rises acutely before death and may continue its ascent 
for some minutes after. Agonic and post-mortem temperatures of 
42.5° and 48° C. (108.5° and 109.5° F.) have been observed. During 
the first days of convalescence the temperature is usually somewhat 
_ below normal. 

Pulse.—At the outset the pulse is usually full and bounding, and 
the number of its beats may register 120 or 125 per minute. As the 
fever progresses the tension and the rapidity of the pulse diminish. 
At intervals in the course of the disease the pulse may be distinctly 
dicrotic. At the close,in fatal cases, it becomes rapid and feeble; in 
those terminating favorably the pulse not infrequently falls to 50 and 
occasionally even less. « It is often stated that slowness is a peculiar 
characteristic of the pulse in yellow fever, but this is not altogether 
correct. While, to be sure, the pulse in this disease is not a rapid 
one, its peculiar character consists in the sluggishness with which it 
responds to the stimulus of a rise in the temperature. This sluggish- 
ness at times amounts to an actual irresponsiveness which is so marked, 
early in many cases, that there is witnessed the phenomenon of a sta- 
tionary or falling pulse rate with a rising temperature, or a falling pulse 
with a stationary temperature. This is not simply a Jack of correlation 
such as is sometimes observed in typhoid, but an actual divergence 
between the two. Attention was first called to this phenomenon by 
Faget, of New Orleans, who considered it pathognomonic. 

Unfortunately this sign is not always present and, when present, it 
is not always as well defined as could be wished. Its minor mani- 
festations are occasionally observable in other febrile affections, such 
as pneumonia, malaria, dengue, and septicemia. 

Respiration.—The number of the respiratory movements is usually 
not notably increased. The character of the respiration is, in many 

_cases, altered somewhat. Many patients experience a feeling of tho- 
racic oppression so that at variable intervals their breathing is punctu- 
ated by a sighing respiration. In the latter stages of some cases 
‘hiccough appears; it is always an ominous sign. 

Blood.—The results of blood examination are characterized chiefly 
by. their negative character. Morphologically the cellular elements 
show no alteration. In uncomplicated cases the number of the red 
corpuscles and the percentage of hemoglobin are not, asa rule, reduced, 
but, on the contrary, frequently show an increase above the normal. 
The number of the white corpuscles is somewhat diminished, and the 
proportion of the different forms is slightly altered. The chief altera- 
tion consists in an increase in the percentage of the polymorphonuclear 


22 


leucocytes and a diminution in the eosinophiles. Sometimes there isa 
slight increase in the large mononuclears. There is usually a notice- 
able increase in the number of the blood platelets. The coagulability 
of the blood does not undergo any material change.“ With the onset 
of convalescence there is a fall in the number of the red corpuscles 
and in the percentage of hemoglobin. 

Hemorrhages.—A tendency to hemorrhage is one of the marked 
characteristics of the disease. Asa rule, this does not manifest itself 
before the third day. The most common and, in a very large propor- | 
tion of the cases, the only manifestation of this tendency is bleeding 
from the gums. The gums become more or less swollen and the blood 
may ooze from them spontaneously or, more commonly, only after 
some traumatism, such as a slight pressure of the examining finger. 
Epistaxis is almost as frequent a symptom as bleeding from the gums; 
it may occur at the onset, but more commonly, like bleeding from the 
mouth, does not appear until the fourth or fifth day. In women, 
menorrhagia or metrorrhagia are common manifestations. During 
pregnancy death of the fetus and miscarriage are of common, though 
not invariable, occurrence. 

Hemorrhage from the stomach, appearing as black vomit, occurs in 
the graver cases only. It varies considerably in amount; in the lighter 
grades it may be barely perceptible, as dark streaks or specks in the 
vomited matter, but in the severer forms it may be yo profuse that 
the vomitus is uniformly dark red or black, like coffee grounds. Blood 
originating in a hemorrhage from the nose or mouth which has been 
swallowed may give to vomited matter precisely the same character 
as blood which has its origin in the stomach. Black vomit, therefore, 
does not necessarily mean gastric hemorrhage. Melena may result 
from passing altered blood which had its origin in the stomach, or it 
may be due to hemorrhage from theintestine. The quantities of black 
vomit ejected and melena discharged per rectum are at times surpris- 
ingly large. 

Digestive tract.—In some of the severer forms the lips become dry 
and cracked and bleeding. In almost all cases the gums become more 
or less swollen, and at first covered with a white epithelial coating 
which rapidly wears off, leaving them red and spongy and disposed to 
bleed on slight pressure. The tongue at first is commonly moist, with 
a gray coating over the center and dorsum and with red tip and edges. 
As the disease progresses, in severe cases, the tongue becomes dry, 
red, fissured, and more or less streaked with blood. The appetite is 
lost from the first, but returns rapidly with convalescence. Thirst is 
frequently marked. Nausea and vomiting are commonly, but not 
invariably, present. In general, they appear with or soon after the 
onset, and, as a rule, become more or less accentuated with the prog- 


@Marks, 1906. 


28 


ress of the disease. There is nothing peculiar about the character of 
the vomited matter in any but some of the grave or the fatal cases. 
At first it may consist of food remnants or of such liquids as may 
have been swallowed; later it consists of ‘a thin mucus, which soon 
becomes bile-stained. In some grave cases, about on the third day, 
sometimes on the second, but more commonly on the fourth or fifth, 
streaks of red or black may be detected in the vomited matter. These 
streaks are more or less altered blood and are the first signs of black 
vomit., In some cases it does not go beyond this, but in some very 
severe cases and in most of the fatal ones the vomited matter soon 
becomes more or less uniformly black in color. In some fatal cases 
black vomit does not manifest itself during life, but is found post- 
mortem. In the severer cases there is sometimes associated with the 
vomiting or retching more or less distressing hiccough. In the cases 
terminating favorably the gastric irritability gradually diminishes and 
disappears. The bowels are usually constipated. The movements are 
at first natural in color and remain so in all but some of the grave 
cases, in which they may become dark and tarry. Some tenderness, 
especially in the severer cases, can usually be elicited by pressure in 
the epigastric region as early as the second day. Abdominal pains of 
a colicky character -are occasionally complained of; sometimes they 
are very severe and cause the patient intense suffering. 

Urine.—In mild cases and in those of moderate severity the urine 
may show but slight alteration in character as regards quantity and 
density. In severer cases it becomes reduced in volume and somewhat 
in specific gravity. Complete suppression is not a rare occurrence in 
fatal cases. The suppression may, however, only be apparent and due 
’ to retention, as may be demonstrated by catheterization. 

In-all but the mildest cases albumin appears in the urine at some 
time in. the course of ‘the disease. It may appear within 24 hours 
after the onset, though usually not until the end of 48 hours; or 
it may delay its appearance until after the subsidence of the fever. 
At first it appears only in small amounts—a slight trace, perhaps— 
which in some cases is not increased, while in others it rapidly aug- 
ments in volume up to 80 to 90 per cent. In favorable cases the’ 
amount begins to diminish almost at once or very soon after the 
maximum has been recorded, and will be found to have disappeared 
in from three or four days to two or three weeks from the time it first 
appeared. In some cases, however, the albuminuria is very transitory 
and .may not be detected unless every specimen of urine passed be 
examined. When jaundice is present, biliary pigment appears in the 
urine, as may frequently be noted when making the nitric-acid test 
for albumin. Albertini and Guiteras® report the absence of the diazo 


@Guiteras, 1904b, p. 594. 


24 


reaction in this disease. Haylin, granular and epithelial casts, which 
may be bile-stained, are commonly encountered in the sediment. 

Liver.—Except jaundice, which has already been discussed, there 
appear in uncomplicated cases no symptoms referable to this organ, 
the dimensions of which are, as a rule, not materially altered.: 

Spleen.—In uncomplicated cases the spleen does not undergo any 
material change in size. 

Nervous system.—Sleeplessness, more or less marked, is a frequent 
symptom. Delirium is of common occurrence; in many cases itis only 
a slight mental wandering during the first or second night after the 
onset. In some of the grave cases this wandering gives place to a 
muttering or an active maniacal delirium; toward the end in some 
fatal cases unconsciousness, more or less profound, supervenes and 
the scene is closed with tonic convulsions involving particularly the 
muscles of the face and flexors of the arms. In all mild, in many’ 
grave, and in some fatal cases the mind is clear and alert throughout 
the course of the attack. : 

Duration:—The great majority (75 per cent) of all cases terminate 
before the ninth day. A fatal termination rarely occurs before the 
third day, but it has been recorded as late as the twenty-second. 

Complications.—In the vast majority of cases yellow fever runs its 
course without any disturbing complications. Occasionally, however, 
a deep-seated muscular abscess or an inflammation of the parotids may 
occur. 

The most common complication is malaria, which may manifest 
itself either during the febrile period or, and more commonly, during 
convalescence. 

Yellow fever may occur as.a complication in the course of some 
chronic diseases such as pulmonary tuberculosis, cirrhosis of the liver, 
dysentery, malarial cachexia and ankylostomiasis, or some acute 
infections such as typhoid fever and gonorrhea. 

Convalescence.—With the termination of the fever the patient finds 
himself, even after a relatively mild attack, markedly depressed in 
strength. As a rule, however, recuperation is rapid. Occasionally 
‘convalescence is retarded by the occurrence of complications such as 
malaria, furunculosis, and peripheral neuritis. 

Relapse and second attacks.—A return of the fever and other symp- 
toms characterizing an attack of yellow fever after convalescence has 
been established is rare. Cases of relapse have, however, been 
observed after an interval of 2 or 3 days to 2-weeks ora month. It 
is a question whether so-called relapses occurring after an interval of 
2 weeks or a month should not more properly be considered second 
attacks. : 

As a rule with but very rare exceptions one attack of the disease 
confers immunity on the individual for life. Nevertheless, there are 


25 


on record some fairly convincing instances of a second more or less 
grave attack a year or longer after the first. 


DIAGNOSIS. 


The increase in knowledge concerning the etiology of various com- 
municable diseases and the improvement in methods “devised for their 
recognition have been followed, among other things, by a broaden- 
ing of our conceptions relating to the degrees of severity which they 
may assume. Thus when, for example, we speak of typhoid or 
cholera we think not only of the severe classical types, but we have 
in mind also those mild and irregular forms which are recognizable 
only because of the improved tests which are at our command. 

We now know that, like cholera and typhoid, yellow fever also mani- 
fests itself in all grades of severity; but unfortunately, unlike the 
former, we have no test whereby in any particular case we can say 
definitely that this is or is not yellow fever. The recognition of this 
fact is of the very highest importance with respect to prevention, for 
it makes it imperative that in infectible regions every case of fever, 
however mild, should be considered as potentially yellow fever will 
this disease can positively be excluded. 

On taking charge of a case of fever the practitioner, in the South, 
should therefore start with the assumption that he is dealing with a 
case of ‘yellow fever, and in formulating his final, definite diagnosis, 
in which this disease is excluded, he must use the greatest care and 
caution. The clinician must fix it firmly in his mind that yellow fever 
is not excluded simply because he knows of no other previous case; 
obviously he may be dealing with the first case himself, or several 
cases may have occurred in such as, for one reason or another, had 
received no medical attention. Nor is yellow fever eliminated from 
consideration because he fails to detect any so-called ‘‘ characteristic” 
sign or symptom. 

Ordinarily the combination of an acute fever with albuminuria, jaun- 
dice, an irresponsive or divergent pulse, a tendency to hemorrhage from 
the mouth, and gastric irritability, with no material alteration in the 
size of the liver and spleen, should leave no doubt in the observer’s 
mind as to the nature of the disease with which he is dealing. 

The diseases with which yellow fever may be confused are malaria, 
hemoglobinuric fever, dengue, grippe, bubonic plague, typhoid fever, 
acute yellow atrophy of the liver, Weil’s disease, and relapsing fever. 

Malaria.—Yellow fever at times simulates certain irregular forms 
of malaria very closely, and in the absence of any known infection the 
grave error of mistaking it for malaria has, not rarely, been com- 
mitted. On the other hand, during epidemic seasons the mistake is 
not infrequently made, both ‘within and without the infected zone, of 


calling malaria yellow fever. 


26 


Careful examination of stained blood smears will show an absence 
of the plasmodia in the former group and their presence in the latter; 
but while the absence. of the plasmodium from the blood excludes 
malaria in the first instance, its presence in cases of the second group 
does not eliminate yellow fever from consideration. In these cases, 
yellow fever should be excluded only after a careful study of the case. 
Careful observation for several days after the adminstration of a few 
doses of quinine, preferably subcutaneously” or intravenously, may 
be neeessary. The abrupt decline in the fever coincident with the 
disappearance of the parasites from the circulation following the exhi- 
bition of the quinine in the manner indicated, with absence of albumen 
from the urine or its presence only asa trace, with no jaundice and no 
tendency to hemorrhage, may generally be interpreted as probably 
excluding yellow fever. The mere decline of the fever after the 
administration of quinine without a previous examination of the blood 
to determine the presence of the malarial parasite does not exclude. 
yellow fever. 

Hemoglobinuric fever.—This grave manifestation of malaria resem- 
bles yellow fever in its abrupt onset, bilious symptoms, jaundice, and 
albuminuria, but differs in being characterized by a rapid blood 
destruction and enlargement and tenderness of the liver and spleen. 
The blood destruction manifests itself by a reduction in the number 
of the red corpuscles, low hemoglobin percentage, and by the red or 
black color of the urine, due to the elimination of hemoglobin. 

Dengue.—The differentiation between well-marked types of dengue 
and yellow fever is a matter presenting no serious difficulty after the 
first two or three days. The points of difference most to be relied 
on are the presence of an eruption and the absence of jaundice in 
dengue. Albuminuria, which is so-prominenta sign even in relatively 
mild attacks of yellow fever, is slight and commonly altogether absent 
in even quite sharp attacks of dengue. In the latter disease the per- 
centage of the polymorphonuclear leucocytes is reduced whereas in 
yellow fever it is more or less increased. 

When, however, we come to deal with cases that are ill-defined, 
cases that present no eruption (or in which none has been detected), 
in which jaundice is doubtful ‘or absent, and in which no albumin or 
only a dubious trace of it can be detected, we encounter a very real 
and serious difficulty in deciding as to which of the two diseases we 
have before us. While it is of the very greatest importance to recog- 
nize that we have no means of surely identifying individual cases of 


@ The injection should be given into a muscle, not into the subcutaneous cellular 
tissue. With good aseptic technique the intravenous injection is preferable. Give 
1 gram (15 grains) of the bimuriate dissolved in 1 cc. (15 minims) of distilled water 
and repeat three times at 12-hour intervals; the solution and syringe must, of course, 
be sterile. 


27 


this type, nevertheless a clue to their nature will, as a rule, be discov- 
ered if a careful study of a series of cases be made. In a group some 
individuals are very likely to be found that will show, if they are yel- 
low fever, unmistakable jaundice and a degree of albuminuria quite 
out of proportion to the mildness of the attack, whereas, if they are 
dengue, some cases will be found that will exhibit the characteristic 
rash. In isolated instances, or until cases presenting distinctive symp- 
toms are encountered, the observer will do well to suspend judgment 
and not assume, as is too frequently done, that mildness of attack and 
a failure to die are pathognomonic of dengue. He should remember, 
also, that the two diseases may occur side by side, thereby multiplying 
the difficulties of the problem and rendering caution imperative. 

Grippe.—An attack of influenza is characterized, as a rule, by 
symptoms referable to a catarrhal condition of the upper air pas- 
sages. Cases in which these symptoms are marked hardly come into 
consideration in the diagnosis of yellow fever. As with dengue it is 
the less well-defined cases of influenza that counterfeit and are simu- 
lated by mild and ill-defined cases of yellow fever; and much that has 
been said concerning the diagnosis from dengue is here also applicable. 

Bubonic: plague—In localities where yellow fever and plague pre- 
vail, and at quarantine stations in connection with vessels from such 
ports, the question of differentiating the-two diseases may arise. 
Clinically there is only a very superficial resemblance between the 
two, but in all cases of doubt a careful bacteriological examination 
should be made of the sputum, blood, or aspirated juice from enlarged 
glands; the latter, by the way, are but very rarely met with in uncom- 
plicated yellow fever, while in plague they are not only enlarged but 
inflamed and the surrounding tissue infiltrated. « 

Typhoid fever.—Early in the disease typhoid may be mistaken for 
yellow fever, but the resemblance is slight and observation of the 
patient for 3 or 4 days will be certain to resolve any doubts. At 
this stage the general appearance and the increasing apathy of the 
patient are distinctive. The’temperature is a gradually ascending one 
or has reached the fastigium, and the pulse, though not fast, follows 
the daily oscillations of the fever and does not, as in yellow fever, 
tend to become slower from day to day. Jaundice is, at-best, but a 
rare complication of typhoid and may be said almost never to occur 
early in the disease. The urine frequently gives the diazo reaction, 
and at this time is usually free of albumin, though occasionally traces 
of the latter constituent may be met with; nephritis is a late and not 
common complication of typhoid fever. The bacillus of Eberth may 
be isolated from the blood. 

In an attack of yellow fever of three or four days duration and with 
a corresponding elevation of temperature the combination of symp- 
toms distinctive of a well-defined attack of this disease would be clearly 


28 


manifested. In some of the severer forms of yellow fever the tem 
perature is occasionally prolonged for two to three weeks, and som 
of the accompanying symptoms are, in some of these cases, suggestiv 
of typhoid. Typhoid fever, in the second or third week, will giv 
the Widal reaction and Eberth’s bacillus may be isolated from th 
blood. These are, of course, absent in yellow fever. 

Acute yellow atrophy of the liver.—This is a very rare disease. I 
occurs most commonly in women, and in these more particularly dur 
ing pregnancy. The disease is ushered in like a case of catarrha 
jaundice. A marked and rapid reduction in the size of the liver i 
distinctive. : 

In yellow fever the size of the liver is unaffected. In malignan 
jaundice albuminuria is of frequent occurrence, but it is not as markec 
nor as constant as in cases of yellow fever of the same degree of viru 
lence. The duration of over 75 per cent of the recorded cases o 
malignant jaundice has been in excess of seven days; the duration o: 
almost 75 per cent of the cases of yellow fever does not exceed sever 
days. An early fatal termination in such a case would decidedly favoi 
a diagnosis of yellow fever, but a later termination should not, how 
ever, be regarded as excluding yellow fever. 

Weil’s disease.—This disorder is characterized by fever, intense 
jaundice, swelling and tenderness of the liver, diarrhea, notabk 
enlargement of the spleen, and nephritis. In yellow fever neithe: 
liver nor spleen are enlarged, a tendency to constipation is the rule 
and in cases of a corresponding grade of severity, the hemorrhagic 
symptoms are likely to be more marked and to appear earlier. 

Leelapsing fever.—The presence of the Spirochzta of Obermeier ir 
the blood is distinctive. ; 

Catarrhal jaundice.—This may in some instances have to be consid 
ered. In this condition the jaundice appears with little or no elevatior 
of temperature, preceded by slight, if any, symptoms of indigestior 
and accompanied by clay-colored stools. In yellow fever the jaundice 
appears after at least two or three days of fever and will be accom 
panied by the other symptoms characterizing a well-defined attack 
the stools are not clay colored. 


REFERENCES. 


BuaNncHaRD (R.). 
1905.—Les moustiques. Paris. 


Barreto DE Barros and Ropricuss. 
1903.—Experiencias realisadas no Hospital de isolamento de 8. Paulo, etc. Rev 
med. de Séo Paulo, February 28, v. 6, p. 69-73. 
Berry (T. D.).. 
1905.— Ability of the larvee and pupe of the Stegomyia fasciata to withstand des 
iccation. Pub. Health Rep., Washington, v. 20, part 1, p. 1148. 


Carter (H. R.). 
1900.—A note on the interval between infecting and secondary cases of yellov 
fever, etc. New Orl. Med. & Surg. Journal, May. 


29 


Carter (H. R. )—Continued. 
1901a.—The period of incubation of yellow fever. Med. Record, N. Y., March 


9, v. 59. 
1901b.—A note on the spread of yellow fever in houses. Med. Record, N. Y., 
June 15, v. 59. 
eee characteristics of Stegomyia fasciata, etc. Med. Record, N. Y., May 
, Vv. 65. : 


CaTHRALL (I.). : : 
1800.—Memoire on the analysis of black vomit. Phila. 


Dow.er (B.). 
1855.—On the natural history of the mosquito. New Orl. Med. & Surg. Journ., 
v. 12, p. 187. 
Faget (J. C.). 
1875.—Monographie sur le type et la spécificité de la fiévre jaune établis avec 
Vaide de la montre et du thermométre. Paris and New Orleans. 


Frirta (STuBBINS). e 
1804.—A treatise on malignant fever with an attempt to prove its non-contagious 
nature. Inaugural dissertation. Phila. 


Fintay (Cartos J.). 

1881.—El mosquito hipotéticamente considerado como agente de transmisién 
de la fiebre amarilla. Ann. de la Real Academia de ciencias med... . de la 
Habana, Aug. 14, v. 18, pp. 147-169. 

Finuay and Dreteapo. 

1890. —Estadistica de las inoculaciones con mosquitos contaminados en enfermos 
de fiebre amarilla. Ann. de la Real Academia de ciencias med.... de la 
Habana, v. 27, pp. 495 and 591. 

Francis (EDWARD). : 

1907.—Observations on the life cycle of Stegomyia calopus. Pub. Health Rep., 

Washington, Apr. 5, v. 22, p. 382. 


Guireras (Juan). 
1901.—Experimental yellow fever. Am. Med., Phila., Nov. 23. 
1904a.—Notes from the laboratory. Rev. de Med. trép., Habana, v. 4, p. 64. 
1904b.—Yellow fever. Buck’s Ref. Handbook Med. Sciences, v. 8, p. 590. 


Howarp (L. 0.). 
1901.—Mosquitoes. New York. 


1903.—Concerning the geographic distribution of the yellow fever mosquito. 
Pub. Health Rep. (Supplement), Washington, November 13, v. 18, No. 46. 


La Rocue (R.). 
1855.—Yellow fever. Phila. 


Marcuovux, SariMBENI, and Simon. ice ; 
1903.—La Fiévre jaune, Rapport de la mission frangaise. Ann. de l’Inst. Pas- 
teur, Paris, Nov., v. 17, p. 665. 


Marcuovux and Srmonp. 
1906 a.—Etudes sur la fiévre jaune. Ann. del’Inst. Pasteur, Jan., v. 25, p. 16. 


1906 b.—Idem. Idem, Feb., v. 25, p. 104. 
1906 c.—Idem. Idem, March, v. 25, p. 161. 


Margs (Lewis Harr). : ; 
1906.—The coagulability of the blood in yellow fever. Am. Journ. Med. Sci- 
ences, November. 
Nort (Jos1au C.). : 
Be ees fever contrasted with bilious fever, etc. New Orl. Med. and 
Surg. Journ., p. 590. 
N & Knapp. 
°¥'1906.--Studies on Spirillum obermeiert and related organisms. Jour. Infect. Dis- 
eases, Chicago, v. 3, No. 8, p. 29. 


380 


Orro & NEUMANN. ; 
1905.—Studien tiber Gelbfieber in Brasilien. Zeit. f. Hyg. u. Infectionsk., v. 5: 
p. 357. 


Parker, Breyer, and PotHiEr. 
1903.—A study of the etiology of yellow fever. Yellow Fever Inst., U. 8. P. 
and M. H. S., Washington, March, Bull. No. 13. 


Reep and Carro.u. 
1901.—The prevention of yellow fever. Med. Record, N. Y., Oct. 26, v. 6( 
p. 641. : 


1902.—The etiology of yellow fever. A supplemental note. Am. Med., Phila, 
Feb. 22, v. 3, p. 301. 


Reep, CaRrouu, and AGRAMONTE. 
1901a.—The etiology of yellow fever. An additional note. Journ. Am. Mec 
Assn., Feb. 16, v. 36, p. 431. 


1901b.—Experimental yellow fever. Am. Med., Phila., July 6, v. 2, pp. 15-22 


Reep, Carrot, AGRaAMontTs, and Lazear. 
1900 a.—The etiology of yellow fever. A preliminary note. Phila. Med. Journ. 
Oct. 27, v. 6, p. 790. 


Rosenavu and GOLDBERGER. : 
1906. —The hereditary transmission of the yellow fever parasite in the mosquitc 
Yellow Fever Inst., U. S. P. H. and M. H.S., Washington, Jan., Bull. No. 18 


Rosenav, PARKER, Francis, and BryEr. 
1904.—Experimental studies in yellow fever and malaria. Yellow Fever Inst. 
U. 8. P. H. and M. H.S., Washington, May, Bull. No. 14. ; 


Ross (Joan W.). 
1902.—Yellow fever contracted from the mosquito. New Orl. Med. & Surg 
Journ., May. 


Sanareuu (Dr. J.). 
1897.—Etiologie et pathogénie de la fiévre jaune. Ann. de l’Inst. Pastew 
v. 11, p. 483. 


ScHAUDINN (FRITz). 
1904.—Generations- und Wirtswechsel bei Zrypanasoma und Spirochxte. Art 
a. d. Kaiser. Gesundheitsamte, v. 20, part 3, p. 435. 
STEPHENSON and CHRISTOPHERS. 
1904.—The practical study of malaria. 2d ed., London. 


Srernperc (GroRGE M.). | 
1890.—Report on the etiology and prevention of yellow fever. Washington. 


Srimson (A. M.). 
1907.—Note on an organism found in yellow fever tissue. Pub. Health Rep 
Washington, May 3, v. 22, No. 18, p. 541. 
THEOBALD (FRED. V.). 
1901.—A monograph of the culicide or mosquitoes, &c. London, vols. 1, 2, an 
plates. 
1903.—Idem. vol. 3. 


Tuomas (H. WoLFerstan). 
1907.—Yellow fever in the chimpanzee. Br. Med. Journ., Jan. 19. 


& 


O 


oe : ' : t 
YELLOW FEVER’ INSTITUTE, BULLETIN: No. 17 


Treasury Denartniens, U. 8. Public: Health and Mairine-Hospital Service 
WALTER way, Surgeon-General 


THE PROPHYLAXIS OF 
"YELLOW FEVER. 


' BY 


G. M. GUITERAS 


FEBRUARY, 1909 


‘WASHINGTON 
GOVERNMENT PRINTING OFFICE 
; 1909 


if 


YELLOW FEVER INSTITUTE, BULLETIN No. 17 
Treasury Department, U. S. Public Health and Marine-Hospital Service 
WALTER WYMAN, Surgeon-General 


THE PROPHYLAXIS OF 
_ YELLOW FEVER 


BY 


G. M. GUITERAS 


FEBRUARY, 1909 


WASHINGTON 
GOVERNMENT PRINTING OFFICE 
1909 


YELLOW FEVER INSTITUTE. 


Treasury Department, Bureau of Public Health and Marine-Hospital Service. 


WALTER WYMAN, Surgeon-General. 


Buiietin No. 17. 


THE PROPHYLAXIS OF YELLOW FEVER. 


& 


By G. M. GuirERAs, Surgeon, U. 8. Public Health and Marine-Hospital Service. 


The study of yellow fever has ever been an interesting one from 
the time it was first observed in the Western Hemisphere to the 
present day. 

Whether the disease is indigenous to America or was introduced 
from the west coast of Africa, is a mooted question. From the his- 
torical data which we have on the subject it would appear as though 
the latter opinion was the correct one. 

The disease has been a scourge to the fair and fertile regions of 
tropical and subtropical America and has greatly retarded their 
material progress. Its existence in an endemic form at various 
points, such as Habana, Rio de Janeiro, and Vera Cruz, has given 
these ports an unenviable reputation with travelers and seriously | 
hampered their commercial interests, and carried from these foci 
to other infectible territory it has caused widespread epidemics 
resulting in great loss of life, interference with commerce, and finan- 
cial disaster. 

The peculiar characteristics of the disease and the mystery which 
shrouded its etiology and method of propagation have invested it 
with remarkable interest, and in our day the solution of this mys- 
tery, in so far as the method of propagation is concerned, has given 
us one of the most important advances in modern science. 

The work of the United States Army Board in establishing beyond 
a doubt the hypothesis enunciated by Carlos Finlay, in 1881, as to 
the transmission of yellow fever by the mosquito, was indeed bril- 
liant. I had the pleasure of being present at the International Sani- 
tary Congress held in Habana when Doctor Reed presented his 


(3) 


+ 


memorable report proclaiming the new dogma. The work ther 
described was so thorough and the results so clearly established as 
leave no doubt in the minds of his hearers as to the truth of his c 
clusions. Considering the number of able men who had been stuc 
ing the subject, it is remarkable that a period of nearly twenty ye: 
should have elapsed before Finlay’s ideas were seriously considei 
and finally accepted. It is still more remarkable when we consic 
that since the early part of the nineteenth century various observ 
had indicated the mosquito as in some way related to the dise: 
under consideration. There is no doubt but that the interesting we 
of Dr. Henry R. Carter, of the Public Health and Marine-Hospi 
Service, in establishing, in 1898, the “ extrinsic ” period of incubati 
of yellow fever—that is, the interval between the infecting and s 
ondary cases—gave renewed impetus to the study of the mosquito 
a factor in yellow fever and indirectly brought about the confirn 
tion of the truth of the hypothesis of Doctor Finlay. 


PRINCIPLES OF PROPHYLAXIS. 


The prophylaxis of yellow fever, which up to a few years ago w 
founded on ideas so uncertain and insecure, is to-day firmly bas 
on the discovery of the transmitting agent of the disease. This age 
can be destroyed and may be prevented from becoming itself ino 
lated and, if inoculated, from transmitting the disease to the we 

In the abstract the measures necessary to accomplish this are pi 
fectly feasible. No extraordinary means or intelligence is requir 
to make them effective; only a careful attention to details. But 
practice, when the peculiarities of human nature, the rights of t 
individual as guaranteed by the law, and the ignorance of the peo} 
have to be taken into account, the problem becomes both difficult a 
onerous. 

The subject of the prophylaxis of yellow fever has been thorougt 
thrashed out during the last few years, and as the matter is so sim} 
in itself there is but little that may be added to what has alrea 
been said. Within the time stated the writer has been connect 
with the two epidemics which have occurred in the United States— 
Laredo, Tex., in 1903, and at New Orleans and Vicksburg in the ge 
eral epidemic of 1905—and has carried out with success the princip 
of prophylaxis which will be referred to in this article. It is n 
however, the purpose to enter herein into the minutiz of the met 
ods of prophylaxis, but rather to invite attention to some of t 
difficulties to be encountered and to suggest some of the mea 
whereby, in the opinion of the writer, the obstacles found in t 
practical application of the principles involved may be lessened 
eliminated. 


5 


IMPORTANCE OF EARLY DIAGNOSIS. 


The knowledge that we now have of the transmission of yellow 
fever gives us a secure basis upon which to lay our plans against the 
introduction of the disease or to prevent its spread when introduced. 
There is, however, one link wanting to give us absolute control of the 
disease, and that is the etiological factor. The consensus of opinion 
up to the present time is that it is a micro-organism, ultramicroscopic, 
and as yet beyond our means of detection. The importance of deter- 
mining this causative agent is apparent from every point of view, but 
especially so as an aid to diagnosis, for the prompt and positive diag- 
nosis of yellow fever is one of the most important factors in the pro- 
phylaxis of the disease, especially when it appears in a locality where 
it was previously unknown or that has been free of it for some time. 

In order to take measures against the spread of a disease it is first 
of all necessary that we should be aware of its presence. In the case 
of yellow fever considerable embarrassment presents itself in deter- 
mining this fact, both on account of the inherent difficulty in making 
the diagnosis and the natural fear of the attending physician of the 
alarm and other unfortunate consequences which will usually follow 
a declaration of its presence, and especially the fear that he-may be, 
after all, mistaken in the diagnosis. This applies particularly to. 
those localities where yellow fever is a new or an infrequent visitor 
and where there exists an unreasonable fear of the disease. 

It is foreign to the purpose of this paper to enter into a discussion 
of the differential diagnosis of yellow fever, but I desire to impress 
upon the reader the importance, from a prophylactic point of view, 
of the early diagnosis of all cases of this disease. We know that the 
Stegomyia calopus can only become infected by biting the patient 
during the first three’ days of the illness; hence the diagnosis should 
be made in its very incipiency. Frequently it is not easy to do this, 
especially in mild cases. It is here that our knowledge is at fault and 
all our energies should be bent to discover some means of making a 
positive diagnosis, one which can not be controverted. When this is 
achieved the citadel will have been won and the last vestige of 
danger from this disease removed. 


USUAL CONDITIONS WHEN YELLOW FEVER IS DECLARED. 


Under present circumstances the following conditions almost inva- 
riably confront us in an outbreak of yellow fever in a locality usually 
free from it, such as, for instance, our South Atlantic and Gulf 
coast: A case of fever presents itself to a physician who is not on 
the lookout for yellow fever and who perhaps has never seen the 
disease. If it be a mild case of yellow fever, it will probably get 
well without his suspicions being even aroused. If, however, it be 


6 


of moderate severity and the physician careful and observant, he will 
soon note symptoms which do not square with the fevers which he has 
been accustomed to see. He may then suspect that all is not right 
and begin to think of the possibility of yellow fever. Immediately 
the purely medical and scientific character of the case becomes 
clouded by the material considerations involved. Is the diagnosis 
positive? Shall the case be reported or not? From where could 
the infection have come? This last question is always given undue 
weight, with fatal results, because as a rule it is impossible to answer, 
and its consideration leads to uncertainty and delay. But why 
should we pause to answer? Do we do so in a case of measles, scar- 
latina, or smallpox? Why not make the diagnosis on the symptoms 
of the disease as presented to us and not bother at that critical mo- 
ment with the abstruse study of its possible origin? That surely 
would be the most rational and practical way to proceed. In any 
case, it is indeed a heavy responsibility to satisfactorily answer these 
questions under the conditions at present affecting our Southern 
States or other localities similarly placed. The usual course of action 
is as follows: The attending physician will consult with his con- 
fréres. Some will opine that it is, others that it is not, yellow fever. 
One who has had some experience with the disease, a so-called 
expert, is finally called in and, we will presume, verifies the diagnosis 
of yellow fever. As an immediate result of this declaration the 
physicians of the place, and with them the public, divide into two 
antagonistic camps, one maintaining that the disease is yellow fever, 
the other that it is not. And thus, with much wrangling and dis- 
order and under the most discouraging circumstances, the work 
of preventing the spread of the disease is inaugurated. The effort 
to stamp it out then becomes a veritable campaign, not only against 
the mosquito, but against a usually small but determined party of 
opposition among the people. Such a condition of affairs would 
not exist if the diagnosis could be promptly established beyond ques- 
tion or cavil. 

To attain this being impossible with the diagnostic means at 
present at our command, I pass on to speak of what seems to me a 
most important indirect prophylactic measure, one which may do 
much to offset the results of our present inefficiency to promptly 
establish an absolutely correct diagnosis—and that is education. 


EDUOATION AS A PROPHYLAOCTIO FACTOR. 


The people in general, and the medical profession as well, should 
be taught the truth about yellow fever, its comparatively low mor- 
tality as treated at present, and the facility with which the disease may 
be avoided and controlled. In a community which is well informed 


7 


on these points the presence of a case of yellow fever could be an- 
hounced without any fear of alarm or panic and the measures, to, 
prevent its propagation put in force at once without clamor or delay. 
The physician could act simply on the merits of the case from a pro- 
fessional standpoint. If the disease under observation presented the 
symptoms of yellow fever, he would announce it as such without 
stopping to consider or, for the time being, trying to determine from 
whence it came or obscure his judgment with considerations as to the 
effect of his diagnosis on the business interests of the locality or on 
his own personal interests. Such a condition of affairs is much to be 
desired and with patience and preserverance may be attained, 

The education of the public on this subject acts not only in this 
indirect. manner, but directly as well, for it will so guide public 
opinion that it will be possible to practically eliminate the transmit- 
ting factor of the disease, the mosquito, the stegomyia, calopus. And 
as it is impracticable to select only the stegomyia calopus for destruc- 
tion, a campaign against thig mosquito must be a general one, and also 
include those responsible for the transmission of malaria, filaria, etc., 
thus removing from the Tropics and subtropics some of the most. 
important causes of morbidity and mortality, and which heretofore 
have, been serious obstacles to their political, commercial, and indus- 
trial progress. Education on this subject, therefore, I consider, of 
prime, importance in the prophylaxis of yellow fever, and it, is sur- 
prising how little has been done or is being done on this line. 

The writer in his report to the surgeon-general on the yellow fever 
epidemic at Laredo, Tex., in 1903, said: 

“ Insistent and continued efforts should be made through the public 
press and other available means to educate the people within the 
sphere of influence of the stegomyia fasciata (calopus) , so that they 
will learn to protect themselves against the invasion or spread of 
yellow fever among them by destroying the means for the propaga- 
tion of said mosquito and by protecting themselves against the mos- 
quito by efficient screening. Above all, to eradicate the existing fear. 
in the medical profession as well as among the laity, of declaring 
the presence of yellow fever. If the first case presenting the slightest 
suspicious symptoms of that disease were promptly made public and 
the proper modern precautions taken, there would be no danger of 
the disease spreading. In fact, the public should be taught to ac- 
knowledge the existence of yellow fever in their midst wat) the same 
equanimity as they do in the case of measles or scarlatina. ae 

And again, in the report of the epidemic in Vicksburg, Miss., in 
1905, the writer stated : - = 

“There is still much ignorance and skepticism (on the Subject of 
the method of transmission of yellow fever). An effort should be 


8 


made to overcome this by widely distributing pertinent literature on 
the subject. And as it is reasonable to suppose that in spite of the 
progress already made and being made to eradicate this'disease from 
Tropical and subtropical America, it: will continue to harass us for 
many years to come, it is believed that a campaign of education 
should be begun with the young. All important facts pertaining to 
the transmission of yellow fever by the stegomyia fasciata (calopus), 
and the mode of propagation of this mosquito should be taught in 
the public and private schools and colleges in infectible territory. 
There may be seen in this way a good chance to completely destroy 
the stegomyia in its present habitat, and even if not successful in 
entirely destroying it, the great advantage will have been gained that 
when yellow fever should make its appearance in a locality the work 
of the sanitarian in checking or stamping out the disease would be 
made easy indeed and the usual panic with its discomforts and 
financial losses avoided.” 

My experience in these two epidemics and what I have seen else- 
where has confirmed in my mind the importance of this matter. I be- 
lieve and would recommend that the method of transmission of yellow 
fever, and malaria as well, be taught in the schools wherever these 
diseases are liable to occur. The subject should be taught in the pri- 
mary grades, for what children then learn they will retain. To 
obtain the desired result the most elementary teaching would suffice. 
Children may be taught to dread a mosquito as they now do other 
insects that are less harmful. In the higher grades, with little labor 
cr time, the reasons for this fear of the mosquito may be demon- 
strated, as also the methods of exterminating the insect and of pro- 
tecting one’s self against its bite. 


ULTIMATE RESULTS OF EDUOATION. 


With the above idea disseminated among the people it would not 
be long before public opinion would demand with irresistible force the 
drainage of swamps and lowlands and the inspection of houses and 
premises to see that they were free of breeding places for mosquitoes. 

To have open cisterns, water barrels, bottles, broken crockery, or, in 
fact, any receptacle capable of holding water exposed for any length 
of time, would be considered as much a nuisance and a menace to 
the public health as ill-ventilated and crowded tenements, dirty 
streets, defective sewerage, and the many other dangers which at 
present excite the social and political activities of national, state, and 
municipal authorities. Such a system would, within a comparatively 
short time?eliminate all danger from both yellow fever and malaria. 


9 
PROPHYLACTIO MEASURES INDICATED IN INFEOTIBLE TERRITORY. 


We will now consider more in detail the prophylactic measures that 
should be observed in infectible territory. These may be divided 
into two classes, to wit: (a) Measures directed against the introduc- 
tion of yellow fever from abroad; (b) those looking to the prevention 
of its spread when it has been introduced. 

Maritime quarantine.—Measures employed to prevent the entrance 
of infection from abroad are usually included under the term “ mari- 
time quarantine ” and are at present well provided for in the United 
States by an efficient national quarantine establishment, which is an 
integral part of the United States Public Health and Marine-Hos- 
pital Service. 

The measures ordained against the introduction of yellow fever by 
the quarantine regulations of this service are based on its well-known 
period of incubation and the processes of disinfection on the mos- 
quito transmission of the disease, and are directed to the destruction 
of this insect both in its larval and adult stage. These measures may 
be stated briefly as follows: 

Vessels which may possibly be infected are detained at the port of 
arrival five days after disinfection; vessels known to be infected, six 
days. The service has medical officers stationed at all the important 
ports within the yellow-fever zone, and if the vessel is disinfected at 
the port of departure under the supervision of this officer, the vessel 
on arrival at a port of the United States within the infectible area 
is subject to the following modified treatment: If arriving in five 
days or less, she may be admitted to pratique without disinfection or 
further detention than is necessary to complete the five days. If ar- 
riving after five days and within ten days, she may be immediately 
* fumigated and admitted without detention. If arriving after a 
longer voyage than ten days, she will be considered as not having 
been subjected to any previous treatment. This last disposition is 
based on the possibility that a case of yellow fever may have occurred 
aboard and recovered within the time mentioned. 

Passenger traffic from infected ports, without detention, is also 
permitted by these regulations under the following conditions: 

Vessels carrying such passengers must be in the best sanitary con- 
dition and must lie at approved moorings in the open harbor. The 
crew must not be allowed ashore at the port of departure. The 
entrance of mosquitoes into the vessel must be prevented, and if they 
do find ingress must be destroyed. Passengers and crew must be 
certified as immune by the medical officer issuing the bill of health. 
The evidences of immunity which may be accepted are proof of a 
previous attack or ten years’ residence in an endemic focus of yellow 
fever. These regulations apply, of course, only during the close quar- 
antine season—that is, from the 1st of May to the 1st of November. 


10 


It will be noted that the above restrictions are liberal enough and 
at the same time give adequate protection. 

Referring for a moment to the evidence upon which certificates of 
immunity are based, the writer is of the opinion that a ten years’ 
residence in an endemic focus should no longer be considered suffi- 
cient, for with our present knowledge of the method of transmission 
of yellow fever it is quite clear that any intelligent person. taking 
certain simple precautions might very well live a lifetime in an 
endemic focus and yet never be exposed to infection. 

Measures against the spread of yellow fever—With reference now 
to class 6—that is, preventive measures against the spread of yellow 
fever once it has been introduced, we find that as a rule we are not 
so well equipped. The principle of prophylaxis is, of course, pre- 
cisely the same, but is much more difficult of application because we 
have to deal with local and conflicting interests and the ignorance 
of the people. Municipalities usually have a sufficiency of ordi- 
nances and regulations covering prophylactic measures against yellow 
fever, but unfortunately these are completely ignored except when 
menaced by an epidemic, and then enforced with difficulty. - These 
ordinances have been enacted during a period of stress and excite- 
ment, when yellow fever was present or dangerously near, and quickly 
forgotten once the danger had passed. Now, this should not be, for 
there is no reason why every port in infectible territory should not 
be so administered as to make it noninfectible, so that if yellow fever 
should gain an entrance from abroad its spread would be impossible. 
To attain this I would outline the following plan: Education and the 
formation of a public opinion that would look upon the mosquito not 
only as a disagreeable pest but a very dangerous one as well; proper 
drainage; a corps of inspectors to, examine all premises avery ten 
days, preferably once a week, to see that they are free from water 
containers capable of harboring mosquito larve; the screening or 
covering with oil of water containers which can not be destroyed, or 
the use of small fish where the above methods are not available; 
the removal of unnecessary vegetation ; the screening of dwellings 
and other buildings. 

In carrying out the above measures there is nothing that requires 
any great expenditure of money or labor, and if efficiently performed 
and consistently kept up it would be but a short time before the intro- 
duction of a case of yellow fever into a locality so governed would be 
unattended with danger and scarcely cause a ripple of excitement. 


GENERAL PLAN FOR HANDLING AN EPIDEMIO. 


Where the ideal conditions above mentioned do not prevail there is, 
of course, imminent danger of the disease spreading. Steps must be 
taken at once to prevent this. The bases of preventive measures may 


11 


be stated succinctly as follows: To prevent the infection of Stegomyia 
mosquitoes by properly protecting all persons ill with yellow fever 
during the first three days of the illness; to protect the well from the 
bite of the mosquito; and, as a corollary to the above, the destruction 
of all mosquitoes and their means of propagation. Given the requi- 
site personnel, sufficient funds, and the necessary authority to enforce 
measures to this effect and there would be little danger of the disease 
spreading. These desiderata, however, are usually wanting or only 
imperfectly supplied. The practical adaptation of the above propo- 
sitions may be considered under the following heads: 

1. Detection of cases or inspection. - 

2. Yellow fever hospital. 

3. Martial law. 

4, Detention camp. 

5. Protection against the bite of the mosquito; screening, etc. 

6. Extermination of mosquitoes, including oiling, fumigation and 
the screening or destruction of water containers. . 

The details of the two latter are so well known and, in fact, so 
simple that it seems unnecessary to take up the reader’s time with a 
discussion of them. Relative to the first three, which I consider of 
great importance and which, in a way, form the tripod on which the 
others rest, it is well to say a few words. 


1. Detection of cases or inspection. 


In order to put in force efficient prophylactic measures it is abso- 
lutely necessary that all cases be reported immediately. For reasons 
before stated this is difficult, and to those already given we may add 
that during an epidemic many cases of fever do not call a phy- 
sician at all. ‘To surmount these obstacles, as well as the difficulty of 
definitely recognizing the disease in its early stages, all cases of 
pyrexia in which the reason of the abnormal temperature is not 
manifest should be treated prophylactically during the first three 
days as though they were yellow fever, or until a positive diagnosis 
to the contrary is made. For the purpose of reaching-all cases of 
fever a thorough inspection is required. Every dwelling in the in- 
fected area must be inspected daily, or, better, twice a day, by com- 
petent inspectors, persons capable of reading the clinical thermometer. 
All cases of pyrexia discovered by the inspectors should be imme- 
diately reported to the officers in charge of the screening and fumi- 
gating parties for proper action. The patient having been protected 
against the bite of the mosquito by screening and his dwelling and 
the surrounding houses fumigated for the purpose of destroying any 
possibly infected mosquitoes, the question of diagnosis may safely 
be left to be determined later. Whenever possible the patient should 
be removed to the hospital. 


12 


a 


2. Yellow-fever hospital. 


This brings us to the second prophylactic measure advocated 
ubove—the advantage, and indeed necessity, of a yellow-fever hos- 
pital in dealing successfully with an epidemic. 

There is a prejudice among the people against the term “ yellow- 
fever hospital,” hence it would be as well to yield to this prejudice 
and call it an “ isolation ” or “ observation ” hospital. The important 
point is that this hospital be absolutely mosquito proof, and that it 
be made attractive, be clean and well managed, so that the people 
may be drawn to it and feel that they will be as well or better 
cared for in the hospital as in their own homes. The greater the 
number of fever patients that can be removed to the hospital the 
easier will be the task of stamping out the disease. 

Such cases as in the opinion of the sanitary officer can not be prop- 
erly screened in their homes should be compelled to go to the hospital. 
The transfer of the patient must be accomplished with such pre- 
cautions as will prevent the possibility of his being bitten by a mos- 
quito—under a mosquito-bar or in a screened ambulance. 


“ 


3. Martial law. 


To make the inspection thorough and effective and to compel the 
transfer of the sick to the hospital when necessary, authority is re- 
quired. In a republican form of government this authority is usually 
wanting and these measures have to be carried out inefficiently and 
in the face of great opposition. 

To obviate this the writer would advocate that martial law be de- 
clared in epidemics when the conditions are such as to warrant it. 
This legal procedure is frequently invoked when the menace to life 
and property is not nearly so great as in an outbreak of yellow fever 
or other infectious or contagious disease. 

With martial law to support the sanitary officer the prophylactic 
measures herein advocated could be enforced in every detail and an 
outbreak of yellow fever effectually controlled. It is easy to under- 
stand why this agent was not invoked prior to the demonstration 
of the transmitting factor of yellow fever, when our efforts to control 
the disease were rather vague and uncertain; but to-day, when our 
system may be made so precise and certain it seems almost criminal 
not to take advantage of such a powerful auxiliary. 

In our epidemics the sanitarian, unsupported by authority, is 
obliged to lose much precious time and energy in his efforts to gain 
the good graces and plaudits of the populace, so that he may be per- 
mitted to perform his work untrammeled. 


Lo 
4, Detention camp. 


In most epidemics it is necessary to provide means to permit per- 
_ Sons to leave the infected district without danger of carrying the 
disease elsewhere. This may be accomplished by a so-called “ de- 
tention camp,” where those wishing to leave the infected locality may 
do so after being detained under observation for the time requisite to 
assure their freedom from infection. 

With our present knowledge of the transmission of yellow fever 
it is unnecessary to establish these “camps,” as heretofore, in out- 
of-the-way or inconvenient places. On the contrary, they may be 
located with perfect safety within the infected district so long as the 
detained persons are kept in mosquito-proof quarters and, when their 
period of observation has terminated, are taken to their destination 
in mosquito-proef conveyances while within the infected area. 

It is plain, however, that in a properly educated community where 
the measures above advocated can be put in practice, there will 
scarcely be any necessity for a detention camp. 

In the foregoing pages the writer has endeavored to outline a 
scheme or plan of prophylaxis which he feels quite sure will do the 
work expected of it. The machinery is there, but where is the power 
to set it in motion? To start it successfully, smoothly, and without 
friction, some central authority with the necessary means and power, 
acting surely and swiftly, must be provided. This should be the 
function of the Government. 


PROPHYLACTIC MEASURES SUGGESTED BY THE FRENCH COMMISSION 
OF THE PASTEUR INSTITUTE. 


Much interest is attached to the means of prophylaxis suggested 
by the results obtained by the French commission of the Pasteur 
Institute in their report on the investigation of yellow fever, pub- 
lished in the Annals of the Institute in November, 1903, to wit: 

1. An injection of virulent blood serum which has been heated for 
five minutes at a temperature of 55°C. confers a relative immunity, 
which may become complete if followed by the injection of a very 
small quantity of virulent serum. 

2. The injection of defibrinated blood which has been kept under 
liquid vaseline for eight days confers a relative immunity. 

3. The serum of a convalescent is endowed with preventive proper- 
ties. 

4. The immunity conferred by the serum of the convalescent is 
still in evidence at the end of twenty-six days.* 


Abstract of Report, French Yellow Fever Commission; Annual Report, 
U. S. Public Health and Marine-Hospital Service, 1904. 


14 


Further study on this line may give us an immunitive serum which 
will be of great value in controlling yellow fever. 

However, even though we attain this and, furthermore, discover 
the etiological factor in yellow fever we will still, in a great measure, 
-have to depend on the means of prophylaxis herein outlined, and I 
desire, therefore, to impress upon the reader the importance of edu- 
cation as a prophylactic factor and the necessity of clothing the 
sanitary officer with the requisite power and authority to enforce 
the measures that we now have at our command, which are simple 
and efficient. 


O