asad caeye wee ats st tata retnterernte med “hea ween eh Sees i eebehca ty atte gt Wet Clee ote Mae HUT OR TNA eas sete’ 13h ae ities ah Oy a 4 Leh REL TT tert PAM ee RU tot way Te Ria ana ia ae vee oa Les druse doc Qid Medea Skee | eedee a foal. taped whetin aw ce up atetees oreiscs era ais een cgesie te we etek mieten Sb nrtorbe Vvanigy int wba ih turtle tyorbodriet bent treedetearbed Wh te ky Ory: chyna eh eta! 4h yea euhare tee tual et oe * Aare Shegresstcraty pare uence areey (eats Peering heaeare vt Sarees 4 be +i Va, Si) feytunia nat ite iene Dee Wesrgwe glen dew Witoves alee tay Wy vty 4 SWecale sain nt eyelet ft En Aelia st A Wi year Suen aat bs nt Pah eA cegraconnects pire ieee aantcarii i " RAW iic4: Gee PewvamverrMr aN: Wega tele iad a Come ta Ut Orit Me HAC ichi ney yt War nent Cn ty Cay ois AoW a fy \ Cherie We) Ce Ra Youre nae eA aeons) MAA NMC Nii CaN ey ne Sasha oo Sr HT hea inal ann " Hecaetinnv aed Wewtnrdude ont seharniala a Be my ) ne A ny hath eas ® vi evened saa Hiss a kaa eanaathe arate be te ise wi Tee MAT TR aed Har anyraan eeaee dade eine 2a ya Heed AEF att ‘sian ane Lig at Ly ia ah + ut srhvivesaet-asncd render inasnchat rit Mors aniivge Wen Wen soars ne i richie ee A ae yet heat ie ees heey ieitine' te Patan Cte tt ‘ Sac aa itr ih Sy eSMeraset Ma Ay a ites! Mite “ Warcenyatite Se Qaheme| heb rasidcuesy re Pista a uioen TNMs iar fobsonhaiese strane sg BCR ee Note Cisrnseorsi tae Term psay Sor ayes att ite Siew liad Yall ian Yatra wit 4 Ved detest Malad seasvons sin bias Fs 2 aw Fivetingy ey iy aa aie i srnteivusyns erdebyiers Andee ele Ve tr Ride lof 4) ni yhgwoatintey Pet hoy fee Rina i thet vt sure Vive ¥ Mach Fy ia titaler ie elaed fetal en Heit Ge Fe tht evans ly At SG eal ss haste <; oe ) \ ovsrric| av * J aaa belie ieaielokaed igang se Mth cpt peree pa stnyy torent | Se See ee VOT STUDIES OF CHOLERA.' By Harry T. MArsuatt. (From the Biological Laboratory, Bureaw of Science, Manila, P. I.) I. VARIATIONS IN VIRULENCE. During the past year or more we have been continuing the studies of cholera at this laboratory, previous reports upon this subject having been published by Dr. Strong. In this paper I will review the results obtained up to the present time. The experiments which I have conducted were undertaken with the view of continuing certain investigations upon the variation of bacteria with special reference to their so-called immunization. This research was begun a few years ago with the dysentery bacillus.* At that time we came to the conclusion that selection and variation are constantly mani- festing their action upon bacteria, and that these processes probably play an important part, not only in the rise of epidemics, but also in the development of each individual case of an infectious disease, in such a manner that in a case of infection a large number of the bacteria are killed by the host, while a relatively small number become adapted to their environment, survive, multiply and produce the disease. At that time, we were able by growing the dysentery bacillus upon media con- taining anti-dysenteric serum, to develop a variety of bacillus which not only was not agglutinated or impeded in its growth by the antiserum, but which actually flourished more luxuriantly in the presence of the serum than it did under other conditions and which no longer united with the agglutinins in specific antidysenteric serum. A preliminary attempt was made in this laboratory to repéat the same experiment with the cholera vibrio. Two or three stock cultures were inoculated into bouillon or peptone solutions containing small amounts of anticholera serum and after intervals varying from a day up to a week or more, transplants were made into fresh flasks of bouillon containing anticholera serum. As many as ten successive transplants in one series were made after this Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, February 28, 1908. ; 2 Marshall and Knox: J. Med. Research (1906), N. 8. 10, 325. 107 108 MARSHALL. fashion, but the cholera vibrio did not lose its capacity to become ag- glutinated, although it grew readily in the new medium. ‘This line of investigation was not carried any further. One interesting observation was made upon a strain which had been transplanted nine times through successive serum bouillon cultures and which had been allowed to remain in the last flask for a long period. The vibrio was plated out and its biological characteristics determined. Among other distinctive features the blood-agar-hzmolysis test was tried simul- taneously with this bacterium and the stock culture from which it was taken for the original transplant into serum. ‘The original stock culture showed no hemolysis within twenty-four hours and only a trace in forty- eight hours, while the vibrio which had been grown in beef broth, con- taining anticholera horse serum, showed a marked ability to produce hemolysis of goat’s blood within twenty-four hours. We haye here a definite variant produced by artificial laboratory means, the only dif- ference between the stock culture and the variant being that the variant grew in the presence of serum from a horse which had been immunized against cholera. The factor which produced the hemolyzing reaction was probably not the specific anticholera substance of the serum but those constituents of it which are close to the ones of the red blood corpuscles. The question of variation was then attacked in a different way by Dr. Philip K. Gilman, of the Philippine Medical School, and myself. We created an artificial epidemic of cholera in guinea pigs in order to observe what changes the vibrio would undergo both in virulence and in other respects. A guinea pig received an inoculation intraperitoneally of 0.1 cubic centimeter of the material taken from the ileum of a man dead of cholera, the diagnosis being based upon clinical history, autopsy appear- ances and laboratory examinations. The guinea pig died within twenty- four hours; 0.1 cubic centimeter of the peritoneal contents from this ani- mal, diluted with salt solution, was inoculated into the peritoneal cavity of a second guinea pig, and upon its death, within twenty-four hours, the peritoneal exudate was used for inoculating a third. Upon its death within twenty-four hours, the exudate was diluted and a series of guinea pigs was inoculated with varying amounts of this material. The mini- mum dose fatal within twenty-four hours was 0.02 cubic centimeter. The exudate from the guinea pig killed by this amount was diluted and a fresh series inoculated. On this occasion, although as small a dose as 0.0005 cubic centimeter was inoculated; the minimal fatal dose was not determined. The exudate from the animal killed by the lowest fatal dose was used for inoculating a sixth series and in this 0.0001 cubie centimeter was the minimal fatal dose. From the exudate obtained from the animal which succumbed to this quantity a new series was inoculated and 0.00002 cubic centimeter proved fatal. An interesting result followed the next inoculation. The exudate was diluted and inoculated STUDIES OF CHOLERA. 109 as usual, but none of the guinea pigs died within twenty-four hours, although the doses inoculated varied from 0.001 to 0.00001 cubic centi- meter. In other words, the virulence had suddenly fallen at least to one-fiftieth of its former strength, and how much more is not known. It is important to. determine the nature of the biological processes asso- qiated with this sudden abatement of virulence, but the only clue fur- nished by this series is that 1 cubic centimeter of a 1 to 1,000,000 dilution of the exudate from the next to the last guinea pig of the series, when plated in agar, contained colonies too numerous to count, so that at least it is clear that the bacteria had not lost their viability. We may account for the sudden loss of virulence either by supposing that the power of toxin formation suddenly disappeared, or that the ability of the bacteria to resist bactericidal action suddenly failed them. It seems clear that there was a sufficient number of surviving bacteria carried over from the next to last guinea pig; this was shown by the results of plating. The results of this series of inoculations are shown in Series I, and the sudden rise and fall in virulence is charted in fig. 1. The strain of cholera which has just been described was obtained from an autopsy during the height of a small epidemic. Several other at- tempts were made to repeat this result subsequently, when the epidemic was on the wane, both with strains of cholera inoculated into guinea pigs directly from the intestine and with laboratory stock cultures. The results are shown in Series II, III, IV, V, and VI and im figs. 2-5. It is seen that no strain was obtained, the virulence of which could be increased so successfully and regularly as that of the first. Turning to Series II, we find the results are less regular, although here again there was a gradual rise in virulence up to a fatal dose of 0.0001 cubic centimeter. The irregularities are difficult to explain. For instance, we find on November 11 that 0.0002 cubic centimeter is fatal, while 0.001 is not so. Again, on November 13 neither 0.01 nor 0.0002 cubie centimeter killed the animal, while 0.0001 and 0.001 did so. It is possible that this difference can be explained upon a physical basis, for the exudate was tenacious and possibly did not spread evenly through- out the diluting salt solution. The virulence was irregular in Series III also. An observation made in this series throws some light upon the mechanism of the fall of an epidemic. In the fifteenth inoculation made on November 28, the only animal which died within twenty-four hours received 0.01 cubic centi- meter of exudate. This animal did not die until 10.15 on the morning of November 29. The autopsy was performed at once and 0.25 cubic centi- meter of tenacious, yellowish, cloudy exudate was recovered from the peritoneal cavity. As the table shows, the animals inoculated with this exudate did not die within twenty-four hours. At the same time 1 cubie centimeter of a 1 to 80 dilution of this exudate was inoculated 683303 110 MARSHALL. into another guinea pig and at intervals a few drops of peritoneal fluid were drawn off and plated. One one-thousandth cubic centimeter of the fluid drawn after half an hour contained two colonies, and the fluid drawn after three and one-half and after twenty-four hours was sterile, while a control plate made with one four hundred thousandth of the exudate used for inoculation showed thirty-eight colonies, and another control with one four thousandth cubic centimeter developed about two hundred and seventy-six colonies. This must be interpreted as proving that the bacteria in the exudate were no longer viable in the guinea pig’s peritoneal cavity, although still viable on artificial media. Reference to the table will show that the cultures and morphology of the peritoneal bacteria were not typical, although cholera-like organisms were found. However, the fact that in the moculations of November 27 the minimal fatal dose was 0.0001 cubic centimeter and that the exudate from this animal gave a surface growth on peptone, indicate that the cholera vibrios were still living up to the next to last of the series, and it is a reasonable presumption that they lived up to the last inoculation. This finding contrasts rather strikingly with the condition observed at the close of Series I. Series IV, inoculated from an autopsy toward the close of the epidemic, showed such low pathogenic power that 0.1 cubic centimeter of a 24-hour peptone culture did not kill a guinea pig. After Series V had been continued four days, the virulence fell on the fifth below 0.01, and the series was discontinued. With Series VI also the virulence rose to 0.01, then fell. These experiments show that there is a great difference between the individual strains of cholera, and that this difference is a deep-seated one, possibly fundamental. ‘They also demonstrate the possibilities of -varia- tion with cholera to be enormous; for here we have the fatal dose for medium-sized guinea pigs one fifty-thousandth and one ten-thousandth of a cubic centimeter of exudate, which minute quantity is not made up entirely of bacteria but contains also serum and cellular contents, while the average standard for cholera as given by Kolle is one-tenth of a platinum loopful, which would be approximately 2 milligrams. DIFFERENCES DURING ROUTINE EXAMINATIONS. It may be well to refer briefly at this point to certain differences which have been noted during the routine examinations upon cases suspected of cholera. In the epidemic of August, 1907, routine examinations were made, according to custom, of the bowel contents of all cases supposed to have died of cholera and of the stools of patients supposed to have been suffering from this disease. At that time Dr. Ralph T. Edwards, STUDIES OF CHOLERA. 111 of this laboratory and I, noted that during the height of the epidemic the vibrios presented the typical morphology, were actively motile and agglutinated in a high dilution of serum; while toward its close the curves of the vibrios became less evident, many forms were found with little or no curve, and the bacteria in general were slenderer and longer; the motility diminished greatly and the movement, if present at all, was very slugglish, while the agglutinatibility remained practically constant. In two patients who recovered from cholera, examined at the close of this epidemic, the vibrios remained in the stools after con- valescence ; in one case for four or five days, while in the other they were still present after ten days, when the patient left the hospital and was lost sight of. The importance of this occurrence in its bearing upon the spread of cholera is sufficiently evident to make comment superfluous. This case recalls at once the findings of Ruffer and Gotschlich, which will be discussed in a later section of this report. The study of the bacterial variation occurring among cholera vibrios.is being pursued along other lines also. A number of different strains of cholera and cholera-like vibrios have been collected and a comparison is being made of their pathogenicity, motility, morphological and cultural characteristics, serum reactions, and ability to form toxins. The results of these studies will be reported later. Up to the present time the chief attention has been devoted to noting the cultural characteristics, and there is evidence of appreciable differences in the manner of growth of the various organisms which are being examined. 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STUDIES OF “panuljUodsIp Satag ‘soqu[d IBSB UIT’ UL WMOIS ON |--au0jded uo YIM0I3 DOBJINS ON |--~-~-~> DInp Apoorq prqing *00/G) |ss55)\ 0) | 0) |) 0. | = |asea|| 0) |nanalemanl to |sacu|paaslaeaslaeee| PL “AON ‘spol paAino Apysys jo oimjjno oand “yuouItpas pus 441 Atuoredds syuv[s pus ‘soyeg | -prqin} [eieues saats auojdeg |- png snoroBud} poi yysiaq “00 fg |----| 0 | O | + | 0 |-- SE ERS) SaaS ONO “UOIBSBABIJXO OU :ULIqY *SpOl paAInod AY STs a1ngynd ou :AIp ysourye AjIABO [Bou eind MOYs sjUBIS puB sazvIq |} -O}Zed ‘uOTWBIO[OO AsOI 4YSITS |—~-|----| 0 | O | O | O | [tira] frm fscor forma] BE AON RE a aT Pea ae 3 I a OO OW se FS OFS ae PSS ne ONE ae Roe ee el O 1 Ol O 1-0 FRA © RA se se SR area Oe AOR ‘ayBpNxX9 pal pIqiny ‘umMoeu -O}f1ed JBAO soyBy Ugg SSeS a eee ae | AMO} B ‘UO[OD IOAO wKlYyda}eq |-7~7|----|----|--—-| + | + | 0 | O | O [tt] -E [> 7]F 7/5] 6 AON “‘quvuseid SBA\ Z00'0 JO ‘a1Bpnxoe [Bauo}ed Apoo[q OSOP B 1ojyB SULAP Bid BOUIMY) |—>9 orn nnn ‘00 $] SUIB]UOD Std Bound z00'0 |----|----1-- |---| 0 | oO |}! 0} od} EY] +14 18) aon ‘97BpNnxd Apoolq prqin} ‘00 [ ‘seyep as Se UlIQY sWINIMOPIOd Popol UY | a ae see a AON 08 900 O1BpNxe WOIJ 91n} -[MO BU0}dad JO 0D Z PAATIVAY [99 | nn nnn OYBPNXS OLIBYLLOUL EY || rs sass aasal=a==|-===1 9 “AON adn} ‘ayBpnxo =1N9, .19}0Y9' Y90}S JO OSOP [BBA \Ssrsew saves cae we aaeT Luanne ee PlOONUA ALOT[OA PIGING! +Dd) GT Geel sawn |p| anal eaal een |eaeeleaan| 0 | 0) || 01) 0) | | 08) 400) el/elelelel/elelelelelelelele S/sisis/sisisisisieisi/sliF ie elelSlelelele i |e] || ‘9]Bpnxa ‘saoByins [eauojfied —— 101 "SHIBUIOY Woy ‘*dJ9 ‘sIvauIs ‘soIny[nO pus o}Bpnxo Jo sduBIveddy ‘s8d vourns ser JO JOS MOU B OJUL WOTB[NIOUL [BAO] IEdBI}UT 19}}B SINOY $G UBYY SSO[ UL [BBY SoAOId YOIYA ssid BouINS pap WIOIT ayepnxe JO (JoJOMIIUd OIqnd B JO SUOTJOBIJ UL) OMIN[OA [uorerndour seqye sINOY FZ UTUIIA [BIB JON —=0 “TOYB[NOOUT 10378 SINOY Fz UIYIIM [8}By = +] ~puajoyo fo ainyna fiLoyn.Logn) yoo}s » fo adnyna UoppN0g noYy-tE D WOLL pajiDjs SuOYMnNdoUT—"T] STIITY MARSHALL. 114 ‘SUOMN[Ip r8qqINy 10} o}Bpnxe Ysnous 4ON *A[[BoUO}TIOdvaZUT poy -B[NDOUL BIO[OYO OSBd [BIRT WOIJ JU9}UOD JAALOG JO ‘00 T ‘diy poAmno WIN OL ULT ‘UlB}s IB_NZoIIT YITAL mn § 4ynoqB’ spol JapudTs Jo d1N}[Nd sind ‘sjuB[sS pus soBIq “B19[0YO 9INy[No sind Apuoredds sozRid pus osu0j}doq “BIO[OYO ainj[nd and Ausivdds ‘sayv[q 4u00 tod 0¢ 19A0 UI JAIND BUITIOD OPUYOP YIIA SOMGIA BIO[OYO eind=Asojoydiom ‘s} UBS ‘soyeid ‘aporjjed ou ‘auoj}deg *BId[0YO d1nj[nd sind Ajjueiedde ‘soyB[q a18pnxe Apoolq ‘00 F 7--uliqyg ‘a7epnxe Apoorq *00 Fg --9JBpNxe piqin} Apoo[q ‘00 GF sereraee PIMP paureys-poorq ‘00 g SnOdSIA AOT[eA plqin} ‘00 F ‘soxBy UqY ‘mneuojed poajzooluy ‘soo BjIns [BauO}TIed I9AO UNQY JO soyBy od1B[ ‘ayepnxe MOEA prqin} ‘00 ¢ ‘SHIBULOY ‘bid naunb fo fyxmo qoauopuad opr hjjoanp viajpoyo-fo asno joyof v fo syuajuoa yamog ayy WoLf appiULn-woMnnI0u;Z—-+F FF SERIA G — ——— ‘O]BPNx9 Mo1g ‘jd ‘srBauis ‘saInq[nD "sad BjiIns [Bouo0}LIed pues ajepnxe jo souvivoddy OE) oO/r 34 en Saal a ee aa FZ “AON sonata ty | Near teas all ip Ol paar | OS |San aloe ete |e ne seen RCCHEAONE joysialas jov=ve jonda id at) aka) (4h PPR) PPS ce sy ar esate) 7] Ge AON: ral [erat scat PRA U sed eval Ne mes cea ts emer | Fear ogre eel Dead be Ed: ONO (aaa Fraps | seb lisa ia af ast a ame | cae (stead easel lesa |)" 02 “AON Feec|eser|facsa|| @) feacsfaooc|] @ |fecce|faeec| felon a] 6 “AON: HO Of Ol OP © PPR Sse Pea ae || 8t “AON ‘uMqy ping TOO MO: se Fa] Se Pe ae Pea ~~] 4T “AON FResiezap| (etases | heaeceten| ugar (oe arrive ar bee PSS se Hae Pl Or AOE ‘PING YSIPPT 09 G0 || 0 | 0 PT 0 PF + || cr “AON Sasa esee alla Samal asneaag | esac eases ones | as | Ras aa eg eal ea | ML AONE S| See 2 S| SSIS 212) 222 $/3/8/s/3/s/sisisieis|s/F\* S i=} i=} i—) So | nN oo - - 2 SSI SiR Sy eye ye ye = Ee “uo ; -B[NDOUT JO ssid BauIns OJUL WOB[NIOUT aed [B0U0}{19dB1] UT 10}}B SINOY FZ ULYIIA [BIBy poAord Yor O1BPNX JO (1o}9UIIWUN OIGND B JO SUOTJOVIF Ut) AUINTOA [uoMBlMoout 10778 sinoy Fz UL [B}ByF JOU = 0 7 HOT B[NOOUT 10}JB SINOY FZ ULYIIA [B1Bj = + ] < [a= iS 2 iS) q ‘S) fe iS) R iS S [=| =) a R *panut}WoOdstp SOMOS Mes POATAING=:S[ CULLUM [Vall srasassctea| eas ae a cas | bs Seabees | RESET te Sas | Ee |e Ole lecsoanca leas aes Sided etapa pee Ob Bliseesses @c “AON *10000'0 | *c0000'0 | ‘0000°0 | ‘*1000°0 | °c000'0 | ‘G000'0 | “L00°0 | *z00'0 | “G00°0 | “10°0 | “cO’0 | “S00 ‘TO 70 ‘SHIBULIY = 9}8@ ‘ssid BOUIN JO WOT} B[NOOU! 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TYPHUS FEVER IN INDO-CHINA. By A. Yersin and J. J. VASSsat.t (From the Pasteur Institute of Nhatrang, Annam.) IL, On May 4, 1906, a thousand or so Tonquin coolies were landed at Nhatrang to serve on the railway in course of construction between Phanrang and) Nhatrang. In spite of their youth they were men who had suffered, and they brought with them the poverty and the disease of their country. They were therefore predisposed to catch local endemiecs, especially malaria, but at the same time they showed affections which are perhaps limited to Tonquin and which in any case have not yet penetrated into South Annam. That recurrent fever came in this way, has already been made known by one of us; typhus fever will now receive our attention. Our observations are not numerous, and if we have delayed their publication it is because we hoped to supplement them with new ones, but the Tonquinese handicraftsmen have disappeared from our district, and with them the means of pursuing a study which now could be under- taken again more easily in Tonquin. Nevertheless, our experimental investigations throw new light on the pathogeny of typhus fever and leave no doubt as to the diagnosis of the eases observed in Nhatrang. If writers have dwelt at length on the distribution of typhus fever in Hurope, records of its extension in Asia are brief. It exists in Persia, China, and Japan (Netter), but it seems to have attracted but little attention in India. It has never before been noted in the French possessions in Indo-China. If. We have been able to follow out seven observations on seven ‘l'onquinese working on the embankment at Hoatan Suoi-Giau, young men between 18 and 20 years old, coming from the Provinces Ninh-Binh, Nam-Dinh. and Ha-nam. Transported under bad sanitary conditions in a crowded and badly organized boat, they were at once obliged to give themselves *Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, February 28, 1908. 131 Ne YERSIN AND VASSAL. up to hard and unfamiliar labor in surroundings to which they were not accustomed. All the cases were observed a short time after their arrival, between May 25 and June 1. The disease disappeared on the spot, without spreading to the native population or the other coolies on the railway. Our observations included five cases of natural and two cases of ex- perimental disease. We will review them briefly. NATURAL INFECTION. Case 1.—Hoan Hiet, 20 years of age, from the village of Coi-Tri (Province of Ninh-Binh, south Tonquin), entered the hospital on May 25, 1906, for sores on the legs. On June | his temperature rose to 38° C., on the 5th to 40° C. A large abscess was discovered at this time, which was immediately opened. The temperature fell, but rose abruptly twenty-four hours later; after a careful examination it was easy to see that it was not caused by the wound, but that - a new affection had begun. Moreover, the sores healed very rapidly. A number of very peculiar symptoms appeared little by little with the pyrexia. The patient fell into a state of profound prostration, which was not stupor but rather a complete annihilation of his strength, accompanied by a nervous upset. He was at times indifferent and dejected, at others delirious-and agitated, his attitude was not without analogy to that shown by patients with bubonic plague. The patient complained and groaned continually. There was headache and insomnia. On the third day nausea began and the tongue remained coated without becoming dry. Constipation persisted during the entire illness; the abdomen was neither distended nor painful. The cardio-pulmonary apparatus revealed nothing abnor- mal on percussion or auscultation, although the breathing was accelerated and the pulse often as high as 120. There was no eruption on the skin nor on the mucosa, but the conjuctiva became considerably injected. On the sixth and ninth days of the illness, the patient seemed more prostrated than ever, but without ceasing to complain; the prognosis became more serious. Suddenly, on the tenth day, a true crisis set in. The fever fell, the appetite returned and cerebral calm was restored. From that moment recovery was certain and continued without complication and with marvelous rapidity. — The temperature chart was high during ten consecutive days, ranging between 38°.2 and 39°.6 C. during the first eight days, and between 37°.9 and 38° C. on the two last ones. There were only three remissions in the morning between 37°.8 C. The defervescence which had been perceptible on the ninth day was sharply accentuated on the tenth. Casze IIl—Ngo Khoat, of the village of Coi-Tri (Province of Ninh-Binh, south Tonquin), from the same village as Case J, entered the hospital the same day as the latter, i The man had been found on the railway embankment already in full pyrexia. He was in a state of great weakness, the conjunctive very much injected; no eruption, and no intestinal phenomena were observed; he had been taken ill very suddenly five or six days before. In the hospital, the same principal phenomena were observed as in the preceding case. There was nervous disorder, cephalagia, delirium succeeded by prostration, habitual insomnia and tremor. The fever fell by crisis on the sixth day of his hospital treatment, which was probably the eleventh or twelfth day of his illness. There was a very rapid improvement and recovery without complications. . TYPHUS FEVER IN INDO-CHINA. 133 In spite of careful observation we did not find the least sign of eruption. Both Cases I and II received quinine in large doses by mouth and subcutaneous injection without result. The analysis of the blood, moreover, showed no signs of specific hamatozoa. CasE IIJ—Pham Khang, 28 years of age, also from the village of Coi- Tri, was ill several days on the railway works. We witnessed in the hospital only the terminal crisis which developed with remarkable suddenness. From the inquiry we made among the comrades of Pham Khang, we elicited the information that the following symptoms had been noted: Bloodshot eyes, prostration, fever without apparent remissions, constipation, rambling and incoherent complaints. The patient left the hospital on June 5, cured. An examination of the blood proved negative. Case 1V.—hLai van Duc, 26 years of age, from the village of Thuong-Huu (Province of Nam-Dinh, south Tonquin), came into hospital on the second or third day of his illness, which had begun on the railway. We observed six consecutive days of very high fever, reaching 39°.9 and 40° C. with two matu- tinal remissions to 38.°4 and 38° C. The fall was abrupt; a slight ascent was noted the next day to 37°.4, then a descent to a point well below the normal during four days. The same phenomena were present as in the preceding cases, except that diarrhea followed several days of great constipation. No spots of any sort were present, but the conjunctive were again excessively red and inflamed. Quinine had no effect and there were no hematozoa in the blood. Case V.—Tran Luan, 24 years of age, from the village of Van-KKhau (Prov- ince of Nam-Dinh, south Tonquin), entered the hospital on June 1, 1906, in the evening. On one of our weekly visits to the railway embankment, we found him very much prostrated and not able to stand alone. We took him into the automobile, but he was unable to remain in a sitting position without help. We learned that he had suffered from a sudden attack of fever the day before. His illness in hospital lasted ten days, the fever remaining high during six days. On the seventh there was a matutinal remission to 37° C. but the same day it again went up to 39°.3 C. in the evening. The next day there was a marked defervescence, and forty-eight hours later a return to normal, however, with a tendency to hypothermia during several consecutive days. Thus this case resembled those of the other patients. ‘The clinical signs were reproduced with remarkable precision. Let us repeat once more the Biaracteriatic Rearanes of this case. First, the sudden attack, fever lasting eleven days, great weakness with delirium, the miserable and distressing aspect of the patient, and lastly the rapid recovery after the crisis, and entire absence of relapse or complications. Quinine medication was inefficacious and all the examinations of the blood were negative. EXPERIMENTAL INFECTION. We had tried in vain to reproduce the disease in the laboratory animals, such as rats, guinea pigs, or rabbits, and we thought that it would be of great scientific interest if we could be enlightened as to the transmis- sion of the disease in the quickest possible manner, namely, by experi- ments on man. The relatively benignity of this cyclie fever justified this procedure. The positive knowledge of the nature of yellow fever and of its prophylaxis only dates from the first experiments on man 134 YERSIN AND VASSAL. (Reed, Carroll, Agramonte and Lazaer, Marchoux, Salimbeni and Simond). With regard to dengue we have profited in the same manner during the last year (Ashburn and Craig). CasE VI.—Neguyen van Ky, coming from the village of Nam-Dinh, Van-Khau (Province of Nam-Dinh, south Tonquin), was admitted into the native hospital for ulcers on the legs. His general state of health was excellent. Of robust constitution with a normal heart and without any symptoms of morbid diathesis, this man submitted voluntarily to an inoculation, of which the probable results were not unknown to him. On June 1 Nguyen van Ky was inoculated under the skin of the arm with 0.50 gm. of blood taken from one of the veins of the arm of Tran Luan (Case V), who was in his second day’s illness. The blood collected in a syringe. previously sterilized by steam, was immediately injected without the addition of any foreign substance. There was no reaction at the site of the inoculation. The lymphatic glands of the arm did not show the slightest modification. The period of incubation lasted fourteen days. Suddenly, without any pre- monitory symptoms, the patient was seized with an intense fever which persisted for eleven days with slight variations, giving a most characteristic chart, identical in character with the ones taken from the natural illness. The tem- perature passed in one night from 35°.7 to 39°.5 C. The symptoms of the natural disease were reproduced with the greatest clearness and in addition congestion~ of the lungs was noted. ‘The excessive prostration of the patient, his wandering thoughts, his insomnia, anorrhexia, coated tongue, constipation, the absence of intestinal phenomena, the suddenness of the attack and the rapid recovery after the crisis, were presented in detail. There was neither eruption nor spots on the skin, but the conjunctive were as usual congested. As in the other cases, our microscopic researches were negative, and no specific febrifuge medication was successful. Case VII.—Tran Minh, 21 years of age, from the village of Do Le (Province of Ha-Nam, south Tonquin), entered the hospital on May 28, 1906, for fever and itch. His blood contained Laverania malarie, and he had a series of irregular paroxysms which were checked by quinine. On the twentieth day in the hospital, when our patient had entirely recovered from his attacks of fever and when his blood contained no more hematozoa, we proposed to him that he should be inoculated with the blood of a typhus patient, at the time warning him of the probable consequences. : On June 20 he was inoculated under the skin of the arm with the blood of Nguyen van Ky (Case VI), who was in the fifth day of his experimental disease. The technique followed was the same as it was in the first instance. The amount of blood injected was 0.50 gm. and it was absolutely pure. The incubation period upon this second passage was longer than it was with the first patient, it being twenty-one days instead of fourteen. There was no local reaction. As is seen from the chart, the temperature rose abruptly and remained at a high level for twelve days. It was impossible not to recognize the almost mathe- matically exact repetition not only of the fever, but of all the other symptoms. We again observed the identical signs; i. e., the abrupt beginning and end, the great weakness, the plague-like delirium, the constipation, insomnia, absence of eruption, blood-shot conjuctive, the inefficacy of quinine, and the absence of blood parasites. eee eee a ee TYPHUS FEVER IN INDO-GHINA. 135 III. The diagnosis of the cases which have been cited was not immediately apparent. We had already observed some cases of spirillar fever among our Tonquinese patients, and therefore we thought ourselves justified in the supposition that we were again dealing with spirillar fever, presenting modified.symptoms in the natives of south Annam. However, we hesi- tated to attribute a new disease, which had never previously been noticed, to the spirilla. The evidence soon became so positive that we were induced to think of typhus fever. ; It is true, the eruption was wanting, and we tried in vain to obtain it in the experimental disease. Although failing in this, we succeeded in reproducing a peculiar, cyclic fever, a well-defined disease which corre- sponded exactly with the description of typhus fever. Although the actual exanthem failed in our cases, it is reasonable to suppose that the congested condition of the conjunctive was in a way a substitute. This is the first time this disease has been described among the An- namese. Is it not possible that it has previously escaped observation because of the absence of an eruption? We know that in sporadic eases and in light ones the eruption generally fails. There have been epidemics without eruption (Dieulafoy), and all writers are agreed in pointing out cases without eruption in the most marked epidemics. Netter observes that “the eruptions in typhus fever are not constant ; their absence is noted in a tenth or twentieth of all cases. These facts are not uncommon in the history of eruptive fevers. Dengue, for instance, causes epidemics where eruptions do not .appear. A diagnosis might also be made by elimination, after having reviewed the diseases which resemble typhus fever most closely. The absence of Laveran’s hematozoa from the peripheral blood and the spleen, the complete inefficacy of quinine, and the characteristic of the chart, permit us to set aside malaria. The points of comparison with typhoid fever are very vague, but the differences are sharply accentuated. It is true that the tongue was coated, but it had not the dry and “roasted” appearance of that of typhoid fever; neither were there any intestinal phenomena, but on the contrary constipation. The abrupt start, the course of the chart and the crisis, differentiate our cases from typhoid or paratyphoid fevers. Spirillar fever would not have passed unperceived at Nhatrang, where it had just been studied for the first time in Indo-China. This fever gives a chart with oscillations and relapses very different from that presented by the disease under discussion ; besides, an examination of the blood settles the question. Kala-Azar is too well known to-day to be confused with this disease. 136 YERSIN AND VASSAL. Dengue is a disease that one meets with in Indo-China, sometimes well characterized, sometimes badly defined. But dengue lasts a still shorter time than typhus, and the charts are in no way comparable, any more than are the different symptoms. Among the “nonclassified tropical fevers’ Manson has described one which he calls “double continued fever,” but this is removed from con- sideration in connection with our typhus by its relapsing pyrexia; and if we even regard the first attack only, the charts are in no way comparable. IV. Experiments were first tried on laboratory animals. A certain number of rats, guinea pigs, and rabbits received subcutaneously one or several inoculations of blood taken from patients at different periods of the disease. They manifested neither pathologic phenomena nor elevation of temperature. We have already related our experiments on man. The examinations of the circulating blood as well as of specimens taken by splenic puncture, which were very numerous, were always negative. These results agree entirely with those of Galesesco and Stalineano, in the typhus epidemic of Bucharest in 1906. Besides, we verified the fact as did these authors, that the terminal crisis is accompanied by a yery- marked and almost pathonomonic increase of mononuclear leucocytes. | HK. Gotschlich, on the contrary, has described protozoa resembling P. bigeminum in typhus patients at Alexandria, which he has called “aplosoma.” Our experiments prove that typhus fever is a disease in which the virus is situated in the circulating blood during the second and fifth days of infection. It is inoculable from man to man, but does not seem to affect the ordinary laboratory animals. It is possible to make at least two passages on man, but it must be remarked that the incubation is longer the. second time than the first (fourteen and twenty-one days). The specific agent of typhus fever is invisible in the blood or at any rate is exceedingly rare. These experiments, which doubtless require confirmation and elabora- tion, authorize us in considering typhus fever as a disease to be classed with the blood infections transmitted by the bites of insects. The trans- mitting agent has yet to be discovered. Medical literature on typhus, so rich in all kinds of epidemiologic documents, does not disprove this hypothesis. We The therapeautic treatment ordinarily employed for malaria fails in typhus feyer.. Quinine particularly is useless. We limited ourselves to symptomatic medication. EE — TYPHUS FEVER IN INDO-CHINA. 13 The origin of our little localized epidemic must either be from the villages of our coolies or the boat which carried them. The infection may be developed later, but the germs seem to come from the south of Tonquin. The first three cases belonged to the same village, Coi Tri (Ninh Binh), and the other two to a bordering province, Nam Binh. The boat need not be considered, for if the disease had originated in it, the number of typhus cases would not have been so limited and there would certainly have been a focus on board, which could not have remained long unnoticed. Moreover, it was a Tonquinese vessel, the home port of which was Haiphong. Inquiry which will be made in the incriminated Tonquinese provinces will soon make it certain whether typhus fever has taken root in Tonquin, and whether new sanitary supervision will not be justified. CONCLUSION. 1. Typhus fever has been observed in Annam in natives who recently arrived from Tonquin. 2. It manifested itself in accordance with the classic description, with the exception that the eruption was wanting. 3. The direct inoculation of blood from man to man has reproduced the disease after an incubation period of fourteen and twenty-one days. 4. Typhus fever seems to be a blood disease transmitted to man by bites of insects. BIBLIOGRAPHY. ASHBURN P. M. and Craig CHartes I’. Experimental investigations regarding the etiology of dengue fever, with a general consideration of the disease. This Journ., Sec. B, Med. Sci. (1907), 2, 93. G. DiruLaroy. Manuel de Pathologie interne, Paris (1907). GALESESCO et STALINEANO. Recherches bact. faites 4 l’occasion de l’épidémie de Typhus Exanthématique de Bucarest; Recherches cytologiques sur le sang, sur le liquide céphalo-rachidien dans le Typhus Ex. Compt. rend. Soc. de biol. Par. (1906), 61, 15, 85, 230. E. GorscHiicH (ALEXANDRIE). Ueber Protozoen befunde (‘‘Apiosoma”) in Blute von Flecktyphuskranken. Deutsche med. Wcehnsch. (1903), 29, 329-331. Manson, P. Tropical diseases: A Manual of the Diseases of Warm Climates. London (1904). MARCHOUX, SALIMBENI et Srmonp. La fiévre jaune rapport de la Mission fran- eaise. Ann. d Vinst. Pasteur (1903), 17, 665. Nerrer. Typhus Exanthématique, in Traité de Méd. et de Thérap. Brouardel, Gilbert et Girode: Paris (1896), 2, 1. REED, CARROLL, AGRAMONTE and Lazear. The etiology of yellow fever: A pre- liminary note. Proc. Am. Pub. Health Asso. 28th an. meet. Columbus (1901). A. YERSIN. Note sur un cas de Fiévre Récurrente obs. en Indo-Chine. Compt. rend. Soc. de biol. Par. (1906), 60, 1037. tee Wiogiay pint haa tt wet i . 4 ‘ :, < / } ‘ i ‘if PUY tiie i | j fy ha Ne Ng Baha te seams LPO DOE 5 baa eke ‘ 4 fair Y ; ‘ * t 4 ‘ 9 i - Z d if 2 . ct ine Fas PM ET eT Ri atelived Rees pat ih Wendy < i DMOGR 7 / ‘ : & > _ ILLUSTRATIONS. ; : eh of Tonkin and Annam. Charts 1 to 7. TYPHUS FEVER IN INDO-CHINA. 125 nee Ninh Bi ay 4 MAP or TONKIN Showing the provinces con. nected with the occurrence of the Typhus outbreak lndeZohine Map or TonKIN AND ANNAM. 68330 5 VASSAL. RSIN AND y yi} YI 142 *T NOILVANUSHO SYyUo seed 145 ‘G NOILV ANAS 9OGT eure 906) Son ES ISESIISESISES IS BLU wie} al Ria] a SISISISINIS & | 1S} ro 1Q | ex] & syuow soseqd oSt AND VASSAL. RSIN 7 vi} ab 144 *€ NOILVANASTO “Qogl aun —° gogk AeTT | Ssyucy so7eq a = N 1A Nu ° ° st FE Saae PEPE EEE EEE EEE EEEE EE EEEEH {_ ° a i) am am a.m. am pom 145 IN INDO-CHINA. EPEVER TYPHUS “fF NOILVAYASAGC, ‘909067 eUuNnL SIS ISIS ISIS ISIN INES ES 3] |i] <]0] Sol Sle Le SypUoy sajeq “G¢ NOILVAUASAO G uolgensasgo wolf poo jor $0 yzim pajejnsoul (g sop) hy ven ualngy ‘9067 eLnp |syUOoWw Ss ) rai) 21V°eq oft 147 HINA. 1 } -C PEVER IN INDO TYPHUS ‘G NOILV AYASAQ WOXAT GOOTA JO “00 G') HEIAM GALVINOONT “906, ‘ANOG ‘9 NOILVANGSAD SAPD I LdAd{ wouenqou Jaye SKep vi wojegniu fo polad so puz 9061 gunp | SsyjuoW;w so1eg |] LY maaes [7 cf IS i=) < 3 Wz i) wr A EA eget a : ; EEEH a ay [7 [| ta y | BI WEEE foooe = is seeae : al ii se [2] 3] aaa ae Ha y BCS SEs gy 5 5 ae as aad Boe GnaAn NIA M aoa Ss SB ft] er wa FEE Sagggo afi cece a OGG! a AA een = fa} = LI Eee seat BARNES Re: fe ce ao rH a a 3 4) oro rr HEH aoe 40 ape 39 38 PT 2a}eayeresfzcia7iasferfaol7 Tatat4ts[ TT TT 7 TT Tt Tt cH as RUEDIGER. No. 10 a = No /1 ER PATO WAEAVEA 4 40 39 38 37 WW a, 179 OF CATTLE PLAGUE WITH VIRUS EXPERIMENTS | [ | | a | i a S| S i sy a a S S Sri GarriEE EE A No. 12‘ 4) 40 39 38 37 RUEDIGER. 180 No./4 Al 40 39 38 37 Nols /0 } 4 40 181 OF CATTLE PLAGUE. EXPERIMENTS WITH VIRUS eC wi hai ie] EDITORIAL. The unification of the medical interests of the Philippine Islands and the harmonizing of the respective attitudes of the American and Fili- pino physicians has been steadily going on for a number of years. The Philippine Islands Medical Association had its first annuaP meeting in 1903, with rather a small attendance and a limited number of papers for discussion. No delegates from other countries were pres- ent. Hach sueceeding year has brought out a larger attendance and a greater interest. In 1906 we had two representatives—one from Hong- kong and one from Japan. In 1907 three delegates attended—one from Hongkong, one from Japan and one from China: In 1908 there were eleven, representing respectively: The Imperial Japanese Government, the Imperial Chinese Government, the Imperial Siamese Government, Ceylon, Saigon, the Federated Maylay States, Singapore, and Hongkong. At the fifth annual meeting, a representation comprising many of the countries included in the so-called territory of the Far Hast was present and the time was thought to be ripe for the formation of the Far Eastern Association of Tropical Medicine, to meet once in two years upon the invitation of one of the Governments of the component coun- tries. ‘This moyement we hope will cement together the medical and scientific fraternities of the territories in question, will stimulate inves- tigation and in addition will bring the center for the publication of research work in Far Hastern tropical medicine where it belongs, namely to some Government or society in the Orient. Oriental medicine is undergoing a rapid expansion and is attracting inereased attention throughout the world. Oriental governments are dealing with peoples whose prejudices and traditions work against the general scientific application of the art of medicine. This attitude must gradually be changed, but the results to be expected are sufficiently great to warrant the outlay of the best energies of the most prominent scientific workers of the world. It means nothing less than an improved hygienic understanding among Oriental peoples and the gradual removal of the causes which underlie certain phases of their stagnation. It will be accompanied by a general movement towards an enlarged sphere of activity among the people. The papers read at the Fifth Annual Meeting of the Philippine Islands Medical Association will be printed in this JouRNAL during 1908 and the discussions on the various topics will be given in its editorial columns. By this system readers can not only become familiar with the experimental data, but also with the opinions of physicians in this portion of the globe. PauL C. Fremr. 183 184. EDITORIAL. DISCUSSION ON THE PAPERS BY DR. VICTOR G. HEISER AND DR. HARRY T. MARSHALL. Colonel L. M. Maus, deputy surgeon-general, United States Army: It affords me much pleasure to have occasion to express myself in regard to the practical conditions involved in the spread of cholera, as I had abundant opportunity during the early part of the epidemic in 1902 to study some of the channels of the dissemination of the disease. The distory given by Dr. Heiser in regard to its origin agrees exactly with my own experience; it seems to be as nearly a correct one as we could find it to be at that time. » Autopsy examinations. 1 While it could not be argued, perhaps, from a comparison of statistics, that the population of the Philippines is necessarily more generally infected with animal parasites than the people of certain other localities for which figures almost as high have been published, the fact remains- that the average number of infections per 100 persons (186) found in examining the 4,106 prisoners at Bilibid, is higher by over 40 than has ever been definitely reported for any other country upon a number of cases sufficiently large to be taken as a fair index to the prevalence of animal parasites in the general population. PARASITES PRESENT. The infections represented at least fifteen genera and probably about twenty species. he genera positively determined were the two hook- worms, Necator and Agchylostoma; the common “round worm,” Ascaris ; the common whipworm, Vrichuris; the common pin or seat worm Oxyuris; the worm of Cochin-China diarrhea, Strongyloides; the cestode genera Tenia and Hymenolepis; the Japanese lung fluke, Paragonimus ; the Japanese liver fluke, Opisthorchis; the Japanese blood fluke, Schisto- soma, and the four protozoal genera, Ameba, Balantidium, Lamblia, and Cercomonas ; in addition, there were a number of undoubted infections in which the identity of the parasites was not even generically determined. MULTIPLE INFECTIONS. Multiple infections were numerous, as is shown by the fact that 7,636 infections were distributed among the 3,447 infected prisoners, ‘an average of 222 infections to each 100 infected persons, or nearly 2.25 infections per infected idividual. One thousand and sixty-seven, or slightly more than one-fourth of the prison- ers examined, showed infection with one species of parasite only; of these single infections, 428 were with hookworms, 384 with whipworms, and the remaining 255 with other species. 196 GARRISON. Nine hundred and thirty, or slightly less than one-fourth of the persons examined, showed a double infection, of which hookworms and Trichuris gave 518, or about one-half, Ascaris and Trichuris nearly one-fourth, and various combinations the remainder. Seven hundred and twenty-three, or about 18 per cent, had triple infections, of which the most common was with Ascaris, hookworms and J'richuris; although combined infections with Ameba, hookworms and Trichuris and with hookworms, Trichuris and flagellates were present with almost equal frequency. Three hundred and sixty-six prisoners, or 9 per cent, were infected with four different parasites, the most common combination being Ameaba, flagellates, hookworms and T'richwris. One hundred and thirty-one prisoners (3 per cent) gave a combined infection with 5 parasites, 80 of which were with Ameba, flagellates, Ascaris, hookworms and T'richuris. A combination of six different infections in one patient occurred fifteen times; in five of these cases the parasites were Amoeba, flagellates, Ascaris, hookworms, Strongyloides and Vrichuris. Two prisoners had seven separate infections, and one man was infected with nine different parasites, the combination in the last case being Amaba, flagellates, Balantidium, Ascaris, hookworms, Strongyloides, Trichuris, Opisthorchis and Schistosoma. GEOGRAPHIC DISTRIBUTION. A rather elaborate attempt was made to determine whether the indi- viduals coming from any particular part of the Islands gave an excess of infection over those from other sections. ‘To this end, a record of the previous residence of prisoners was taken and the infections found were tabulated by separate provinces, separate islands and various groups of provinces and of islands. No significant difference in the total per- centage of infection could be detected. Prisoners from the extreme northerly provinces presented about the same percentage (with all parasites) as did those from the Visayas or from central or southern Luzon. The same even geographic distribution seemed to prevail for each separate species of parasite, with the exception of infections with the three trematode genera, Paragonimus, Schistosoma and Opisthorchis, especially the two former, which appeared to originate almost exclusively in certain of the southern islands. The distribution of the infections with the three trematodes mentioned will be considered more in detail under each genus. While practically all parts of the Islands are fairly well represented at Bilibid, an investigation conducted at such long range would be able to discover none but very marked imequalities in the distribution of the parasites and it is by no means excluded that further work, done in the various provinces themselves, would indicate an excess of infection in certain parts of the Islands, which did not appear among the prisoners examined at Bilibid. ANIMAL PARASITES OF MAN. 197 INFECTIONS WITH TRICHURIS. (59 per cent.) If we confine ourselves to statistical reports based upon an adequate number of cases (several hundred), much higher percentages of infection with whipworms have been published for temperate than for tropical climates. The highest rate of infection with V'richwris definitely reported was found by Heisig in Germany in 1893 (45.21 per cent); the next, by Gubareff in Russia, in 1896 (43.62 per cent). In these cases, the total percentages of infections with all intestinal worms were only 60.85 and 76.32, respectively. Boycott in 1904 reported 38.78 per cent of whipworm infections from Cornwall, England, but only 98 men were examined. Grechaninoff (1890) found this parasite in 26.41 per cent of 583 persons examined in St. Petersburg. Other German statistics for whipworms are: Sievers, Kiel, 1887, 2,629 persons examined, 19.81 per cent infected; Roth, Bale, 1877-1880, 752 persons examined, 23.67 per cent infected; Gribbohm, IJsiel, 1872-1877, 972 persons examined, 32.20 per cent infected; Heller, Kiel, 1872-1875, 611 persons examined, 30.60 per cent infected; Miiller, Erlangen, 1862-1873, and Dresden, 1852-1862, 1,755 and 1,939 persons examined and 11.11 and 2.57 per cent infected, respectively. Stiles and Garrison (1906) in examining 3,457 persons in the United States found 7.72 per cent to be infected with whipworms. Cima (1893 and 1896) in the vicinity of Naples, Italy (subtropical), found 37.27 per cent of infection in examining 110 children. On the other hand, we have the following statistics for whipworms from populations in the tropics: Anemia Commission, 1904, Porto Rico, 4,482 persons examined, 7.27 per cent infected; Daniels, 1901, British Central Africa, 251 examined, 2.79 per cent infected; Fearnside, 1900, India, 878 examined, 6.95 per cent infected; Dobson, India, 1893, 1,249 examined, 4.40 per cent infected. While estimates have been made regarding the frequency of whipworm infection in different populations ranging from 50 per cent (in Italy)® to 100 per cent (in Paris)® it appears that our figures for the Philippines (59 per cent) give a higher rate of infection with this parasite than has ever been definitely reported upon a number of cases sufficiently large to serve as an index to the general population.‘ his fact would seem to give fairly conclusive proof to the view that the relatively low rates of ° Blanchard, Raphael: Traite De Zodlogie Medicale. Paris (1889), 1, 785. * Braun, Max: Die Thierischen Parasiten. Wiirtzburg (1903), 277. “Estimates of the frequency of infection, without actual statistical proof, would appear to be absolutely unreliable. While from 50 to 100 per cent of the population of southern Italy was estimated to harbor whipworms, Cima’s examination of 110 children gave only 37.27 per cent of infection. Ascaris had been estimated to be the most common intestinal parasite of man in the Philip- pines, but actual statistics show it to be about one-half as frequent as whipworms or hookworms. When the present investigation had proceeded to the examination of 1,000 patients, the author estimated that the percentage infected with whip- worms would approach very nearly to 90, and even expressed such an opinion in a meeting of the local medical society; our final figures show only 59 per cent. 198 GARRISON. infection with whipworms reported from the tropics are due to the failure of workers in tropical countries to record whipworm infections. A number of authors * have found whipworm to be more common in females than in males and in children (under 15 years of age) than in adults and therefore it is probable that the actual frequency of the parasite in the Philippine population as a whole is higher than is shown by our figures, which are exclusively based upon the examination of adults and almost exclusively of males. So far as could be determined from the records of the previous residences of the prisoners examined, the percentage of infections with whipworms appears to be about equal throughout the different provinces of the Islands. INFECTIONS WITH HOOKWORMS. (52 per cent.) Hookworms, after Trichuwris, were the parasites most frequently en- countered (52 per cent). Much higher rates of infection with hook- worms have been reported from other countries, but some of these, notably those detailed in the report of the Porto Rican Anzmia Commission, are not suitable for purposes of comparison, for the reason that the examinations were primarily directed to the study of hookworms, while in our own work hookworm infections were recorded no more faithfully than were those with other parasites. Calvert, Fearnside and Dobson in India reported 83 per cent, 65.83 per cent, and 75.58 per cent, respectively, and with the exception of their comparatively low rates of infection with whipworms, these authors appear to have recorded all intestinal verminous infections impartially—their rates of total infections being 143, 104.9 and 107.28 per cent, respectively. The recognized pathogenicity of hookworms, their relatively great importance from the view point of clinical medicine and public hygiene, and the seriousness of the problems presented by uncinariasis in other countries, urge us to depart here from a purely statistical presentation of the case and briefly to consider the clinical aspect of hookworm disease in the Philippines, so far as we have been able to determine it by observation and inquiry during the past year, in relation with the apparent frequency of hookworm infections. While our figures show 52 per cent of the 4,106 prisoners which were examined to be infected with hookworms, clinical manifestations of uncinariasis were rare; in fact, cases of severe anemia, in the absence of tuberculosis, malaria, or other anewmia-producing diseases, were practi- cally absent. While hundreds of patients come from the provinces to the hospitals of Manila annually, general inquiry among the physicians elicits ‘Bull. Hyg. Lab.. U. S. Pub. Health & Mar.-Hosp. Serv., Wash. (1906), 28, 70-71. ANIMAL PARASITES OF MAN. 199 the information that although hookworm infections are common, they are usually first diagnosed in routine examinations of the feeces and if severe anzmia is present, a concurrent infection of malaria, tuberculosis or of some other disease which would account for the condition exists. Furthermore, after careful and general inquiry among numerous medical officers of the Army, Navy, and the Bureau of Health who had served or were serving in the provinces, we have failed to obtain any knowledge of any general or marked prevalence of hookworm disease among the natives.° Accordingly, while further investigation may discover a greater frequency of uncinariasis in its severer forms than now appears to be the case, it would seem to be reasonably certain that there is no such prevalence of this disease with severe manifestations among the natives of the Philippines as we might expect in view of the apparent fact that over one-half of the population harbors this parasite. Whether or not the explanation of this apparent rarity of clinical symptoms in hookworm infections among the Filipinos is a racial im- munity on the part of the people to the toxins secreted by the worms, as has been suggested in regard to the similar condition found by Stiles in negroes in the Southern States, by the Anzemia Commission in Porto Rico and by Zinn and Jacoby in Africa, the fact that severe clinical manifestations of uncinariasis are rare in the Philippines materially alters the problem which is presented. Instead of producing an acute condition such as was presented in Porto Rico, St. Gothard Tunnel, the Westphalian coal mines, and in other places where uncinariasis prevailed in its severer forms, it would appear that in the Philippines hookworm infections play a part more nearly resembling that of the other common intestinal worms to which no definite pathology or severe symptomatology is usually attributed. INFECTIONS WITH ASCARIS. (26 per cent.) Rates of infection with “round worms” have been reported ranging from 0.49 per cent (Stiles and Garrison, United States, 1906) to 50.97 per cent (Wellman, west Africa, 1904). A compilation of statistics obtained from nearly 3,000 persons ex- amined and reported upon by various authors, shows Ascaris to have been found almost twice as frequently in females as in males, as follows: Males examined, 1,732; infected with Ascaris, 138, or 7.97 per cent; females examined, 1,103 ; infected, 159, or 14.42 per cent.1° ® The most severe case of hookworm disease seen by the author in Manila and the only one showing in a marked degree the cardinal symptoms of extreme anemia, with cardiac murmurs, cedema, dyspnea, and great weakness, was a Japanese male infected with the “Old World” hookworm (Agchylostoma duo- denale) . * 2 Bull. Hyg., U. S. Pub. Health & Mar.-Hosp. Serv. Wash. (1906), 28, 70-72. 200 GARRISON. A similar compilation with regard to age demonstrates that “round worms” are encountered with over twice as great frequency in children under 15 years than in adults of middle life, the number of children from 1 to 15 years examined being 2,381; those infected, 400, or 16.80 per cent; adults, from 15 to 50 years, examined, 1,461; infected, 107, or 7.82 per cent. It is evident that our figures (26 per cent), based entirely upon adults and almost entirely on males, are considerably below the proportion of the total Philippine population harboring this worm, should a like sex and age relation with regard to Ascaris infections hold in the Philippines. INFECTIONS WITH AM@BA. (23 per cent.) Statistics regarding the frequency of Amebe in the human intestine have varied greatly in the percentage of infection found, numbers as high as 50 and even 70 per cent having been reported; a comparison is rendered more unsatisfactory by the fact that some authors have at- tempted to distinguish between Hntameba coli and Entameba histolytica and others have not done so. In the work here reported no attempt at such differentiation was made after the investigation had progressed for a few weeks, for the reason that it was not found possible to dif- ferentiate the two species with any certaimty in a routine microscopic examination of the fresh feeces, and also because we are of the opinion that, until more light has been thrown upon the problems of the specific identity and the relative pathogenicity of intestinal amceba, the only safe attitude to hold toward amcebic infection of the intestine in the Philip- pines is to consider all intestinal amceba potentially pathogenic and to treat them accordingly. In view of such an opinion, the practical pur- pose of the investigation expressed in the introduction would be served by recording the frequency of infection with Amaba without attempting a possible specific determination of the parasites. A diagnosis of Amaba was made only upon finding the motile or- ganism. All encysted forms or cellular structures resembling the vege- tative form of the parasite were reported to be negative with a query, and other examinations were made until the motile organism was ob- served or its absence rendered reasonably certain. The percentage of infections with Amaba among the 4,106 prisoners examined (23 per cent) agrees. rather closely with figures previously reported by Musgrave and Clegg who found 154 (26 per cent) of 587 prisoners examined at Bilibid to have Ameba in the feces. ANIMAL PARASITES OF MAN. 201 INFECTIONS WITH INTESTINAL PROTOZOA OTHER THAN AMGBA. (21 per cent.) So many atypical forms of flagellates and forms, which could not with certainty be readily placed in known genera, were encountered that the attempt to differentiate all of these organisms was abandoned at an early period and the diagnosis was made under the general term, monads. The flagellate most frequently present was Cercomonas, prcb- ably the usual Cercomonas honuwims of other localities. There were three infections with Balantidiwm and three with Lamblia. As in the case of Amaba, only the observation of the motile forms of these organisms was considered to be a safe basis for a positive diagnosis. INFECTIONS WITH STRONGYLOIDES. (3 per cent.) The statistics at command for the prevalence of Strongyloides are the following : Strong, 1901, Philippine Islands, 2,179 persons examined, 13, or 0.6 per cent, infected; Daniels, 1901, British Central Africa, 251 persons examined, 3, or 1.50 per cent, infected; Wellman, 1904, West Africa, 310 examined, 2 or 0.65 per cent, infected; Anemia Commission, 1904, Porto Rico, 4,482 examined, 36, or 0.8 per cent, infected; Stiles & Garrison, 1906, United States, 3,457 examined, 8, or 0.23 per cent, infected. Our figures (132 infections, 3 per cent) are somewhat higher than any hitherto reported. The diagnosis in every case was based upon finding the free embryo in specimens examined not more than four hours after the stool was passed. To the best of our knowledge, hookworm ova, even in a tropical climate, never hatch in less than twelve hours after the feces are passed. INFECTION WITH OXYURIS. (0.8 per cent.) As has been repeatedly pointed out by various workers, the microscopic examination of fxces for ova is not a reliable method for the diagnosis of the pinworm, for the reason that the migration of the adult female worm to the exterior prevents such a distribution of the ova through the feeces as occurs in the case of ova which are deposited in the intestine. The highest rate of infection with pinworms reported from microscopic examination of the feces was that of Dobson, in India, who found 15.37 per cent of 1,249 persons to be infected; the next highest, 10.98 per cent, was reported by Grechaninoff, in St. Petersburg, in 1890, upon the microscopic examination of the feces of 583 persons. Some statistics based upon findings at autopsy show higher figures. Both Gribbohm and Heller encountered a fraction over 23 per cent of infection with 202 GARRISON. Oxyuris in autopsies done at Kiel, and Banik reported 30.16 per cent found in 315 autopsies at Munich. Muller, however, found only 2.21 per cent in 1,939 autopsies at Dresden and 12.13 per cent in 1,755 autopsies at Erlangen. This parasite is directly transmissable from one person to another by means of the freshly deposited ova in the feeces, thus making it a simple matter for one person to spread the infection among those in intimate personal association with him. ‘The chief significance of our figures for Oxyuris (23 cases, 0.8 per cent) probably lies in the fact that they are a favorable commentary upon the sanitary condition of the prison and also, perhaps, upon the personal cleanliness of the Filipino of the lower classes; for it might naturally be expected that when from 200 to 400 men sleep side by side im close proximity as the natives do at Builibid, favorable conditions would arise for the spread of pimworm infection if once it was introduced.1t Although the microscopic examination of feces is unreliable for the diagnosis of oxyuriasis, more cases would undoubtedly have been found had there been any widespread prevalence of the infection in the prison population. It would appear that Oxyuris, like Ascaris, tends to occur more fre- quently in children than in adults and (to a less degree) in women than in men, the figures compiled from different authors being as follows: Males examined, 1,543; infected, 178, or 11.54 per cent; females exam- ined, 810; infected, 115, or 14.20 per cent; adults (over 15 years) examined, 860; infected, 39, or 4.54 per cent; children (under 15 years) examined, 1,272; infected, 305, or 23.97 per cent.” Our figures (0.8 per cent) for adult males may safely be presumed to be below the percentage of infection in the total population of the Philippines. INFECTIONS WITH TANIA. (0.7 per cent.) Rather well-defined distinctions are given between the ova of Tenia saginata and Tenia soliwm, but we do not consider them to be sufficiently constant and well marked to make a differential diagnosis between the two species practical from a microscopic examination of the ova alone in the general run of cases. ‘Therefore, the distinction was not attempted unless segments of the worms were obtained. As has been u As an example of the tendency of Oxyuwris infection to spread among persons in intimate contact, we may cite the case of a single ward in a hospital for the insane, which came under our observation in the United States. Of the 45 men in the ward, 11, or 24.44 per cent, were infected with pinworms; five other wards in the same building gave 1, 2, 0, 2, and 1 infections, respectively. In the remaining 36 wards in other buildings (796 patients) there were only 8 infections with this parasite. Bull. Hyg. Lab., U. 8S. Pub. Health & Mar.-Hosp. Serv., Wash. (1906), 28, 56, 61. “Bull. Hyg. Lab., U. S. Pub. Health & Mar-Hosp. Serv., Wash. (1906), 28, 71-72. ANIMAL PARASITES OF MAN. 203 shown in an earlier paper,!® the relative number of adult specimens of T. saginata and T. solium, deposited in the Helminthological Collection of the Bureau of Science, indicated a considerably greater prevalence of the former species. Figures for the frequency of infection with the beef and the pork tapeworms in different localities have ranged from 0.06 to 3.66 per cent for the former and from 0.02 to 3 per cent for the latter species. Several authors have reported no infections found in large series of cases examined.** INFECTIONS WITH PARAGONIMUS. (0.4 per cent.) The infections with lung flukes here reported were diagnosed by finding the ova in the feces. In most of the cases they were also found in the sputum and it can not be excluded that they were present in the sputum in all cases and reached the intestines as a result of the swallow- ing of the eggs.” Geographic distribution—TVhe history of the 18 patients infected with Paragonimus with regard to place of residence before commitment to the prison was as follows: One from Manila, one from Cavite, one from Camarines Norte, one from Albay, two from Sorsogon, four from Samar, six from Leyte, and two from Mindanao. The central and northern provinces of Luzon were fully as well represented among the prisoners examined as were the southern prov- inces and the southern islands of the Archipelago, yet no patient infected with Paragonimus gave a history of residence north of Manila and, with the exception of the cases from Manila and Cavite, in neither of which could the possibility of previous residence in the southern proyinces be eliminated, all instances of paragonimiasis gave a history of origin in the islands south of Luzon or in the peninsula forming the southern extremity of that island. 2 This Journal, Sec. B., (1907), 2, 537. 4 Bull. Hyg. Lab., U. S. Pub. Health & Mar.-Hosp. Serv., Wash. (1906) 28, 66-67. *7t¢ would appear from our experience, that the value of examination of the feces in the diagnosis of paragonimiasis has not been sufficiently emphasized, the examination of the sputum alone being usually stated as the method for diagnosis. In several cases, repeated examination of the sputum was necessary before ova could be found, although they were present almost constantly in the stools. When found in the sputum they were usually more abundant than in the feces. If, as appears, the discharge of ova of the lung fluke in the sputum is, in some cases at least, intermittent, it is not illogical to suppose that the ova swallowed with the sputum become more or less scattered along the alimentary tract and are discharged more gradually, in less concentration, but with relatively greater constancy in the feces. We would suggest, therefore, the value of microscopic examination of the faeces as well as of the sputum in the diagnosis of lung-fluke infection. 204 GARRISON. Therefore, the conclusion would appear to be warranted that infection with lung flukes is not evenly distributed throughout the Philippines, as appears to be the case with the parasites above considered, but that it is to be found chiefly in the southern portions of the Archipelago. It is quite within the bounds of probability that the distribution of — this parasite may be found to be even more strictly localized. ''o the best of our knowledge, all cases of paragonimiasis reported for the Philippines, mm which the history of previous residence was known, have originated in the southern part of the Islands, and further investigation may show the infection to be confined to this region. The possibility can not be excluded that the infection is limited more or less strictly to certain of these southern islands. Some indication of this was found in our own figures. For instance, 239 prisoners from the Island of Leyte were examined and 6 had paragonimiasis; 127 prisoners from the Island of Samar gave four infections with lung flukes; on the other hand, while 248 prisoners from Panay were examined, no fluke infections occurred. However, until the matter has been further investigated, we believe that the only generalization justified by our results is as already stated: namely, that paragonimiasis prevails in the southern rather than in the northern parts of the Philippines. INFECTIONS WITH SCHISTOSOMA JAPONICUM. (0.6 per cent.) The use of the specific name seems desirable in the present case in order to differentiate Schistosoma japonicum from S. hematobium, all of our infections being with the former species. Geographical distribution—As in the case of Paragonimus, the ap- parently uneven geographical distribution of Schistosoma infections appears to be of greater interest and importance than the actual percent- age of infection found among the prisoners examined. ‘The cases of schistosomiasis were distributed geographically as follows: Manila, 1; Samar, 6; Leyte, 5; and Mindanao, 4. Therefore, excepting the one case from Manila, all infections with Schistosoma appear to have origi- nated on the three southern islands, Samar, Leyte, and Mindanao. INFECTIONS WILH OPISTHORCHIS. (0.3 per cent. ) Racial and geographical distribution.—In only five of the eleven cases of opisthorchiasis could a definite history of previous residence he ob- tained. Three of these came from the Island of Mindanao, one from ANIMAL PARASITES OF MAN. 205 Rizal Province, Luzon, and one from Nagasaki, Japan. Five of the prisoners having Opisthorchis infections were Chinese, five were Filipi- nos, and one was Japanese. The results for Opisthorchis are not sufficiently complete to show any marked inequality of distribution among different localities. However, there does appear a relatively greater prevalence of this parasite among the Chinese. In one case it was certain that the infection was contracted in China, but in the other instances this pomt could not definitely be determined. | INFECTIONS WITH HYMENOLEPIS. (0.1 per cent.) Four of the five infections with Hymenolepis were with the “dwarf tapeworm” of man, H. nana; the remaining one was with H. diminuta. Statistics by several authors show that the dwarf tapeworm is consist- ently more common among children than among adults, and therefore we would expect our figures to be somewhat higher for this parasite had children been included among the cases examined. DISCUSSION. The purpose of the investigation, as was stated in the introduction, was to obtain accurate knowledge of the prevalence and distribution of animal parasites among the Filipinos so as to secure more definite judg- ment regarding the importance of animal parasites as factors in deter- mining the hygienic and industrial condition of the people, and to obtain a clearer idea in regard to the nature and magnitude of the medical and sanitary problems presented and, perhaps, also to make some contribution toward their solution. The results of this investigation show one of the most striking in- stances in the history of medicine of a population almost universally infested with animal parasites; and the medical and sanitary problems presented would seem to offer three rather distinct aspects, namely, the infections with intestinal protozoa, chiefly Ameba, the trematode infections, and the infections with intestinal worms. The situation in the Philippines in regard to ameebiasis is involved in differences of opinion both as to the specific identity of Ameba found in the intestine and to their pathogenicity. Whether or no the validity of Schaudinn’s Hntameba histolytica and #. coli and the nonpathogenic nature claimed for the latter species be ultimately established, we are forced to believe, as we have already indicated, that in our present state of knowledge the only safe position for the medical man to hold in 206 GARRISON. the Philippines toward amoebic infections is to consider all intestinal Ameba as potentially pathogenic. Accepting such a view, our figures would appear to prove from a statistical view point the wide prevalence of amoebiasis already recog- nized by clinicians and to emphasize the extreme value of the prophylactic measures urged by the Bureau of Health and the great need of rapidly extending sanitary measures against this parasite. The magnitude of the problem appears when we consider that if our figures for the Bilibid prisoners (23 per cent) be applied to the total population of the Islands, from 1,500,000 to 2,000,000 people in the Philippine Islands harbor intestinal Ameba. The unsolved biological problems in connection with Paragonimus, Schistosoma and Opisthorchis, involving their embryonic development, and intermediate hosts and modes of infection, leave us only general measures of treatment and of prophylaxis in these infections. The apparent localization of Paragonimus and Schistosoma in the southern part of the Islands renders our figures of little statistical value, and further work in the localities m question will be necessary in order to determine their actual frequency of infection in infected localities. The situation in the Philippines in regard to the prevalence of in- testinal worms calls for special consideration because of the high rate of infection found, the peculiar character of the hookworm situation, and because these infections are apt to be lightly regarded in the tropics. The prisoners at Bilibid showed an average of 142 infections with intestinal worms for each 100 examined. Fifty-two per cent were in- fected with hookworms, but it would appear that these parasites do not produce the serious effects in the Filipino that they do in other races; hence, they should be placed in the same category with other intestinal worms. While it is generally recognized that verminous infections of the intestine are indirectly and in an indefinite degree injurious, it is extremely difficult to obtain and it is practically impossible to demon- strate any accurate measure of the injury done. So far as we are aware, the work which by its results has come nearest to demonstrating the *Tt would not be within the purpose of the present paper to enter into a discussion of the merits of the questions regarding the specific identity and relative pathogenicity of intestinal Ameba. If all intestinal Amcba are patho- genic, it is a rather startling condition of affairs to find 23 per cent of a population harboring this parasite; but it would appear that such a view is rather in harmony than otherwise with the frequency of amebic lesions found at autopsy. In this connection, the reader is referred to earlier publications of Musgrave and Clegg in the Philippine Journal of Science, and to Gilman’s report upon a series of 100 autopsies at the Philippine Medical School which appears in the current number. a ANIMAL PARASITES OF MAN. 207 effects of infections with intestinal worms upon the health of a popula- tion is that carried on by Dr. Shattuck of the Bureau of Health at Bilibid Prison during the time our own investigation was in progress, the results of the same examinations being used as far as practicable in both investigations. These results have been placed at our disposal by Dr. Heiser, Director of Health, from the manuscript of his Annual Report for 1906-7, and are briefly as follows: The annual death rate in the prison when it came in charge of the Bureau of Health was 238 per one thousand. The institution of general measures of sanitation reduced this rate to 75 per one thousand where it remained stationary, resisting further reduction. Up to this time little attention had been paid to infection with intestinal worms. In the latter part of 1906, systematic treatment of the prisoners for intestinal worms was begun and vigorously carried out until practically the entire population of the prison had been treated. Following, and, in Dr. Heiser’s opinion, largely as the result of this antihelminthic campaign among the prisoners, the death rate dropped to 13 per one thousand per annum. Whether or not this apparent relationship between intestinal worms and the death rate at Bilibid will be substantiated by future records at the Prison, or would be confirmed by the institution of a similar campaign throughout the Islands, its significance can scarcely be over- estimated even though ultimately the results should prove to be but a fraction of what was-apparently accomplished among the Bilibid prison- ers. It moreover sharply emphasizes the fact that the absence of direct, acute manifestations of intestinal. helminthiasis should not blind us to the vital importance of these infections as factors in determining the hygienic condition of a people. Applying the rates of infection obtained from the 4,106 prisoners examined at Bilibid to the total population of the Islands (about 7,000,000), it would appear that about 5,000,000 persons in the Philip- pines are infected with intestinal worms and that the inhabitants of the Islands harbor over 9,000,000 infections. The magnitude of these figures indicates in part the tremendous proportions of the problems involved in any radical movement toward improvement of existing conditions, especially when we consider that the situation does not ap- pear to be simplified by any marked confinement of the infections to limited areas. Even a casual knowledge of sanitary conditions prevail- ing throughout the Islands throws additional light upon the difficulties to be encountered and leads to the question whether it is practicable at the present time to institute special prophylactic measures directed toward the eradication of intestinal worms, or whether we must content ourselves with the gradual sanitary improvement of the country. Ts 208 GARRISON. In this connection, one practical suggestion would seem to offer itself. The source of all infections with intestinal worms, followed back to its origin, is necessarily the feeces of persons already infected.‘ With this fact in mind, we have carefully inquired into the different methods of the disposal of exereta customary among the Filipino people and it would appear that it would scarcely be possible to establish more ideal conditions for the spreading of intestinal parasites throughout the Islands. The native, if living near a stream, defecates along its banks, either in, or at varying distances from the water; in the rainy season, the streams overflow their banks and naturally scatter any mmfection they carry oyer the adjacent country. Another manner of disposing of the feeces, equally or perhaps more prevalent, is simply through a hole in the floor of the bamboo house, the exereta falling to the ground to be partly devoured and partly scattered about by the universally present hogs and chickens. Such conditions go together with the extremely high prevalence of intestinal worms among the people, and we can scarcely escape the conclu- sion that the one sanitary measure preéminently demanded for the preven- tion of infection with intestinal worms in the Philippines is a proper disposal of human excreta. In fact it would appear scarcely too strong a statement to say that the spread of infections with intestinal worms could be in time satisfactorily controlled by the proper establishment of this measure alone. The urgency of the demand for a proper disposal of human excreta is further emphasized by the effect which it might reasonably be expected to bear directly upon the prevalence of other diseases, in that it would lessen the distribution of pathogenic organisms other than animal parasites which escape im the feces. To devise a working system, practical, economical, and adapted to Philippine conditions, is a special problem which requires special and, perhaps, experimental study. That a radical sanitary measure can be effectively and promptly enforced in the Philippines has been strikingly exemplified by the campaign of vaccination against smallpox so success- fully carried out by the Bureau of Health. In conclusion, we believe that the most valuable practical lesson to be drawn from the results of the examination of the Bilibid prisoners is the imperative need of establishing throughout the Philippines a system for the proper disposal of human excreta. Moreover, it does not seem unreasonable to expect, in the light of the striking results apparently accomplished at Bilibid by treating infections with intestinal worms, that with the reduction in the present exceedingly high prevalence of * Those cases in which the parasite may infect other animals as well as man would, of course, constitute rare exceptions to this statement; for example, Hymenolepsis in rats, Tenia solium in hogs. a ANIMAL PARASITES OF MAN. 209 intestinal worms in the population, the general hygienic condition of the people would be improved to such a degree that there would follow a material reduction in the present high rates of morbidity and of mortality from tuberculosis and other prevailing diseases."* “The following resolution was unanimously adopted at the recent annual meeting of the Philippine Islands Medical Association, held at Manila, February, 1908: “Whereas, it would appear that the rate of infection with intestinal worms is higher among the Filipinos than has ever been definitely reported for any other people; and “Whereas, it would appear further that the death rate at Bilibid Prison has been materially reduced following the treatment of the prisoners for these infections; and ‘ “Whereas the spread of infection with intestinal worms can he controlled almost absolutely by the proper disposal of human excreta; and “Whereas, the proper disposal of human excreta would, at the same time, remove one of the most dangerous channels for the dissemination of other infectious diseases: Therefore, be it “Resolved, That the Philippine Islands Medical Association does petition the Government of the Philippine Islands, through the honorable the Secretary of the Interior, that a commission of five properly qualified members be appointed to decide upon the most practical and efficient methods for the disposal of human excreta that can be established in these Islands and that such appro- priation be made and such means provided in accordance with the report of this commission as may be necessary to put into effect a practical and expedient working system for the disposal of human excreta.” A REPORT ON THE FIRST ONE HUNDRED AUTOPSIES AT THE PHILIPPINE MEDICAL SCHOOL. By Puitie K. GILMAN. (From the Depariment of Pathology and Bacteriology, Philippine Medical School.) There have been a large number of autopsies performed by the Bureau of Government Laboratories and its successor, the Bureau of Science since the American occupation of these Islands. While in the cases of acute infectious diseases the diagnoses have been carefully made and recorded, and in other special cases full protocols have been preserved, in general the records are not adapted to furnish the basis for a complete statistical study of the relative frequency with which the different chronic diseases occur. A systematic study has been made, by gross and histologic methods, of the pathologic material, and complete records of the findings have been kept since the opening of the Philippe Medical School, in the depart- ment of pathology and bacteriology organized by Dr. H. T. Marshall. The examinations are made according to the usual Virchow routine, and are designed especially to furnish material and records for a general statistical inquiry. ‘The routine includes the preservation of pieces of the organs in Zenker’s fluid and subsequent histologic examinations. No unusual efforts have been made to discover remote foci of tuber- culosis or syphilis, and the examination for the presence of intestinal parasites has not been altogether complete. Cultures were made in only a few instances. ‘The nerves were examined for degenerations in only one or two cases in which a clinical report rendered the diagnosis of beriberi probable. The following report is based upon the findings in the first one hundred autopsies performed at the. Philippine Medical School between August, 1907, and January, 1908. Although the number of cases is comparatively small, these findings should give a good conception of the relative frequency among the lower classes of Filipinos of the commoner diseases, with the exception of the acute epidemic ones, for the bodies came from the free wards of the large hospitals and from the poorer quarters of the city of Manila. Cholera, smallpox, leprosy, etc., are treated only in the special hospital for these diseases, and such conditions would not enter into our records except on rare occasions. 211 212 GILMAN. Of the 100 bodies examined, 67 were males and 33 females, 97 being Filipinos and 3 Japanese. As is shown in the following table, the third and fourth decades contributed the greatest number of cases, these two furnishing nearly equal numbers: | Total. Decade. = j | | Decade. | Male. | Female. | Total. Male. | Female. | | | 1] | | | 1 7 7 we 6 | 7 2 9] 2 a.) BY |) 10%} a | 4 | ate | 4 | Sait 17 ‘| 6 93 || 8 | 3 Dy} 5 | AN ay | 6 | a | 9 | 1 >, || 3 | 8 | Dy | 10 |} 1 i Tuberculosis was found to be the cause of death in 35 of the cases; pneumonia in 27; chronic cardiac disease and arterial change in 6; nephritis im 5; typhoid fever, beriberi, and septicemia each in 4; amcebie dysentery and acute bacillary dysentery each in 3; acute endo- carditis in 1; carcinoma in 2; and acute pleurisy, acute peritonitis, sple- nomegaly, cerebral abscess, cerebellar hemorrhage, and acute yellow atrophy each in 1 ease. TUBERCULOSIS. Tuberculous lesions were found forty-five times im the series of 100 cases and tuberculosis was the cause of death thirty-five times; 22 of these cases were males and 8 females. The autopsy on the youngest person was of a child 1 year old, on the oldest, of a man of 90 years. The greatest number of cases, 18, occurred between the ages of 25 and 35, the next greatest, 12, between the ages of 45 and 55 years. The disease was confined to the thorax in 21 cases, to the lungs and alimentary tract in 6, to the lungs and kidneys in 2, to the peri- toneum in 4, and was a generalized process in 2. Nearly an equal number of the cases occurred in people who had lived in the country and in those coming from the city of Manila proper, in both of which situations the elevation of the land is very little above that of the sea level. The large amount of lung tissue involved was of particular interest in the cases of pulmonary tuberculosis. Im six instances the greater part of all the lobes of both lungs was thickly studded with lesions. Complete, massive involyement of both upper lobes occurred in 7, one entire lung and at least one lobe of the opposite lung were involved in 2, the entire upper right lobe m 3, and the left in 2 cases. The left upper lobe was diseased in 26, the right upper lobe in 23 cases. The type of tuberculous lesion most frequently met with consisted of a chronic ulcerated condition in which ragged, irregular cavities, fre- quently of great size, connected with one another and with bronchi. This AUTOPSIES AT THE PHILIPPINE MEDICAL SCHOOL. 213 condition was found to a greater or less degree twenty-seven times, or in about 90 per cent of the cases of pulmonary involvement. Histologically, the irregular, ragged walls of these cavities were in the majority of instances not definitely limited by any marked reaction on the part of the surrounding lung tissue. A definite formation of new fibrous tissue was found in but one-third of the cases and this zone was nearly always lined with a layer of newly formed tuberculous tissue. Extensive areas of consolidation were frequently found associated with the cavity formation, and in a contiguous portion or adjoining lobe great showers of miliary and conglomerate tubercles were encountered. The pleura was involved in all cases, the involvement consisting in a chronic, fibrous thickening and obliteration of the cavity which varied from a localized area to complete union of the surfaces. In addition to the cases of tuberculosis, pleural lesions were found very frequently, 50 per cent of the cases included in this report showing some pleural involvement. Tuberculous peritonitis was the cause of death im four cases. One of these showed a small, active focus of the disease in the lungs, one an apparently healed apical lesion, and after a prolonged search the other two revealed no pulmonary involvement. ‘Tuberculosis of the vertebrae occurred but once and of the bladder three times; psoas abscess was also present once. Latent tubercular lesions were found in the lungs in but 2 of the 100 cases, and healed foci oceurred in but 6. ‘In connection with this evidence of the virulence of the tubercle bacillus, it is interesting to note that cultures of the organism obtained by subcutaneous inoculation of guinea pigs and subsequent transference from their glands to suitable media, were kept alive with considerable difficulty and soon died out after a very sparse growth. PNEUMONIA.” = Pneumonia was the cause of, death in 27 cases, 11 of these being croupous or lobar, and 16 broncho-pneumonia, the majority of the cases occurring in young adults and three-fourths coming from the city proper. A summary of the cases of lobar pneumonia shows that all lobes of both lungs were involved in 1 case, the entire right lung in 1, the left lower lobe in 5, the remaining 4 cases showing involvement of but one lobe. All were accompanied by an exudation of a fibrinous nature upon the pleural surface of the involved lung. ‘Death in this series of 11 cases occurred early in the disease in four instances, and during the stage of red hepatization in two instances. Tn the former, the tissue involved was in an early stage of engorgement with greatly distended capillaries and swollen epithelium surrounding but a small number of red corpuscles. The remaining five cases showed typical, gray hepatization. 214 GILMAN. Unresolved pneumonia was found in one case, with typical fibroid. induration of the entire lobe. The patient died of an acute beriberi. The following complications of pneumonia were presented: endo- carditis in 2 cases, pericarditis in 1, nephritis in 5, and pleurisy in all but 2 of the early cases. Primary broncho-pneumonia occurred in 3 of the 15 cases of this disease, all of these being in children of 3 years of age. Seven cases of the secondary form of disease had developed during the course of infectious diseases and 5 were in old, emaciated subjects and were of the aspiration or deglutition type. Other pulmonary lesions were encountered in the routine examination of the organs from autopsies, as follows: cedema and congestion in 27 cases, infarction in 5, and emphysema in but 2 cases. HEART AND BLOOD VESSELS. Death could be ascribed to chronic cardiac change associated with arterial degeneration in but 6 of the 100 cases, but it is also true that a normal heart was the exception, some change in or within the walls occurring in 62 instances. In 4 of the above-mentioned 6 cases, an acute dilatation of an hypertrophied organ was found associated with more or less rigid curling of the mitral valves and damage to the lining of the aorta; in the other two cases, there was a marked grade of fatty infiltration, the muscle fibers being completely occupied with rows of small globules. Stenosis was observed but once, the mitral orifice being affected. The common type of heart found in the majority of imstances was a flabby, relaxed, more or less dilated organ, showing practically no at- tempt at hypertrophy. The heart muscle in these cases was pale brown- ish or yellowish-brown in color, possessed a turbid appearance and was very soft. Histologically, the fibers showed varying grades of granular degeneration. Fragmentation was frequently observed and in the greater number of the specimens studied very little new formation of scar tissue had occurred. A condition of relative insufficiency was found in 26 cases. Acute disease of the endocardium followed an operation for imper- forate anus in a child of 5 days, and occurred as a complication of pneu- monia twice. In each of the cases there was a vegetative inflammation of the mitral valves. Acute myocarditis was present in five instances, four in cases of beri- beri and one in acute yellow atrophy of the liver. Acute pericarditis occurred once in a child of 1 year and 8 months, who died of broncho- pneumonia. Arterial changes were the exception in this series of examinations. The vessels in only 6 of the 100 bodies showed thickening and loss of elasticity and of the 6, but 2 evidenced a marked grade of degeneration ‘ AUTOPSIES AT THE PHILIPPINE MEDICAL SCHOOL. 215 with scattered plates of calcification confined to the abdominal aorta. The other 4 showed numerous flat, yellowish, oval projections scattered over the surface of the aorta near its origin. No change more marked than a partial loss of elasticity was encountered in the vessel walls, even in cases over 60 years of age. Arterio-sclerosis was found in but one of the 25 individuals infected with tuberculosis. Aneurism was not encountered in any of the series, nor has a case been admitted in the hospital wards or been seen among the patients of the large free clinic at St. Paul’s Hospital during the past eight months. DISEASES OF THE KIDNEYS. Lesions of the kidneys occurred more frequently than one might expect from the generally good condition of the arterial tissue. Of 100 cases, nephritis was present in 48, acute in 23 and chronic in 25. Retention eysts occurred. in 7, infarcts im 2, and tuberculous foci in 4 cases. The kidneys usually appeared swollen and markedly congested in the instances of acute nephritis, the capsule stripping readily and leaving a dark, smoky surface. Histologically, the glomerular changes predom- inated, the capsules and tubules frequently containing red and a few white blood cells. The swelling and granular appearance of the tubular epithelium was in most instances less marked than the glomerular change. The kidneys with chronic nephritic changes were of the large, pale type in 6, and the small granular in 19 cases. ‘Two cases of the first group showed large, pale, swollen organs with numerous opaque areas scattered over the smooth surface beneath the capsule; the pale cortex forming a sharp contrast to the darkly injected pyramids. Histologically, the tubules, glomeruli, and interstitial tissue were all more or less involved in the imflammatory process. The four other cases of this group evi- denced somewhat small, pale kidneys with thickened capsules and rough- ened surfaces. Glomerular degeneration and a rather marked grade of of interstitial change was present, hyaline changes being frequent. Contracted, roughened kidneys with firmly adherent capsules were found in seven instances in the remaining nineteen cases of chronic nephritis. The capsules covered small cysts. This type of kidney could only be cut with increased resistance; it showed an attenuated cortex which contained a greatly increased amount of interstitial tissue, with marked degenerative and atrophic changes in the glomeruli and plugging of distorted tubules with débris. The arterial change in these cases of chronic nephritis is less marked than the general change in the organs would lead one to expect, with the exception of those cases in which there was a general arterio-sclerosis. Fatty degeneration of the kidney was found in 4 cases, 3 of which died of tuberculosis and 1 of ameebic dysentery. The suprarenal bodies were tuberculous in two instances, both of which contained, in addition, marked pulmonary lesions. 216 GILMAN. SEPTIC AUMTA. Death from a septicaemia advancing from local infection occurred in 4 cases. The post-partum uterus served as the point of entrance in 1 instance, in 2 the foci resulted from compound fractures, and in the fourth, a small pustule on the lower lip was the beginning of the infec- tion. It is of interest to note that in none of these cases was a strep- tococeus demonstrated. Staphylococcus aureus and albus and Bacillus pyocyaneus were obtained from the body in which infection had taken place from the lip and also from the puerperal case. Judging from the difficulty experienced in endeavoring to obtain a culture of the Strep- tococcus pyogenes for class work in the Medical School, this organism does not play as important a role in the Philippines as it does in other parts of the world. LESIONS OF THE ALIMENTARY CANAL. The condition of the teeth in this series was bad. Black, discolored cavites and decayed areas were frequent. The gums were irregular and receding and pyorrhcea alveolaris was common. Disease of the hard palate, a perforation probably of a syphilitic nature, oceurred in one case. Chronic ulceration of the stomach occurred once, the punched-out ulcer with irregular edges lying on the greater curvature, 5 centimeters from the cardiac orifice. An acute hemorrhagic inflammation of the mucosa of the stomach occurred in two cases, dead of beriberi. One instance of malignant disease of the stomach was encountered. The tumor, an adeno-carcinoma, infiltrated the lesser curvature of the organ from the cardiac orifice to within 3 centimeters of the pylorus. The surface of the tumor within the stomach was ulcerated and sur- rounded by a rolled, irregular edge. The stomach was adherent to the pancreas and the under surface of the liver, the latter beg infiltrated with scattered metastatic growths. Two of the cases of pneumonia and one of chronic Bright’s disease showed an acute colitis with a thin layer of exudate on a markedly congested base. In one case of acute nephritis, the solitary follicles of the ileum were enlarged and many were topped with areas of necrosis. Ulceration in the ileum was present in all of the cases of typhoid fever. One hundred appendices were examined; 19 were over 12 centimeters in length, 6 showed a chronic obliterative process, 7 contained fecal masses and adhesions were present four times. The appendix in 24 cases was found to extend dorsally around the end of the cecum and up between the cecum and the parietal peritoneum. Death from acute bacillary dysentery occurred in three cases. ‘Two of these were in Japanese brothers, aged 2 and 4 years, dying the same day. AUTOPSIES AT THE PHILIPPINE MEDICAL SCHOOL. 217 t The lesions most frequently met with in the entire series of cases were ulcerations of the large bowel. ‘The lining of the large intestine in 32 cases showed active ameebic ulcerations of typical appearance, while in 22 additional individuals there were abundant evidences of previous lesions as shown by numerous, irregular pigmented scars and depressions. While these lesions were spread generally over the entire extent of membrane from the ileo-cecal valve to the rectum, in 11 cases the ulcer- ations were confined to the terminal few centimeters of the rectum. Intestinal worms were found in 32 cases, Ascaris lumbricordes alone in 17, T’richocephalus dispar in 7, and the two together in 8. A liver fluke, Opisthorchis sinensis, was encountered in one body. A persistent Meckel’s diverticulum was present in a female child, dead of pneumonia, and an imperforate anus in a male child. LESIONS OF THE LIVER. Only one case of abscess of the liver occurred in the series. The body was that of a Japanese aged 36, in whom the entire large bowel was lined with ameebic ulcerations. The abscess occupied the lateral portion of the right lobe of the liver and measured 10 centimeters in diameter. The cavity was limited above by the diaphragm and contained a thick, yellow-brown pus. Numerous amcebe appeared in the sections of the wall of the cavity. The livers from 2 cases of typhoid fever, 1 of broncho-pneumonia, and 2 of pulmonary tuberculosis, showed well-marked areas of focal necrosis, in addition to a general parenchymatous degeneration. In 38 cases the same organ evidenced chronic passive congestion. The en- larged, dark red, firm organ was more frequent than the so-called “nutmeg” liver. The majority of the 38 cases were those of patients dead of pulmonary tuberculosis, and in addition they showed degenerative changes in the myocardium. A mild grade of fatty infiltration was demonstrated in 17 of the livers from eases of tuberculosis and a very marked grade in 4 additional instances, 2 of tuberculosis, 1 of ameebic dysentery, and 1 of chronic heart disease. ‘The general picture in the series of sections of fatty livers was of large fat-droplets occupying the greater part of an entire cell and often: causing complete disappearance of the cell plasm. Amyloid occurred in the livers in two of the tuberculous cases. In nine cases the liver was the seat of cirrhotic changes. The organ was generally enlarged and firm. Three of the cases had fluid in considerable amount in the peritoneal cavity. The new tissue through- out the liver substance was rather closely confined to the periphery of the lobules, often inclosing groups of several lobules, the inclosed cells showing atrophy. Of the 9 cases, 5 died of pulmonary tuberculosis, and 1 of peritoneal tuberculosis. No marked “hobnailed” liver was Ziley GILMAN.’ found. Acute, yellow atrophy of the liver occurred in one case, that of a woman 20 years old in the fifth month of pregnancy. The liver measured 18 by 5 centimeters; the edge was rounded, the organ was soft and of an opaque, grayish-yellow, mottled color. The organ was largely made up of degenerated and necrotic cells, irregular collections of fat-droplets and detritus. There was but one instance of neoplasm of the liver, which occurred in the case of gastric carcinoma; the liver showed numerous metastases distributed throughout its substance. PERITONEUM. The single case of acute peritonitis followed a stab wound in which an opening into the descending colon had occurred. In four cases, in addition to those of ascites associated with cirrhosis of the liver, there was a large amount of peritoneal effusion. One of these was associated with splenomegaly, two with cardiac failure, and one ~ with nephritis. LESIONS OF THE SPLEEN. An acute swelling of the spleen was found in ten instances, in cases of typhoid fever, septicemia and pneumonia. A chronic enlargement of this organ was encountered in sixteen instances, its enlarged condition apparently having no direct connection with the disease causing death. A chronic, indurative splenitis with a diffuse extensive formation of connective tissue was the rule in these specimens. The capsule, more or less thickened, had lost its smooth surface and was not infrequently ridged and seared. The organ was firm, although not hard, and usually increased in size and weight. The cut surface of this type of spleen was of a uniform, red-brown color and crossed in all directions by a prominent interlacing framework of connective tissue. As a rule, the Malpighian bodies could not readily be distinguished. Microscopically, the finer connective tissue framework was increased or thickened and there was generally an increase in the number of parenchyma cells. Pigmentation was uncommon. It was observed four or five times and then the areas were made up of extremely fine, brown-black granules. An atrophied spleen, wrinkled and firm, with prominent Malpighian bodies and decreased parenchyma, occurred.in four cases, of which three were in patients who had lived to over 80 years, the other being an emaciated woman of 45, dead of carcinoma. ‘The spleen in the series of cases of tuberculosis was the seat of tuberculous foci in two instances. A single case of splenomegaly was encountered. ‘The spleen weighed 1.2 kilos. The body was that of a well-nourished laborer 33 years old; the peritoneal cavity contained 2 liters of pale, turbid fluid, although AUTOPSIES AT THE PHILIPPINE MEDICAL SCHOOL. 219 there was no cirrhosis of the liver. The enlarged spleen was attached by cedematous adhesions to the former organ, the stomach, kidney and - bowel. The thymus and lymphatic glands were not enlarged. There were eleven smaller accessory spleens, measuring from 0.5 to 1.8 centi- meters in diameter, extending in an irregular chain along the tail of the pancreas from the hilum of the main organ to the mid-line of the body. The accessory organs showed a shrinkage of the Malpighian areas and proliferation of the endothelial lining of the cavernous spaces in common with the main organ. ; In addition to the above case, accessory spleens were encountered in three other subjects. LYMPHATIC SYSTEM. The bronchial lymph glands were involved in 27 of the tuberculous eases. A general involvement of the mediastinal glands also occurred in 3 cases. The bronchial glands were diseased twice in company with the mesenteric, and in 3 other cases the latter showed a general involve- ment alone. The glands of the axilla were enlarged in but one instance in the entire series of cases. The glands of the groin, on the other hand, were found as a rule to be somewhat enlarged and firm. Histologically, they showed an increased growth of reticular tissue. Old scars, proving previous abscess formation in the glands of the groin, were found in two cases. In none of the glands could signs of syphilitic induration and cell change be detected, and in but one case was there evidence of a primary syphilitic lesion. In this instance there was a perforation of the hard palate.* NEOPLASM. Carcinoma as a cause of death was found twice, once involving the stomach, and once the cheek and antrum. There is a belief prevalent among some medical men that malignant disease is rare in this part of the world, but if reference be made to records of the department of surgical pathology this is shown not to be the case. Of 100 specimens sent from the surgical clinic at St. Paul’s for routine examination, 6 were malignant, 4 sarcomata, and 2 carcinomata. The sarcomata were all of periosteal origin and of the lower limb. There was one case of dermoid cyst of the ovary among the autopsies, the tumor measuring 14 centimeters in diameter. It contained several areas of calcification, in addition to the usual cuticular structures. Uterine myomata—all subserous—were found in 3 cases. *This case was clinically considered one of gangosa. 220) GILMAN. THRYOID GLAND. The only case of disease of this gland was one of general symmetrical enlargement occurring in a woman who had suffered from tuberculosis. Colloid formation was the principal change associated with several small eysts. The thryoid glands were otherwise quite small, often showing irregular lobulations. No instances of accessory thryoids were encountered. NERVOUS SYSTEM. Degeneration of the vagus and phrenic nerves were demonstrated in one case of beriberi which caused death in an infant of 3 months.” Lesions of the central nervous system included one case of cerebellar abscess following otitis media, one of cerebral softening and one of hemorrhage following an occipital fracture. The meningeal coverings of the two cerebral hemispheres in a case of arterio-sclerosis were adherent and thickened, and inclosed numerous small collections of clear fluid in cyst-like, flattened spaces within the opaque membranes. Microscopically, this thickened layer of adherent membrane showed a richly interlacing meshwork of fibers, in the spaces of which there were many large polyhedral cells with large, deeply staining nuclei and granular protoplasm. The blood supply was poor, the walls of the vessels showing an advanced grade of atheroma. No gross syphilitic disturbances of the central nervous system were encountered. GENITALIA. Disease of the male generative system was uncommon. ‘There was one case of scrotal and one of prostatic abscess. ‘Three cases of hydrocele on the left side were encountered. Tubercular cystitis occurred in three cases, nontubercular im one. - SKIN. The cutaneous lesions included 1 case of Impetigo contagiosa, 1 of leucoderma, and 4 of chronic ulceration. The ulcers in 3 cases were confined to the yentral aspect of the leg and in the fourth an ulcer 4 centimeters in diameter was present on the dorsal surface of the right elbow. One case of supernumerary thumb was seen. The two thumbs were of equal size, each 1 centimeter shorter and smaller in proportion than the normal thumb on the left hand. They formed a Y-shaped junction at their union, being articulated side by side, with separate surfaces at the end of each of the two metacarpals. Each thumb was well formed and bore a perfect nail. *This case was reported by Dr. Albert at the Fifth Annual Meeting of the Philippine Islands Medical Association, Manila, February 26-29, 1908. AUTOPSIES AT THE PHILIPPINE MEDICAL SCHOOL. 2?) SUMMARY. A summary of the findings in these cases brings out certain points, some of which at least are of particular interest. Some idea of the importance of tuberculosis as a cause of death in these Islands is shown by the number of cases in this series, 35 per cent, and an idea of the virulence of the disease when once established may be drawn by com- paring these figures with the number of cases showing healed tuberculous foci, 6 per cent, and latent foci, 2 per cent. The disease as encountered here is a rapidly progressing one, and the amount of tissue destroyed and thrown out of function is marked. The frequency of chronic degenerative change of the myocardium and of nephritis is more noticeable when compared with the relatively small number of cases of arterial degeneration. The number of ulcera- tions of the large bowel, 32 per cent, and scarring, 22 per cent, while large, is smaller than the percentage of cases found by Musgrave in his series of examinations. A feature by no means the least interesting is the absence of syphilitic lesion in all but one case. NOTES ON THE CONDITION OF THE LIVER IN SCHISTOSOMIASIS.* By J. M. Praven and Henry J. Nicwons.? I. INTRODUCTION. Il. Case ReEcorp. III. PATHOGENESIS OF THE CIRRHOSIS OF THE Livur. IV. Comparison or INFECTION WITH SCHISTOSOMUM JAPONICUM AND SCHISTOSOMUM H@MATOBIUM. V. GEOGRAPHICAL LocATION. I. INTRODUCTION. Schistosomum japomcunr was discovered and described as recently as 1904, although the disease which it produces had been recognized in Japan for nearly two decades previously. Outside of a small area in Japan, cases of infection with this blood fluke are still so infrequently seen that each one is worthly of report and discussion, as such reports will aid in locating the geographical distribution of the parasite and in clearing up its life history and pathologic effects. Im discussing the present case, we wish to speak particularly of the pathologic findings in it and in other recorded cases, and to draw a contrast between these and those of infection with the closely allied Schistosomum haematobium. Il. CASE RECORD. The patient, P. O., was admitted on January 16, 1908, to Dr. Ruffner’s service in the Division Hospital in this city, and died on the following morning. He was a Filipino soldier 30 years old, belonging to a Visayan Scout company, single, and a native of Calbayog, Samar, in which town he lived continuously until his twenty-fourth year. He then enlisted and during the six years of his service was stationed on the Islands of Panay, Cebu, Leyte and Samar. He had never been out of the Visayas except for short visits, and he was on furlough in Manila when he entered the Division Hospital. The sick record of his company shows that during the six years of his service he was in hospital one hundred and nineteen days and in quarters eighty-three days, although the causes of admission to sick report are not given. 1Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, Manila, February 27, 1908. * Captain, Medical Corps, United States Army, and first lieutenant, Medical Corps, United States Army, constituting the United States Army Board for the Study of Tropical Diseases, as they occur in the Philippine Islands. 713313 223 224 PHALEN AND NICHOLS. When he was admitted to the Division Hospital he was suffering from diarrhea and cramps. His heart action was weak, rapid and irregular, and a diagnosis of myocarditis, probably due to beriberi, was made. Autopsy by Dr. Whitmore three hours after death of the patient. The body is well developed and well nourished and, with the exceptions hereafter noted, the organs present no macroscopical alterations. Upon opening the abdomen, the liver and spleen are found to be moderately enlarged, the latter being somewhat adherent. The liver is not cirrhotic in appearance, but presents pale patches over its surface, and, more particularly, many whitish nodules varying in size up to the head of a pin, and situated under the capsule. On excising and crushing these nodules, oval eggs are found measuring approximately 70 by 40 uw. On section, many more nodules are seen scattered throughout the entire organ. The small intestines harbor a small number of hookworms; they present no gross changes, while the large intestine shows only one small area situated low down in the bowel, where the mucous membrane is swollen and injected. The bowel contents show ova similar to those in the liver, but these are few in number, and ova of uncinaria are also present. Histologic examination.—Tissues were secured from the liver, kidneys, lungs and intestines. These were preserved in Kaiserling’s solution and in formalin, imbedded in paraffin, sectioned and stained with hematoxylin and eosin and with Bismarck brown and eosin. A microscopic study of the liver shows the presence of ova either in groups or singly, usually occurring in the interlobular connective tissue (PI. I, fig. 1), but also occasionally throughout the parenchyma, and in one instance an ovum is found apparently lodged in the intralobular vein. There is a considerable increase in the connective tissue around the lobules and encroaching upon them. The staining of the tissue is irregular, being quite faint in places. The most striking feature is the presence of the miliary nodules noted above: (Pl. I, fig. 2.) These tubercular-like nodules are mentioned by Katsurada, but are said to oceur rarely in the parenchyma. Our sections show them situated exclusively in the parenchyma occupying the place of a lobule or of two or more lobules fused together. The central area stains deepest, and is composed of an indefinite mass of nuclei, red blood cells and fibrin. It is quite sharply defined from the next zone which is made up of young connective tissue radiating toward the center. This zone gradually merges with a ring of still younger connective tissue belonging to the interlobular tissues. Some nodules have a small center and are evidently being gradually walled off and replaced by new connective tissue growth beginning at their peripheries. Throughout this connective tissue there is a new formation of bile channels, apparently an effort to repair the damage to the lobule. Ova are usually present in small numbers in these nodules. (Pl. I, fig. 3.) F Sections of the large intestine show the presence of ova in small numbers in the submucosa, accompanied by a moderate increase in the connective tissue. They occur in small groups outside the vessels close to the muscularis mucose. Ova are also found in the mucosa lying close to the epithelial cells of the glands of Lieberkiihn. The muscular layers are apparently unchanged. No ova are found in the small intestine nor in the other tissues. The ova in the walls of the intestine seem much more compressed and distorted than those in the liver. The vessels of the mesentery of the large intestine were carefully searched for the adult parasites, but without success. Measurements were made of a number of the ova in the tissues, and they were found to average 62 » in length by 39 » in width, dimensions which are approximately those give by Stiles, Woolley, Katsurada and CONDITION OF THE LIVER IN SCHISTOSOMIASIS. 225 Catto in their accounts of the ova of Schistosomum japonicum. ‘They were studied in comparison with a section of the liver from Catto’s case, which shows ova of a similar appearance. Til. PATILOGENHSIS OF THE CIRRMOSIS OF THE LIVER. It is clearly evident that in this case the liver was the organ to bear the brunt of the infection, the invasion of the intestinal walls being of but secondary importance to the lesions in the liver. In this respect the findings here are in accord with those hitherto reported in cases of this malady. In the earliest Japanese writings on the disease, the latter is described as a peculiar cirrhosis of the liver due to a parasite, while Katsurada, in his original description, speaks of it as an affection of the liver both of man and of cats. In the case described by Catto, the extreme enlargement of the liver and spleen was noted during life, while at autopsy, although there were marked changes in the other organs, espe- cially in the large intestine. the cirrhotic condition of the liver was perhaps the most striking feature. In Woolley’s case, the first to be described in the Philippine Islands, the liver was smaller than normal and markedly cirrhotic. In both of these instances numerous ova were found in the perivascular tissues of the liver, where they apparently caused a marked hypertrophy of the connective tissue. In two of three cases reported by Dr. Logan in China, enlargement of the liver was a prominent feature of the malady while in all three, cedema of the legs and ascites were present, possibly due to hepatic diseases. This list in- cludes all the reported cases that have come to our knowledge, and in practically all of them changes in the liver have been found either clinic- ally or by post-mortem examination. The pathogenesis of the cirrhosis im these cases is difficult to estab- lish. A moderate increase in the interlobular tissues might be due to the presence alone of the ova, but how can we account for the destruction of whole lobules in the presence of but a very few ova? The anastomosis of the blood vessels within the lobule is so free that it is difficult to see how the ova, acting as emboli, could produce this result, but Katsurada, according to Stiles, believes this to be the explanation of the cirrhosis, although he speaks also of a toxin which he thinks is elaborated by the worm and which plays a part in producing the liver changes. IV. COMPARISON OF INFECTION WITH SCHISTOSOMUM JAPONICUM AND SCHISTOSOMUM THU&MATOBIUM. Let us contrast the pathology of the above case with that encountered in Bilharzia infections. Madden, in his excellent monograph on Bilhar- zia, devotes a score of pages to the pathologic anatomy of the intestinal and urinary tracts, and in four lines disposes of the liver with the state- ment, “Kartulis and Symmes have described a periportal cirrhosis as having occurred in this disease.” Scheube says that the ova have been 226 PHALEN AND NICHOLS. found in the liver, with slight cirrhotic changes. Manson speaks of the occasional presence of small numbers of ova im the liver, but knows of no pathological change caused by their presence. Other writers on the subject are a unit in regarding the liver as a neglible factor in Bilhar- Z10S1S. The question immediately suggests itself, why, in Bilharzia disease, should the ova cause such profound changes in the intestines and bladder, to the practical excluson of alterations in the liver, while, in a disease as closely allied as the one under discussion in our paper, the liver should be the chief site for the lodgement of the ova and its pathology the chief features of the malady? Dr. Letulle has published an extremely interesting article * in which he worked out, with the most faithful attention to details, the histologic changes in a case of intestinal Bilharziosis, and from them drew some convincing conclusions. It is not our purpose to discuss the process of reasoning by which these conclusions were reached, and, therefore, we will give only his explanation of the local distribution of the ova and the resulting pathologic changes. According to his idea the pair of worms, with the female occupying the gynocophoric canal of the male, habitually inhabit the larger venous radicles of the portal system. When the time comes for the deposition of the ova, the worms, still together, migrate to the smaller veins until, having reached such a vessel of a caliber of about 1,000 p, the male can go no further because of his size. The female then leaves the male and migrates. as nearly as possible to the lumen of the intestine or bladder, that 1s, into the venules of the submucosa where the vessels are narrowed to 80 to 120 », and where she can go no farther. She takes position in one of these small ves, completely blocking it, and produces a stasis in the vessels ahead. She attaches herself by her suckers to the intima of the vessel and evacuates her ova into the distal portion of the vein. ‘The pressure of the mass of ova, as well as that of the blood, enable their spines to pierce the walls of the vessels, and the whole mass is forced into the perivascular tissue so quickly, according to Letulle, that although he saw many masses just without the vessel, he did not find a single ovum within the lumen. The female having de- posited her ova and waited a sufficient length of time for their migra- tion, joins the male in the large vessels. Let us apply these facts to Schistosomum japonicum. Here we have a similar pair of worms of the same relative size, although both are somewhat smaller than in the Bilharzia species. Although itis not proved that Schistosomwm japonicum inhabits exclusively or even habitually the arterial side of the pelvic blood supply, Catto found worms in the arte- rioles in this location, and we have Manson as an authority for their ®* Arch. de Parasit. (1905) 9, 329. CONDITION OF THE LIVER IN SCHISTOSOMIASIS. 227 presence on the arterial side. Now let us conjecture that the female, leaving the male in the larger arteriole, migrates into a small vessel which she will just occlude. Attaching herself as in the case of Bilharzia, she deposits her ova, not into a venous radicle, but into the distal side of the arteriole where the ova will be aspirated onward, the more so as in this case they are not provided with spines. Finally they reach the intervening capillaries which have a caliber of perhaps 12 to 20 p, while the ova which must pass, measure, on the average, 40 ». If the pressure on the mass of ova is sufficiently great to force a portion of their num- - bers through the vessel wall, it is not unlikely that another part will be forced through a distended capillary, especially as under the latter cir- cumstances they would be compelled to pass through a distance of no more than 0.5 millimeter before larger venous radicles would be reached, this distance being the average length of a capillary. Having success- fully passed the capillaries, nothing would intervene until the liver was reached, where all but the exceptional ovum would lodge. The fact: that these exceptions exist, as is proved by the occasional ovum found in the lungs, kidneys and elsewhere, strengthens the evidence of their pass- ing through the capillaries of the pelvis. The marked difference in the pathology of the two diseases, bilharziosis and schistosomiasis, may there- fore depend first, on the location of the parasites: the one in the venous and the other in the arterial side of the portal circulation; and, second, on the morphological difference in the ova.* V. GEOGRAPHICAL LOCATION. There is nothing in the history of the case we report that is of any assistance toward clearing up the mystery of the mode of infection, nor, on the other hand, anything inconsistent with the theory put forward by the Japanese physicians that the infection is acquired by contact with stagnant water containing the embryos of the parasite. From the relatively small number of ova present it is fair to infer that the infection we studied was of a comparatively recent origin, and that it was acquired after the patient joined the military service. The Scout companies in the Visayas have performed much active duty in the field during the past few years and probably have frequently found it necessary to wade stagnant pools similar to those described by Katsurada as being the habitat of the embryo of this parasite. “Professor Akira Fujinami has recently published an article on Schisto- somum japonicum in which he states that the usual habitat of the adult parasite is in the portal system, it having been found by him in the intestinal veins, the mesenteric veins, the branches of the portal vein within the liver, and in the splenic vein. It therefore appears as if the morphology of the ova, rather than the location of the adult parasite, is the chief factor in the distribution of the ova in the tissues of the body. | 228 PHALEN AND NICHOLS. The most important fact in the history is the continuous residence of the patient in the Visayas and the practical certainty of his haying acquired the infection in that part of the Philippine Archipelago. REFERENCES. Carro, JounN. A New Blood Fluke in Man. Brit. Med. Jowrn. (1905), 1, 11. Journ. Trop. Med. (1905), 8, 70. Stites, C. W. A New Asiatic Blood Fluke. Amer. Med. (1905), 9, 821. Logan, O. T. Schistosum Japonicum in Chinese Subjects. Journ. Trop. Med. (1906), 9, 294. Woottry, PAuL G. Schistosomum Japonicum in the Philippine Islands. Phil. Journ. Sei. (1906), 1, 83. KkarsurapA, F. An Endemic Disease Caused by a Special Parasite Previously Unknowr in Japan. Sei. J. Kivai, XXIIT and XXIV. Review in Journ. Amer. Med. Ass. (1905), 45, 80. MappeN, J. C. Bilharziosis. Cairo, 1907. MANSON, Sir P. Tropical Diseases. London (1907), 650. Lectures on Tropical Medicine. Chicago (1905), 50. ScneuBE, B.. The Diseases of Warm Countries. Translated from the German by Pauline Falcke. London (1903), 366. LETuLLE, Maurice. Bilharziose Intestinale. Arch. de Parasit. (1905), 9, 329. FusINAMI, AxrrA. Weitere Mitteilung tiber die “Katayama-Krankheit.” yoto Igaku Zassi (1907), 4, Heft 4. ILLUSTRATIONS. PLATE I. Fic. 1. Ova of Schistosomum japonicum in connective tissue of the liver. 380. - Miliary nodule in the liver. 100. . Nodule showing presence of ova. 8. oo bo PHALEN AND NICHOLS: CONDITION OF THE LIVER.] [PHIL. Journ. S Cl VOL TilNon 3s Fie. 3. PLATE 1. THE DIAGNOSIS OF AFRICAN TICK FEVER FROM THE EXAMINATION OF THE BLOOD. By Ricuarp P. Srrone. (Prom the Institut fiir Schiffs-und Tropenkrankheiten, Hamburg, Professor Nocht, Direktor ; Abteilung Professor Prowazek.) The study of the various forms of relapsing fever has attracted consid- erable attention during the past four years. In 1904 P. Ross and Milne, working in Uganda,* were able to demonstrate that the disease heretofore known as tick fever and supposedly conveyed by the bite of a tick, was due to a Spirocheta which was found in the circulating blood, though usually present here only in very small numbers. Although the disease termed tick fever had been recognized for a long period of time, and was mentioned by Livingstone in 1857,* its etiology had previously remained obscure. In 1905 Dutton and Todd* in the Congo were able to confirm the observation of Ross and Milne, and to show that the parasite could pass into the ege and larva of the tick Ornithodorus moubata (Murray) and so confer infective power upon the mature form of the succeeding generation. They also frequently found the spirochetwe to be very scanty in the circulating blood. R. Koch,‘ in his studies in Africa in 1905 and 1906 also concluded that the African recurrent fever was transmitted by the bite of the tick Ornithodorus moubata. He reported ‘that the malady might be considered an African variety of relapsing fever, but not a distinct and different disease from the European one. He emphasized the fact that the parasites were not numerous in the peripheral blood. He believed that these organisms were usually a little longer than in the case of Spirocheta recurrens and that the febrile periods were shorter in the African than in the European variety, but that the two were otherwise similar. Until the past year (1906) but one distinctive form of relapsing fever in man caused by spirochzete had been distinguished, although Manson ° and later Sambon ° had previously suggested that there might be several 1 Brit. Med. Jowrn. (1904), 2, 1453. * Mission. Travels and Research: J. Murray, London (1857), 1, 283, ete. * Brit. Med. Jowrn. (1905), 2, Noy. 14, 1259. Mem. Liv. School Trop. Med. (1905), 17, 1. * Deutsche Med. Wehnsch. (1905), 31, Part Il (Nov. 23), 1865. Berl. klin. Wehnsch. (1906), 43, 185. “ Brit. Med. Jowrn. (1904), 1, 538. ® Brit. Med. Journ. (1905), 2, 126. Doar STRONG. forms of this type of disease due to different species of spirochetse, and Ross and Milne had stated that it was possible there might be more than one variety of tick fever. In 1906, Novy and Knapp,’ after a study of a case of relapsing fever in the United States, concluded that because of morphological characteristics which they were able to detect in stained specimens of the spirochetxe from their own case, and in those of African spirochete obtained by them from the Liverpool School of ‘Tropical Medicine, relapsing fever and tick fever are distinct. They also based this claim upon the published experiments of Dutton and Todd and particularly of Breinl and Kinghorn,’ who found that the spirochzta of the tick variety was frequently fatal to rats and mice and that in rats from three to four relapses occurred before death. Novy and Knapp found that in the case of the spirocheta, which they regarded as Spirillum obermeieri, the infection in rats was shorter and that no relapses occurred. They also believed that the diffuse flagella of the organism of tick fever as pictured by Zettnow® served as an additional “clinching” proof and effectually differentiated it from Sp. ober- meieri which had, according to their observations, but a single terminal flagellum. However, according to later observers, Uhlenhuth and Heendel,” Novy was not working with NSpirocheta obermeieri, but with another species, an American variety. Breinl and Kinghorn” also found that a monkey and several rats immunized against the American spirocheta (supposed to be identical with Sp. obermeieri) remained susceptible to the African species. They were also able to infect a horse, dogs, rabbits, guinea pigs and other animals with the tick-fever parasite. They therefore concluded that the two varieties, American and African relapsing fever, are distinct. Novy and Knapp proposed to dif- ferentiate the different species of spirochete by serum reactions, specific agglu- tinins and bacteriolysins, as well as by animal inoculations. Uhlenhuth and Haendel and Frankel,” during the present year, and very recently Manteufel,* by means of animal inoculations as well as by agglutinative and bacteriolytic reactions, have found that different results are obtained with the European, African and American spirochete, and they regard them as three distinct species. Schellack* has also very recently recounted the morphological differences in the European, American and African spirochete of the recurring fevers. During a recent visit to the Institut fiir Schiffs- und Tropenkrank- heiten in Hamburg, I had the opportunity, through the kindness of Professor Prowazek, of studying strains of spirocheete obtaimed from America and from Africa, and since this time, in different countries, I have examined the other strains of spirochzete already described in the literature. In the present paper I shall not consider particularly the work in regard to the differentiation of all the spirochzte of the relapsing 7 J. Am. Med. Ass. (1906), 46, 116. J. Infect. Dis. (1906), 3, 291. * Lancet (1906), March 10, 668. Mem. Liv. School Trop. Med. 20, 61. * Zischr. —. Hyg. wu. Infectionskrankh. (1906), 52, 539. “ 4drb.a. d. k. Gsndtsamte (1907), 26, Heft I, 1. Lancet (1906), June 16, 1690. Mem. Liv. School Trop. Med. (1906), 20, GIR 69vand 21) Le ™ Berl. klin. Wehnsch. (1907), 44, 681. M Arb. a. d. lk. Gsndhtsamte (1907). 27, Hefte II, 327. “Arb. a. d.k. Gsndhtsamte (1907), 27, Hefte II, 364. DIAGNOSIS OF AFRICAN TICK FEVER. 233 fevers, but shall merely record the results of some experiments carried on in relation to the diagnosis and differentiation of the African tick variety of the disease. Ross and Milne,’ in examining cases of spirillum fever in Uganda, Africa, found that the organism might be exceedingly rare in the blood, even when the examination was made at the height of the fever and from cases which from a clinical standpoint were well marked. Sometimes it was necessary to spend several hours before finding a single spirillum, and in some instances only two or three were found in the whole blood film. In one case of tick fever out of eight which were studied, about one spirillum was found in every thirty fields, in the other seven very few spirilla were present. These authors refer to the fact that Daniels examined a case of the disease in the second week with negative results. Dutton and Todd, It. Koch and Manson all agree that the parasites in tick fever are much more scanty than in Huropean relapsing fever. I observed a patient in Africa who was in approximately the second week of fever, in whom no spirochete could be found in the circulating blood in a single, but careful and prolonged examination of the fresh film and of one stained preparation. However, a small amount of blood collected at the same time that the microscopic specimens were examined, was inoculated into a mouse and three days later spirochaete were found in its blood. Therefore, it is clear that in some cases of tick fever, during its active periods, a diagnosis may not be arrived at froma study of the blood with reference alone to the presence of spirochete. Moreoyer, in both the European and African yarieties of the disease, the parasites may be entirely absent from the blood during the relapses or in the later stages, and then even animal inoculations may fail as a means of diagnosis. It is also true in relation to the employment of animal inoculations as a means of diagnosis, white or gray mice, or white rats, the animals which are most valuable for use in this connection, are usually very scanty or impossible to obtain in most tropical or subtropical countries. I have recently been able to show that wild mice captured in these districts are not sufficiently susceptible to infection with the African species of spirocheetee to be of yalue for use in diagnostic purposes. In addition, neither of these means permits of a differentiation of the species of spirochete and of the separation of tick fever from the other forms of relapsing fever. Hence, other methods of diagnosis are desirable. As long ago as 1896 and 1897 Gabritschewsky '° and Loyenthal suggested and employed the serum for diagnostic purposes in cases of relapsing feyer. They recommended that a drop of serum of the patient to be tested and which contained no visible spirochxte be added to a drop % Loe. cit. Ww Ann. Inst. Past. (1896), 10, 630. ™ Deutsche med. Wehnsch. (1897), 23, 560. 234 STRONG. of blood of a patient known to be suffering with relapsing fever and in whose circulation the parasite was present. The bactericidal action of the first serum was then observed under the microscope for various periods of time. Later Karlinski,"* Routkewitsch,’® Mielkich *° and particularly Hodlmoser *+ also employed this method for diagnostic purposes in Kuropean relapsing fever, although not always with favorable results. Hodlmoser emphasized the fact that in the sero-diagnostic method of European relapsing fever, the most striking feature is the spirolytic action of the serum rather than the agglutinative one. While he believed that the reaction could not be obtained with absolute certainty in all cases of relapsing fever, it nevertheless constituted in many a valuable means of diagnosis. In all of these experiments the blood of another patient containing spirochaete was employed in making the test of the suspected patient’s serum. Hence, fresh cases of relapsing fever in human beimgs were always necessary in order that the test might be performed. It therefore naturally oceurred to me that an examination of the blood serum in African tick-fever infections for specific agglutinins and bacte- riolysins might sometimes prove of additional value in obtaining a diag- nosis, the blood of animals infected with the spirochete instead of that of human beings being employed in testing fhe serum. However, I found that while sometimes by means of the agglutination or bacteriolytic reac- tion a satisfactory result might be obtained with an immune spirochaete serum, neyertheless it soon became apparent that the reaction was frequently too uncertain and inconstant to be depended upon for diag- nostic purposes. Moreover, it could not be considered to be of any prac- tical use to the average physician. There are many difficulties to be encountered in performing the agelutinative and spirolytic test with the spirochete of this group, and it is perhaps unnecessary to emphasize that the reaction can not be carried out with nearly the same facility as the agglutination reaction with immune sera and bacteria. Perhaps the greatest difficulty is experienced in securing the proper culture of the spirochztz in the blood to be used in testing the agglutinative and bacteriolytic power of the serum of the affected patient. While, in general, it may be stated that the white mouse is the most suitable animal to employ and that the blood containing spirochetee should be collected in citrate solution on the second or third day after infection, because the parasites are apt to be most numerous and most active at this period of time, nevertheless it frequently occurs 8 Wien. klin. Wehnsch. (1903), 16, 447. Centrbl. f. Bakteriol. (1902), 1, 31, 566. : * Baumg. Jahresb. (1898), 14, 613. Original article in Russiches archives d. Pathol. ete. (1898), July 5. ~~ Baumg. Jahresb. (1900), 16, 434. *\ Wien. med. Wehnsch. (1904), 54, 2310. Ztsehr. f. Heilk. Abt. Interne Med. (1905), new series 6, 506. DIAGNOSIS OF AFRICAN TICIX FEVER. 235 that the blood of the animal when taken at these periods contains too few spirochaete to render the test satisfactory or conclusive, and this may occur although the animal was previously inoculated with a large amount of blood richly infected with spirochets. In some instances the spiro- cheetze in the blood may appear to be ideal for the performance of the test, the parasites being numerous, active and not agglutinated, yet when they are added to a normal serum they may undergo spontaneous agegluti- nation as marked as if an immune serum had been employed. Again, im some instances in the same period of time that they become aggluti- nated and clumped in the immune serum, they may undergo the same apparent process in their own serum, without the addition of that of the blood to be tested. The parasites at other times may appear to be very numerous in the blood at the time of the examination and in the few minutes required to bleed the animal they may apparently all disappear before anything is added to the blood. ‘These phenomena may be understood at least partially when one considers that in the infected animal the agglutinins and spirolysins are being developed gradually with the development and increase in number of the spirochetx, and hence in animals which show a very rich infection with spirochete, agglutinins and spirolysins are already present to a greater or less extent. Sometimes the withdrawal of the blood seems to be all that is necessary to stimulate the complements and antibodies to action and in other instances the additional amount of these corresponding substances, either present in the normal or immune serum, may be necessary to bring about the phenomenon of agglutination or of bacteriolysis. Sometimes it will be necessary to take the blood from several animals before one is found in which a satisfactory condition of the spirochetz exists for the perform- ance of the agglutinative or bacteriolytic test. Indeed, on some occasions it has taken me three or four days before satisfactory conditions for even the proper performance of these tests could be obtaimed. Obviously, the employment of the spirolytic test in the abdominal cavity of an animal presented even greater difficulties. It therefore seemed highly desirable that some other means be found that would serve as an aid in the diagnosis of the disease and in the differentiation of its different varieties, and I determined to see if the precipitin reaction might be employed for this purpose. Evidently if this reaction could be shown to be satisfactory for this purpose the diagnosis of this group of diseases would be much simplified and at once placed upon a practical basis. As is well known, Kraus* in 1907 first showed the existence of specific pre- cipitins for the albuminous bodies found in bacterial cultures. Later it was demonstrated that the reaction might be employed for the differentiation from one another of the vibrios of Finkler and Prior, Nasik, Denecke, and of Metch- nikoff, and also for differentiating colon from paracolon bacilli. Wladimiroff ~ = Wien. klin. Wehnsch. (1897), 10, 736. *3 Kolle und Wassermann Handbuch d. pathogen Mikrorgan. (1904), 4, 1055. 236 STRONG. employed the reaction in the diagnosis of glanders, using a glycerine-free culture filtrate of Bacillus mallei added to the serum of the glandered horse. The em- ployment of the reaction with sera prepared by injecting into one animal certain albuminous bodies of another one has also proved of great value for diagnostic purposes, and in some instances a very delicate test. Thus Wassermann and Uhlenhuth,* with proper immune sera, showed that a specific precipitin reaction might be obtained against the dissolved albuminous substances in human blood in the dilution of 1 to 50,000. The precipitins have been proved to be absolutely specific against those of unrelated species, although they sometimes react on closely related albumens. The reaction has also been employed for the differentia- tion of other microérganisms, including bovine and human strains of tubercule bacilli and even for the various species of trypanosomata, with varying results. Shortly after my experiments were begun with the precipitin test in the diagnosis of the spirochete of relapsing fever, the work of Fornet, Shereschewsky, Hisen- zimmer and Rosenfeld,” on the subject of “Spezifische Niederschliige bei Lues Tabes und Paralyse” appeared. These authors found that upon mixing the serum from acute cases of syphilis with that from cases of the same disease of long standing, with tabetic and paralytic symptoms, that a precipitin was obtained. They believed that in the more acute cases of syphilis, those in which spirochetie were found to be present, the precipitinogen was present in the serum and that in the older cases of long standing the precipitin existed. They employed the ring test for these reactions, placing the heavier serum at the bottom of a small test tube and adding gradually the lighter serum in a layer on top. At the junction of the two sera in the case of a positive reaction, the precipitate appeared as a narrow band or ring. Still more recently Michaelis * has reported that he obtained a specific precipitin reaction with the blood sera in cases of syphilis, employing an extract of the liver as the solution containing the precipitinogen. The experiments to be recorded here were conducted with two strains of spirochzetee, one obtained from Africa and the other from America. At first the precipitin reactions were carried on in small, conical reagent glasses by mixing the serum supposed to contain an-excess of precipi- tinogen with the immune serum supposed to contain an excess of precipitin. The resulting mixture was then compared with one con- sisting of the first serum to which a normal serum had been added. After reading the article of Fornet and his colleagues, the reactions were carried on by superimposing one serum upon the other, as was suggested by these authors, the second serum being allowed to flow down the side of the reagent glass from a capillary pipette until a layer of equal thickness to that of the first below had been introduced. Care was taken to observe that the blood from which the serum was separated and used for the precipitin contained no spirocheetee which could be detected by microscopical examination, both before and at the time the blood was collected for the test, and that the blood from which the serum was separated for use as the precipitinogen contained numerous parasites. 4 Loc. cit., 594. *° Deutsche med. Wehnsch. (1907), 33, 1679. ** Berl. klin. Wehnsch. (1907), 44, 1477. DIAGNOSIS OF AFRICAN TICK FEVER. 237 The blood serum tested for the precipitin was collected from animals which had received one, two and three separate infections of spirochete respectively, and {rom which the spirochetz had disappeared so far as could be determined by microscopical examination. Since it has been observed in the study of the precipitin reaction that the precipitin is sometimes soluble in an excess of precipitable substance, and that there must exist a certain quantitative relationship between the amount of precipitin and precipitable substances for the optimum reac- tion, many of these experiments were also performed in various dilutions of the sera. Finally, these same sera were examined for the presence of agglutinins, and in some instances for bacteriolysins. The following series of experiments illustrates the value of the pre- cipitin reaction for diagnostic purposes in this disease. EXPERIMENTS. SERIES NO. I. Mouse No. 1 inoculated on two different occasions with African NSpirocheta recurrens; the Jast inoculation ten days previously. Microscopic examination shows no spirochete in the circulating blood. Mouse No. 2 inoculated on two previous occasions with the American spiro- cheta; the last inoculation twelve days previously. Microscopic examination of blood negative for spirochete. Mouse No. 3 inoculated three days previously with the African spirocheta. Microscopic examination shows very few spirochete present in the circulating blood. Mouse No. 4 inoculated three days previously with the American spirocheta. Microscopic examination shows very rich infection with spirochete. All four animals were bled to death; the blood placed on ice over night; * the next morning it was centrifugated, the serum drawn off from the clot and recentrifugated in each instance. All sera were obtained clear. The following reactions were performed: Conditions of reaction. SE at dee AP a i Se Precipitin i : | reaction. Serum of— Plus serum of— | | ee t ee | eee aS Bees ‘ | Mouse 1 (immune to African 5) Mouse 3 (infected with African spirocheta) -__| Negative. | | 5 = - : . . ars: | Mouse 1 (immune to African S.)_| Mouse 4 (infected with American spirocheta)_| Slightcloud- | | } | | ing of the | | | | mixture of | : | sera. Mouse 2(immune to American S.} __--- (6 oe ce en ee ee ee | Negative. | Mouse 2(immune to American S.)| Mouse 3 (infected with African spirocheta)___ Do. | |) Normal mouse == --= = [Wena CL eee es oS Pea ht yeaa Do. | | INOW WAOS® a eee Mouse 4 (infected with American spirocheta)_ Do. “Tt was thought advisable to allow the blood containing the spirochete to stand over night in order to aid in the breaking up of the spirochete and thus favor the passing of the soluble albumens into the serum. 238 STRONG. Remarks.—Only in one instance is there a suggestion of a reaction, and this is between the American spirocheta and the African immune serum. With the African spirocheta and the African immune serum there is no evidence of a reaction. However, since the parasites were very scanty in the serum containing African spirochete, it is possible there was not sufficient precipitinogen present to give rise to a precipitate. SERIES NO, IT. Heperiments with the African strain.—Rats numbered 1, 2 and 3 having had one inoculation of African spirochetes twelve days BEC OUSI were inoculated November 8 each with 0.25 cubie centimeter of mouse’s blood, containing fairly numerous African spirochetie, diluted with saline solution. November 11, micro- scopical examination; no parasites were found in the blood of any of the rats. Evidently relatively immune to the infection. Rats numbered 4, 5, 6 and 7 (all normal rats) were each infected on November $8 with 0.25 cubic centimeter of the same mouse’s blood containing African spirochete used to immunize rats numbered 1, 2 and 3. November 11 one rat, number 5, has succumbed. In numbers 4 and 6 a few spirochetze are present in the blood. In number 7 the parasites can not be found. November 12 a blood examination of rats numbered 1 and 2 again shows no spirochetie to be present. The animals were bled to death, the blood put aside for one and one-half hours and then centrifugated and the serum drawn off. A blood examination of rats numbered 4, 6 and 7 shows in each instance fair numbers of spirochetie; more were found to be present than in the examination of November 11. Numbers 4 and 6 were also bled to death, the blood centri- fugated, placed aside for a few hours and the serum drawn off. Experiments with the American strain.—Mice numbered 8 to 14 have Tel one previous infection with American spirochete ten days previously; they were reinoculated November 8, each with 0.125 cubie centimeter of mouse’s blood, containing numerous American spirocheti, diluted with saline solution. Novem- ber 11 an examination of the blood shows the absence of spirochetex in the circulating blood. The animals are evidently immune. November 8, rats numbered 15 to 18, normal rats, each infected with 0.25 cubic centimeter of mouse’s blood containing numerous American spirochete. This same blood was used to immunize mice numbered 8 to 14. November 11] all of these rats (numbered 15 to 18) are found to be infected with spirochetx, although only a few of the parasites are present in the circulat- ing blood. : November 12 an examination of mice numbered 8 to 14 shows no spirochete in the circulating blood. Numbers 8 to 12 were bled to death and serum col- lected. Rats numbered 15 to 18 were also examined, only one, number 15, shows a rather rich infection, while the others show very few parasites, although more are present than on November 1]. Rat. number 15 was bled to death and the serum collected. DIAGNOSIS OF AFRIGAN TICK FEVER. 239 The following precipitin reactions were performed with the sera of the above animals: 3 Conditions of reaction. == “ =o me fceewe a S a) = Precipitin reaction. Serum of— Plus serum of— | | Rat 1 (immune to African $)_----_--____ Rat 4 (infected with African §)____--____| Negative. Rat 2 (immune to African S) -----_-_-___ | Rat 6 (infected with African S)_-________ Do. Rat 1 (immune to African $)_------______ | Rat 15 (infected with American S)_______ | Do. Rat 2 (immune to African S)_-_-____ Do. | Mice § to 10 (immune to American $)_ | Do. Mice 11 and 12 (immune to American §S)| Do. i Mice 8 to 10 (immune to American $)___| Rat 4 (infected with African §) --__---___ Do. | Mice 11 and 12 (immune to American S)} Rat 6 (infected with African §)_-_-______ Do. Remarks.—There was no trace of a reaction in any of the tubes after ~ two hours, after eighteen hours, or even after forty-eight hours. November 13 another of the rats, number 17, infected with American spiro- cheta on November 8, -shows numerous spirochetes in the circulating blood. The animal was bled to death. Some drops of the fresh blood were mixed with citrate solution; after fifteen minutes the parasites had disappeared and could no longer be found on microscopic examination. It seems probable that the blood was collected just before the crisis, that the parasites were about to undergo bacteriolysis, and that the withdrawal of the blood hastened this reaction. The remainder of the blood collected was centrifugated and the serum separated. The following precipitin reactions were performed, the serum of rat number 17 being used for the precipitinogen. | Conditions of reaction. Precipitin reaction. Serum of— Plus serum of— | = | Rat 1 (immune to African S)_-----______ | Rat 17 (infected with American $)___-___ Negative. Rat 2 (immune to African S)________-___ jeer (a ea oa a ee ie SL, Do. Micelsitor.0) Gm esto Paine nic agS) | eae OF ee nee henner ee eee Do. Mice 11 and 12 (immune to American §))____- Oe See a Be ee Do. | | Remark.—No trace of a reaction occurred in any of the tubes after two and after twenty-four hours. In order to be sure that antibodies were already present in the sera of animals numbered 1 and 2 and 8 to 12, attempts were made to test the agglutinative value of the sera with the blood of mice numbered 19 - and 20, which had been .infected two days previously with African spirochaete and with the blood of rat number 17, the blood of which showed a rich infection with American spirochete. However, although the reactions were performed with the blood of mice numbered 19 and 20, there were too few parasites present to allow me to arrive at any 71331——4 240 STRONG. definite conclusions, and as has already been stated, the parasites disap- peared from the blood of rat number 17 a few minutes after its with- drawal. As the examination of the blood of all the other infected animals on hand on this date showed none containing parasites in a satisfactory condition for the performance of the agglutination or bacteriolytic test, these reactions could not be performed satisfactorily. SERIES NO. Il. BHuperiments with the African spirocheta.—Mice numbered J and 2 had been infected about one month before with the African spirocheta. tion on November 8 showed no parasites to be present. death and the serum separated. Mice numbered 3 and 4 were infected with the African spirocheta on Novem- A blood examina- The animals were bled to ber 5. A blood examination on November 8 showed the parasites to be very numerous. The animals were bled and a small quantity of the blood mixed with citrate solution for agglutination reactions. remainder. é Haperiments with the American spirocheta.—Mice numbered 5, 6 and 7 had been infected about one month before with the American spirocheta. A blood examination on November 8 showed no parasites. The animals were bled to death and the serum separated. Mice numbered 8 and 9 were infected with American spirochetze on November 5. A blood examination on November 8 showed a fair number of parasites present. The animals were bled to death and a small quantity of the blood mixed with citrate solution for agglutinative reactions. The serum was separated from the remainder. The serum was separated from the The following agglutination reactions were performed: : ae Conditions of reaction. Agglutination. Serum of— Plus citrated blood of— 1-10. Mice 1 and 2 (im- mune to African S$). Mice 1 and 2 (im- mune to African S$). Mice 5, 6, 7 (immune Mice 3 and 4 (infected with African S). Mice 8 and 9 (infected with American S). Mice 3 and 4 (infected Marked after 15 minutes. No agglutination but too few parasites pre- sent for a decisive test. Negative after 15 minutes; Marked after 15 minutes. Practically no . to American §). with African S). after one-half hour mod- agglutina- erate agglutination. tion. Parasites too scanty to judge definitely of reaction, few found scattered. Not agglu- tinated. Mice 5, 6, 7 (immune to American S). Mice 8 and 9 (infected with American S). The following precipitin reactions were performed with the same sera: Conditions of reaction. Precipitin i sae s reaction | after 3 Sera of Plus sera of— hours. if Mice 1 and 2 (immune to African $)____| Mice 3 and 4 (infected with African S$) __| Negative. | Mice 1 and 2 (immune to African $)____| Mice 8 and 9(infected with American S)_ Do. Mice 5, 6, 7 (immune to American Sya-e| Bene 0 ae Se SAE ee eee Do. Mice 5, 6, 7 (immune to American $) ___| Mice 3 and 4 (infected with African S) —- Do. ! DIAGNOSIS OF AFRICAN TICK FEVER. Bal Remarks.—The precipitin experiments performed in duplicate and in dilutions of the different sera of 1 to 5 and 1 to 10 were all negative. However, it is to be noted that agglutinins had already develdéped in some of the sera. On November 11 the following further agglutinative reactions were performed with the same sera of animals numbered 1 and 2, and 5, 6 and 7; the citrated blood of mice numbered 10 and 11, infected with spirochetes on November 8, being used to furnish the spivochete which were numerous and very active at the time of the test: Conditions of reaction. = Agglutination. | Sera of— | Plus citrated blood of— | | | i Mice 1and2(immune to | Mouse 10 (infected | Positive good clumps and starforms | African S). | with African S). in 5 to 10 minutes in dilutions of 1-10 and 1-20. Parasites have lost almost entirely their motility. | II Mice 5, 6, 7 (immune to |_--__ owes: eas ee Negative. Parasites retain their | American §). | motility and remain singly. No clumps or agglutination in dilu- tions of 1-5, 1-10. III | Mice 5, 6, 7 (immune to | Mouse 11 (infected | Positive. Very large clumps and American $8). | with American §). balls of organisms in 5 minutes. | Marked reactions in dilutions of 1-10 and 1-20. IV Mice 1 and 2 (immune to |____- Oa 2 Sse eee Negative. Organisms remain sin- African ). gle even in dilutions 1-2 and 1-10; also still motile. Remarks.—The above reactions were observed in moist preparations and were confirmed also by stained ones. In experiments I and III, in the dilution 1 to 2, the agglutination was not so visibly marked because of the spirolytic action of the sera on the spirocheete. SERIES NO. Iv. Experiments with the African spirocheta.—November 15, rat number 1 which had received two previous injections with African spirochete on October 4 and November 8 was again inoculated November 15 with blood containing numerous African spirochete. Rat number 2, which had been given one previous injection of the African spirocheta on November 8, was again inoculated November 15 in the same manner as rat number 1. j Rat number 3, which had not been previously injected with spirochete, was also inoculated on November 15 in the same manner as rats numbered | and 2. Haperiments with the American spirocheta.—Rat number 4, which had received two previous injections with American spirochetse on October 4 and November §, was again inoculated on November 15 with blood containing numerous American spirochete. Rat number 5, which had been given one previous injection with the American spirocheta on November 8, was again inoculated on November 15 in the same manner as rat number 4. ‘ Rat number 6, which had not previously been inoculated with spirochiete, was also injected on November 15 in the same manner as rat number 4. 242 STRONG. On November 17 a blood examination of all the animals was made. In rats numbered 1 and 4 no parasites whatever were found; in rats numbered 2 and 3 very fey parasites were seen; in rats numbered 5 and 6 a moderate number of parasites were encountered. On November 18 no parasites were found in rat number 2 but in rat number 3 they had increased in number; in rat number 5 they were still present. November 21, rat number 7, a normal rat, was injected with African spiro- chet and rat number 8, a normal rat, with American spirochete. On November 23 microscopical examination showed rats numbered 1 to 6 all to be free from parasites; rats numbered 7 and 8 each showed moderate infections with spiro- chet. The animals were all bled to death and the serum separated. The following precipitin reactions were performed: | Conditions of reaction. fe ae Ss = £: Precipitin reaction. Serum of— | Plus serum of— | = = Rat 1 (immune to African S)__- | Rat 7 (infected with African $) —_---_____ | Negative. | Rat 2 (immune to African $)_ | Rat 7 (infected with African S$) _________ | Do. | Rat 3 (immune to African $)---___-_--__ Rat 7 (infected with African $) | Do. | Rat4 (immune to American S) ________- | Rat 8 (infected with American S$) -_- | Do. | Rat 5 (immune to American §) ----_-__- | Rat 8 (infected with American S) ________| Do. Rat 6 (immune to American S$) _.---____| Rat 8 (infected with American §$)_-_-_-___ | Do. Rat 1 (immune to African $)___-__-_____| Rat 7 (infected with African §) ______-___ | Do. | ~ } The following agglutination reactions were performed: Conditions of reaction. | re | Agglutination, dilutions 1 to 10 Serum of— Plus citrated blood of— | | | es Rat 1 (immune to African S)________ | Rat 7 (infected with African S)_______| Strong reaction. Rat 1 (immune to African S)__-__-_- Rat 8 (infected with American S)______ Negative. | Rat2 (immune to African S)________| Rat 7 (infected with African S)________ | Strong reaction. | Rat 5 (immune to American $)_____-| Rat 7 (infected with African S)________ Negative. | Rat 5 (immune to American $) -____- Rat 8 (infected with American §) -_____ Positive reac- tion. Rat 6 (immune to American $)___--- | Rat 8 (infected with American $)______ Negative. The above-described experiments demonstrate that the precipitin re- action in the manner employed is of no yalue for the purpose either of the differentiation of the spirochete of relapsing fever or for the diagnosis of the infection. It would appear from the series of experiments numbered 3 and 4, that during immunization with these spirochzete, as in some bacterial infections, the agglutinins and bacteriolysms become developed in demonstrable quantities more quickly than the precip- itins. It is very probable that an animal might be sufficiently highly immunized so that a precipitin test for these spirochet could eventually be obtained; but the above experiments conclusively demonstrate that this test is not a practical one as a means of diagnosis of the infection. DIAGNOSIS OF AFRICAN TICK FEVER. 243 ‘It may be stated in relation to the employment of the agglutinative test for this purpose, that, as has already been pointed out, owing to the difficulties of technique in performing the reaction and to the fact that in tick fever infections the agglutinins sometimes do not become de- veloped until after several relapses or reinfections with the spriocheete have occurred (a fact to which Manteufel ** recently called attention for infections with Spirocheta obermeiert) the agglutinative reaction even in low dilutions also does not constitute a satisfactory means of diagnosis.?° For the present, the most efficacious methods at our disposal are the microscopic examination of the peripheral blood and of that obtained by puncture of the liver and spleen, both in fresh and in stained preparations, and by animal inoculations with the blood when suitable species are at hand for this purpose. Usually, a marked polymorphonuclear leucocytosis oceurs, frequently before the crisis, and it usually persists for a day or two after it. At the latter time, an increase of the large mononuclear cells may be encountered. It should be remembered that even in cases well marked from a clinical standpoint, the microscopic specimens of the centrifugated blood may be examined an hour or two before a single parasite is finally discovered. If the parasites are not found by the examination of the blood, imoculations of white mice, white rats or monkeys with the blood of the suspected patient should be carried out if practicable. I the spirochzets develop in the blood of the animal, they may if it is thought desirable be differentiated by means of specific agelutinating sera. Clinically, it is sometimes quite impossible to dis- tinguish African tick fever from several other febrile infections. T have seen in a hospital at one time as many as five cases diagnosed as spirocheetal fever infections by a competent physician, thoroughly familiar with the clinical picture of relapsing fever and accustomed to seeing numerous cases of this disease. I was unable to find a single spirocheta in the blood of any of these patients. Theoretically, it is very easy to distinguish tick fever from typhus fever, malaria, trypanosomiasis and Kala-azar by the blood changes. In practice, this is at times most difficult, and the individual case may require considerable study before a correct diagnosis can he made. In conclusion, I wish to express my thanks to Professor Nocht, Professor Fullerborne, Professor Geimsa and Professor Prowazek, for many courtesies extended to me during my stay at the Institut fir Schiffs- und T'ropen-Krankheiten, where most of the laboratory ex-. periments described in this paper were performed. *8 Loc. cit. : » No attempt was made to employ the reaction of the deflection of the com- plement for diagnostic purposes in these spirochete infections, for the reason that it appears that the definite value of this reaction has not as yet been entirely determined for bacterial infections. ES ae EO by y “ ‘ ' Fever bebe Fetans) Tipe ; z 1 Lara list . ve pare ; ‘ Ty ha aah Ne) We ET yas 4 nN 4 4 Mag ele tenea yy TE Ya M, anf Petia Woda ; t Pato ete re: + ghiiveedrat ToD ieee. ret Racine il rt ne soba aat ts 24) ~~ ry io i “ seh + A ; i: \ OBSTETRICS IN THE PHILIPPINE ISLANDS. By FERNANDO CALDERON.* (From the Department of Obstetrics, Philippine Medical School.) INTRODUCTION. More than two years ago, in a lecture which I gave in the Liceo de Manila, by request of the Asociacién Feminista Filipina, I had an op- portunity to express my personal opinions on the interesting problem of infant mortality in Manila and at the same time to propose means for ameliorating this condition. I believed the most efticacious measure, along with popular education, to be the organization of a good service of midwives, with a lying-in dispensary to which the poor women of this city could go for assistance. In this manner we would remedy the necessity which compels women, neglected by fortune, to give birth to their children in miserable habitations lacking every hygienic facility and to place their lives and those of their new-born infants at the mercy of ignorant midwives, audacious in the abuse of obstetrical practice. It is necessary to establish a school for midwives who, when sufficiently instructed, would be excellent disseminators of the teachings derived from the practice of modern obstetrics. The suggestion then made did not fall on barren soil, for the Philippine Commission, at the instigation of Dean C. Worcester, Secretary of the Interior, appropriated the funds necessary for the building in Manila, within a short time, of a pavilion hospital planned according to modern standards. One of these pavilions will constitute the beginning of the future lying-in hospital of Manila. However, we are confronted by another question of equal importance. When the obstetrical pavilion is erected, can we count on the women of the lower classes, who form the majority of the population of these Tslands, attending this new clinic and renouncing once for all the irrational practices of ignorant midwives and illegal practitioners ? Before we can respond in the affirmative, it will be necessary for the Philippine Medical School and the Bureau of Health to agree to lead 1Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, Manila, February 29, 1908. 245 246 CALDERON. and direct the education of these ignorant women into new channels, overthrowing routine customs and traditional means, many of which I shall briefly discuss in this analytical study of obstetrics in the Philippines. BARLY SUPERSTITIONS. During many centuries the mission of assisting in childbirth was confined exclusively to midwives, who were the oldest women of the community in which they resided and who, taught by their own personal experience, advised and aided the young and inexpert. A certain number of precepts acquired by experience and observation, and a still larger number of individual practices and superstitions, represented the whole fund of knowledge employed in difficult cases. ‘These midwives, who in primitive times existed in all countries, are still known in the Philip- pines by the name of hilot, a Tagalog word which has come down to us through many generations, in the same manner as the term salag, by which is known the person who assists the hilof in her empirical manipulations. The conjunction of the moon, the appearance of comets, the flow and ebb of the tides, the direction of the winds and the influence of heat and cold were, for the hilot and salags, the etiologic agents which decided the development of pregnancy, or the evolution and progress of childbirth. In view of such prejudices, it is not surprising that even in the most aggravated cases of dystocia, the unfortunate patient was abandoned to the sole efforts of nature, any rational intervention for saying her from certain death being absolutely unknown. Failure was attributed by the midwite to the fatal influence of the aswang, a malignant spirit which, according to the common people, lies in wait for pregnant women and, at the moment of labor, penetrates into the uterus to devour the foetus; just as another spirit called patianac, in the shape of a strange animal, intro- duces itself into the genitals of pregnant women in order to deyour the product of conception. The influence of the patianac was to the midwife the logical explanation of the pathologic phenomena of pregnancy, which we now know as abortion, expulsion of a macerated foetus, uterine mole, placenta previa, etc. In my opinion, these superstitions have their origin in the ancient beliefs of paganism predominating in the Philippine Islands before the arrival of the Spaniards, and they gained such a hold on the minds of the people that they are still preserved latent in some parts of the Archipelago, and have on some occasions given rise to barbarous practices and manipulations which are an outrage to civiliza- tion and which have cost the lives of many women in childbirth. While I was an interne in the San Juan de Dios Hospital in the year 1889, I performed an autopsy on a poor woman who had died in the district of Tondo because a quack had barbarously beaten her with the OBSTETRICS IN THE PHILIPPINE ISLANDS. 247 tail of a sting-ray. This woman, after a normal delivery, had con- tracted puerpal fever, and the violent chills which seized her were attributed by the quack to the presence of the aswang, which needed to be driven out of her by a severe whipping with some bruising instrument which, like the tail of the sting-ray, had the medicinal virtue of expelling all malignant spirits. INFLUENCE OF THE MISSIONARIES. At a later period, bearers of a new civilization arrived on these shores in the shape of the Spanish missionaries or friars. These representatives of the church spread throughout the villages of the Philippines and there they organized parishes. ‘These holy men, ministers of a religion which is all peace and charity, could not long remain indifferent to the ailments of the body, and in the same manner as that in which they ministered to the afflictions of the soul, the woman in the throes of childbirth was also made the object of their solicitous care. In order to give a slight idea of remedies which were used by the friars in these early days, I will here transcribe a curious chapter from the work of Father Pablo Clain, 8. J., entitled “Hasy Remedies for Various Diseases.” The work was published in Manila in the year 1710, being practically two centuries old. The chapter mentioned, which is entitled “Parturition, How to Facilitate it,’ reads, literally translated, as follows : “Cause the woman about to give birth to sneeze, by blowing into her nostrils some of the powder known as Verbo apoplegia, or mustard seed, and white pepper. Give her a spoonful of mass wine from time to time, or give her to drink, in tepid water, the balls of hair formed on deer or hogs (weight of nine or ten grains of pepper). “As to the exterior, the midwife should frequently anoint the abdomen with tepid coconut oil, mixed with escobilla juice? (Sida carpinifolia L.). “Apply to the abdomen fomentations of a decoction of emollient herbs, such as escobilla, mallows, castiogan root (Hibiscus abelmoschus L.), camantigue leaves (Impatiens balsamina Ll.) and costmary (Tanacetum balsamita L.). Give her acrid and irritating injections. Some praise the gall of a black hen applied to the navel; others mouse excrements dissolved in tepid wine or tepid water given to drink (as high as six grains). A duferro*® stone should be tied to the thighs (or applied to the lower parts) ; but it should be removed im- mediately after the placenta has been expelled. A loadstone tied to the thigh, on the inner side, is likewise efficacious. If the new-born infant is weak, strengthen it by giving ‘the mother a swallow or spoonful of tepid Castile wine, and externally, by placing on her abdomen a piece of toasted bread, sprinkled with hot mass wine and powdered cloves, cinnamon and nutmeg. If the child begins to emerge in an unfavorable manner, such as presenting first an arm or a foot, * The scientific names of the plants mentioned have been supplied by Dr. Leon Guerrero and by Mr. Merrill, Bureau of Science. * A translation of this word can not be supplied. 248 CALDERON. or in some other manner, the midwife must push it back inside of the mother, who must then lie on her back, with the head low and the nates raised, and after having put back the arm or foot which the child presented, the midwife must make it retrocede by gently pressing the abdomen of the pregnant woman upwards and towards the epigastrie region, or the breast, and after the child is again within, she must manipulate it so that it will emerge in due form; the midwife endeavoring, using her hands, to make the child turn its face towards the back of its mother, and then by raising its nates and legs to the navel of the mother, to have it emerge in the proper manner. “The common people use the following remedies: They make the parturient drink some of the mill of a woman nursing a child, or make her suck the nipples of such a woman; they cautiously apply to her body a snake skin shed by a snake, but remove it as soon as she has been delivered, because otherwise her entrails might come out. On the groins they put bruised salibutbut (Taberne- montana Pandacaqui Poir.), warming it in hot ashes. The parturient is made to drink costmary juice in strong wine. She is given mint, bruised and mixed with water and honey, and forced to drink a decoction of raiz oriental (Andro- pagon nardus L.), palasan (Calamus albus Pers.) and panara plantain in water, as well as to drink hezoar taken from a deer or wild hog, burned on a potsherd and dissolved in a little wine or water. If the patient has any strength left, she is made to drink dog urine, or horse or cow excrements, three reales weight, dried, crushed and mixed with water or wine; this is also useful for ejecting a dead infant. She must hold a jasper stone in her hand. She is given sweet-basil juice (Ocimum basilicwm Linn.) to drink.” However ridiculous these prescriptions may seem, the fact remains that they were faithfully observed and carried out in the treatment of many parturients, for the reason that they had come from the authori- tative lips of a missionary priest, compelled by the force of cireumstances -to serve as physician as well. It was for good reasons that the Reverend Father Gregorio Sanz, of the Barefooted Order of Saint Agustine, writes as follows in his treatise on “Sacred Embryology” (p. 39), edited in Manila in the year 1856: “In the Philippine Islands, where in a way it may be said that outside of the capitals there is no physician but Providence, nothing was more common than to see the curates practice medicine among the natives of their parishes, whether the latter were men or women.” On pages 167 and 168 he adds the following words: “The number of midwives in a parish haying been ascertained, it is advisable to communicate to them individually the instructions which we give hereinafter, if they have not already received them; it is of the greatest importance to have them well instructed in this respect and for this purpose it is very advisable, in view of the facility with which these good people forget what has been taught them, especially if it be something that they have to practice only a few times, that every year after their first instruction, at the time of the examination in the catechism for the perfection of the parish, they be reéxamined in every- thing that was taught them upon their admission into the profession of midwifery. If, though this is hardly to be expected, the midwives should object and refuse to receive instruction from their ecurates on this subject, it will become necessary to notify the civil authorities, in order that they may be aS, ve OBSTETRICS IN THE PHILIPPINE ISLANDS. 249 suspended from their profession and to inform the people of this fact in the sermon on the following Sunday.” These words show that in each parish the missionary priests exercised a certain control over a given number of midwives who received direct instructions from them. These instructions, in a special manner, referred to everything relating to proper baptism which, in cases of necessity, was administered to the child either within or without the mother’s womb; but they also extensively entered into the manner of attending parturients. A proof of this is found in the following paragraph taken from the above-mentioned work of Father Gregorio Sanz, relative to the treatment of abortions: “The first and most important thing is to advise the patient to remain in a horizontal position and to preserve absolute repose of body and mind; the second is to bleed the arm if the woman is robust, and if she is weak or nervous, to apply ten or twelve leeches or cupping-glasses to the breasts, these being the organs best indicated at this epoch; the blood-letting and likewise the applica- tion of leeches should be employed only when recommended by a medical person; at the same time a lemonade of cream of tartar, with sugar and small quantity of saltpeter, should be administered and the loins and abdomen should be gently rubbed with hot essence of mastic. “If the woman is in convulsions, or if she is nervous and suffers very intense pain, then she must be given an antispasmodic potion composed of one ounce of almond oil, another of simple sirup, and one grain of extract of henbane, of which one spoonful must be taken every half hour; at the same time the abdomen should be rubbed with a mixture of one ounce of henbane and one drachm of tincture of opium. Experience has demonstrated that in the majority of cases simple means are sufficient to check abortion at the outset, but as they are not all within the reach of the native midwives, and it is not easy for all to secure them, we shall indicate another remedy which is simpler, but assuredly not so efficacious. “As soon as the pregnant woman feels the symptoms which we have indicated above she must remain very quiet, speak very little and keep to her bed for several days. Cupping-glasses may be applied to her arms and she may be given copious drafts of common water prepared in this manner: Two ounces of unhusked rice are boiled in half a ganta (1.5 liters) of water until the grains burst open; then the water is strained and two spoonfuls of lemon juice are added. “She must abstain from eating meat, chicken, eggs and fish; her food should consist of rice broth or puspas (stewed rice and meat), of little substance if the patient is robust or sanguine. She may also be given a light enema of a decoction of mallow, with the yolk of an ege; but this is only in cases where the evacuations are accompanied by tenemus, or where the bowels have not moved for many days.” The same author, who is more modern than Father Clain and who seems to be inclined toward surgery, in an address to his colleagues, the parish priests, wrote the following in connection with the Czsarian section performed after the death of the mother: “Hvery curate should secure the proper instrument, which is none other than a convex bistoury, the price of which is only one peso in Manila. Surgeons bo 50 CALDERON. usually employ another bistoury with a blunt point, but we believe that this can be replaced by putting a small ball of wax on the point of the convex bistoury; and it is my opinion that in practice it is sufficient to cut the skin and the cellular tissue with a well-sharpened knife, reserving the bistoury with the ball of wax for the section of the peritoneum and the womb. If a razor is used, the handle should be firm and strong.” Judging from these statements, it appears that the medico-social influence of the missionary friars in the Philippines has been exceedingly important, especially im the field of obstetrics, and it is believed that with their evangelic advice, these priests dissipated the innumerable pagan superstitions relating to parturition, but, on the other hand, they sanc- tioned the use of many remedies utterly in conflict with common sense, some of which are to-day used by the lower classes. All of this is very excusable in these men, who were as full of the best desires and of love for their fellow-men as they were lacking in obstetrical knowledge. It is therefore not surprising that one still hears at the present time of some parturient to whom repulsive substances, such as dog urine, or mouse, horse or cow excrement have been administered. Dr. Benito Valdez, of the faculty of the University of Santo Tomas, Manila, has recently told me of a parturient to whom a decoction of horse excrement was administered in order to facilitate labor, whereupon tetanus set in and the woman died. According to my informant, this case happened in Manila, approximately two years ago. There are women who palliate the sufferings of childbirth by applying to the abdomen scapularies, images, medals, or to the feet, hands or other portions of the body relics of some famous saint venerated in the churches, or who drink, instead of urine or excrements, the miraculous water from Lourdes, accredited among pious people as an excellent medicine for facilitating parturition. INFLUENCE OF THE CHINESE. A yery important factor which should be taken imto consideration in this analytical study is the geographical proximity of the Celestial Empire to the Philippine Islands. Thousands of Chinese immigrants have invaded even the most remote parts of this Archipelago. One of the consequences of this immigration has been the introduction into this country of many superstitions originating in China which have become general among the Filipinos, and which haye been strengthened by the arrival here of several Chinese physicians who practiced medicine among the natives according to Chinese usage. hese so-called doctors acquired such influence that it is not an exaggeration to state that their queer therapeutic theories and practices are still followed by a portion of the population of the Philippine Islands. While I was municipal physician in Carigara, Leyte, in the year OBSTETRICS IN THE PHILIPPINE ISLANDS. 251 1894, I noticed that some of the inhabitants when ill preferred to call quacks who treated diseases according to Chinese methods and who used Chinese drugs. The latter were, at least at that time, freely sold in public establishments. There are to-day in Manila old people who remember with pleasure the Chinamen who practiced medicine and acquired fame and popularity in this city even among families of the best social standing and position. Tt goes without saying that the ideas originating in China necessarily influenced Philippine obstetrics, the result being that in regard to parturition, the exotic superstitions of the Asiatics were added to the autochthonous superstitions of the Malay race. It would be curious, were it possible, to make a comparative study of obstetrics in the Philippine Islands and in China and to ascertain the mutual relationship which must exist between the two. Historical documents which might shed light upon this labyrinthie subject are, of course, lacking, but my own experience and the descriptions which I have secured from authentic sources, war- rants my giving some personal information on the subject of certain Philippine superstitions of Chinese origin. What I have learned is as follows : When a woman has on the palm of the hand a transverse line completely crossing it, it is a sign that she will have difficult births and it is necessary that at the moment of parturition the line mentioned be covered with a hand- kerchief. Dr. Castaneda, extern in obstetricts in the Philippine Medical School, recently saw a woman in the distret of Sampaloe who was about to give birth to a child, and noticed that she had on each hand a silk handkerchief covering the lines on the palms. Certain bricks of cylindrical form (lavio) are manufactured in this country especially for parturients. They are well heated and then applied to the abdomen of the patient for the purpose of expelling from the womb wind and cold, two atmospheric agents which, according to Chinese tradition, are mortal enemies of the parturient. The patient is never given chicken broth, for as the chicken is winged and flies, it carries with it much wind which it might transmit to the patient and thus injure her. Women who are menstruating are prohibited from entering the lying-in room, because the effluvia of the former might be transmitted to the patient and give her fever or cause some other complication. In cases of difficult parturition, the husband steps over the patient two or three times in order to cause delivery; and if this should not be sufficient, a pair of drawers which has been worn by the husband is tied to the woman’s hair so that the smell of his father may cause the foetus to emerge at once. Where swooning occurs, and especially where there is hemorrhage, the hair is bound in a tight knot, and the patient is not permitted to sit down, this to prevent the spirit from escaping from the body. A colleague told me of a terrible case resulting from this last superstition and witnessed by him in the Province of Ambos Camarines a few years ago. The wife of a Chinaman had a post-partum hemorrhage, caused by the retention of the placenta, and in order to stop the hemorrhage, either the Chinaman himself or the midwife, or both, had the w 252 CALDERON. patient’s coil of hair drawn very tight and by means of it they hung her from one of the beams of the house. The woman died in horrible convulsions while thus suspended. In China the umbilical cord is not cut until the placenta has been expelled, for fear that the latter might rise, envelop the heart and kill the patient. Many Filipino midwives, influenced perhaps by this superstition, do not cut the umbilical cord until the placenta has been delivered, leaving the child sometimes for hours between the mother’s thighs, covered with the sebaceous matter, meconium, amniotic fluid, blood and feces. The placenta is cremated and then administered to the patient. The umbilical cord is burned, the ashes to be used as a remedy for stomach ache in children. In China, when the parturient is in a very serious condition due to hemor- rhage, a chicken is killed, cut open and applied to the patient’s breast to give her life. I have seen this done in the town of Ormoc, Leyte, when I was municipal physician in that settlement. Tf the fetus has coils of the cord around the neck, superstition has it that the boy will become a great man, as this condition recalls the Chinese mandarins and great dignataries who have bands covered with symbolic ornamental dragons wrapped around their bodies. MODERN ADVANCES IN THE PHILIPPINES. I wish here to render a tribute of consideration and affection to our colleagues who preceded us in the practice of medicine in these Islands and who planted in them the first milestones of rational obstetrics, according to the knowledge of that epoch. I do not allude particularly to the Spanish physicians, called fisicos, who, together with the troops and missions from Spain, landed each year from the famous Acapulco galleons, nor to those who came to this country between the years 1764 and 1869 with the expeditions organized at the port of Cadiz, sailing for Manila, by way of the Cape of Good Hope. These men formed such a small minority and had such scanty knowledge of obstetrics that their influence may well be disregarded in the evolution of this important branch of medicine in the Philippine Islands. I wish to speak of the foreign, Spanish and Filipino physicians who, beginning in the years 1870, established themselves in Manila and the provincial capitals, shedding the first rays of the light of medical science on the chaotic state of affairs then prevailing. Among these pioneers of happy memory, I make special mention of the Englishmen Fullerton and the Burke brothers, the Germans Neizen and Koeniger, the French- man Permantier, the Portuguese Silva Magalhaes, the Spaniards Ginard, Marti, Meynet, Nalda, Pina, Torrejon, Sacristan, Mallen, Farimos and others who practiced medicine in this country. They are all deserving of gratitude and praise, because they contributed their grain of sand to the erection of the scientific edifice of obstetrics in the Philippine Islands. The codperation of Filipino physicians in the scientific labor already initiated was not long wanting after the creation im this capital of the a faculty of medicine of the University of Santo Tomas. Beginning with OBSTETRICS IN THE PHILIPPINE ISLANDS. 253 the year 1867, diplomas to licentiates in medicine and surgery were issued every year to young men who scattered throughout the Archipelago to practice medicine, either as private physicians or in some public capacity under the former Spanish Government. Although, so far as parturition was concerned, it must be admitted that the clinical educa- tion given in the lecture rooms of the university was exceedingly deficient because of lack of a practical foundation, yet it is no more than just to acknowledge that, thanks to spontaneous efforts and ex- tensive personal experience, many of the native physicians became expert obstetricians and contributed materially to the advancement of this branch of medical knowledge in the Philippines. Prominent among these men is the figure of Dr. Felipe Zamora, who for many years and until the close of Spanish rule, was the best obste- trician of Manila and the adjacent provinces. More recently, excellent obstetricians have developed in the persons of Drs. Pablo Nalda and Manuel Madrigal, both deceased, and among our own contemporaries. Another event connected with the history of obstetrics in the Phil- ippine Islands was the establishment in 1879 of a school of midwives annexed to the University of Santo 'omas. ‘The course consisted of four semesters. Fifty-six of the one hundred and thirteen pupils who were matriculated received the degree of midwife. The school suspended operations in the month of March, 1903. Nine years after ifs creation, by virtue of a royal order of February 28, 1888, the service of official midwives who might render gratuitous service to poor parturients was established for Manila and the provinces, but nearly all the provincial positions remained vacant, probably because of the lack of competent, qualified persons. There followed the establishment of the imspeccion general de beneficiencia y sanidad, by virtue of the royal order of Sep- tember 10, 1888, to replace the old swbdelegacion de medicina y farmacia, which had existed since the year 1862. Later, there was founded the service of official physicians (médicos titulares) for the Archipelago, the latter being charged with the obligatory and gratuitous attendance of poor parturients within the municipal limits of Manila. American sovereignty came in the year 1898 to replace that of Spain in the government and administration of these Isalnds, and after civil government had been established, the Board of Health was created in October, 1901. In December of the same year, the Board of Medical Examiners was constituted, charged with qualifying physicians, prac- titioners of medicine and midwives who wished to follow their profession in the Archipelago. Of the latter, thirty-three were registered, certainly a very insignificant number for the entire Philippine population. Thirty- one of these were from Manila, one from Iloilo, and one from Ilocos Sur, there being none from the other provinces. Hight of these thirty- three qualified midwives were appointed municipal midwives, to render, 254. CALDERON. in conjunction with the municipal physicians, gratuitous services to parturients of the poor classes in the suburbs of Manila. The Philippine Medical School was established by act of the Philip- pine Commission, December 1, 1905. It began operations July 1, 1907, and the chair of obstetrics was organized with its clinic in St. Paul’s Hospital. Here several beds were reserved for poor parturients of this city. Similar action was taken by the San Juan de Dios Hospital, in consequence of the adoption of a new curriculum by the medical depart- ment of the Santo Tomas University. ADVANCES IN THE USE OF INSTRUMENTS. In the last two decades many obstetrical operations have been per- formed in the Philippines, such as the application of the forceps in its several varieties, versions by external, internal and mixed manipulation, the Czsarian section on living patients, embryotomy, basiotripsy, provoca- tion of premature labor, curettage, and perimeorrhaphia of all kinds, with the exception of symphysiotomy and pubiotomy. CONCLUSIONS. It has clearly been demonstrated that in the Philippine Islands work has been going on for some time which tends to lead obstetrics into . modern channels and to eradicate from the minds of the people the charlatanism, superstitions and irrational practices predominating. in this branch of medicine. What has been the result of this scientific evolution? That it has been efficacious and useful to a large number of women belonging to the cultured families of this country who have at least realized that for confinements a physician should be called, is un- disputed; but it has been negative in regard to the nameless mass of parturients of the lower classes who are completely given over to the illegal practitioners and midwives, with great danger to their own lives and to those of their new-born babes. The services of a physician are, as a rule, dispensed with among the people of this stratum of society, even in the most serious cases of dystocia, and the patient is left to her fate. If a physician is sent for, he is almost always called after the moment has passed when a simple intervention on his part might have prevented the death of the mother, or of the child, or of both. A few instances might be cited in this connection: Last September (1907) I received an urgent call to attend a parturient in Calle C, district of Malate. It was a very serious case of retention of the placenta and the woman, who had been delivered of a live child at 2 o'clock in the morning, was, five hours later, at 7 o’clock in the morning when I was summoned to her bedside, in the last moments of a terrible hemorrhage. Intervention at that time was useless and the life of OBSTETRICS IN THE PHILIPPINE ISLANDS. 255 the patient could not be saved. The midwife was tranquil, believing that she had done her duty. A little over a year ago I was called to the bedside of a woman in Calle Barbosa, district of Quiapo. This woman had been delivered of a live child at 10 o’clock in the evening. When I arrived at 2 o'clock the next morning, the placenta had not been expelled. A copious hemor- rhage had ensued, and while I was attempting to intervene, the patient began to collapse. The family subsequently informed me that a Chinese quack had acted as accoucher in the unfortunate delivery, but that he had disappeared upon my arrival. Many other cases might be cited of parturients who have died of hemorrhage, victims of the ignorance of the midwives. It is impossible to estimate the number of infants sacrificed by illegal practitioners who have folded their arms, content with a stupid temporizing in the frequent cases of inertia uteri, with the result that the child has died from prolonged detention in the vaginal canal, when a simple applica- tion of the forceps might have saved it. Among numerous cases of this kind I shall cite only one, which I witnessed in an interior street in the barrio of Santa Mesa at the beginning of the present year (1908). The woman was a multipara, her bladder had not been emptied for more than five hours, and the lack of uterine contractions had detained the child in the canal during the period of expulsion. When I sought to intervene with the forceps, the woman spontaneously gaye birth to a beautiful and well-formed child which was born dead hecause of intra- uterine asphyxia, and which could have been delivered alive if the midwife had had intelligence enough to calla physician at the proper time. A large number of women die eyery year in the Philippines as a result of puerpal infections, not only because the midwives are ignorant of the most rudimentary conceptions of asepsis and antisepsis, but also because the rooms in which the confinements take place are absolutely lacking in hygienic conditions. In the miserable huts in which the poorer classes live, there are at times neither clean water nor soap with which to wash the hands, the work of attending a birth becoming a veritable sacrifice for the physician who finds himself compelled to labor under such conditions, but even under these circumstances it is as a rule useless to advise the patient of the absolute necessity of being taken to a hospital where she can have proper attention, such a proposal being acceded to by herself and her family only with the greatest reluctance. } The aversion which Filipino women have to entering hospitals is due principally to their great attachment to their homes, together with an excessive love, sometimes ridiculous and mistaken, for their families and relatives from whom they are seldom separated. They cling to this notion even at the cost of their lives. It is also certain that the 71331 5 256 CALDDRON. improbable tales concerning the hospitals cireulated by ignorant midwives and meddlesome practitioners of the neighborhood, add not a little to the fomenting of this spirit of aversion. For example, it is said among a certain class of people that all the parturients who go to the hospital are operated upon there, sometimes the abdomen being opened to extract the child. It is also told that parturients are placed in beds in proximity to those of dying patients and that they are compelled to witness the sadness and horrors of death and also that at midnight they hear the moans and laments of those seriously ill. These systematic detractors of hospital service also take pains to spread abroad a revised and exaggerated account of the bad administration of hospitals, especially with reference to alimentation and care. As a result of all this, months and months pass during which the beds arranged for parturition in the hospitals are unoccupied by Filipimo women. This is not only injurious to the parturients and their new- born infants, many of whom die without medical attendance, but is detrimental also to the students in obstetrics who do not and can not have an opportunity for practical study, bemmg thus limited to being mere theorists in this branch of medicine so essentially practical and experiential. However, it has been possible to correct this difficulty to a certain extent, by the appointment of two externs in obstetrics, charged with gratuitously attending poor women in Manila during childbirth at their homes, the students taking advantage of these opportunities for their clinical instruction. Without such recourse, which we owe to the initiative of the Philippine Medical School, students would finish their entire course without any practical experience in obstetrics. The dif- ference between the number of births witnessed by students in the hospital and those which took place in private houses is instructive. In St. Paul’s Hospital the students saw only two births during the semester from July 1 to December 31 of the year 1907, whereas during the same period they attended 76 births im private houses, classified as follows : Normal births 47 Application of forceps 9 Versions, shoulder presentation 6 Placenta previa 5 Breech presentation 4 Post-partum hemorrhage 2 Puerpal eclampsia 2 Retention of the placenta ] Total 76 Perineorrhaphia was performed in several instances. The 76 births witnessed by students in the various districts of the city is a much greater number than the two which they saw in St. Paul’s OBSTETRICS IN THE PHILIPPINE ISLANDS. 257 Hospital; but, taking them all together, what do 76 births, during a period of six months, signify fora city the size of Manila? This insig- nificant total is an eloquent proof of the exceedingly small moral in- fluence the physician exerts on Filipino women of the lower classes and, on the other hand, demonstrates the palpable preponderance of illegal practitioners and ignorant midwives, monopolizers of almost all the parturitions among the poor and ignorant women of the city. It is even true that the two externes in obstetrics have been compelled to avail them- selves of the influence of illegal practitioners, by means of a wise policy of attraction, in order to attend confinements. To eliminate the illegal practitioner is, for the moment, a problem difficult of solution, for of what advantage would an energetic campaign against them at present be when we lack competent midwives? If the externs in obstetrics are reduced to attending maternity cases in miser- able, small habitations, it will be possible for them to take along not more than two or three students to each case, and for this purpose the students would have to confine themselves strictly to fortmghtly turns. Lacking the most necessary things, at times even clean water, soap and towels for washing their hands, the students have been compelled by circumstances to perform operations in filthy beds in unsanitary places and in an unhy- gienic atmosphere, the lying-in room serving at the same time as bed- chamber, kitchen and even workshop to an entire family ! In view of the data cited, it is not difficult to foresee that the obstet- rical pavilion of the future hospital will be a failure unless energetic measures are resorted to and certain reforms adopted to bring the poor and ignorant women of this city there for confinement. One of the first steps, after the construction of this pavilion, should be the enact- ment of a law establishing a school of midwifery for the entire Archipel- ago, and, as a measure of attraction to induce the ignorant women of the city to go there for confinement, I propose that some of the most popular and best-known illegal practitioners from the several suburbs of Manila be admitted as students in that school. his suggestion, however strange it may seem, will give positive results in the field of practice, because eight or ten of these practitioners, matriculated as students and enabled to secure the degree of qualified midwife, would serve as excellent prop- agandists for attracting parturients to the obstetrical ward, much better than all theoretical means of doubtful success. In a word, the great prestige which some of these illegal practitioners now enjoy among the lower classes of Manila should be used, through a wise policy of at- traction, to further the beneficent ends of scientific propaganda. The defective midwifery service now existing in Manila should be organized by regulations rendering efficacious the gratuitous treatment of poor parturients. Nothing would serve this purpose better than to place the midwives under the immediate control of the externs in ob- stetrics, whose duty it would be to approve the birth certificates issued 258 CALDERON. and to watch the obstetrical operations in their respective districts. The existing provisions regarding birth certificates should he strictly enforced in each instance, and for this purpose the curates and pastors of the churches in this capital should be required to comply with their obligation not to administer baptism to any child without the previous presentation of that document, in the same manner as death certificates are required in the case of funerals. If this should require an increase in the number of municipal midwives in Manila, then, for the sake of the poor, let the number be increased and, incidentally, the miserable pittance of 20 pesos per month which is now their stipend. As soon as the obstetrical pavilion has been constructed, a circular should be sent to all the practicing physicians in this capital, courteously inyiting them to bring to the clinic such maternity cases as they choose, leaving them complete liberty of action for intervention should they so require. In order to remoye common prejudices and traditions, ad- mission into the clinic should be permitted during the first year of its establishment, not alone to the parturient, but also to two or three of her nearest relatives, so that they may spread a knowledge of the un- doubted advantages of confinement in the maternity ward as compared with those of private dwellings. When the necessity for the establishment of a medical school for this Archipelago was discussed before the Philippine Commission, the theory was advanced that the project would result in a heavy burden on the Insular budget, it being more feasible and economical to send young Filipinos to America as Government students to study medicine. In making this objection, it was not taken into consideration that instead of an educational labor for the benefit of certain elements, a social labor within the Philippine Archipelago would be undertaken, involying the exceedingly important problem of infant mortality and of the practice in the Philippine Islands of obstetrics in accordance with modern methods and standards. ILLUSTRATIONS. PuaTes I-III. Conditions surrounding obstetrical practice in Manila among the poorer classes. 259 Scr., Vou. III, No. 3. (PHIL. JOURN. CALDERON: OBSTETRICS IN THE PHILIPPINES. ] PLATE Tl S1vw4ada Wir (pigs a Wz “1Ls ‘S$ ON TI] “TOA “IOS ‘Nuno -aIEHg] ('SaNIddiIng IHL NI sormtaasag > NOWAAIVO "tht Stv1d "€ ‘ON ‘III “IOA “10S ‘Nunor ‘tIHd] [SQNIddITIHG WH NI SomgEaisag : NOUWdIvOD EDITORIAL. DISCUSSIONS ON THE PAPERS OF DR. GARRISON AND DR. GILMAN. (The papers of Dr. Garrison and Dr. Gilman were considered conjointly.) Dr. Thomas W. Jackson, contract surgeon, United States Army, San Isidro, Nueva Ecija, P. 1—I was much interested in Dr. Garrison’s paper and I have been much impressed with the statistics that have been com- piled. My observations haye been comparatively limited, but I believe that the conditions which Dr. Garrison has outlined for Bilibid Prison prevail throughout the provinces. They are of common occurrence, and from three to five distinct infections have often been noted among Fili- pino Scouts by many Army men. Indeed it is exceptional to find a solitary variety of worms in a native Scout. ‘Two or more varieties are usually in association. The effect of multiple ascaris infection was not mentioned by Dr. Garrison. By this I mean the occurrence of a large number of worms in the same individual and when the discussion closes | would like him to state the maximum number which has been observed in a single indi- vidual. I have already found in a child forty-eight round worms. The child was also infested with hookworms and amoebe. Dr. N. M. Saleeby, superintendent of the University Hospital, Ma- nila.—One thing particularly interests me. A child in this city passed more than one hundred round worms, and I understand that a few days later it died. Does any one present know the death rate in these cases? I never investigated the subject, and I would be yery glad if someone could enlighten me. : Dr. W. H. Musgrave, Biological Laboratory, Bureau of Science, profes- sor of clinical medicine, Philippine Medical School, President of the Association.—lt seems to me that these papers have brought out two prominent facts. In the first place, we find a large percentage of amcebic infection, both in diagnostic work (Garrison) and at autopsy (Gilman). This brings up the question of so much importance to the practicing physician of the means of diagnosis of amoebic infection of the bowel during the life of the patient. Dr. Gilman, in one hundred autopsies, found 54 cases with lesions of the colon, and it is altogether likely that at least 50 per cent of these were due to ameebe. Dr. Garrison found 261 262 EDITORIAL. that 25 per cent of stools of all people examined contained ameebze, which is a smaller percentage than the findings in the autopsy room. These figures would indicate infestation without infection to be very rare and would justify the conclusion that we are all too prone to require the presence of blood and mucus in the stools before we state that actual amoebic ulceration of the bowel is present. Dr. Henry S. Greenleaf, captain, United States Army.—Has anyone who has been making a study of these parasites found evidences of guinea worms? When I was in Mindanao [I found a Moro pulling something out of a sore and I asked the interpreter what he was domg. The man pointed to a little worm which had been pulled out of the sore and from his description I thought it might be a guinea worm. Is this parasite common among the natives? I have not looked up the subject. Dr. Musgrave.—I have been looking for a guinea worm for nine years. Dr, Henry J. Nichols, first liewtenant, United States Army, Division Hospital, Manila.—\ haye had an opportunity to examine 400 soldiers doing active field duty, and 200 of these had amcebe present in their stools. Twenty-five per cent had symptoms of dysentery, and of this 25 per cent only about one-half showed the presence of active amoebe. Dean C. Worcester, Secretary of the Interior, Philippine Commission, Manila.—I have seen evidence on the subject of amoebic infection and it leads me to believe that if an amceba is not pathogenic at one time, it may become so at another. It has been suggested, in connection with some of our diseases in the Philippines, that dysentery is a white man’s disease, but I believe it is true that a very large percentage of the native inhabitants have dysentery in a chronic form, and this is one of the causes tending toward their disinclination to labor. I was very much interested in Dr. Garrison’s paper. The Secretary of War, while in Manila, called my attention to the yery satisfactory results which had attended the efforts made on such a large scale in Porto Rico to rid the inhabitants of intestinal parasitic worms and suggested that similar work might be necessary here. It would appear from Dr. Garrison’s paper that this is not probable. However, it sticks in my memory that I have read a report of Dr. Heiser on conditions in Bilibid Prison which showed infection with parasitic worms to be quite general among the inmates of that institution and that when systematic measures were taken to rid the convicts of these parasites, the death rate from other causes was immediately and materially reduced, showing that the patients had been so weakened by the presence of these parasites that they had fallen ready victims to other diseases. I should like to know whether Dr. Heiser can confirm this statement. Dr. Victor G. Heiser, Director of the Bureau of Health, Manila; pro- fessor of hygiene, Philippine Medical School.—l believe the mortality incidence in the Philippines to be very intimately associated with the EDITORIAL. 263 intestinal parasites with which the inhabitants of these Islands are afflicted ; we think we have statistics from Bilibid Prison that are fairly “conclusive on this point. Several years ago the death rate was something over 200 per thousand. Ordinary sanitary methods were instituted— more air space was provided, drains were put in and other needful things done. These measures reduced the mortality to 60 per thousand, but this rate was still far in excess of what an institution of that character should have. We spent some six months examining into the various causes which might influence it. It finally occurred to us that intestinal parasites had some connection with the result, and I think the statistics will bear us out in our conclusions as they show that in each brigade of the 200 examined the mortality came down in a marked manner after the institution of remedial measures. When the prison was remodeled and the prisoners cured of their parasitic intestinal diseases, the mortality fell to 12 per thousand and has remained at that figure for the last six months. T think this result is one of the greatest triumphs of modern prophylactic medicine that has occurred in these Islands, and I believe that when the facts become known they will induce the laity to look with favor upon a campaign in these Islands for the elimination of intestinal parasites. Dr. Philip B. Garrison, assistant surgeon, United States Navy; medical zoologist, Biological Laboratory, Bureau of Science; associate professor of medical zoology in the Philippine Medical School—We have reports of several hundred Ascaris removed from one individual. I think Dr. Musgrave recently recovered about 150 from a Filipino child at one treatment. In our examinations a positive diagnosis of Amaba was made only when the moving organism was found in the stool. A systematic clinical study of infected cases was not included in the purpose of my investigations and I am not prepared to offer any new information regarding the symptoms or pathology found in these infec- _tions. In considering the importance of intestinal worms as factors in either the death or sick rate of a community, the fact must be recognized that they play their most important role by predisposing to other diseases. Intestinal worms are’rarely mentioned in mortality statistics, and it is exceedingly difficult to measure the relative participation in the death of the patient of the infection with intestinal worms which lowers the resistance of the host and the terminal infection which the mortality table recognizes as the immediate cause of death. The remarkable fall in the death rate at Bilibid following the institution of a systematic treatment for intestinal worms, of which Dr. Heiser has already spoken, is a striking contribution to our information on this very point, and if future records at the prison and the institution of similar measures in other communities should confirm the results which appear to have been accomplished there, even in a much less striking degree than the figures 264 EDITORIAL. * Dr. Heiser has quoted would indicate, we shall be forced to the conclusion that intestinal worms, as predisposing factors to disease, are of greater importance from the viewpoint of the public health than the bacillary infections, such as tuberculosis, pneumonia, dysentery, etc., to which the weakened subject eventually succumbs. With regard to the inquiry of the Secretary of War, of which Mr. Worcester has spoken, as to the need in the Philippines of a special, organized campaign against intestinal worms similar to that of the Anw- mia Commission in Porto Rico, it would appear that in these Islands we have to deal with a condition different in several respects from that which confronted the health authorities in Porto Rico, the chief differ- ence being the comparative rarity of severe manifestations of uncinariasis ; and another, the greater population here. The results of the examina- tions at Bilibid indicate that not less than 5,000,000 of Filipinos are infested with intestinal worms and that these infections have a fairly even geographical distribution. To attempt to establish a helmintho- logical clinic for these 5,000,000 of people would appear absolutely impracticable, even though we had ten times the means at hand that we now have, and took ten years for the campaign. Furthermore, such an effort would prove entirely unayailing without a practical revolution in certain sanitary conditions which prevail, as reinfection would constantly oceur. The one measure urgently demanded in the Philippines, in the light of our present knowledge of intestinal worms here, would appear to be the establishment of a system for the proper disposal of human excreta, thereby removing the almost exclusive channel by which these infections are spread. Until this is done, other measures would seem quite futile. We need only mention that in disposing of human excreta we eliminate one of the most dangerous channels for the dissemination of certain other prevailing diseases in addition to infections with intestinal worms. The methods to be employed and the question as to whether the work could be done better by a special commission or through existing organi- zations of the Government are subjects requiring special investigations. REVIEW. Hygiene and Public Health. By Louis C. Parkes, M. D., D. P. H., and Henry R. Kenwood, M. B., D. P. H. Third edition, with illustrations. Cloth. pp., xii+620. Price, $3 net. Philadelphia: P. Blackiston’s Son & Co., 1907. The third edition of this work shows evidence of haying been thor- oughly revised and considerable new matter has been introduced, so that it easily maintains the reputation of being one of the most practical treatises upon hygiene that is published in the English language. Much of the useless theoretical matter found in works of this kind has been omitted. The authors’ practical experience in dealing with public health matters in this regard is shown to excellent advantage. It would seem that in a new work of this kind the means now so commonly used in the United States of cleaning houses by the vacuum method should have been mentioned. Many of the data published in this work are derived from conditions as they obtain in Great Britain, and more particularly is this true with regard to legislation, so that because of this much of the value of the work is lost to the American student. Wo Gr. Jel. 265 PRIZES OFFERED BY THE INTERNATIONAL CONGRESS ON TUBERCULOSIS, TO BE HELD IN WASHINGTON, D. C., IN SEPTEMBER, 1908. The central committee of the International Congress on Tubereulosis has announced the offer of the following prizes: I. A prize of $1,000 is offered for the best evidence of effective work in the prevention or relief of tuberculosis by any voluntary association since the last International Congress in 1905. In addition to the prize of $1,000, two gold medals and three silver medals will be awarded. he prize and medals will be accompanied by diplomas or certificates of award. Hvidence is to include all forms of printed matter, educational leaflets, etc.; report showing increase of membership, organization, classes reached—such as labor unions, schools, churches, ete.; lectures given; influence in stimulating local boards of health, schools, dispensaries, hospitals for the care of tuberculosis; newspaper clippings of meetings held ; methods of raising money ; method of keeping accounts. Kach competitor must present a brief or report in printed form. No formal announcement of intention to compete is required. Il. A prize of $1,000 is offered for the best exhibit of an existing sanatorium for the treatment of curable cases of tuberculosis among the working classes. In addition to the prize of $1,000, two gold medals and three silver medals will be awarded. The prize and medals will be accompanied by diplomas or certificates of award. The exhibit must show in detail construction, equipment, management, and results obtained. Hach competitor must present a brief or report in printed form. Ill. A prize of $1,000 is offered for the best exhibit of a furnished house, for a family or group of families of the working class, designed in the interest of the crusade against tuberculosis. In addition to the prize of $1,000, two gold medals and three silver medals will be awarded. The prize and medals will be accompanied by diplomas or certificates of award. This prize is designed to stimulate efforts toward securing a maximum of sunlight, ventilation, proper heating, and general sanitary arrangement for an inexpensive home. A model of house and furnishing is required. Hach competitor must present a brief with drawings, specifications, esti- mates, ete., with an explanation of points of special excellence. Entry may be made under competitor’s own name. IV. A prize of $1,000 is offered for the best exhibit of a dispensary or kindred institution for the treatment of the tuberculous poor. In 266 rs PRIZES OFFERED BY TUBERCULOSIS CONGRESS. 267 addition to the prize of $1,000, two gold medals and three silver medals will be awarded. The prize and medals will be accompanied by diplomas or certificates of award. The exhibit must show in detail construction, equipment, management, and results obtained. Hach competitor must present a brief or report in printed form. VY. A prize of $1,000 is offered for the best exhibit of a hospital for the treatment of advanced pulmonary tuberculosis. In addition to the prize of $1,000, two gold medals and three silver medals will be awarded. The prize and medals will be accompanied by diplomas or certificates of award. The exhibit must show in detail construction, equipment, management, and results obtained. Hach competitor must present a brief or report in printed form. VI. The Hodgkins fund prize of $1,500 is offered by the Smithsonian Institution for the best treatise that may be submitted on “The Relation of Atmospheric Air to Tuberculosis.” The detailed definition of this prize may be obtained from the secretary- general of the International Congress or Secretary of Smithsonian In- stitution, Chas. D. Walcott. VII. Prizes for educational leaflets. A prize of $100 is offered for the best educational leaflet submitted in each of the seven classes defined below. In addition to the prize of $100, a gold medal and two silver medals will be awarded in each class. Hach prize and medal will be accompanied by a diploma or certificate of award. Competitors must be entered under assumed names. A. For adults generally (not to exceed 1,000 words). B. For teachers (not to exceed 2,000 words). C. For mothers (not to exceed 1,000 words). D. For indoor workers (not to exceed 1,000 words). EH. For dairy farmers (not to exceed 1,000 words). F. For school children in grammer school grades (not to exceed 500 words). In classes A, B, C, D, E, and F, brevity of statement without sacrifice of clearness will be of weight in awarding. All leaflets entered must be printed in the form they are designed to take. G. Pictorial booklet for school children in primary grades and-for the nursery. Class G is designed to produce an artistic picture-book for children, extolling the value of fresh air, sunlight, cleanliness, etc., and showing contrasting conditions. “Slovenly Peter” has been suggested as a pos- sible type. Entry may be made in the form of original designs without printing. VIII. A gold medal and two silver medals are offered for the best exhibits sent in by any States of the United States, illustrating effective 268 PRIZES OFFERED BY TUBERCULOSIS CONGRESS. organization for the restriction of tuberculosis. Hach medal will be accompanied by a diploma or certificate of award. IX. A gold medal and two silver medals are offered for the best ex- hibits sent in by any State or country (the United States excluded), illustrating effective organization for the restriction of tuberculosis. Each medal will be accompanied by a diploma or certificate of award. X. A gold medal and two silver medals are offered for each of the following exhibits; each medal will be accompanied by a diploma or certificate of award; wherever possible each competitor is required to file a brief or printed report: A. For the best contribution to the pathological exhibit. B. For the best exhibit of laws and ordinances in force June 1, 1908, for the prevention of tuberculosis by any State of the United States. Brief required. C. For the best exhibit of laws and ordinances in force June 1, 1908, for the prevention of tuberculosis hy any State or country (the United States excluded). Brief required. D. For the best exhibit of laws and ordinances in force June 1, 1908, for the prevention of tuberculosis by any municipality in the world. Brief required. i. For the society engaged in the crusade against tuberculosis having the largest membership in relation to population. Brief required. F. For the plans which have been proven best for raising money for the crusade against tuberculosis. Brief required. G. For the best exhibit of a passenger railway car in the interest of the crusade against tuberculosis. Brief required. H. For the best plans for employment for arrested cases of tuberculosis. Brief required. : XI. Prizes of two gold medals and three silver medals will be awarded for the best exhibit of a workshop or factory im the interest of the crusade against tuberculosis. ‘These medals will be accompanied by diplomas or certificates of award. The exhibit must show in detail construction, equipment, management, and results obtained. Each competitor must present a brief or report in printed form. The following constitute the committee on prizes: Dr. Charles J. Hat- field, Philadelphia (chairman); Dr. Thomas G. Ashton, Philadelphia (secretary) ; Dr. Edward R. Baldwin, Saranac Lake; Dr. Sherman G. Bonney, Denver; Dr. John L. Dawson, Charleston, 8S. C.; Dr. H. B. Favyill, Chicago; Dr. John B. Hawes, 2d, Boston; Dr. H. D. Holton, Brattleboro ; Dr. E. C. Levy, Richmond, Wa.; Dr. Charles L. Minor, Asheville, N. C.; Dr. Estes Nichols, Augusta, Me.; Dr. M. J. Rosenau, Washington; Dr. J. Madison Taylor, Philadelphia; Dr. Wiliam 8. Thayer, Baltimore; Dr. Louis M. Warfield, St. Louis. PREVIOUS PUBLICATIONS OF THE BUREAU OF GOVERNMENT LABORATORIES—Continued, (Concluded from second page of cover.) No. 32, 1905.—Biological Laboratory: J. Intestinal Hemorrhage as a Fatal Com- plication in Amebie Dysentery and Its Association with Liver Abscess. By Richard P, Strong,’ M.’D. II. The Action of Various Chemical Substances upon Cultures of Amebz. By J. B. Thomas, M. D., Baguio, Benguet. Biological and Serum Laboratories : Ill. The Pathology of Intestinal Amebiasis. By Paul G. Woolley, M. D., and W. E. Musgrave, M. D. % B No. 33, 1905, Biological Laboratory.—Further Observations on Fibrin Thrombosis in the Glomerular and in Other Renal Vessels in Bubonic Plague. By Maximilian Herzog, M. D. 1 No. 34, 1905.—1. Birds from Mindoro and Small Adjacent Islands. II. Notes on Three Rare Luzon Birds. By Richard C, McGregor. No. 35, 1905.—1. New or Noteworthy Philippine Plants, IV. II. Notes on Cuming’s Philippine Plants in the Herbarium of the Bureau of Government Laboratories, IIT. Hackel, ‘“‘Notes on Philippine Grasses.” IV. Ridley, “Scitimines Philippinenses.” V. Clarke, ‘“‘Philippine Acanthacez.”” By Elmer D. Merrill, Botanist. No. 36, 1905.—A Hand-List of the Birds of the Philippine Islands. By Richard C. McGregor and Dean C. Worcester. LIST OF PREVIOUS PUBLICATIONS OF THE MINING BUREAU (NOW DIVISION OF MINES OF THE BUREAU OF SCIENCE). 1890.—Descripeion fisica, geologica y minera en bosquejo de la Isla de Panay por D. Enrique Abella y Casariego, Inspector General de Minas del Archipiélago. 1890.—Memoria descriptiva de los manantiales minero-medicinales de la Isla de Luzon, estudiados por la comisién compuesta de los Senores D. José Centeno, Ingeniero de Minas y Vocal Presidente, D. Anacleto del Rosario y Sales, Vocal Farmacéutico, y D. José de Vera y Gomez, Vocal Médico. : 1893.—Estudio descriptivo de algunos manantiales minerales de Filipinas. ejecutado por la comisién formada por D. Hnrique Abella y Casariego, Inspector General de Minas D. José de Vera y Gomez, Médico, y D. Anacleto del Rosario y Sales, Marmacéutico ; precedido de un prologo escrito por el Excmo. Sr. D. Angel de Avilés, Director General de Administracion Civil. ' 1893.—Terremotos experimentados en la Isla de Luz6n durante los meses de Marzo y Abril de 1892, especialmente desastrosos en Pangasinan, Unidn y Benguet. Estudio ejecu- tado por D. Enrique Abella y Casariego, Inspector General de Minas del Archipiélago. 1901.—The Coal Measures of the Philippines. Charles H. Burritt. 1902.— Abstract of the Mining Laws (in force in the Philippines, 1902). Charles H. Burritt. ; 1902, Bulletin No. 1.—Platinum and Associated Rare Metals in Placer Formations. H, D. McCaskey, B. 8. _ pe Oe aa cuet of the Chief of the Mining Bureau of the Philippine Islands. Charles . Burritt. 1908, Bulletin No. 2.—Complete List of Spanish Mining Claims Recorded in the Mining Bureau. Charles H. Burritt. ; 1908, Bulletin No. 3.—Report on a Geological Reconnoissance of the Iron Region of Angat, Bulacan. H. D. McCaskey, B. §. 1904.—Fifth Annual Report of the Mining Bureau. H. D. McCaskey. 1905.—Sixth Annual Report of the Chief of the Mining Bureau. H. D. McCaskey. . 1905, Bulletin No. 4.—A Preliminary Reconnoissance of the Mancayan-Suyoc Mineral Region, Lepanto, P. I. A. J. Eveland, Geologist. 1905, Bulletin No. 5.—The Coal Deposits of Batan Island. Warren D. Smith, B. S., M*VA 3 Geologist. .7 y DIVISION OF MINES. _~41908.—The Mineral Resources of the Philippine Islands, with a Statement of the Production of Commercial Mineral Products during the year 1907, issued by Warren D: Smith, Chief of the Division of Mines. LIST OF PREVIOUS PUBLICATIONS OF THE ETHNOLOGICAL SURVEY (NOW DIVI- SION OF ETHNOLOGY, BUREAU OF SCIENCE). Vol. I.—Theé Bontoe Igorot, by Albert Ernest Jenks. Paper, ®2; half morocco, ®3. £Vol. II, Part 1—WNegritos of Zambales, by William Allen Reed. Paper, P0.50; half morocco, P1.50. Vol.II, Part 2 and Part 8.—The Nabaloi Dialect, by Otto Scheerer. The Bataks of Palawan, by Edward Y. Miller. - (Bound also in one yolume with Part 1, Negritos of Zambales.) Paper, $0.50; half morocco, 71.50. Combined, half morocco, #3. i Vol. I117.—Relaciones Agustinianas de las razas del Norte de Luz6n, by Pérez. Paper, 0.75; half morocco, #2. Vol. IV, Part 1,—Studies in Moro History, Law, and Religion, by Najeeb M, Saleeby. Paper, $0.50; half morocco, P1.50. ; DIVISION OF ETHNOLOGY. Vol. IV, Part 2.—The History of Sulu, by Najeeb M. Saleeby. Paper, $1.50. Vol, V, Part 1 and Part 2—The Batam Dialect as a Member of the Philippine Group of Malayan Languages, by Otto Scheerer. The F and V in the Philippine Languages, by CG. H. Conant. Paper, P1.60. Directions for Ethnographic Observations and Collections, 1908. For free distribution. All the above publications which are for sale may be obtained from the Director of Printing, Manila, P. I. All publications for free distribution may be obtained from the Librarian, Bureau of Science, Manila, P. I. Correspondents will confer a favor by returning to the Library of the Bureau of Science any bulletins which they may have in duplicate, as there is a considerable demand for bulletins out of print. 1 Qut of print. GARRISON, PHILIP E. The Prevalence and Distribu- tion of the Animal Parasites of Man in the Philippine Islands, with a Consideration of their Possible Influ- ence upon the Public Health_______1____-__-__-_---_-. I9r GILMAN, PHILIP K. A Report on the First One. Beis Hundred Autopsies at the Philippine Medical School. 211 PHALEN, J. N., and NICHOLS, HENRY J. Notes on the Condition of the Liver in Schistosomiasis_______ 223 STRONG, RICHARD P. The Diagnosis of African Tick ~ Fever from the Examination of the Blood__-___-_____ 231 CALDERON,FERNANDO. Obstetricsinthe Philippine 1 SH EE) os KG IMU AC OnE RUCHED RCA Ue 3 245 PES EDO RTA By 22 00 00 1A Wa FPN SO a TP) SD 11 DAY ASI EIN oh ap AL Rt cM aL Eel a NIE La 265 The ‘‘Philippine Journal of Science” is issued as follows: Section A. General Science, $2, United States currency, per year. ' Section B. Medical Sciences, $3, United States currency, per year. Section C. Botany, $2, United States currency, per year. The entire “Journal” $5, United States currenoy, per year. Single numbers, 50 cents, United States currency. Authors receive 100 copies of their papers free. The numbers in each section will appear as rapidly as material is available. Each sec- tion will be separately paged and indexed, Ae Oe may be sent to the DIRECTOR OF PRINTING, Manila, P. I. FOREIGN AGENTS. THE MACMILLAN COMPANY, 64-66 Fifth Avenue, New York. Messrs. WM. WESLEY & SON, 28 Essex Street, Strand, London, W. ¢. MARTINUS NIJHOFF, Nobelstraat 18, ’s Gravenhage, Holland. Messrs. MAYER & MULLER, Prinz Louis Ferdinandstrasse 2, Berlin, N. W. Messrs. KELLY & WALSH, LIMITED, 32 Raffles Place, Singapore, §. 8. Messrs. A. M. & J. FERGUSON ,19 Baillie Street, Colombo, Ceylon. (Entered at the post-office at Manila, P. I., as second-class matter.) A limited number of complete copies of Volume I and Sup- plement to Volume I and Volume II, all sections, are still available for sale. Price of the complete volumes, unbound, $5, United States currency; of the Botanical Supplements to Volume I, unbound, $2.50, United States currency. Volume I was not divided into sections. =’ : PAUL 6 FREE, i D., Pu. D. ; 2) COEDITOR | RICHARD P. STRONG, Pu. B., M. D. et i “WITH THE COLLABORATION OF VICTOR G. HEISER, M. D.; W. E. MUSGRAVE, M. D. JOHN R. McDILL, M. D.; FERNANDO CALDERON, M. D. JOSE ALBERT, M. D.; PHILIP K. GILMAN, A. B., M. D. PHILIP E. GARRISON, B. A., M. D. THE BUREAU OF SCIENCE OF THE a4] GOVERNMENT OF THE PHILIPPINE ISLANDS __ _ B. MEDICAL SCIENCES | MANILA I aa BUREAU OF PRINTING nal Museutis 7 1908 : 3 PREVIOUS PUBLICATIONS OF THE BUREAU Wg GOVERNMENT LABORATORIES, 1No. 1, 1902, Biological Laboratory.—Preliminary Report i the oe ence in the Philippine’ Islands of a Disease Clinically Resembling Glanders. By R. Strong, M. D. No. 2, 1902, Chemical Laboratory.—The Preparation of Denon oAcatal | Peroxide and Its Use as an Intestinal Patan in Cholera and Dysentery. Preliminary Notes. By Paul C. acer M. D., Ph. 1No. 1908, Biological Laboratory.—A Preliminary Report on Trypanosomiasis of Horses ie the Philippine Islands. By W. E. Musgrave, M. D., and Norman ®. Williamson. 1No, 4, 1908, Serum Laboratory.—Preliminary Report on the Study of Rinderpest of Cattle ane Carabaos in the Philippine Islands. By James W. Jobling, M. D. 1No. 5, 1903, Biological Laboratory.—Trypanosoma and Trypanosomiasis, with Special Reference, to Surra in the Philippine Islands. By W. E. Musgayve, M. D., and Moses Ivo 6, 1903.—New and Noteworthy Plants, I. The American Element in the Philip- pine Flora. By Elmer D. Merrill, Botanist. (Issued January 20, 1904.) 7, 1908, Chemical Laboratory. —The Gutta Percha and Rubber of the Philippine Islands, By Penoyer L, Sherman, jr., Ph. 1No. 8, 1903—A Dictionary of the Plant Names of the Philippine Islands. By Elmer D. Merrill, Botanist. 1No. 9, 1908, Biological and Serum Laboratories.—A Report on Hemorrhagic Septi- Soblin pace Animals in the Philippine Islands. By Paul G. Woolley, M. D., and J. W. obling, M. 1No. 10, 11908, Biological Laboratory.—Two Cases of a Peculiar Form of Hand Infection (Due to an Organism Resembling the Koch-Weeks Bacillus). By John R, McDill, M. D., and Wm. B. Wherry, M. D. 1No. 11, 1908, rcieinca Laboratory.—Entomological Division, Bulletin No. 1: Prelimi- nary Bulletin on Insects of the Cacao. (Prepared Especially for the Benefit of Farmers.) By iene S. Banks, Entomologist. 1Wo. 12, 1908, Biological Laboratory.—Report on Some Pulmonary Lesions Brogucen by the Beate of Hemorrhagic Septicemia of Carabaos. By Paul G. Woolley, M. No. 18, 1904, Biological Laboratory.—A Fatal Infection by a Hitherto Undescribed Chromogenic Bacterium: Bacillus Aureus Fetidus. By Maximilian Herzog, M. D. 1 No. 14, 1904.—Serum Laboratory: Texas Fever in the Philippine Islands and the Far East. By J. W. Jobling, M. D., and Paul G. Woolley, M. D. Biological Laboratory: Entomological Division, Bulletin No. 2: The Australian Thick (Boophilus Australis Fuller) in the Philippine Islands. By Charles 8. Banks, Entomologist. Wo. 15, 1904, Biological and Serum Laboratories. —Report on Bacillus Violaceus Ma- nile: A Pathogenic Micro-Organism. By Paul G. Woolley, M. 1No. 16, 1904, Biological Laboratory.—Protective Inoculation Against Asiatic Cholera: An Experimental Study. By Richard P. Strong, M. D. , No. 17, 1904.—New or Noteworthy Philippine Plants, if, By Elmer D. Merrill, Botanist. 1No. 18, 1904, Biological Laboratory.—I. Amebas: Their Cultivation and Etiologic Significance. By W. E. Musgrave, M. D., and Moses T. Clegg. Il. The Treatment of Intestinal Amebiasis (Amebic Dysentery) in the Tropics. By W. BE. Musgrave, M. D. No. 19, nue rola gic Laboratory.—Some Observations on the Biology of the Cholera Spirillum. y W. Wherry, M. D. No. 20, 104, Merion vical Painonaery: ‘I. Does Latent or Dormant Plague Hxist Where the Disease is Endemic? By Maximilian Herzog, M. D., and Charles B. Hare. Serum Laboratory: II. Broncho-Pneumonia of Cattle: Its Association with B. Bovisepticus. By Paul G. Woolley, M. D., and Walter Sorrell, D. V. S. III. Pinto (Patio Blanco). By Paul G. Woolley, M. D. Chemical Laboratory: ane Notes on Analysis of the Water from the Manila Water Supply. By Charles L. Bliss, S$. Serum Laboratory: V. Frambesia : Its Occurrence in Natives in the Philippine Tene By Paul G. Woolley, M. D. Wo. 21, 1904, Biological Laboratory.—Some Questions Relating He ‘the Virulence of aero eae with Particular Reference to Their Immunizing Powers. By Richard rong, M. No. 22, 1904, Bureau of Government Laboratories.—1I. A Description of the New Build- ings of the Bureau of Government Laboratories. By Paul C. Freer, M. D., Ph. D. If. A. CAtBIGE UG) of the Library of the Bureau of EERSTE Laboratories. By Mary Polk, ibrarian. iWNo. 28, 1904, Biological Laboratory.—Plague: Bacteriology, Morbid Anatomy, and Histopathology (Including a Consideration of Insects as Plague Carriers). By Maximilian erzog, M. No, 24, 1904, Biological Laboratory.—Glanders: Its Diagnosis and Prevention (Together witha Report on Two Cases of Human Glanders Occurring in Manila and Some Notes on the Bacteriology and Polymorphism of Bacterium Mallei). By William B. Wherry, M. D. No. 25, 1904.2—Birds from the Islands of Romblon, Sibuyan, and Cresta de Gallo. By Richard C. McGregor. No. 26, 1904, Biological Laboratory.—The Clinical and Pathological Significance of Balantidium Coli. By Richard P. Strong, M. D. 1904.—A Review of the Identification of the Species Described in Blanco’s No. 27, Flora de Filipinas. By Elmer D. Merrill, Botanist. No. 28, 1904.—1I. The ply pees: of the Philippine Islands. II. Edible Philippine Fungi. By Edwin B. Copeland, Ph. No. 29, 1904.—I. New or Naeaonthy Philippine Plants, III. II. The Source of Manila Elemi. By Elmer D. Merrill, Botanist. Wo. 30, 1905, Chemical ‘Laboratory: —I. Autocalytic Decomposition of Silver Oxide. II, Hydration in Solution. By Gilbert N. Lewis, Ph. D. No, 31, 1905, Biological Laboratory.—1. Notes on a Case of Hematochyluria (Together with Some Observations on the Morphology of the ee Nematode, Filaria Nocturna). By William B. Wherry, M. D., and John R. McDill, M. Manila, P. I. II. A Search Into the Nitrate and Nitrite Content of Witte’s “Peptone, ” with Special Reference to Its nt ene Hos ae Demonstration of the Indol and Cholera-Red Reactions. By William B. erry, M. D. 1 Out of print. 2The first four bulletins in the ornithological series were published by the Ethnological Survey under the title “Bulletins of the Philippine Museum.” Later ornithological publications of the Government appeared as publications of the Bureau of Government Laboratories. (Concluded on third page of cover.) THE PHILIPPINE JOURNAL OF SCIENCE B. MEDICAL SCIENCES Vou. III SEPTEMBER, 1908 No. 4 HEALTH CONDITIONS IN THE PHILIPPINES.’ By Witr1am 8. WASHBURN.? The health conditions of any locality or country are only relative at best, and not absolute. ‘he opposite state to that of health is disease, the principal causative factors of which are microdrganisms, myriads of which surround us as unseen friends or foes. The maintenance of health appears to be dependent principally on an environment favorable to normal growth and development. It is now realized that the observance of the laws of personal, domestic, and public hygiene is the best protec- tion against the invasion of the agencies of disease. Ignorance of these laws destroyed the health or lives of nearly 100,000 Spanish soldiers in Cuba in three years; and in the civil war, for every man killed by bullets there were two who died, and probably five whose health was permanently destroyed, by camp diseases which are now known to be preventable. Instances of this character were formerly frequent and were not con- fined to military operations in the tropics; it is certain that such ap- palling death rates could have been greatly reduced by the intelligent application of modern sanitary measures. It would appear that the loss of Spain’s tropical possessions is partly attributable to her failure to cope successfully with the lurking enemy, disease. Under American administration, however, as early as 1903, the Sur- geon-General of the United States Army was able to state that the admis- sion rate in Cuba and Porto Rico of 1,300.24 per thousand and a death rate of only 6.72 per thousand indicated that the troops on those islands were as healthy as the Army at home in the United States during the *Read at the Fifth Annual Meeting of the Philippine Islands Medical As- sociation, February 29, 1908. 2 Director of Ciyil Service, Philippine Islands. 73846 269 270 WASHBURN. decade 1888 to 1897, prior to the Spanish-American war, when sickness and mortality were the lowest recorded. It appears from the records that during the last five years of the decade, now nearly completed, of American occupation of the Philippines, the Army in the United States “proper has reached an almost unprecedented state of health, measured by the death rate from all causes for the year 1906 of 5.28 and a rate from disease of 2.84, the lowest recorded, as against the death rate of 6.72 for all causes for the decade prior to the Spanish-American war, when no troops were in the Tropics. A death rate of 5.61 for 1905 was reported in the British army. The discharge, death, and total loss rates were lower in Cuba for the last three months of 1906—during which time American troops were again stationed in Cuba—than in any other country where American troops were serving, including the United States. Since the days of Spanish occupation yellow fever, the scourge of the Spanish army, has become nonexistent in Cuba and Porto Rico. It is my purpose to give a brief review of the advances made by the American Government toward better health conditions in the Philippines, and to indicate, though quite cursorily, the comparative health conditions at the present time, as shown by records and reports. In July, 1901, military government in the Philippines was formally succeeded by civil government. Until the spring of 1905 the health department was under the immediate charge of officers detailed from the Medical Department of the Army, and thereafter has been under the immediate direction of a medical officer of the United States Public Health and Marine-Hospital Service. The health phase of civil government responsibility has there- fore been continuously under the immediate direction of men well trained in matters of public health and sanitation, who have carried on the work so well begun under the military régime and subsequently so faith- fully supported in times of stress by the Medical Corps of the United States Army and the Public Health and Marine-Hospital Service in the fight against disease. When the marines and troops were landed in Cavite and Manila in 1898, these places were described as being filthy im the extreme. Other cities and towns in the Archipelago were subsequently found to be also generally insanitary and unsuitable for occupation. For three years the work of sanitation was carried on under the military government, during which period the troops were for the most part engaged in active opera- tions in the field, necessitating exposure frequently to all manner of disease and rendering difficult the observance of the laws of hygiene. Notwithstanding such adyerse conditions, the chief surgeon of the Phil- ippines Division reached the conclusion in July, 1900, that the relatively small percentage of sick in the army in the Philippines was largely due to the care and attention given by officers and men to sanitation; that increased appreciation on their part of its beneficial result to health and .% ot 7 HEALTH IN THE PHILIPPINES. Dial consequent increased efforts to carry out its rules with thoroughness, would result in a further diminution of the sick report; and that, roughly stated, one-half of the sickness in the Army could haye been prevented if everybody had obeyed the sanitary’ recommendations of the medical officers. In 1902 “The greatest noneffectiveness from disease and injury in the United States was reported in January, February, and March, during which the sick report of troops at home was larger than in the Pacific islands. In March the cholera epidemic began in Manila and the island rates began at once to increase, the greatest number of admissions and the highest monthly mortality being re- ported in July of that year.” * The value of the application of sanitary science and its influence on health conditions is shown by the decrease in the death rate and admis- sions to sick report per thousand among American troops in the Philip- pimes from certain diseases, as follows: 1898. - 1899. 1906. Diseases. i= te a er Death | Admis- | Death | Admis- | Death | Admis- rate. sions. rate. sions. rate. sions. Dy phodeteyersaassas=seas 7,58 | 6852 Ty|ere aN See 0,00 | 3.88 Undetermined fevers______ 0. 00 | 63. 04 0.00 | 8.97 Mallemien Reve. | 0.55 | 304.20 Muperculosisj=="=—s- eens (Peas |e 0.79 | 5.49 Diamnb cea CISGASCS nee | eee | ees | 0.40) 174.55 TM Sain bya 0. 34 20% ence hn ue oe 0.00 | 2.02 iVenerealsdiseaScS = se= sss =e | aaee nes || sceorese=a||sao=s5- aes ae 0.08 | 310.34 The statistics for the year 1907 show a marked further decrease for nearly all diseases in admission, death, and noneffective rates in the Philippines and in the number of sick invalided home from the Philip- pines for that year. The mortality rate for the year 1906 of American troops in the Phil- ippines was much lower than that of the native troops for every disease except tuberculosis, which caused 17.5 per cent of all American deaths from disease,* as against 6.66 per cent of all deaths from disease among the native troops, but the discharge rate for tuberculosis was only 27.10 per cent of the total discharges because of disease among the American troops as against 51.06 per cent for this infection among native troops, thus probably making the actual death rate from this disease, if those who died after discharge are included, greater among the native troops than among the American. One-seyenth of the deaths in Manila are due * Report of the Surgeon-General, United States Army, for year ended June 30, 1903. ‘The statistics for 1906 on death and discharge rates of American troops serving in the Philippines include the number of those who were invalided to the United States, died, or were discharged. Pile WASHBURN. to tuberculosis. The relative death rate because of tuberculosis in the Army serving in the United States was 0.78, as against 0.79 for American troops in the Philippines. The mortality rates of native troops in the Philippines were 2.58 per thousand from injuries and 8.93 from disease, 4.55 of which was due to beri-beri, Asiatic cholera, and malarial fever, all preventable, and 4.37 to other diseases. For the year 1907 the mortality rate from all causes (diseases and injuries) of American troops in the Philippines was 5.92. The death rate among the native troops from disease was 5.06, while the rate among American troops from disease was only 3.61. The deaths among American troops in the Philippines from injuries were 39 per cent of their total mortality (fourteen men having been drowned, the same number as in the preceding year), the fatalities from disease being only 61 per cent of the total mortality. In 1906 over 50 per cent of the deaths among troops serving in the Philippines were due to injuries. Deaths from disease on account of service in the Philippines therefore appear to be approaching the low mortality rate from disease for the army in the United States. For 1906 the admission to sick report rate for the army in the United States was 1,179.93 per thousand; in the Dutch army for 1903 the admission rate was 1,321 per thousand. ‘The admission rate in the Philippines for the calendar year 1907 was 1,401. The average duration of each case in the Philippines was twelve days. The following is an interesting comparative exhibit on the causes e ill health of American troops serving in the United States and in the Philippines: For 1906 in the Philippines the noneffective relative rates were, respectively, for venereal diseases 22.04, malarial fevers 6.39, diarrheeal diseases 5.49, and dengue 1.69—the noneffectiveness on account of venereal disease being nearly double the total of the other three named and more than double that of the army in the United States from this cause. “Of the 1,364 men discharged for disability in the United States, over 64 per cent were for disabilities not incurred in the line of duty, and of these, 51 per cent were contracted before enlistment. The principal causes of discharge, with the number for each cause, were: tuberculosis 149; venereal diseases 165; defective vision 141; defective hearing 90; and organic disease of the heart 71.’° Of 181 discharges of American troops serving in the Philippines in the year 1906, 38 were for causes existing previous to service in the Philippines, 22 or 15.4 per cent for causes not originating in the line of duty, 33 on account of injuries received in the line of duty, and 3 not im the line of duty, and the remaining, only 85, or 47 per cent of the total number discharged, from diseases incurred because of service in the Philippines and in the line of duty. * Report of the Surgeon-General, United States Army, for year ended June 30, 1907. ’ HEALTH IN THE PHILIPPINES. 273 The chief surgeon of the Philippines Division, in his report covering 1907, states that “The number of days lost not imcident to the service was 85,062 for the American troops,’ as against 156,267 days lost incident to the service, and in further comment says: “The very large proportion of total nonefliciency from sickness due to causes not incident to the service is the occasion of great solicitude to the authorities of the division, and active efforts are being made to reduce it. Could such be eliminated the health of the troops in the Archipelago would compare favorably with that of the army in the United States. Of these causes venereal diseases are by far the most important. aa Eliminate malarial diseases and our admission rate per thousand per annum would be 1,192. Eliminate venereal diseases and the rate would be 1,178. Eliminate them both and the rate would be 969, or for sickness alone 764 per thousand, a rate unequaled in our territory except in Alaska. I should be glad to see this reached and have no doubt it can be if the suggested means are zealously employed.” EKyen by the strictest isolation of infected soldiers it will be difficult for the military authorities to reduce venereal disease so long as infected women near military posts are not also isolated. ‘The responsibility for their isolation rests with the civil and not the military authorities. Referring to malarial fever the Surgeon-General in his report issued in 1906 states: “This increase in a disease which is entirely preventable, and which last year caused seven deaths and an immense amount of noneffectiveness, should cause serious consideration as to the sufficiency of the preventive measures heretofore taken.” ‘The natives suffered more severely than the Americans from malarial fevers, but appeared to be less affected by diarrhoeal diseases. Tt was formerly thought that “natives of the Philippines eat and drink with comparative impunity articles of food and foul water, the use of which by white men is disastrous.” They certainly have no such immunity to cholera, and the reports on autopsies and investigations made here by Gilman, of the Philippine Medical School and Bureau of Science, and by medical officers of the Army indicate that the natives do not possess the heretofore supposed immunity against intestinal parasitic diseases. During the calendar year 1906 there were only forty-eight admissions and no deaths from typhoid fever among American soldiers in the Phil- ippines. There was one death from this disease among the native troops. The death rate per thousand from this disease in the army in the United States was 0.28. Comment is made upon an outbreak of beri-beri among the Filipinos at the Louisiana Purchase Exposition, the only epidemic of this disease which has been reported in the United States. There were 59 cases, with four deaths, among the Filipinos. No other people were affected. The points of interest were the entire escape of 450 Filipino Scouts, who were living in a model camp under the best sanitary conditions, and 274 WASHBURN. of 38 other Filipinos whose sanitary surroundings were good, while all - of the cases occurred among the remaining 788 natives, who were for some time crowded into one small building under conditions of filth, bad ventilation, and extreme overcrowding. ‘There were in this building twelve bunks for as many people in each room 10 by 12 feet. After the overcrowding and other insanitary conditions were removed, the disease ceased. Food as a factor could be excluded, because all the Filipinos— those who escaped entirely, like the Scouts, and those severely affected— had practically the same diet and a liberal one. A good quality of Louisiana rice was used by all. As to the influence of race, the comparative records, all facts con- sidered, do not seem to warrant the conclusion that colored and native troops are more resistant than white soldiers to the effects of tropical service. The death rates from all causes and from disease alone are highest among the Filipinos. While other rates are lower for the natives, it is to be borne in mind that American soldiers excused from any portion of their military duty, no matter how trivial the cause, are placed on sick report, which is not the case with native troops. “During the cholera epidemic in 1902 the admission and death rates for native troops greatly exceeded those of white soldiers, although the American negroes were the greatest sufferers of all.” According to statistics the physique of the average colored soldier when enlisted is superior to that of the average white soldier. ; The diseases more prevalent in the Philippines among the American troops in 1906, with the admission rate per thousand for each, are shown in the following comparative table: American troops. Disease. = eae Total. White. | Colored. - Venereal/discases 22S) 2 == SS eee ee 310.34 309.17 322, 27 63.25 | Diarrhcea, including enteritis 130.69 | 1380.63 131. 96 95. 40 (D0 8 UC ee ee | 88.77 85, 52 149. 44 15.55 Dysentery: 2.22252 4 oe ee ee eee 43. 86 41, 61 85. 86 20. 38 DYSpepSial; (2-35 ess 5 UE re Sat eae ee 35. 46 33.79 66.77 27.53 Alcoholism 30, 37 31.57 7.95 63 Articular rheumatism, acute and chronic —___--------____ 11.39 11.15 15. 90 5. 46 Diseasesiof the Nver-222= =a oe ee eed 6.54 6.73 3.18 1.89 Appendicitis 22-2 eee ee ee SE a eae eae 5. 41 5, 36 6.36 1.26 Measlesso2o2 2222 eet = ity 0. ee See eee ios Os D201] oe a ee - 63 Typhoid Wey eres Brit. Med. Journ. (1902), 2, 844. 13846——2 bo ee) oO 286 ROGERS. In a second paper, in 1903,* I gaye an account of ameebic dysentery in India, illustrated by a colored plate, and discussed the mode of formation of amoebic abscess of the liver, and in 1905,° I dealt with the value of leucocytosis in the early diagnosis of amcebic abscess, and pointed out that, although occasionally an attack of acute hepatitis with leucocytosis may clear up without suppuration occurring, yet if such cases are followed up, sooner or later an abscess of the liver nearly always forms. I also narrated a case of acute hepatitis with leucocytosis, which cleared wp under large doses of ipecacuanha. In 1906°® I pub- lished an article on two cases of amcebic abscess of the liver successfully treated by aspiration and injection of the soluble acid quinine hydro- chloride, without drainage, having found that the amcebee in thick liver abscess pus could readily be killed by that drug in a strength of from 1 in 100 to 1 in 500, a method which has since proved effective in other hands, especially in early, deep-seated abscesses although it fails in many more advanced cases. While on the lookout for the early stages of the disease for this line of treatment, I met with a number of cases of feyer with leucocytosis and symptoms of acute hepatitis, in some of which aspiration failed to reveal any abscess; they yielded, however, very rapidly to full doses of ipeca- cuanha, thus showing that the increase of the leucocytes takes place before actual suppuration has set in and sometimes many days earlier. Last year (1907)* I published a series of such cases which were rapidly cut short in the presuppurative stage by the ipecacuanha treatment, which may be briefly summarized as follows: Fifteen cases were met with during twelve months in the Calcutta European General Hospital. In only three was there a clear history of dysentery or symptoms of it while’ in hospital, while these lost their fever and hepatitis after two to four days treatment with ipecacuanha, although they had previously suffered from fever for fifteen, thirty-four, and forty-one days respectively, and one had been aspirated for liver abscess with a negative result. In three more cases of acute hepatitis, without dysentery, not treated by ipecacuanha, the fever only subsided after from thirty-four to forty-nine days. In five similar cases treated with ipecacuanha the fever subsided in from one to six days, although it had previously persisted for from thirteen to fifty days, one patient having been aspirated with a negative result. Lastly, there were three cases of fever with no signs of either dysentery or hepatitis, other than very slight painless enlargement of the liver, but with leucocytosis of the same type as in the other cases, namely without very marked increase of the proportion of the polynuclears (usually from 70 to 80 per cent.) They had suffered from fever for thirty-five, forty-five, and fifty-three days, respectively, which ceased in from two to fifteen * Brit. Med. Journ. (1903), 1, 1315. 5Tbid. (1905), 2, 1291. , ° Ibid. (1906), 1, 1397. “ Practitioner (1907), 78, 766; Fevers in the Tropics (Oxford Medical Publications) (1908). PREVENTION OF ABSCESS OF THE LIVER. 287 days under ipecacuanha. This is the class of case in which a large, deep-scated, fibrous walled amoebic abscess of the liver forms very insidiously with irregular intermittent fever; it is commonly treated as malarial, and there are no obvious signs of hepatitis until a very late stage. Two of the above fifteen cases relapsed and returned to the hospital four and seven months later, respectively, with an amvebie abscess of the liver. When dysentery is present and complicated by hepatitis, ipecacuanha is advised by Sir Patrick Manson and other authorities, but at the time the above paper was published I was unable to find any recent writer who recommended large doses of ipecacuanha for hepatitis when ac- companied by dysentery, although several of the older authors in India, especially MeClean and Norman Cheyers, also strongly urged its use for this purpose. The considerations which led me regularly to adopt this treatment were the finding of dysentery associated with 90 per cent of tropical liver abscesses, and the fact mentioned above, that in many patients dying of liver abscess, without history or symptoms of dysentery, amcebic ulcers are found post-mortem in the upper part of the large bowel. I therefore regarded hepatitis, accompanied by leuco- eytosis, as an indication of the presence of latent amcebic ulceration of the large bowel, which indicated large doses of ipecacuanha for its cure. The results of this treatment, both of those cases mentioned above and of subsequent ones, have been so successful that during the last two years no instance of liver abscess has developed while the patient was in the Huropean General Hospital, Calcutta, although a few patients have been admitted with an abscess already formed. A number of cases of such acute hepatitis in which an abscess was suspected (and in five instances sought for in vain by the aspirating needle) have cleared up entirely under the ipecacuanha treatment. The following three exam- ples, which have occurred during the last two months, will serve to illustrate the value of this method of treatment. CAsE 1. Very acute hepatitis following on dysentery, rapidly cured by ipeca- cuanha.—A European male, aged 25, was admitted for dysentery of six weeks’ duration, passing, without pain or straining, about six stools daily containing blood and mucus. He was treated with a castor oil mixture and with creolin enemas and the blood and mucus disappeared from the stools after ten days. Seven days later (September 11) he began to suffer pain in the hepatic region and in the right shoulder and his temperature, which had previously been slightly subnormal, began to rise. (See chart 1.) The liver dullness was not increased, extending from the sixth rib to the costal margin. The pains con- tinued to be severe, and on the 13th the breath sounds were noted to be weak at the base of the right lung. Morphine was given for the pain, and quinine, 10 grains, three times a day for the fever. On the 15th there was profuse sweating, while the liver dullness reached up to the fifth rib. Five leeches over the liver relieved the pain somewhat. On the 16th, the right chest was observed to be moving less than the left, and on the 18th, X rays showed that the diaphragm on the right side was quite motionless, while there appeared to be a slight shadow in the right lobe of the liver. 288 ROGERS. Abscess of the liver was diagnosed. However, as there had heen recent dysentery, which had not been treated by full doses of ipecacuanha, the physician in charge of the patient (who had over twenty years’ experience with Indian diseases) agreed to use the ipecacuanha treat- ment for a short time before operating on the liver abscess, the existence of which he did not doubt. Thirty grains of the diug were given daily from the 19th to the 27th, with the result that the temperature steadily fell as shown in chart 1, and the signs of acute hepatitis simultaneously completely subsided. On the 20th, the pain over the liver and the sweating had both diminished, and the patient slept better. By the 21st, the pain had ceased over the liver, although it continued in a slight degree in the right shoulder for another day. On the 23d, the temperature was normal and there was no pain or sweating, and all suspicion of liver abscess had disappeared. The patient was kept in the hospital up to the 22d of November, but had no more signs of dysentery or hepatitis and gained weight steadily. There was no shadow of doubt in the minds of all who watched this patient that the ipecacuanha treat- ment ayerted suppuration in the liver. Casp 2. Disentery followed by hepatitis with temporary recovery; very acute hepatitis successfully treated two and one-half months later with ipecacuanha.— European male, aged 26, admitted August 20, 1907, with a history of dysentery eight months before, followed after three weeks by pain in the epigastrium. On admission there was slight enlargement of the liver with pain over it. Stools loose, but no blood or mucus; intermittent fever rising to 101° or 102° F. in the evenings. The diaphragm moved well, and there was only a slight increase of the leucocytes, with but 65 per cent of polynuclears. The symptoms of hepatitis subsided in three weeks under salines and quinine, and the patient left the hospital apparently well. He returned two and a half months later (November 26) having had fever every evening for the previous month and a half, with rigors at times and intermittent, sharp pain over the liver. His bowels had been constipated. He was now weak and thin. There was slight bulging in the hepatic region, without marked tenderness. The breath sounds at the right base were diminished, with a decrease of yocal fremitus and vocal resonance. The liver dullness extended from the fifth space to 3 inches below the costal margin in the nipple line. No edema was present. The spleen was not enlarged. Under X rays the right half of the diaphragm was observed to be 2 inches higher than the left and scarcely moved, even with deep respiration, but there was no shadow. A blood count showed red corpuscles 3,570,000, white 15,000, ratio of white to red, 1 to 236; polynuclears 77, lymphocytes 23; large mononuclears 9 and eosinophiles 1 per cent. Because of the acuteness of the symptoms and the fullness in the hepatic region, liver abscess was suspected, but 1t was determined to try the 1pecacuanha treatment before operating, so 30 grains were given on the evening of the 27th, and 40 grains on the following four evenings. On the 28th and 29th the hepatic pain was distinctly less, and the patient could turn oyer on his right side, which he could not do before. On the 30th there was no pain or tenderness over the liver. On the 2nd | PREVENTION OF ABSCESS OF THE LIVER. 289 of December his temperature remained normal for the first time, and a steady convalescence followed, the liver receding until it was only just felt beneath the costal margin. The ipecacuanha was continued in 30-grain doses at increasing intervals up to January 5, 1908, in order to guard against the possibility of a relapse, and the patient left the hospital apparently quite well on January 9. The rapid lessening of the pain, followed by the decline of the fever and decrease in the enlargement of the liver under the ipecacuanha was most striking in this case, and indicated that the treatment prevented suppuration of the liver. Case 3. Hepatitis, history or symptoms of dysentery rapidly subsiding wnder. ipecacuanha treatment.—Kuropean male, aged 51, admitted on December 3, 1907, for fever. He had been ill for two weeks with fever and pain in the right hypochondrium, with nausea and loss of appetite. No rigors, but the patient felt chilly at times, with sweats at night. The bowels were constipated. The liver extended 1 inch below the costal margin, and was very tender. Other organs Qn normal. A blood count on the 11th showed 4,670,000 red corpuscles, 12,875 white, ratio of white to red 1 to 363, polynuclears 81, lymphocytes 12, large mononuclears 6, and eosinophiles ] per cent. Tpecacuanha was commenced on the 7th of December, 30 grains being given each evening. ‘Two days later the temperature began to decline and reached normal on the 11th, after which there was only one rise on the 13th accompanied by a rigor, being possibly malarial in nature. On the 17th the liver had become reduced in size, being only just felt below the ribs, and the patient left the hospital apparently quite well on the 22d of December. (See chart 3.) This is an example of the less acute form of hepatitis, which drifts’ insidiously on into suppuration after weeks of intermittent fever. It is only one step further to the class already mentioned, in which there is no pain or tenderness over the liver, and the leucocytosis alone raises a suspicion as to the true nature of the case, which suspicion is confirmed by the chronic fever rapidly yielding to large doses of ipecacuanha. METHLODS OF GIVING IPECACUANTIA. In giving large doses of ipecacuanha in amoebic dysentery and hepa- titis, precautions must be taken to avoid vomiting, especially if it is pos- sible that an abscess of the liver has already formed. The usual method is to give either tincture of opium or chloral hydrate some twenty minutes before the powdered ipecacuanha, no food or drink being given for several hours before and after the dose, which is best administered once a day in the evening. Recently I have had the drug put up in quantities of 5 grains in keratinized capsules, which are not dissolved until they reach the small intestines, and this has worked very well, no antecedent sedative being required. Dr. R. B. Grubbs, of the United States Army, has recently informed me that the same effect is produced by coating 290 ROGERS. ipecacuanha pills with melted salol, but I have not yet had an opportunity of trying this method. From 30 to 60 grain doses of the drug have been used, but the smaller quantity appears to be sufficient. It should be continued for at least two weeks at increasing intervals, as two of my earlier cases, in which the ipecacuanha was discontinued as soon as the temperature fell, subsequently relapsed some months later, presumably owing to the latent amoebic ulcers not having been completely cured. DURATION OF THE PRESUPPURATIVE STAGE OF AMGBIC HEPATITIS. There remains to be considered a very important question. What is the usual duration of the presuppurative stage of amoebic hepatitis, during which the ipecacuanha treatment will avert the formation of an abscess in the liver? An examination of my records during the last seven years has furnished the following data: Out of fifty-three native patients admitted to the hospital with liver abscess, often bulging through the thoracic or abdominal wall, 51 per cent gave a history of over two months’ illness, and an additional 38 per cent, one of between one and two months; 9 per cent from two weeks to a month, and only 2 per cent under two weeks. Among 26 cases in Huropeans there had been fever or hepatitis for over one month in 50 per cent, from two weeks to a month in 34.6, and of less than two weeks in only 13.4 per cent (4 cases of 9, 11, 7, 13 days respectively). It is clear from these figures that in the vast majority of instances there is ample time for the diagnosis _ by the blood examinations and for the ipecacuanha treatment during the presuppurative stage. Very rarely multiple abscesses may develop within a few days with extreme acuteness, yet I believe it is not too much to say that over 90 per cent of ameebic abscesses of the liver can and should be prevented by the methods described in this communication, and thus one of the greatest scourges of some tropical countries may be conquered. i canaanear ae i PREVENTION OF TROPIC#HIL. JoURN. Scr., Vou. III, No. 4. GERS : Ro 9° 38° 37° 36° 35° + es g ie) LEWISS CLINICAL CHART J COPYRIENT) nr i rT aes ROGERS: PREVENTION OF TROPICAL ABSCESS.] . Prt. Journ. Scr, Vou. TH, No. 4. — Age AS Disease © A v Lot Sees =e aC) eens LAID el 7 Z z z zr a El z 4 ZI re THe | Mre|MTe MIE |MiE|Mpe(Mie| Mie) Lenpersrire [Fkrenbett) FOS Resp. 4 t—f e Z Bowels tre PEPE : ZC ae ahs ae ae a ol oe ae ee aaah ; z nerTaTenT By UE Lanse. 198 Comer lon Tare We Zewisa ELTA /CaE_CWAAT]— FF ST LEWIS CLINICAL. CHART, Hime Oe B,vtge SI Dixease Creer LBEER Result CAR 3412) 1 Cal Cs Helmy MIE Ei ele y ei & Temperature [lantuyraste) 2 oe x 36° 35° : TES > reals A Gaia Gel Urine H i EPYATExTT Fim rad By LE Ena Llano = 7 kawisa CLINICAL CHART] meena) i» A OTe + yom ed Past. steal » A 7 Pe am Oe cs i: we) ALA a. Nd oa Ly ri err ad 0 Span all ie “ek Caewseek adr * ae 9 ra bane Faas ee ee a | ' ’ % ; 4 = ae ,4 e 7 werent —+ rien}. 2, - BOIS <5 hae tes intep 4 , “ee a : ¥ a : } : . pa 28 rE] e iB 7 RS, OLE if Gieh do > ; ae. re : . PR OTE. e ee a ah WTP ER ER Re Aye. . ' ‘ | : b +a a See Hie p< seh i io SF tepk 3 GA — a A en ee FILARIASIS AND ELEPHANTIASIS IN SOUTHERN LUZON.’ By JAMES M. PHALEN and Hmnry J. NicHoLs.* I. IntRopucTORY AND Hisvrorican. Il. ELEepHaAntTrAsis. IJ. Frnartrasts. IV. THE PARASITE. V. Mosqurrors. VI. RELATIONSHIP OF FILARIA TO HLEPHANTIASIS. VII. TreatMENT AND PROPHYLAXIS. VIII. Summary anp ConcLusion. I. INTRODUCTORY AND HISTORICAL. It has been well known for years that filarial disease exists in the Philippine Islands, and the occurrence of its sequele, elephantiasis in its various phases also has been noted occasionally; but at the present time little is known concerning the frequency and distribution of these important maladies. A circular issued in 1901 from the office of the chief surgeon, Philippines Division, makes the first mention of filariasis m the Philippine Islands, as far as we are able to discover. This cireular notes the discovery by Strong of a microfilaria in the blood of a European resident of Iloilo, the parasite being designated the Milaria nocturna. Calvert, in 1902, performed an autopsy upon the body of a Filipino plague victim, and found groups of lymphatic varices in the pelvis and later an adult filaria in sections of the iliac lymphatics. This led him to examine the blood of a number of Filipino prisoners of war, with the result that he found two filarial-infections out of four hundred and twenty-six persons examined. It is interesting to note that these two infections were in natives of the Province of Albay. The species of filarial embryo found was not given, but it had a nocturnal periodicity. Doctors W. B. Wherry and J. R. McDill in May, 1906, reported a 1 James M. Phalen, captain, Medical Corps, United States Army, and Henry J. Nichols, first lieutenant, Medical Corps, United States Army, constituting the United States Army Board for the Study of Tropical Diseases as they oceur in the Philippine Islands. 2 Publications of the Bureau of Government Laboratories, Manila, Biological Laboratory (1905), 31. 293 294 PHALEN AND NICHOLS. case of hemotochyluria in a Japanese girl in whose blood were found microfilarie haying a nocturnal periodicity, and which were considered to be Microfilarie bancroftv. Ashburn and Craig, in 1906, described as a new blood filaria, Pilaria philippinensis, and the same writers in 1907 published an excellent article relating to the development of this par- asite in Culex fatigans, Wied.* Their observations were made upon five cases: one, a Visayan prisoner in Bilibid in Manila, and four, members of a Bicol company of Scouts, stationed at Imus, Cavite Province. Dr. HE. R. Whitmore, United States Army, reported recently before the Philippine Islands Medical Society the case of an American negro soldier from Parang, Mindanao, in whose blood were found microfilariz morphologically identical with the Pilaria philippinensis, but having a nocturnal periodicity. This man came from Charleston, South Carolina, and had been in the Philippines less than six months when the parasite was found by Dr. Hastman, United States Army, at Parang; hence there is a question as to the locality in which this infection occurred. The writers, im conjunction with Dr. H. C. Shattuck, reported before the same society a case of chylocele in a Bilibid prisoner, resident of Manila, whose blood showed the presence of an occasional microfilaria, answering the description of the Pilaria philippinensis and apparently without periodicity. Dr. Shattuck has also given us the history of another Bilibid prisoner, a native of Camalig, Province of Albay, upon whom he operated for a hydrocele with great thickening of the scrotum and whose blood harbored a microfilaria of undetermined type. We haye been told by medical officers of the United States Army of cases of filariasis occurring in various parts of the southern Islands, but no study has been made of them nor has the species in these cases been determined. A number of cases of elephantiasis were observed among the natives of Sorsogon Province and the results of the investigations of these cases furnishes the basis of this paper. These patients were brought into the towns of Donsol, Bulan, and Sorsogon by the local health officers as suspected cases of leprosy during the segregation of lepers in this province. The presence of such a number of these cases suggested that the focus of a large amount of elephantiasis and consequently of filariasis might be found in this section of Luzon; and with this idea in view, a trip was made into this region, Camp Daraga constituting our headquarters. The Provinces of Ambos Camarines, Albay, and Sorsogon occupy the most southern and eastern part of Luzon. ‘They form a narrow strip with a high, central ridge broken by volcanic peaks, such as Bulasan, Mayon and Isarog, from which the land slopes gradually to the Mindoro Sea on one side and the Pacific Ocean on the other. The land is high and well drained except along the coast. Short, rapid streams, with deeply worn courses abound everywhere. The annual rainfall is higher *This Jowrnal (1907), 2, 106. FILARIASIS AND ELEPHANTIASIS. 295 than in almost any other section of the Archipelago, the northeast and southwest monsoons bringing rains to a large part of this section. Vegetation is luxuriant, even for the Tropics. This is the greatest hemp district on the Island, the greater part of the land being given over to the cultivation of the abacé plant. Altogether it is difficult to find anywhere in the Islands a prettier or a more prosperous region than this country of the Bicols. II. PLEPHANTIASIS. This malady is well known among the native population by the name of titibac. Practically the entire laboring class of this section work at some time or other with hemp (abaca), hence it is not surprising that they should attribute the disease to the effect of that plant. There seems to be a diversity of opinion as to the way in which the plant affects the individual. Some believe that elephantiasis is due to the direct action of the sap of the abaci upon the skin, but the more prevalent idea connects the disease with the strain upon the legs incident to hemp stripping and followed by getting the feet wet. Many of the women as well as the men are workers in hemp, but those who have never engaged in work of this kind usually attribute the disease to the strain of working a loom, one of which is found in every home. Another cause of the disease is said to be getting the feet wet during menstruation. The typical history given by the patients, however, is that of a day’s hard work at hemp stripping and wading, while still warm, through some stream on their way home. he following day brings on an attack, which in different towns, is variously called sorip, wbag or culibra; during the attack the leg becomes swollen, red, and painful. There is also fever and loss of appetite. With the subsidence of fever and pain, some swelling of the leg persists. In many instances the history of but one such attack can be elicited, while in many cases, especially in the aged, the enlargement seems to have come on gradually without acute symptoms. One patient was observed during such an attack. This was a woman aged 28, a resident of Daraga, Albay Province, who, ten months before, suffered her primary attack, which left the left lee markedly swollen. There was also some swelling and induration of the lower part of the thigh. When seen she had a temperature of 37°.5 C. (103°.4 F.), and complained of headache; the left lez and thigh were hot and tense to the touch and tender on pressure; large, scattered erysipelatoid patches were situated over the inner side of both leg and ‘Probably because of the distribution of the mosquito carriers of filaria, these infections do not seem to be as numerous along the coast as in the higher lands of the interior. A European merchant of Legaspi explained the fact of there being no elephantiasis in that town by the statement that Legaspi was not in the hemp district. One man, living near the coast, attributed his elephantiasis to pulling bejuco (rattan), which necessitated his wading in the water. 296 PHALEN AND NIGHOLS. thigh. The femoral glands were also swollen and tender. As this patient lived a long distance from the post of Daraga, the further course of the disease could not be observed. Thirty-four well marked cases of elephantoid disease were seen. Of this number, nineteen were males and fifteen females. The ages varied from 12 to 80 years, a large proportion being aboye 50 years of age. The ayerage age at which the disease first made its appearance was somewhat between 30 and 35 years. The parts affected, either alone or in association with other parts, were as follows: Both lower ex- tremities, 13 cases or 36.4 per cent; one lower extremity, 20 cases or 58.8 per cent; one upper extremity, 2 cases or 5.8 per cent; scrotum, 11 cases or nearly 58 per cent of the males; and groin glands, 3 cases or nearly 8 per cent of the total number. The lower extrenities—Nearly eyery case of elephantoid disease observed had some involvement of either one or both of the lower ex- tremities. The degree of enlargement varied from the most moderate grade up to instances where the calf exceeded 25 inches in circumference. (Plate I, fig. 1.) Usually, the foot and leg were involved, but in a few cases only the foot and ankle, and in others the foot, leg, and thigh. The skin was usually tense and glossy over the enlargement of the leg and thigh, while it was rough and warty around the ankle and over the foot. In one case large tuberose swellings were situated entirely over the ankle and foot. (Plate I, fig. 1.) Increased pigmentation was usual, the glandular structures were atrophied, the hair thinned and roughened or absent, the nails rough, thick, and brittle. Sensation was diminished. Deep pressure, long continued, produced pitting, but the under tissues were felt to be hard and indurated. The subcutaneous tissues were seen to be increased in yolume. At the ankle the skin was thrown into folds, deep fissures intervening, permitting a small range of motion to the joint. The knee joint, when the thigh was involved, was less affected and in the cases observed, movement was not interfered with. Despite the hypertrophy of these parts, the vitality appeared to be good, ulceration or abscess was not observed in any of these cases. The cases of enlargement of the upper extremity were of moderate degree, and presented no features of importance. The scrotum.—Somewhat over half of the males affected with ele- phantoid disease had some involvement of the scrotum. Usually, the enlargement was of a moderate degree, the sizé of a coconut or a little larger. The largest seen hung to the level of the patient’s knees, was 30 inches in circumference and weighed approximately 30 pounds. No case of lymph scrotum as described by Manson or Scheube was observed, the lesion bemg invariably an elephantiasis. The skin was rough and coarse and the subjacent tissues enormously thickened. The penis was always retracted to some degree, and in the extreme cases (Plate I, aes FILARIASIS AND ELEPHANTIASIS. 297 fig. 2.) was lost sight of in the folds of the scrotum, the urine reaching the surface along a channel formed by skin. Fluctuation could be distinguished in a large proportion of these eases, but frequently the thickening of the subcutaneous tissues was so extreme that the fluid could not be reached with an ordinary needle. This fluid, when obtained, may be milky or more commonly of a clear, straw color. In our cases the amount obtained was about 350 to 500 cubic centimeters.and was highly albuminous. Filarial embryos were usually found in great numbers in this fluid. Glands of the groin.—Although some enlargement of the glands of the groin was present in nearly every instance, but three cases were observed, answering the classical description of varicose groin glands. The patients were all men, 40 to 50 years old, and in each case other manifestations of filarial disease coéxisted. ‘The glands involved were the superficial inguinal, lying above and parallel to Poupart’s ligament, and the disease was bilateral in all of the cases observed. The swelling was larger than that of the ordmary bubo, and was hard, without fluctuation, and could be felt to be separated into a small number of detachable masses. It was painless and not tender to the touch. The subjacent skin was freely movable over the mass, which, however, was firmly fixed to the deeper tissues. Attempts were made to obtain fluid from these glandular masses with a hypodermic needle, but with the exception of a little blood and serum nothing could be withdrawn. No history of an acute inflammation in these glands could be obtained from any of the patients, except that during the attacks of lymphangitis in the legs, they were tender. Til. FILARIASIS. Examination of the blood of these patients showed the presence of filarial embryos in but three instances. However, it was possible to make examinations extending over the twenty-four hours of the day in only seven of the number. In the other twenty-seven only specimens taken during the daytime could be obtained. Two specimens out of the seven examined, both day and night, had filarial embryos in their blood, while of the twenty-seven whose blood was examined only during the day, one showed the parasite. A number of examinations were made upon the general population. Of a total of eighty persons examined, filarial parasites were found in the blood of eleven; out of thirty-seven prisoners in the provincial jail at Albay, nine showed the presence of filarial embryos in blood specimens taken at 10 o’clock at night. These were all short-term prisoners from different towns in the Province of Albay. Out of 93 members of the Thirty-second Company, Philippine Scouts, recruited from Bicol Proy- inces, blood specimens from whom were sent to us by Dr. Warriner, United States Army, nine, or 9.6 per cent were found to be infected. 298 PHALEN AND NICHOLS. IV. THE PARASITE. The filarial embryos present in the blood of these patients were studied both in fresh preparations and by appropriate staining. The parasites. so far as we could make out, were of one variety; the chief features are as follows: Motility.—In fresh specimens of the infected blood, the parasite was observed to have the usual wriggling, lashing movements, which changed its position, but which could not be called progressive as the movement was accomplished in no orderly manner. It was only by observing that the lashing movements eventually removed the parasite from the field of the microscope that any change of position could be determined. Size—The average length of the microfilaria in the fresh preparation is about 0.300 millimeter and in stained specimens about 0.270 millimeter. The average diameter is 0.007 millimeter. Head.—The head is smooth and hemispherical, surrounded by a notched prepuce having five or six notches. Upon the anterior end of the head is a slightly refractive spot, from which at times is projected forward a short, needle-like process, which is as quickly withdrawn. ; Tail—tThe tail slopes gradually to a very fine point. Body—The body is cylindrical for the greater part of its length, and is marked by the anterior V spot, the central viscus and the posterior V spot. The anterior V spot is a triangular area, highly refractive, occupying one side of the worm, 0.090 millimeter, on an average, from the anterior extremity. The central viscus is situated in the posterior part of the central third of the body. It is granular in appearance, but upon focussing carefully a con- voluted tube can be seen to occupy this granular mass. The length of the central viscus is about 0.040 millimeter. Posterior V spot.—We were unable to do more than to make out the presence of such an organ, and were not able to distinguish any details of the structure. By appropriate staining, a granular, central column is shown occupying the center of the entire length of the worm. ‘This column is broken by occasional unstained areas. ‘The only one which showed at all constantly was situated in front of the anterior V spot, from 0.055 to 0.060 millimeter from the anterior extremity. The stains which gave the best results in the embryo were gentian violet, Bismarck brown and hematoxylin in weak solutions, Borrell’s blue and poly- chrome methylene blue. The latter two, mixed with glycerin, each gave ex- cellent results, not only staining the parasite, but preserving its size and appearance as in fresh specimens. Sheath—The embryo has a sheath which exceeds the length of its occupant by one-third to one-half of the latter, but which appears to be tightly applied to the body laterally. Ordinarily it may be observed as a fine flagellum at either end of the embryo, but at times may be seen as a flattened band. Stained specimens show the size and shape of the sheath very well. No move- ment of the filaria within the sheath has been observed. Periodicity —While it was not possible to obtain day and night specimens of blood from all of the cases, a sufficient number were examined at different hours to show that a nocturnal periodicity was the rule. The following table FILARIASIS AND ELEPHANTIASIS. 299 shows the result of the examination of a daylight and a night specimen from all patients from whom we were able to obtain them at both times: | Pa- Pa- tient |10p.m.|10a.m./|| tient |10p.m.|10a.m. No. No. 1 21 0 6 73 0 2 124 il 7 8 i 3 4 0 8 g) 0 4 22 0 9 3 0 5 7 0 10 23 0 Method.—In taking these specimens, four rather large drops of blood were placed close together on a slide. They were then run together with a needle, forming a thick, square smear. After being allowed to dry thoroughly, the hemoglobin was dissolved by placing the slides face downward in a shallow dish of water with each end resting upon a glass rod. When the hemoglobin was discharged, which took but a few minutes, the slides were quickly run over with a low-power objective while still wet and without staining, the filarial embryo catching the eye immediately as it came into the field. Blood counts —VWifferential leucocyte counts were made upon a number of the subjects of elephantiasis to determine the degree of eosinophilia present. ‘The counts showed an ayerage of little less than five per cent, the highest being 8.5 per cent and the lowest 1 per cent. The other leucocytes were present in the normal proportion. The percentage of eosinophiles in filarial disease is usually given higher than this, but here we are dealing with many old cases from whose blood the filaria had long since disappeared, and it is not to be expected that as high an average of eosinophilia would be found as in more recent infections. V. MOSQUITOES. The following is the list of the mosquitoes reported from the post of Camp Daraga, the identification haying been made by Miss Ludlow of the laboratory of the Surgeon-General, United States Army: Mansonia uniforms Theob., Stegomyia fasciata persistans Banks, Uranotenia ceruleocephala lateralis Ludlow, Culex microannulatus Theob., Culex gelidus Theob., var. cuneatus, Myzorhynchus barbirostris V. d. W., and Myzorhynchus vanus Walk., the latter two belonging to the Anopheline. With the exception of Culex microannulatus none of the mosquitoes of this list, so far as we know, have been identified as filaria carriers, though with the limited knowledge that we have, none of these species can with certainty be acquitted of the charge of spreading the disease. 300 PHALEN AND NICHOLS. VI. RELATIONSHIP OF FILARIA TO ELEPHANTIASIS. Prout, at a recent meeting of the London Society of Tropical Medicine, presented a paper in which the theory of filarial infection as the essential cause of elephantoid disease was brought into question. He gave it as his opinion that a majority, 1f not all the cases of elephantiasis, in the Tropics as in temperate regions, are due to an ordimary streptococcic lymphangitis, aggravated by lack of attention, and he brings forward a formidable array of evidence in support of his position. To be sure, the arguments in support of the relationship between the Microfilaria ban- crofti and elephantoid disease are few in number: namely, that the Filaria bancrofti is a parasite of the lymphatic vessels, and elephantiasis is a disease of the same vessels, and also that the geographical distribution of elephantiasis and filariasis coincide. Our own investigations add their mite of evidence to the generally accepted view that elephantoid disease is directly due to filarial infection. Although our examinations for filariasis have not been yery numerous, nevertheless they indicate a higher percentage of infection for the Bicol provinces than has been shown for any other part of the Islands, with probably the exception of the Davao district in Mindanao, and in no other portion of the Archi- pelago has elephantiasis been encountered in any like degree. Other writers have also observed that the subjects of elephantiasis showed a lesser percentage of filarial infection than the general population. Sir Patrick Manson speaks of finding but one filarial infection among four- teen subjects of elephantiasis, and twenty among seventy-four persons not so affected, all the specimens coming from the same locality. He explains this phenomenon by the view that the production of elephantoid disease results from some injury to the adult filaria, causing her to evacuate her eggs instead of the living embryos into the lymphatic vessels. The eggs, being of much greater diameter than the embryo, can not pass through the lymphatics, but obstruct them instead. Then, either because of the death of the adult worm, or of the clogged condition of the lymphatics, filarial embryos are no longer able to get into the circulation. VII. TREATMENT AND PROPHYLAXIS. The household remedies of a people are always of interest to the physician. The popular remedy for acute attacks of the lymphangitis is the leaf of an indigenous plant which the natives call anonang (Corda blancot Vid.). This is first bruised and mixed with salt and then ap- plied to the affected parts. Azafran (Curcuma longa Linn.), the juice of the root of a local plant, is also commonly used as a local application. Multiple parallel imcisions through the skin are also employed for the relief of the swelling, a penknife being used for the operation. The only treatment of elephantiasis observed by us was that of a FILARIASIS AND ELEPHANTIASIS. 301 cord tied around the leg to prevent the swelling advancing higher. (Plate I, fig. 2.) However, quite as futile as the string have been the numerous parasiticidal drugs that have been used from time to time for the treatment of filariasis: thymol, quinine, boric and benzoic acid, sodium benzoate, and numerous others. Scheube records a cure with picric-nitrate of potassium, and reports another by Flint, who used methylene blue for the purpose. Rest, elevation of the parts, and compression by means of bandages are the means most frequently employed for the treatment of elephan- tiasis of the extremities. Hot baths and local applications of mercurial ointment are also used with benefit. Surgical measures, such as excision of longitudinal strips of skin, and the ligation and compression of the arteries supplying the part have been proposed, but are of no value and are dangerous as well. The combination of rest, elevation and compres- sion together with injections of thiosinamin has been quite successfully employed by Castellani in Colombo, who, in 1907, reported the result of such treatment on a number of cases. His method of treatment ® is to keep the patient in bed for a week, in the meantime bandaging the affected part with flannel or rubber bandages, and using massage twice daily. The thiosinamin solution is then injected into different parts of the affected area, 2 cubic centimeters of the solution every day or every other day. After the injections, the part is again tightly bandaged. A month or more of this treatment usually suffices greatly to reduce the affected parts, and the use of a puttee or elastic stocking will keep the swelling down. This treatment is only palliative and the enlargement will return if all compression is removed. 'The treatment of elephantoid disease of the scrotum is largely surgical and will not be considered here. The prevention of such diseases is of great interest to us. The only way to insure protection against filarial disease in an endemic locality is by the methods of prophylaxis, based upon our knowledge of the life- history of the parasite. The anti-mosquito measures taken to insure protection from malaria will be equally efficient in warding off filarial disease. In addition, the blood of native servants should be examined after 10 o’clock at night for the presence of filarial embryos, and no person harboring the parasite should be employed about the house. Sporadic cases reported from widely separated sections indicate that these precautions would not be out of place anywhere in the Islands. In the military service it would be advisable to have not only the house servants examined, but also all natiyes employed in any capacity about the posts, and to prevent those infected from holding any position that would bring them about the posts at night.. The routine examination of the blood of recruits for the Scout organizations would keep many men so affected out of the service, thereby removing a source of infection to their 'This Journal (1908), 3, 311. 73846——3 302 PHALEN AND NICHOLS. fellows. While filariasis of itself is apparently in no way incompatible with the enjoyment of excellent health, the possibilities of its sequele should not be lost sight of. he discovery and rejection of these men before enlistment would be the most satisfactory method of prevention. VIII. SUMMARY AND CONCLUSION. lt is evident that filariasis is not as rare a disease in the Philippine Islands as has been supposed. From our own observations and the fact that seven out of nine previously reported cases of filariasis among the native population have been natives of the Bicol provinces, we are convinced that in these districts we have the largest endemic focus of filarial disease, with, perhaps, the exception of Davao, that exists in these Islands. It.is our belief that the microfilaria found in the cases here reported are the Microfilaria bancrofti, more commonly known as the Filaria nocturna, and that this is the common filaria of the Islands. It is also our belief that all microfilaria heretofore coming under our observation have been examples of this same species. In conclusion we wish to express our appreciation of the assistance given us by the governor of Albay Proyince, to the various municipal physicians of the Bicol provinces in general, and to Captaim C. C. Collins, Medical Corps, United States Army, medical officer at Camp Daraga, who, by his zeal and energy, assisted us greatly in collecting the material for this investigation. REFERENCES. Srrone, R. P. Report of the Surgeon General, U. S. A. (1901). Cireular on Tropical Diseases, Chief Surgeon’s Office, Manila, P. I. (1901), No. 1. Catvert, W. J. A Preliminary Report on the Blood in Two Cases of Filariasis. Bull. Johns Hopkins Hospital (1902), 13, 23. : EKosinophilia in Filariasis. Bull. Johns Hopkins Hospital, (1902), 13, 133. Wuerry, W. B., and McDirn, J. R. Notes on a Case of Hematochyluria. Bull. Bur. Gov. Lab., Biological Laboratory, Manila, P. I. (1905), 3, 5. Asupurn, P. M., and Craie, C. F. A New Blood Filaria in Man, Filaria Philippinensis. Amer. Journ. Med. Sci. (1906), 132, 435. MANSON, Sir PATRICK. Tropical Medicine. London and New York (1905), 349. ScHEUBE, A. Diseases of Warm Countries. London (1904), 392. CASTELLANI, A. Notes on Palliative Treatment of Elephantiasis. Jowrn. Trop. Med. & Hyg. (1907), 10, 250. Further Observations on the Treatment of Elephantiasis. Journ. Trop. Med. & Hyg. (1907), 10, 297. Prout, M. T. On the Role of Filaria in the Production of Disease. Journ. Trop. Med. & Hyg. (1908), 11, 109. Fig. 1. Fig. Fic. bo 1. ILLUSTRATIONS. PLATE I. ~ Hlephantiasis of right leg and left forearm. ‘Tuberose growths upon dorsum of foot. . Elephantiasis of both legs and scrotum. . Elephantiasis of both legs in a boy of 12 years. Pirate II. . Elephantiasis of right leg and scrotum, and varicose groin glands. Filarial embryos were found in the man’s blood and in the fluid obtained by tapping the scrotum. . Elephantiasis of right lee and thigh. . Elephantiasis of left leg. Filarial embryos in blood. Prate IIT. Hlephantiasis of foot and leg, showing warty growth over foot and ankle. . Elephantiasis of left leg. . Elephantiasis of both legs and scrotum. 303 11 S41vVv1d "€ “Old *g Old “Lold ‘F ON ‘III “IOA “IOS ‘Nunor “TIHg] [‘SISVILNVHdaTG GNV SISVINVIIY :STIOHOIN GNVY Na&IVHd hh S1ivdd *§ ‘SI4 "S “9ld ay IE) ‘F ‘ON ‘III “IOA “10S ‘Naoor ‘TIHgq] [‘SISVIENVHdd1Igq ONY SISVIUVIIY : STOHOIN GNV N@IvHd 18 Sid 6 “Old “bh Slg ‘F ‘ON ‘III “OA “IOS “Nunor ‘T1Hg] [‘SISVIENVHda1Ig] GNV SISVINVIIW :STOHOIN GNV NatvyHd NOTES ON THE DISTRIBUTION OF FILARIA NOCTURNA IN THE PHILIPPINE ISLANDS. By James M. PHaten and Henry J. NicHors.* The origin of filariasis in the Philippine Islands, as well as that of most other diseases is, and apparently must remain, a matter of con- jecture. Anthropologists are not agreed as to whether the Philippines in their island-form ever had any original inhabitants or, if so, who they were. However, Foreman states that, at the present time, “the Filipinos are a mixed people, descendants of Papuan, Arabian, Hindoo, Malay, Japanese, Chinese, and European forefathers.” ilaria nocturna is common in China, India, Samoa, the Friendly and Society Islands, but we have no data to decide from which of these places, if any, the parasite was originally introduced. Our data on the present distribution of filariasis relate only to Pilaria nocturna, as this is the only one we ourselves have observed. As we have shown in the preceding paper, southeastern Luzon is a marked focus of filariasis, over 10 per cent of 80 persons from Albay Province being infected. Unpublished reports lead us to believe that the same may be true of Davao, Mindanao, and possibly of the east coast of Samar. Out- side of these regions we haye the results of the examination of 1,178 of the general population, which are as follows: | | | | | Place. exam Nomber | Pergent wisipinos, wroros. | J8P* | chinese. | 3 ined. | | be | = | HecParani ge eanen we Seeks | 267 | 6 2.3 14 | 95 39 19 (Cotabato enna 188 | 3 5 159 iis || aa Se | ts Sd Cudarangan_______-______ 115 6 BuO fees mei Seva) Sete ZL Ne ER Sa Duluan 60 | 0 (0) Bee 60 |_ beeen Overton 113 | 1 8 | 113 | Pach Ear Seema ee oe Cepuesateaee ibe a 203 | 2 se) cs 2p: tr Meta et Pee 1 MMemila eee soins eons pey) ||) al ABS eet DBO) i aces ae! [eee 2 Total examined___| 1,178 |____-_____ (Sara | 933 184 39 22 Total infected ______ ee sie serosa i fem peatise 25 3 1 0 | Total infected (per | | Geni ore swe ee te eta ee 2 | OY (| eee 2.6 1.6 2.5 0 Of 74 women, 3.4 per cent were infected. 1 James M. Phalen, captain, Medical Corps, United States Army, and Henry J. Nichols, first lieutenant, Medical Corps, United States Army, constituting the United States Army Board for the Study of Tropical Diseases as they occur in the Philippine Islands. 305 306 PHALEN AND NICHOLS. SUMMARY OF CASES. Parang.—Of 267 residents of Parang, Bacolod, and the quarters near the dock, 6 cases—3 Filipinos, 2 Moros, 1 Japanese—were found infected. Two of the Filipinos were young muchachos who had been employed in officers’ families in near-by posts for several years. One, 19 years of age, was born in Misamis and the other, 16 years old, in Cotabato; both had traveled about the island a good deal. The third Filipino, found by Captain Rand, M. C., was employed in one of the infantry companies. He was born in Misamis and had also traveled about the island. The two Moros, 19 and 30 years of age, were quartermaster employees ; they were born near Cotabato; all of their life was spent in this section of the country. The Japanese, aged 26 years, had resided in the Philippines for five years, in Luzon for three years and in Parang for two years. CGotabato.—Of 85 men, Highth Company, Macabebe Scouts, who had been in Cotabato valley two years, none were found infected. Of 73 men, Forty-second Company, Philippine Scouts, Visayans, 2 infected cases were found by Lieutenant Love, M. C.; both had enlisted several years ago. Among 30 Moro prisoners, one individual, 31 years of age, who had lived near Cotabato alJl of his life was found infected. Oudarangan.—Of 92 men in the Forty-fifth Company, Philippine Scouts, Vi- sayans, 4 cases, aged 22, 23, 25, and 26 years, were encountered. All of these were recruits from Ivisan, Panay, Initao and Mambogao, Mindanao, and Cebu. Of 23 women, families of members of the same company; 2 infected cases, aged 17 and 32 years were met with. Both of these had come from Davao a few months before. : Duluan—Among 60 of Datto Piang’s Moros, no cases of infection were en- countered. ; Overton.—Of 104 quartermaster employees; one individual 19 years old was found infected. He had been in Tacloban for thirteen years, in Manila for one year, and in Overton for five. 9 applicants for Scout service were not infected. Cebu.—Among 203 prisoners, policemen, and Constabulary, 2 cases were found; 1 a policeman, 26 years of age, a native of Samboan, Cebu, all of whose life had been spent in different parts of the island; the other a woman, aged 26 years, the wife of a man affected with lymph scrotum. Both had lived all their lives near Limao, 6 miles from Cebu. — : Manila.—Among 60 employees of the Germinal Factory, Manila; one case aged 16 years was found. He was porn in Paco and had always lived there; three other members of the family were not infected. Of 169 prisoners from Manila at Bilibid Prison, 10 cases were encountered; all had been in the prison only a few months. ‘Their ages were from 18 to 36; 4 were born and had lived in Manila; 4 had lived in Manila most of their lives; the other 2 had lived for seven and for two years respectively in Manila. ‘Two were born in Pampanga, 2 in Bulacan, 1 in Negros and | in Panay. wo live in Binondo, 3 in Tondo, 2 in Santa Cruz, 1 in Santa Mesa, 1 in Sampaloc and 1 in Intramuros. hese statistics show that a small amount of filariasis is very widely distributed in the Islands. Infections can probably be found almost everywhere, if a thorough and persistent search is made. The most striking feature is the relatively large number of infections in Manila, and the small number among Moros. Datto Piang’s men at Duluan are the type of the real natives of the Cotabato Valley and among them no cases of infection were encountered, while at Cudarangan, just across the river, 6 imported cases among the Visayans were found. DISTRIBUTION OF FILARIA NOCTURNA. 307 None of these cases showed symptoms which could definitely be at- tributed to filaria, but as noted above, the husband of one of the infected women had a lymph-scrotum and varicose groin glands. (Plate I.) This man, age 27, had noticed a gradual enlargement of his scrotum for nine years. His three healthy appearing children were not infected with parasites. Periodicity was determined by the examination of specimens taken every two hours for at least one case in each place. The parasite in all showed a marked nocturnal periodicity except in one case at Parang, in which very few filaria could be found at any time either during the day or night. The morphology of the parasite in this case agreed with that observed in all the others. We wish especially to thank Lieutenants Wiegenstein and Bugbee of Parang; Lieutenant Glass and Dr. Delacroix, of Cudarangan, and Major Dutcher, of Cebu, for assistance in these examinations. A great deal of perseverance and diplomacy was necessary on the part of the officers at Cudarangan, to induce Datto Piang to permit his Mohammedans to be examined ; it was necessary to collect the blood from the forearm and not from the ear or finger. ILLUSTRATION. PLATE 1. Lymph-serotum and varicose groin glands. 309 PHALEN AND NICHOLS: FILARIA NocTuRNA. | [ PHIL. JourN. Sct., Vou. III, No. 4. OBSERVATIONS ON A PALLIATIVE TREATMENT OF ELEPHANTIASIS.’ By Apo CASTELLANI.* Hlephantiasis is considered to be an incurable infection except in those cases where the scrotum is affected or where there are localized, ndulous tumors which may be treated surgically. For some time past I have been experimenting with a view to devising a palliative treatment for this disease, which is extremely common in some parts of the tropics. At first, following the example of my predecessors, I tried injections of various antiseptics with the idea of destroying the organism which causes the disease. The chemicals experimented with were the following: 1. Methylene blue, given by the mouth as well as by subcutaneous injections. 2. Solutions of bichloride of mercury, carbolic acid, eyllin, and other antiseptics given hypodermically. 3. Various arsenical compounds: cacodylate of sodium, of quinine, etc., given by the mouth and by subcutaneous injections. The result of the investigations was negative and not the slightest improvement was ever noticed in any case. It then occurred to me that since one of the anatomical features of elephantiasis is the enormous increase of the fibrous tissue, thiosinamin might be useful in the treat- ment of the disease, especially in case of long standing. It is well known that thiosinamin, according to Hebra, Van Hoorn, Lengemann, ete., has the power of softening various kinds of fibrous tissue, facilitating its absorption, although the mechanism of this action is not known. Thiosinamin was discovered in 1828 by Berzelius; it is obtamed by treating two parts of mustard essence with one part of absolute alcohol and seven parts of ammonia, heating at 40° for several hours, and then + NH, slowly cooling. The chemical formula of thiosinamin is, C =S NHC,H, The crystals of thiosinamin have a bitter taste, a garlic-like odor and are easily soluble in alcohol and ether, but not in water. Thiosinamin, 1Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, February 29, 1908. 2 Director of the clinic for tropical diseases, Colombo, Ceylon. 312 CASTELLANI. in addition to its peculiar softening action on various fibrous tissue, possesses also some antiseptic properties. Thiosinamin injections are very painful and I have therefore used fibrolysin; which is a water soluble combination of thiosinamin with sodium salicylate, prepared by Mendel and manufactured by Merck. Fibrolysin can be obtained in sterile glass ampullx, each containing 2 cubic centimeters of liquid cor- responding to 0.2 gram of thiosinamin. I may state at once that the simple injection of thiosinamin without rest, massage, and most important of all, proper systematic pressure is not conducive to improvement. TECHNIQUE OF THE TREATMENT. The patient is first kept at complete rest in bed for a week, the affected parts bandaged with flannel or India rubber, and massaged regularly twice daily; they do not show much improvement as regards size after these manipulations, but they become somewhat softer. Next I begin injecting thiosinamin. I make the injections in various parts of the affected regions, using ordinary antiseptic precautions. I use an anti- toxin syringe supplied with a strong needle. A sterile pad of gauze is applied at the place of the injection and the whole limb is tightly band- aged with flannel. ‘To increase the pressure, pads of inelastic material, like stiff compressed gauze or bailed cotton wool or wood or iron bars, may be applied on the more prominent or harder parts, before bandaging. | In some cases an elastic rubber bandage is applied for one hour two or three times daily over the flannel bandages directly over the skin. The injections are almost painless; after two or three hours there may be a little pain locally, and the following day the part may feel harder than before, but in the successful cases, after two or three days the spot where the injection was made and the parts surrounding it become softer. As regards dosage, I generally moculate 2 or 3 cubic centimeters of fibrolysin every day or every other day, according to the features of the case, for about a month, and then discontinue the injec- tions for a week, during which time the use of flannel and India-rubber bandages is continued. ‘The India-rubber bandaging is most useful in cases of elephantiasis verrucosa, because it has no action on the deep lesions of the disease, but renders the skin much smoother, the hard yerrucose-lke projections disappearing or becoming smaller. The dis- appearance of the hard, corneous formations is facilitated by applying before bandaging a spirit lotion containing resorcin and salicylic acid, 10 grams of each to thirty of rectified spirit. After a week or ten days, a second course of thirty or more injections is given; then again a week’s rest with rubber bandaging, followed by another course or several other courses of injections. It is to be noted that while rubber bandages are yery useful in elephantiasis verrucosa, they are of very PALLIATIVE TREATMENT OF ELEPHANTIASIS. Bulle little advantage and occasionally may do harm in those cases of elephan- tiasis which present a smooth skin. After this treatment, the affected parts, in successful cases, are of much smaller size, although the enlargement of the bones so frequently found does not decrease. ‘The skin becomes softer, more elastic, and can be pinched up in folds. At this stage, when most of the subcutaneous tissue has been absorbed, I suggest the surgical removal of the portions of the redundant skin, when the disease affects the legs. Long elliptical strips of skin and the subcutaneous tissue are removed and the margins of each wound stitched together. This would not be practicable before the medical treatment, as the coaptation of the opposed surfaces of the skin, they being enormously thickened and elastic, would not be feasible. When the wounds have healed, the patient is advised to wear elastic stockings and eyery night for an hour, an elastic bandage. 4 CASHES TREATED. Case. 1. Elephantiasis verrucosa of the right leg—Ganegada Singhappu, Sing- halese, 18 years old, admitted to the clinic January 2, 1907. The first symptoms of the disease appeared twelve years ago, when he suffered from repeated attacks of fever accompanied by painful temporary swelling of the right leg. Later on the enlargement of the leg became permanent, increasing gradually to such an extent that the patient had to give up his work. He was an indoor servant. At the time of admission the whole limb below the knee was greatly enlarged, the skin being thickened, hard, and rough; on the dorsum of the foot and toes, numerous, horny, hard prominences were present. The limb measured round the ankle, 234 imches; round the calf, 253 inches; the inguinal glands were not enlarged, the scrotum and the left leg were not affected. No filarie were found in the blood. The patient was first kept in bed for two weeks with the right leg slightly elevated and tightly bandaged with flannel. Massage was given twice daily. At the end of the two weeks the parts were slightly softer, but the dimensions of the leg were practically the same. The thiosinamin treatment was then begun using the precautions already mentioned. The patient received altogether sixty-two injections. During the last period of treatment the limb was very tightly bandaged for one hour, three times daily with a rubber bandage. At the end of the course of the injections, the condition of the affected leg was strikingly improved, the circumference of the ankle being reduced to 93 inches, and of the calf to 12 inches. Moreover, the skin had become soft and of almost normal elasticity. The patient, finding himself so much improved and able to walk easily, whereas when admitted he could scarcely move without help, asked to be allowed to leave the clinie temporarily to go to his village where he had some business to transact. I told him to use a flannel bandage continuously, and to come to the clinic at the earliest practicable date. He returned two weeks later, con- fessing that he had never used the bandages given him. The lower parts of the leg and the foot were much enlarged (circumference of the ankle 12 inches), cde- matous and soft. After twenty-four hours of complete rest in bed and rubber bandaging, the swelling disappeared, and the measurements of the limb gave the same results as when he had left. 314 CASTELLANL. The patient remained in the clinic for several weeks more without having any more thiosinamin injections. The use of a rubber bandage was, however, regularly continued; the size of the leg increased very slightly. In July I advised him that long elliptical strips of the redundant skin should be removed. IT asked Dr. Paul, surgeon to the General Hospital, to perform the operation and he very kindly consented to do so. he operation took place on the 10th of July. The patient was given chloroform and, after a thorough disinfection, a long elliptical strip of the skin and sub- cutaneous tissue was removed from the anterior part of the leg and dorsum of the foot. Thesmargins of the wound were brought into contact by means of an interrupted suture. The stitches were removed after eleven days. The wound healed rapidly. Three weeks later another strip of skin was similarly removed from the posterior region of the leg. This wound also healed quickly. The patient left the hospital in the latter part of August, but has been seen by me regularly. So far, five months after the first operation, the leg is not enlarged; he has been regularly wearing an elastic stocking and at night has used a rubber bandage for an hour after having massage applied. If he does not wear the elastic stocking, and does not employ the bandage, the lower part of the leg becomes somewhat swollen and cedematous, although much less by far than before the operation. Case. 2.—The patient, a private case, consulted me in October, 1906. He was suffering from elephantiasis of the right thigh, leg and foot, of twenty years’ duration. The skin of the lower part of the leg and foot was extremely hard, inelastic, and covered with numerous small, wart-like protuberances. Measurements: Round the ankle, 244 inches; round the calf, 27 inches; round the thigh, 25 inches. : The patient underwent a treatment of ninety thiosinamin injections, combined with complete rest in bed, the use of the flannel bandages at first, and the India- rubber bandages later. The case improved greatly, the skin becoming softer, more elastic, and much smoother. The cireumference round the thigh was reduced to 21 inches, round the calf to 16 inches, and round the ankle to 144 inches. The patient was able to walk with much greater ease and following my instructions, has been wearing puttees and has continued regularly the use of the rubber bandaging twice daily for an hour. He states that if he stops the bandaging and the wearing of puttees, even for two or three days, the lez becomes swollen and oedematous; the swelling disappears, however, after a few hours, rest and bandaging. He refused operation, and has not been seen by me lately. Case 3.—The patient, a private case from India, had elephantiasis for fifteen years, confined to the lower part of the left leg and foot. He underwent a course of fifty-six thiosinamin injections, combined with rest, massage, and the use of the rubber bandages. The improvement was very slight; the skin became some- what smoother, but the dimensions of the affected parts remained practically the same. I think that rest, massage, and bandaging alone, without the injections, would have induced the same improvement. g Case 4.—Singhalese woman, aged 56; admitted to the clinic April 2, 1907. The disease was of fifteen years’ standing, and was localized in the lower two thirds of the left leg and in the foot. The skin was thick and inelastic, but not so rough as in the other cases. Circumference round the ankle, 19 inches. PALLIATIVE TREATMENT OF ELEPHANTIASIS. 315 The woman was kept in bed for ten days, and the parts bandaged with flannel bandages; after this treatment the skin became softer, but the dimensions of the limb remained practically unchanged. I then began giving thiosinamin injections. After having received thirty-five injections, she left the clinic at her own request, wishing to visit her family in a distant village. She was better at the time of leaving, the dimensions of the foot and leg having greatly decreased. When the patient was admitted to the clinic she could not move her toes; on leaving, such movements could easily be made. Case 5.—Bennet Gregory, Singhalese boy, aged 10 years; admitted to the clinic on June 25, 1907. Three years ago the patient began suffering from attacks of fever with contemporary swelling of the left leg and of the lymphatic inguinal glands of the left side. On admission, the left leg and foot were greatly enlarged, the skin being thick and hard, but with a smooth surface. The lymphatic inguinal glands of the left side were slightly enlarged and hard. The maximum cirecum- ference of the calf was 144 inches. Treatment was begun on June 28, 1907. He received twenty-five injections and the limb was regularly tightly bandaged with flannel and for one hour every other day with rubber bandages. On July 23 the injections were discontinued; they were resumed on the 29th of the same month. During the interval only massage and the use of India-rubber and flannel bandages were continued. After the first twelve injections a distinct improvement was noticeable, the parts having become softer and the size of the limb decreased. On July 15 and 16, however, the affected parts again became enlarged and very hard, although there was no fever. This condition lasted for three days, when on the 17th the improvement again began and steadily continued. At the time of writing (January, 1908) the improvement is well marked, the maximum circumference of the calf being 7 inches. The skin is much more élastic and can be pinched up in folds almost everywhere. I hope it will soon be possible to perform the same operation as in Case 1. It is to be noted that the patient remained without any treatment during November and December, 1907, as his parents took him back to their bungalow. CasE 6—Elephantiasis verrucosa of the right leg. Vekanda, Singhalese man 40 years of age. Admitted to the clinic on September 3, 1907. The disease was of fifteen years’ standing; the right leg and foot were enormously enlarged, the maximum circumference of the calf being 28% inches; the skin was thick, inelastic, and covered with numerous, hard, corneous projections; the lymphatic glands of the right side were enlarged and hard; the scrotum was not affected. Numerous cosinophiles (15 per cent), but no Pilaria noctwrna, were encountered in the blood. Treatment was started on the 9th of September, 1907; the patient up to the present time (January, 1908) has received seventy-five thiosinamin injections. He remained without treatment during the month of November. The whole limb has been regularly bandaged, flannel pads, etc., being applied. The case has much improved; the maximum circumference of the calf now being 16 inches and the skin has become much softer. I propose to continue the treatment for one month and then, if the skin has become elastic, the same operation as in Case 1 will be performed. CONCLUSIONS. 1. The treatment I have devised for elephantiasis, namely thiosinamin (fibrolysin) injections and methodical bandaging, followed by removal of portions of the redundant skin when most of the subcutaneous tissue has been absorbed, is of utility in a certain number of suitable cases. 316 CASTELLANL 2. I am not yet in position to give any definite explanation on the mode of action of the treatment, which I consider only palliative. Probably thiosinamin acts by softening the fibrous tissue so profuse in elephantiasis, and possibly, the antiseptic properties of thiosinamin, though very slight, may play a certain role. An observation which, if confirmed, may throw some light on the question, is that in the majority of my cases (five out of seven), the thiosimamin injections induced a fairly well-marked, though transient, leucocytosis; in one case (Case 1) the number of leucocytes rose from 9,000 to 17,500 per cubic millimeter. It is to be noted that the thiosimamin treatment without a constant, well-distributed pressure on the affected parts, best obtained by the application of hard pads and by careful bandaging, does not cause any marked improvement. Constant pressure on the affected parts by means of bandaging, etc., without thiosinamin injections, has practically no effect in severe chronic cases, although it may be of temporary benefit in recent ones. ILLUSTRATIONS. Prare J. Fig. 1. Elephantiasis. Case 5, before treatment. 2. The same, after five months’ treatment, no operation. Prare II. Fic. 1. Elephantiasis. Case 6, before treatment. 2. The same, after four months’ treatment, no operation. 73846——=4 217 "| S4tv1da “6 “9d oh BE) ‘F ‘ON ‘III “I0A “IOS ‘NuaOr ‘TIHg] [‘SISVILNVHda1Tg JO INTNLVEYL : INVITALSVO Il S31ivid “Z -9l4 “L "5l4 ‘Ff ON ‘IIT “IOA “10S “Nuoor “ITH g] [‘SISVILNVHdd1gq WO INANLVYANL + INVITALSVO FURTHER FILTRATION EXPERIMENTS WITH VIRUS OF CATTLE PLAGUE. By E. H. RurpicEr. (From the Serum Section of the Biological Laboratory, Bureau of Science, Manila, P. I.) It was shown in a previous report? that the laked or unlaked blood and the bile of bullocks sick with cattle plague, lost the power of transmitting the disease to other animals after being passed through Berkefeld filters marked VY, N or W; while peritoneal fluid retained this property on being passed through either one of these filters.” It was considered necessary to repeat the experiments with peritoneal fluid with all possible precautions, owing to the danger of accidental infection of the animals used for the previous experiment. The bullocks used in the former experiments were kept in a fly-proof stable and so far as could be determined, there was no cattle plague within a radius of three miles, neither did the attendants, feed, utensils, etc., come in contact with animals suffering from that disease, nor with excreta from such animals. The results here reported were obtained with peritoneal fluid after it had been passed through one of the following filters: Berkefeld N, Berkefeld W, Chamberland F, and Chamberland B. Five liters of citrate solution (the addition of 0.5 per cent solution of potassium or sodium citrate became necessary to prevent subsequent clotting of the fluid) was injected into the peritoneal cavity of a bullock sick with cattle plague. About one hour later the animal was bled to death, the abdomen opened and the peritoneal fluid collected. EXPERIMENTAL. No. 1. Peritoneal fluid obtained as above on the 13th day of January was divided into two parts, a and b. Fifty cubic centimeters of part a, unfiltered, were injected under the skin of bullock No. 27. The temperature of the bullock rose rapidly three days later, and on the 18th day of January, five days after inoculation, the animal. was bled to death and the lesions found post-mortem were those characteristic of cattle plague. (See Chart No. 27.) 1This Journal (1908). 3, 165. k The Berkefeld filters V, N, and W are coarse, medium, and fine grained, respectively. The filter marked W, the finest grained Berkefeld filter, is consider- ably coarser than the Chamberland filter marked F. 319 9 320 RUEDIGER. Part b was passed through a Berkefeld filter marked N and 50 cubic centi- meters of it injected under the skin of bullock No. 28. Cattle plague set in on the fourth day and the animal was bled to death on the sixth day after inoculation. (See Chart No. 28.) Bullock No. 48, kept as a control, was not inoculated; it remained well. (See Chart No. 48.) Fifty cubie centimeters of unfiltered fluid were injected on the 11th day of March. The animal sickened with cattle plague and was bled to death on the fifth day after inoculation.* No. 2. Peritoneal fluid received on the 11th day of March was divided into four parts: a, b,c, and d. Part a remained unfiltered; part b was passed through a Berkefeld filter marked W; part ¢ was passed through a Chamberland filter marked F; and part d@ was passed through a Chamberland filter marked B. Bullock No. 48 received subcutaneously 50 cubic centimeters of part a. It sickened with cattle plague. (See Chart No. 48.) Fifty cubic centimeters of part b were injected under the skin of Bullock No. 68 which sickened with cattle plague and was bled to death on the fifth day after inoculation. (See Chart No. 68.) : Bullock No. 69 was inoculated with 50 cubic centimeters of part c, and showed an irregular temperature for some time following the inoculation, but there was no manifestation of cattle plague. (See Chart No. 69.) On the 27th day of April, 50 cubic centimeters of unfiltered peritoneal fluid were injected under the skin of this animal which sickened and was bled to death on the 3d day of May, six days after inoculation. The diagnosis of cattle plague was verified - post-mortem. (See Chart No. 69.) Attention was called in my previous report to the fact that Nicolle and Adil-Bey and Yersin found that the etiologic factor of cattle plague may at times pass through the pores of the Chamberland filter marked F, probably due to difference in the size of the pores in different filters. Considerable variation is found in the stream of water from a number of filters, supposed to be of the same grade, such as Chamberland F for instance, delivered by them under identical conditions as shown by the following test: Five new Chamberland filters were tested with distilled water. The first delivered a liter of filtrate in five minutes, the second one in eight minutes, the third in eighteen minutes, the fourth in eleven minutes, and the fifth in sixteen minutes. Hence, one can easily understand how different results may be obtained with filters of the same grade. As only one Chamberland F filter was used in this experiment on cattle plague, the result must not be considered conclusive. Fifty cubic centimeters of part d were injected under the skin of bullock No. 70. It remained well. (See Chart No. 70.) On the 27th day of April this animal was inoculated with 50 cubie centimeters of unfiltered peritoneal fiuid. Cattle plague followed. (See Chart No. 70.) Bullock No. 71, kept as a control, was not inoculated and remained well. (See Chart No. 71.) The immunity test was applied on the 27th day of April and cattle plague followed the injection of 50 cubic centimeters of un- filtered peritoneal fluid. (See Chart No. 71.) ° ® Charts Nos. 27, 28, and 48 show a decided rise of temperature on the 9th . day of January. On this date the animals were driven a distance of three miles to the laboratory of the Bureau of Science, but it was a very warm day and the animals, practically wild, became overheated. EXPERIMENTS WITH VIRUS OF CATTLE PLAGUE. all CONCLUSIONS. The following conclusions seem justified from the experiments’ pre- viously reported and those here recorded : 1. Blood, laked or unlaked, and bile of animals sick with cattle plague, lose their virulence on being passed through Berkefeld filters marked Ve NE or W.. 2. Peritoneal fluid retains its virulence on being passed through Berkefeld filters marked V, N, or W, but is harmless after having been passed through a Chamberland filter marked B. 3. Conelusions relative to the Chamberland filter marked F will be reserved for the present. It is intended to test a larger number of these filters when opportunity permits, and the results therefrom will be reported later. I wish to express my gratitude to Dr. Nesom, Director of the Bureau of Agriculture, and to Dr. Shealy, of the same Bureau, for the peritoneal fluid and for the bullocks used in this work. EXPERIMENTS WITH VIRUS OF CATTLE PLAGUE. By) iS JAN Tf tat stat stat 7} yt | 12 Soa oa vaeaee Sosa eee eeeeaaee = sasaaid sfae Nos aa Banoo ELECTS ae ia a | | CI Cece PEEL EERE f\ 39 Ga pp cee AA LY 1908 No. 4 § JAN 1/1213 F161 7] 8) FI Ol UZ 73 | 4S) 161/718 1191201211 221231 24125) 26 Al 40 39 38 37 326 RUEDIGER. ; No. b9 [718 [9 [rol iat 73] r4 rs] rel 77178 [77120] 2/]22|23|24\25|261 BSS onoaeoe FEE aoG EXPERIMENTS WITH VIRUS OF CATTLE PLAGUE. Bat 1908 Nob9' A (AFL UG ITIL 720121224 23(24|25126(27123(29|30| / | 213 41 Glu 40 Lyel |Plt 39 38 37 PER. FL 50.C.C. TIOS No. 70 MAR. /[2[3 [4] 5 6) 71319 [loli [2[i3 47s [76 [77] 8 [72 [2ol2i [22[23[2ylasl2c} = i Al : 39 : 38 37 PER. FL 50.C.C. 328 RUEDIGER. 1308 No. 7/ 1/1213 Fb 1718 1 [loli [12473 | 4115 | 16 77478 1/7 120421 (22123124 |25 | 46 A\ 40 39 38 37 ; - NOT INOCULAT, 1908 Wel APR.I/5 [76 [7/7 /8 |/7 (2021 [22(23 | 24)25(26(27123 |27\30| / 4} : 40 = 39 : 38 37 CC.) PER. FL. A REPORT OF SEVERAL CASES WITH UNUSUAL SYMPTOMS CAUSED BY CONTACT WITH SOME UNKNOWN VARIETY OF JELLYFISH (SCYPHOZOA),.' By Epwarp H. H. Oxp~ The cases reported under this title were observed during the summer months of 1906 and 1907. Two were reported from Olongapo; the others occurred in the waters of Canacao Bay, an offshoot of Manila Bay lying between Cavite and the peninsula opposite, on which is located the United States Naval Hospital. The first case was seen in 1906 and the account which the patient gave of his symptoms after having been stung by the jellyfish seemed so exaggerated that it was not seriously considered at the time and his actions and complaints were looked upon merely as a marked hysterical attack following an ordinary sting from one of these fish. Not until other cases were observed in 1907, were such symptoms following the sting of a jellyfish looked upon as possibly something peculiar to these waters. Notes were made on the cases as they were observed. These notes showed a regular symptom complex, and those cases noted independently by medical officers stationed at Cavite and Olongapo go to prove that the symptoms were not accidental. Case 1.—In August, 1906, a call was received at the hospital stating that a man, who had been in swimming off Sangley Point, had been stung by a jellyfish and was very sick. A friend who was with him at the time said that the patient, when he came out of the water shortly after he had been stung, complained of pain over his thigh, and soon afterward of pain elsewhere; then he became prostrated and began to vomit, to cough, and to breathe rapidly. On admission to the hospital, an area of erythema slightly raised and streaked and about the size of the palm of the hand was seen on his right thigh; vomiting had ceased, but his respirations were much increased and he continued’ to cough almost incessantly. The cough was short and hacking in character as if a foreign body had lodged in the larynx, and a thin, mucoid sputum was expectorated. His face was congested and anxious in expression and he wept at intervals. He threw himself constantly about on 1Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, February 28, 1908. 2 Assistant surgeon, United States Navy. 329 330 OLD. the bed, seemed to be in great pain and expressed much anxiety as to his con- dition. As stated above, his actions were looked upon as hysterical, for this was the first case of this nature seen here. The patient was given morphine sulphate, one-fourth grain by hypodermic injec- tion; the local condition was treated with an alkaline solution and was relieved in about half an hour. The next day he felt only a little weak, and otherwise appeared well and reported for duty. No record of his temperature was kept; the pulse was of good force and the rate slightly increased. Case 2.—V., a hospital attendant at Cafiacao, on June 21, 1907, while in bathing off the hospital wharf was stung by a jellyfish. He said that he was some distance from the landing and, as soon as he felt the sting, he turned back to the wharf; that on his way he felt some pain across his back, but thought it was due to swimming. On his way up from the wharf to the hospital he began to feel badly and sat down for a little while. When be reached the hospital, about thirty minutes after he had been stung, he became prostrated and had to be carried to a bed. On arrival I found a slightly raised, vesiculated, red area oyer the left biceps muscle. This “wept” like an eczema. The patient was throwing himself around the bed and coughing almost incessantly, expectorating a thin mucus. He com- plained of nausea but did not vomit. His face was congested and anxious. He wept at intervals, a stream of tears flowing down his face. The nose was occluded as in a bad case of coryza and from it a thin mucus was discharging. He com- plained of pain in his head and of marked pain in the lumbar region. He expressed much anxiety as to his condition and exclaimed now and then: “I don’t know why, but I've lost all my nerve.” His temperature was 38° C. (100°.2 F.) ; pulse 100, strong and full. The examination of urine and blood showed nothing abnormal. : Morphine sulphate one-sixth grain was given by hypodermie injection, an alkaline solution was applied to the arm. The symptoms subsided shortly after and in a few hours the temperature was normal and the pulse 60. The next morning the patient felt weak and complained of a slight sore throat; the pharynx was slightly inflamed. CASE 3.—S., a hospital attendant on duty at Cafacao on June 24, 1907, while swimming off the hospital wharf was struck by a jellyfish on the left side of his chin. He felt the sting immediately, but had no general symptoms until fifteen minutes later. Knowing the effect in the previous cases he came immediately to the hospital. There was a small, red-streaked area and a few vesicles on the side of his chin. The symptoms began with sharp, shooting pains throughout the body, but chiefly across the posterior lumbar region. The patient felt nauseated, but did not vomit. The same symptoms of congested mucous membranes, cough with thin mucoid sputum and lachrymation, were present, but he was not hysterical. His tem- perature was 37°.5 C. (99°.6 F.). No treatment was given. The symptoms lasted two hours. : Case 4.—On the same day as that on which the previous case occurred, M., a hospital attendant, was stung on the right forearm. A raised, red-streaked area appeared covered with little vesicles which “wept.” He said that at first his arm felt as if paralyzed and that he could hardly use it to swim. Ten or fifteen minutes later, after reaching the hospital, general symptoms began with sharp, shooting pains throughout the whole body, but chiefly in the back. The patient felt nauseated but did not vomit. There was no cough or excessive lachrymation, nor were hysterical symptoms noticeable. An alkaline solution was applied locally. The symptoms continued for about an hour. SYMPTOMS CAUSED BY CONTACT WITH JELLYFISH. Boll Case 5.—D., a hospital apprentice, while swimming off the hospital wharf was stung by a jellyfish on his arm. The symptoms appeared in about twenty minutes. I did not see him, but obtained a description of his symptoms, which were exactly like those of the other cases quoted, except that this patient did not have the severe pain in his back nor was he hysterical (this latter fact was obtained from one who saw him). The symptoms lasted two hours. No treatment was in- stituted. CasE 6.—This was reported to me by Assistant Surgeon A. B. Clifford, United States Navy. The case came to the dispensary at the United States naval station, Cavite, on July 6, 1907. This patient was a Filipino seaman. He was stung by a jellyfish while in swimming. Slightly raised, red-streaked areas ap- peared on both arms and neck. He said this happened about an hour before he was seen, but at that time there was marked congestion of the respiratory tract with almost constant coughing and expectoration of a thin mucoid sputum. Ex- cessive lachrymation was present. There was no vomiting or headache. Pain all over the body was complained of, but chiefly in the back. The patient threw himself about the bed in an hysterical manner. The temperature by axilla was 37° C (98°.6 F.). He was given morphine sulphate one-eighth grain by hypo- dermic injection and sodium bromide by the mouth. The patient became quiet shortly afterwards, but continued to have some pain over the streaked areas and in the back. Case 7.—Reported to me by Surgeon D. N. Carpenter, United States Navy, who had the ease in charge at the United States naval station, Cavite. This case, H. D., oceurred on the afternoon of August 11, 1907. While in bathing off this station the patient says that he was stung by a jellyfish. About fifteen minutes later when he reported at the dispensary the symptoms had already appeared. Over the region of the right deltoid and scapula there was an erythematous hyperesthetic area which was covered with perspiration and this would im- mediately reappear on being wiped off, or rather it “wept.” The symtoms noted were: respiratory spasm, holding of the breath for several seconds with short expirations and nervous cough; venous engorgement of the jugular veins from holding the breath. The face was flushed, the skin of the face relaxed and perspiring profusely; the head felt hot; there was a discharge from the nose; the pupils were partially and equally dilated. Pain was complained of in the back and pit of the stomach. Hysterical nervous symptoms manifested themselves by great restlessness and complaint of constriction of the throat appeared. The lungs were clear. The heart was normal. The pulse regular and of good volume, about 80. The temperature was not taken. j Treatment.—The remedy advocated by the natives was first tried, namely of vinegar externally and sugar internally. This was without effect. Amyl nitrite inhalations were also given without result. Morphine sulphate one-eighth grain by hypodermic injection was administered and in five minutes the patient com- plained of no pain and the restlessness and hysterical symptoms had subsided. The following cases were reported to me by Surgeon C. P. Kindle- berger, United States Navy, they having come under his observation at the United States naval station, Olongapo: CasE 8.—The patient was a Filipino boy, 14 years old, who was seen on July 16, 1907. He was stung on the right forearm by a white jellyfish; a red welt was seen over the effected area. He cried with pain, was restless and became partially unconscious. The lesion was treated locally with applications of alcohol and internally with a solution of sodium bicarbonate with bromides; he became quiet and was apparently in good condition. His father insisted on taking him 332 OLD. home and as soon as the patient saw the water he again became hysterical. Shortly after he reached home a call was received for some one to see him, to which a hospital steward responded; he reported that the boy’s heart and respiration showed signs of failure, and that he gave stimulants both by mouth and hypodermic injection, but these had no effect and the boy died at 7.30 p. m., just three and a half hours after he was stung. Case 9.—An American woman was stung on both forearms and hands by a jellyfish. The fingers of one hand became so swollen that a ring caused con- siderable constriction of the tissues. In this case there was severe pain locally; pallor from pain and fright; the pulse was weak. The patient did not sleep well for several nights because of the pain. Under lead and opium lotion the red welts and swelling began to disappear, but about three days after the sting an eruption resembling lesions of poison oak appeared on both arms and responded to treatment by fluid extract of grindelia robusta. No other symptoms were noted in this case. The reason more cases were not seen is probably due to the fact that few if any of the men at the hospital went swimming in 1906, the one case quoted being a man from a ship anchored in the bay. In June, 1907, many of the hospital corps and few patients began to bathe every afternoon off the hospital wharf and it was then that the cases quoted appeared ; a few days later the men stopped going into the water, being deterred by the sufferings of the other men. The symptoms, as noted, appeared in from ten minutes to an hour, but usually in from ten to fifteen minutes. In the nine cases quoted, one death occurred (case 8) that of a Filipino boy. I wrote to Dr. Kindleberger about the symptoms I had observed in the other cases here, but he replied that he noticed none of them in this boy except that he was badly frightened and hysterical. Four cases (1, 2, 6, and 7), one of whom was a Filipino, had the marked hysterical symptoms, with the incessant cough, restlessness, pain, nausea, etc., and all presented about the same picture. This is the type of case to be recognized as caused by some unknown irritant or poison. While some of the symptoms in cases 3, 4, 5, and 9 are like those in the type named, still the marked hysterical condition was not present and the latter is what would impress a physician most on reaching the bedside. I have been stung many times by the jellyfish found abundantly in the waters of Chesapeake Bay, Virginia, called there “stinging nettles” and “blood-suckers,” but beyond the local erythema and pain no other symptoms were noticed. From this experience, and considering the sufferings of some of the above quoted cases, I can not but believe that there is some absorbable substance present in the secretion of the fish concerned. The irritation of the mucous membrane of the mouth, throat, nose, and eyes, as seen in some cases and not in others, may be explained by the fact that some of the water around the fish which contained the cell secretion came into contact with these areas; and this might also explain the nausea and yomiting, but the severe general body SYMPTOMS CAUSED BY CONTACT WITH JELLYFISH. 333 pain suggests the possibility of an absorbable substance, as does also the case of death in which a depressing effect was noted. The part which such a cause might play in drowning is also of interest aside from that of diagnosis. A person when stung generally strikes out for the shore or a boat, but should he be very far away from either, and symptoms of the severe type come on while he is still beyond his depth, I doubt if he would be able to reach the land safely. The particular variety of jellyfish that causes these symptoms so far is unknown to me. I made inquiries among the fishermen along the shore near the hospital concerning the nature of this fish, but although they disagreed as to which variety caused the sting, they agreed that there was one which made a man sick when he was stung, and mentioned vomiting as one of the symptoms after the sting. Some said it was the red variety, which is the most common in the water thereabouts through the summer months; while others said the white variety was the factor. Several attempts were made by men at the hospital to produce these symptoms artificially by rubbing the fish, both the red and the white varieties, on their arms and legs, but with no result. I do not believe that the sting comes from the common variety, but from one less frequently seen. Some of the men said they were stung by the red fish, others by the white, but none of them waited to capture their tormentor. I used some alkaline solution locally and morphine sulphate hypo- dermically for the treatment of such cases. The alkaline solution was employed on the basis that the irritant was of an acid type, as formic acid has been generally looked on as the agent in the different kinds of stings, including those of ants, bees, jellyfish, ete. As the patients seemed to suffer a great deal and were so anxious about their condition, morphine sulphate was resorted to. I hope that should any such cases be seen during this coming summer by the members of the Philippine Islands Medical Association they will be able not only to locate the culpable variety of this particular kind of fish, but also be able to determine the nature of the irritant or poison secreted. 738465 A MOSQUITO WHICH BREEDS IN SALT AND FRESH WATER. By CHarues §. BANKS. (From the Entomological Section, Biological Laboratory, Bureau of Science, Ma- nila, P. I.) INTRODUCTION. The finding of members of a given species of animal breeding under such different conditions as those which obtain in fresh and salt water, especially where experiments have proved that a given lot of individuals when found in salt water and transferred to fresh for purposes of observa- tion, have invariably died before reaching maturity, becomes a matter of the gravest economic importance; more particularly so when the question narrows itself down to the discovery of a pathophoric mosquito having such habits. It was stated by me in a former publication* that while the majority of mosquitoes breed in fresh water, and while few are known to breed in the water of the sea, yet Myzomyia ludloww Theob. is among this number. This form of mosquito has been proved to be a transmitter of malarial fever. The statement? was also made that this mosquito had never been found in these Islands breeding in fresh water; that as a result of transferring a large number of laryee from sea to fresh water, all had died; and putting them into sea water at the point of saturation likewise killed them. The interesting and crucial feature of this discussion develops as the result of a trip to the mountain Province of Lepanto-Bontoc to investi- gate an epidemic of malarial fever, said by the officials in that region to be of the most pernicious type. Naturally, I expected to meet with another species of mosquito causing malaria in this isolated and elevated region, but instead I encountered adults of WM. ludlowti Vheob. in the dwellings during the first night of my stay in Cervantes, the capital of the province, and I was greatly astonished to find thew larve breeding in the greatest abundance in the rivers and small streams of the vicinity, while a thorough search extending 1This Journal, Sec. B. (1907), 2, 513. 2 Loc. cit. ; icy) (eo) oO 336 BANKS. over two weeks and including the rice fields, which were flooded at this time of the year, the water tanks near buildings, the streams, the wells, and in fact all probable breeding places revealed no other species of Anopheline. GEOGRAPHY AND TOPOGRAPHY. The town of Cervantes is situated near the center of the subprovince of Lepanto. It lies at an altitude of 508.8 meters upon a north-south hill 60 to 80 meters high between, and south of two forks of the Abra River. Hach of these forks flows through a rather flat valley which fayors the wandering of the streams from their habitual channels so that in reality from about 1 kilometer above the town to approximately a kilometer below there are, in the bed of each fork, four or five sub- parallel streams running more or less obliquely to the main course of the river as shown on Map 1. The entire river bed is coyered with rocks of various sizes, some of which are sufficiently large to impede or change the course of the stream during the dry season. The hill upon which Cervantes stands is composed of primitive rock of which the principal constituent is diorite with a more or less eroded, clayey, top soil. The base of this hill is cut into small, sharp gullies by the action of the water during the rainy season and in many of these gullies during the dry period there are springs, usually with a very small and slow flow. Algw, upon which the mosquito larve feed, ac- cumulate upon the wet rocks in these springs. This entire valley lying between the Cordillera Central and the Cor- dillera Occidental has but one outlet to the sea, namely through Abra Pass, which is north of Cervantes. The mountaims to the west average 1,000 meters in height while those to the south reach an elevation of 2,200 meters. The town of Sagada lies 17 kilometers northeast of Cervantes at an altitude of 1,445 meters, on the east side of the Cordillera Central and in a region of limestone formation. A number of small streams and springs are found in its vicinity and some of these are subterranean. Bontoe, 8.5 kilometers due east of Sagada, in the subprovince of Bontoe, has an altitude of 842 meters and lies on a slightly elevated bluff on the Anguinak River (Baduyan or Cagayan). The valley through which the Anguinak flows in the region of Bontoc is narrow south and southwest of the town, but widens east of it, allowing the river to divide into several streams during the dry season, but during the rainy period making it a wide, impassable current. There are a number of islands in the stream below the town during the dry season, several of which are shown on Map 2, and one toward the northeast. These islands have practically the same formation as the ones in the inner bed at Cervantes and facilities of the same character, but in less degree, are offered for the breeding of Myzomyia ludlowiw Theob. MOSQUITO BREEDING IN SALT AND FRESH WATER. 337 CLIMATE AND TEMPERATURE. The inhabitants of the region about Cervantes state that the temper- ature at that point, in the daytime during the dry season, is little if any lower than that of Manila, and certainly this was so during my stay there; the average day temperature was 30°, the night temperature 25°, which was even higher than in Manila. At Sagada the thermometer ranges at a very much lower point, while at Bontoc it is slightly lower than at Cervantes. Cervantes is surrounded by hills on all sides except toward the north, and so the town is cooled only to a moderate degree, even during the monsoons, by the breezes which blow from that direction. The breezes become heated by passing through the valley from the northern ex- tremity and find no outlet at the south; hence Cervantes during the dry season is subjected, as it were, to an almost continuous sirocco-like wind, which circulates and recireulates within the bowl-like valley. This region, like others in the Philippines, is subject to occasional showers during the dry weather, but at Cervantes these are very in- frequent. CHARACTER OF THE RIVER AND SPRING WATER. While the water in this region is strongly impregnated with lime, one of its peculiar features appears to be its large content of aluminium sulphate, which is also a characteristic of the water found in the breeding places of Myzomyia ludlowii Vheob. at Olongapo. Many of the springs near Cervantes are hot and the water from these and the cold ones evaporating during the dry season, leaves an incrustation which when analyzed in the laboratory yields, approximately, 33 per cent of alumi- nium sulphate. OBSERVATIONS ON MOSQUITO LARVZ.® The larvee of M. ludloww Theob., found in the Province of Lepanto- Bontoc, were always observed in water in which alge were growing, either floating on the surface or attached to the stones over which the water trickled. This same fact was noted in a previous publication referring to the same species of mosquito at Olongapo. Those observed in streams from springs were most abundant where there were shght depressions in which water a half centimeter or more in depth might collect; in the rivers they were always encountered where an obstructing rock or the friction of the bank caused either a back current or an eddy and where the water was comparatively still. It was very difficult to discover the larve in such situations except during periods of the brightest sunshine and then only when, after disturbing the surface, the investigator patiently awaited their reappearance at the top. Any 3 This Journal, Sec. B. (1907), 2, 518. 338 BANKS. motion on the part of the observer, or a shadow caused by any object passing near, would send the full grown larve to the bottom, while the smaller ones would hide themselves in the entanglement of the alge. The most practical way of obtaining the larvae was to dip up algw and water in a porcelain plate whereupon each larva, however minute, was at once thrown into silhouette against the white background. No difference, either in general or in minute appearance could be observed, even upon microscopic examination, between these larye and the ones which breed in salt water. The breeding places were in every case exposed to the direct rays of the sun; often no vegetation was present within 10 or 15 meters of the streams. Culicine larvee of a species not yet determined were associated with those of Myzomyia ludlowti Theob. This former species has been found breeding in open fields in the city of Manila in water containing alg, but has never been seen in salt water at places on the sea where the larve of M. ludlown Theob. have been encountered. The mosquito lary were found breeding at Sagada and Bontoe under conditions identical with those at Cervantes, so that the question of altitude with reference to the influence upon the species appears not to enter into the discussion as to why these mosquitoes should be found thriving under such different environments. DEDUCTIONS AND CONCLUSIONS. I am not aware of any other record of a species of mosquito propa- gating naturally in both salt and fresh water. Previous laboratory ex- periments along this line made by me, both in America and in the tropics, have always demonstrated that mosquito larvee removed from fresh to salt water or vice versa, have perished within a short time, either as a direct result of the difference in media or because of the effect of either fresh or salt water upon their food. No attempt has been made by me gradually to transfer IM. Judlowi Theob. from salt to fresh water and it was likewise impossible at the time of my visit to Cervantes to bring living larve, from there to the coast for experiment. There are two theories which might be advanced to account for the different environments of MM. ludlowii Theob. One is that the insects, originally salt-water breeders, have gradually been migrating by way of the Abra and Cagayan Rivers from the mouth of the latter up toward the higher regions, adapting themselves’ slowly first, to the brackish waters near the sea, then to the tidal fresh waters and finally extending up as far as Sagada and Cervantes. The other and more natural deduction, in view of the fact that most mosquitoes are fresh-water breeders, would be that originally all mos- quitoes breed in fresh water. This would appear the more reasonable since very many species breed in isolated water and in forests far inland. MOSQUITO BREEDING IN SALT AND FRESH WATER. 339 Tf this was the ease with M. Judlowti Theob., then the ease with which the larvae might be carried by the river currents toward to sea would explain their present marine or littoral habitat. HYGIENIC FEATURES. The most important feature of this discovery from an economic stand- point appears to be its bearing upon the general dispersal of pernicious malaria in the Philippines. There would appear to be no barrier against it from the standpoint of geographical position, either in altitude or in remoteness from the sea. In fact, the demonstration of the parasites of estivo-autumnal malaria in individuals who have never been out of the highland region, would be an accusation of overwhelming force against M. ludloww TVheob., which has already been shown to carry the same parasite at sea level.* In Cervantes the crescent form of the parasite was found in the blood of a little girl, P. C., aged 6 years and 5 months who had been suffering from chills and feyer for about two months previous to the time when I saw her. She had always lived in the town of Cervantes and therefore certainly contracted the disease locally and with MZ. ludloww Theob. as the transmitting agent. CONCLUSIONS. The most obvious conclusions are: That Myzomyia ludlowii Theob. is a species which, in the Philippines, breeds in both salt and fresh water. That altitude has (up to 1,500 meters) no appreciable influence upon its development. That there is little hope of ridding a community, like Cervantes, of this insect, owing to the peculiar topographical features which are practically irremediable because of their extent. That the present investigation made in a region where M. ludlowti Theob. is found in great abundance and where no other anopheline was encountered, gives a strong additional proof of its réle as a transmitter of estivo-autumnal malaria. *This Journal, Sec. B. (1907), 2, 531 et seq. ILLUSTRATIONS. Map 1. Sketch of northern Luzon showing Cordilleras Occidental and Central with the courses of the Abra and Cagayan Chico Rivers. 2. Town of Cervantes and vicinity showing character of Abra River bed at this place. 3. Towns of Sagada and Bontoc, showing character of Cagayan River bed near Bontoc. Note the great width of the river south and northeast of Bontoc. In the dry season the river channel breaks up into a series of small streams which make ideal breeding places for Myzomyia lud- lowii Theob. This condition is worse at Cervantes than at Bontoc. Pxrate I. Dam in the Cagayan Chico River near Bontoc with a view of the island below it and the streams which traverse the island. Bontoe lies around behind the hill at the left. II. Cagayan Chico River, showing a characteristic spot favorable to the breeding of mosquitoes. The Abra River at Cervantes is of the same type. 341 BANKS: SALT AND FRESH WATER MOSQUITOES. ] [PHI. Journ., Scr., Vou. III, No. 4. a, oo niten Mig genres tes yas Hearst Ay, S t S "py o Rn eet are Ne GO Usv o 0 Pee, | “ys ERVANTES oP, ~aV ) Ly Ts ¥ 20 4 Not & ae Sae< Sig =fOSE S37 ry} Sag wags 3 353 Ea CS i Ee s PS eal ene SENG Oat 24 sj é Pix 2 gore = yy ® a eS 6: (Ss) EW shana BOS oo zozaés cs BRS c8 Zueod 2 SSs « tes = o o 3 SRL of es ju o Sag as 3S ra Ges Gh a 3 cis r=) RES REE * osu pagiTnow 30 AM = ZARIINORY aniweH®” saTasad OHA JART M33 2ATAIOIIe ARMA BHT Ad 2nigas 34T AHA o. ARAR VIR BANOS OMA. ee ry es $ nee i) Fe Sg Ve t as, Sei . ‘ a \ ese: ‘ . -) bal ae ™ Vi Bisayetel Layee WORE iat eken = ra et : aie hel wir 7 Racanm tien, Yet + ovis mv, “< shat Baaleue?. 3 on gary wa 256% : beep ghost wk _ evil 3 lj ‘ 4 y + t iain ksi pain onc speenan eccel pona eles ~ a ea ee ee ae ater Seve ee } ’ ; ioe as ; : =f 2 a x . ai teeiekeeeilemting hc iaieecmeamameieniat on casera ee a ne ae MOSQUITO BREEDING IN SALT AND FRESH WATER. 343 BANKS: SALT AND FRESH WATER MOSQUITOES. | (PHIL. JourN., Scr., Vou. III, No. 4. 2, Houses g? Stones Scale Tynes Mile ° nh % __1Sfe. Mile. Map or CERVANTES, PROVINCE OF LEPANTO-BONTOC. i Rage . BaNKS: SALT AND FRESH WA [PHIL. JourN., Scr., Vou, III, No. 4. e eo; Compited,frem Mape furnished dy Capt. W. H Section of Military Information Bivision, of 4 (Pim, Journ., Scr, Vor. III, No. 4. Banxws: SALT AND FRESH WATER MOosquitogs.) fy s/f \ i Ais KApadae Compt, from. apt fora % SHAITan at Mibtary Talarmaten 8iiban, of the PA prea Map oF SAGana AND Bontoc, ProyiNce or LEPANTO-BoNToc, soe : pact’ = 2) sueweisdt slay <0 ay * eetth ate ee kt conse & cm : r— ‘ asia : ath be cd lee - Ey x cS s NN a i PE AN SND qva anpahea sah : ‘F ON ‘III “TOA “IOS -NunO¢ “11Hg] [UGIYM HSdugd GNV LIvg NI SNIdddug SUOLINOSOW : SUNVA ‘F ON ‘III OA “10S -NunOC “"TIHG] [SGLVM HSTYY GNV LIVS NI ONIdqUyg SHOLINOSOW : SHNVE A CASE OF INFANTILE BERIBERI WITH AUTOPSY REPORT.* By José ALBERT. The case under discussion is that of an infant three months of age, which was brought to my clinic at St. Paul’s Hospital on the afternoon of December 3 last, and died during the next night. Upon examining the child, she was seen to be of robust frame. In general the face was pallid, but cyanosis was present around the mouth and nostrils. There was no rise of temperature; cedema of the legs and anterior chestwall was present ; the urine was scanty; nausea was present, but not vomiting. From the previous afternoon until the time she was examined, two normal stools had been passed; the respirations numbered from 30 to 40, and the pulse 120 to 130 beats per minute. Pronounced aphonia was present, although the patient was constantly moaning. The history of the case as given by the mother is as follows: Two weeks previously the child lost her voice, as the result, so the mother thinks, of a bath. She vomited a good deal at this time and had frequent stools of a very dark color. It was these gastric and intestinal symptoms which caused the mother to bring her to the hospital. Upon examining the mother, it was seen that she was suffering from a drop- sical form of beriberi. There was edema and swelling of the feet, the patellar reflexes were absent; there was a sensation of weight in the epigastrium; tachy- cardia was present. The mother said she had suffered from beriberi for a long time; she had besides the present child four other children of whom the first three, all of whom she had nursed, had died during the first months of infancy. The fourth child, immediately preceding the one whose case I am reporting, was not suckled, but had been brought up by the bottle, and is alive and in good health. With the foregoing data there could be no doubt that the case was one of beriberi. As has already been mentioned above, the child died a little more than twenty-four hours later, and the autopsy and micros- copical examination for the results of which I am indebted to Drs. Marshall and Gilman showed that the most important lesions were: _ First, degeneration of both yagi and swelling of the cells of the right cervical ganglion; second, dilatation of the right side of the heart to a degree which threw 1Read at the Fifth Annual Meeting of the Philippine Islands Medical Associa- tion, February 29, 1908. 2 Professor of pediatrics in the Philippine Medical School. 345 346 ALBERT. it forward in contact with the sternum; third, collection of fluid in the pericar-. dium; fourth, hemorrhagic areas in both lungs; fifth, subcutaneous edema in the legs and chestwall. As is seen, these lesions correspond exactly to those found in adults affected with the pernicious or cardiac form of beriberi, and the state- ment of Hirota, of Tokyo, to the effect that infantile beriberi is symp- tomatically and pathologically identical with the acute cardiac form in the adult is again born out. The full report of the autopsy findings is as follows: Autopsy—Body of Vilipina infant 56 centimeters lone. Rigor mortis absent. Very little edema of ankles. Slight @dema over chest. No cdema of face or hands. The subcutaneous fat is moderately abundant and firm. The peritoneal cavity is dry. ‘The peritoneal surfaces are smooth and glistening. There is no injection along the vessels leading to the umbilicus. The diaphragm reaches the 4th space on the right side and to the fifth rib on the left. The thymus gland extends to a normal distance on top of the pericardium. There is a small amount of clear fluid in each pleural cavity. Heart: The right auricle is considerably dilated; a post-mortem clot is found inside the right auricle. The tricuspid valves are normal. ‘The left ventricle is small]. The mitral valve and aortic valve are normal. ‘The surface of the heart is pale; the muscle is firm. The length of the heart from the auriculo-ventricular groove to the apex is 4.5 centimeters. The walls of the left ventricle average 4 millimeters and of the right 4 millimeters in thickness. At the base of the aorta there are a few hemorrhagic points beneath the pericardium, but no ecchymosis heneath the epicardium. The left lwng is moderately voluminous and shows few ecchymoses beneath the pleura. The color is mottled, pale, and red. The consistence, fairly firm. On section the lung is pale, uniform, and apparently normal. The hemorrhagie points under the pleura correspond to small areas one-half millimeter in diameter extending into the substance of the lung. The right lung is also moderately voluminous and shows a few hemorrhagic points and in general resembles the left lung. On section it.also appears normal. The lymph glands at the root of the lung also appear normal in size, consistence, and color. The omentum and mesentery contain very little fat. The contents of the duodenum is normal. The stomach is small, contracted, and contains 5 cubic centimeters of thick, tenacious mucus mixed with a small amount of curded milk. The left kidney measures 4 by 2 by 2 centimeters. The capsule strips readily, leaving a mottled surface. Post-mortem discolorations and traces of foetal lobulation are present. On section the cortex is dark brown and post-mortem change is evident. The structures are not clearly visible. The right kidney measures 4 by 3 by 3 centimeters and presents the same general appearance as the left. The spleen shows post-mortem change; it measures 5 by 3 by 2 centimeters. Its consistence is firm, the edges are sharp and the capsule smooth. On section the structures are clearly visible, the malpighian bodies being more conspicious than normal. The pulp is firm and dark. The left suprarenal is apparently normal, being pale yellow in color. On section the cortex is seen as a yellow-white band, with a pale, dark color. The trachea, larynx, and bronchi are clear. A CASP OF INFANTILE BERIBERI. 347 The liver measures 12 by 7 by 4 centimeters. Its consistence is firm, the edges are sharp, the color is mottled. On section there is a pale yellow area near the surface while the general color is a brownish red and opaque. Intestines: The mucous membrane is pale. There are swollen areas in Peyer’s patches in the lower portion of the Ileum. : Histological examination by Dr. Gilman.—Microscopically the heart shows a diffuse, cloudy appearance with some separation of the muscle fiber and in places rather an abundant infiltration of round cells. The lungs show a slight edema with a few red blood cells free in the alveoli in various areas. The bronchial glands are normal. The kidneys show early post-mortem degeneration. The glomeruli are generally congested, the tufts being packed with red blood corpuscles. The spleen shows a marked grade of congestion; the malpighian areas appear smaller than normal and are widely separated by the pulp, the sinuses of which are markedly engorged with red corpuscles. The liver is markedly congested and the cells forming the periphery of the lobules show quite advanced fatty infiltration. Both vagi show swelling of the fibers with complete degeneration of about one- half of the nerve; the remaining fibers stained poorly and showed in areas a slight round cell infiltration. A section of the right cervical ganglion shows a general swelling of the nerve cells and their nuclei with an eccentric arrangement of the latter. A few of the cells show a granular change in the protoplasm. I have been led to present this report since, with the confirmation by autopsy of this case of infantile beriberi, that nosological entity acquires definitely and indisputably, a rightful place in the pathology and statis- tics of infantile mortality in the Philippines. The discovery of the existence of beriberi in nursing infants is due to Professor Hirota, of Tokyo, who first published, in the “Centralblatt ftir Innere Medizin,” in 1898, his studies on this condition which he began in 1888. Before the publication of his studies, such eminent authors as Baelz and Scheube denied the existence of beriberi in nursing infants. Hyen at the present time, Scheube is not convinced that nurs- lings may acquire beriberi from their mothers through the milk. Tt may be said that the recognition of the existence of infantile beri- beri in the Philippines is of rather recent origin, since it is only four or five years ago, and due to Scheube’s work on tropical diseases, that the observations of Hirota became accessible to the Filipino physicians, especially through Drs. Luis and Manuel Guerrero. But our clinical recognition was little more. than a mere suspicion, as it had not been confirmed by a pathological demonstration on the cadaver as in the present case. Dr. Herzog, of the biological laboratory of the Bureau of Science, in Manila, who published in 1906 a most thorough research on beriberi, was not able to adduce a single autopsy on a case of beriberi in a nursing infant, undoubtedly because there had been no opportunity to perform one. He therefore limited himself to admitting the exist- ence of infantile beriberi and citing the clinical testimony of the Filipino physicians. : 348 ALBERT. How far infantile beriberi, acquired through nursing the mother, may or does increase mortality in the Philippines is a question to be reserved for the future. What may be confidently affirmed is that the best method of establishing a sound basis for the fight against infant mortality in the Philippines is to commence by revising the form of death certificate used for infants of less than one year in such a manner as to have a statement on the death certificate of each infant under one year of age dying in Manila, of the kind of nourishment which the infant has received during life, as is the practice in many other countries. KDITORIAL. DYSENTERIC ABSCESS OF THE LIVER. The passing of abscess of the liver among Americans in the Philip- pines is so apparent from recent available statistics, that this most dreaded and most serious complication of intestinal amcebiasis should soon to a great extent lose its terrors, at least for Americans. During the interval from 1901 to 1905 the writer operated on about 100 cases of this form of abscess in both military and private practice, and 95 per cent at least of the patients were Americans; the percentage of recoveries was about 90 per cent. Exact data are not now available. The following operations were performed in St. Paul’s Hospital, Manila. Operations for amoebic abscess of the liver, St. Paul’s Hospital, Manila. Ameri-| Euro- | Japa- | Ne- | Filipi- cams. | peams.| nese. | groes. | nos. it Ee 3 ih | Aiea 2 1 1 2 pate een) Sa cd |e 4 i |L Al | Wee cee eee 3 | 5 2 6 The admission to the hospital of all classes of cases during this period was over 7,000. A number of cases of liver abscess have been treated in the military and other hospitals of Manila during these years and a marked recent decrease of the disease among Americans is shown by the records of these institutions as far as could be learned. ‘These figures prove in a most striking manner the efficacy of rational treatment of amcebic disease of the colon. But a short time ago, the discovery of amecebe in their stools came as such a shock to sensitive patients that the overcoming of the dread and depression following the discovery of the parasites was no small part of the treatment. 73846——6 349 350 EDITORIAL. During the interval of years from 1899 to 1903 the fear of ameebic dysentery in the American Army of occupation was so great that one amoeba observed in a specimen of the stools of an officer or enlisted man was followed by an order for immediate transfer for treatment to the United States, where physicians knew even less about the disease than they did here, although the first two years of our occupation represented a period when every man was needed and no soldier was allowed to leave the Islands unless medical officers decided a return to be necessary in order to save life. Ameebic disease was regarded at that time as being practically incurable. That this was so is shown by a study of our best text-books of that period in which, although little space was devoted to the malady, a most gloomy picture of ten to twelve weeks’ duration of the infection was drawn and the tendency to relapses and. resulting chronicity and abscess of the liver was mentioned as the common sequence. Thanks to the studies made of this disease and the rational methods in its treatment by Strong, Musgrave and Clegg and to the dissemination of knowledge, particularly among the laity, of the cause, methods of infections, prophylaxis, and curability of the infection, amce- biasis is now recognized at the onset eyen by the laity themselves, with the result that nowadays few amoebic patients lose any time from their duties. An intelligent person can learn in a few lessons how to take the necessary colonic injections, and taking a diet as heayy and stimulating as the digestive system can care for, instead of the starvation treatment, only periodical examinations of the stools can convince him that he still harbors amcebe. Much of the general confidence in the profession’s ability to cure the great majority of cases is strengthened by the fact that we now know that a considerable number of bowel disturbances due to amcebee are mild in nature and recover with little and often with no treatment whatever. The result of all this, as far as the liver abscess complication is concerned, is that this complication is now encountered only in neglected or improperly treated cases. Of course, a few generations will pass before the peoples of temperate climes will lose the widespread fear of abscess of the liver which they associate with a residence in the tropics. A number of our colleagues in Far Hastern countries have given statistical reports which are of interest in this connection. Sir Allan Perry, principal medical officer of Colombo, Ceylon, sends us the following : : 1Qsler (1897). EDITORIAL. 351 The General Hospital, Colombo—Cases of liver abscess, 1897-1906. S History Year. uber en Natives. ea Ameebic. |Bacteria. Rae Number (whites). alcolol on. 5 a 4 4 3 2 5 9 Bl 4 7 8 8 3 11 4 12 5 7 7 7 5 12 6 7 8 9 13 17 6 16 6 9 3 6 7 5 4 9 1 6 2 4 5 4) 2 6 2 18 10 8 14 13 5 18 9 12 | 4 8 9 8 4 12 5 30 | 16 14 18 | 18 12 30 10 33 10 23 19 22) i 33 15 153 63 90 104 | 99 54 152 60 « Among Europeans a yery large proportion of the cases of liver abscess has been in French soldiers from Saigon homeward bound by reason of ill health. bIn 1899 one had history of trauma only; in 1905 two. Dr. J. J. Vassal, of the Institut Pasteur, Nhatrang, Indo-China, gives us the following table from the service of Dr. Gaide, senior major surgeon of colonial troops, Hanoi, Tonquin, China: Morbidity and mortality in patients by sanitary districts, in French Indo-China, after operation for suppurating hepatitis, in the years 1904, 1905. 1906, and 1907. 1904. 1905. 1906. 1907. Cases. |Deaths.| Cases. |Deaths.| Cases. | Deaths.| Cases. |Deaths. Sanitary districts. = = = = = 5 5 z SB/S/Sl/e/S/ael/5l/el/S/S/Sl/e)/5)/8/5)e BIZ/F/4/8|4/e/4\/a8|4)/e8l|424\eal|42\ala4 TS (GOO) Ge eae eae CE BN Oy aS By EU ON a) al WO) ah eS) a Ee ph on ce eee B) ©} 2 Om | O} B) OF By -O} BT -O} 2] OF Bye Quang Yen_ 3 QO} 2] OI} OF] By O} Bi} a 3] Ov Gy O} 2B o Cooban gases. Gee ee Hi) ity) Oy OF t]) Of ay OF OF O}] OF OF By OF 24 oO Tilers eyelet Ul} O} OF} OF OF O}] OG) ©] OF} O} OF Oh O} OF} O}-O agian panne te = ase Li O} Of OF OF} OF OF O} OF O} Ole @] OH OF OO SEIS et 2 5 See 8 Ee 1 O} Of} O} 2 @ jj al O}) O} OF OF O} 0} Oi ©} Oo InaAN SSOU Shee e es ea ae OO} ©} Of O} O}- OF OF - O} OF OF O} OF O} OF} O}O Ifehioo ieayjneeee eee ani Ne Ol) 2} ©} 2] @| Of O} O} O} ©} O} oO] Oo] 2} ola IMOUC ay; =e nes alan 0/ 0] Of 0} 1) O}-1] oO} 0} OF 0} 0} O| 0} O}O Ghu Langthuong___---_-__- MO} @O} OF OF 2) wy wy al VS} oO Bye @] sy wy ato Soutaysas ss sSs2e. SS eas OO} ©} OF OF O} OF @) O} MO} OF} O} OF} O}-OF} O}O Mouran'e ees aan ti O} OF O} 4) OF a) Oo 4 | Oi ab) OF 3) OO} O10 Tuyen Quang Pi PAP QO) @ |) al O} O} O} OF} OY) OO} O} OF O Wiletry sees et Se ee 3) O} OF} OF SB] OF} OF OW 42) OF By OR oO} Mil ONO SVenvB aye enn ss ao oe Se | @} Of Of OF OF OO} Bi Ol} LI} Oy @)) al 0/0 Po talzess SUS leek Ss 43) 7) 11 3) 57) 4) 17 1 | 42 | 2) 24 1/43] 4) 16)0 General total _-_-_-_-- 50 14 61 18 44 25 47 16 352 EDITORIAL. Dr. Vassal, in connection with the above table gives the following details furnished by Dr. Gaide, senior major surgeon of colonial troops, Hanoi, Tonquin. : Although suppurating hepatitis is not rare at Hanoi, the greater part of the patients treated for this trouble at the military hospital of the city come from different parts of the upper country invalided for paludisine, dysentery, or some other trouble, hepatitis appearing only after their arrival at Hanoi, or they were sent because of this trouble by ambulance to the hospital at Hanoi, in order to be operated on under the most favorable conditions. In the course of the last four years the proportion of the mortality in eyery 100 patients treated has been as follows: 28 per cent in 1904; 29 per cent in 1905; 26 per cent in 1906; 34 per cent in 1907. The mean mortality per 100 patients treated, calculated for the four years indicated above, reaches the average of 41 in 100. Dr. R. D. Keith, of the Straits and Federated Malay States Medical School, Singapore, Straits Settlements, has sent us the following table for Singapore: Consecutive records examined, 1,564 ;° dysentery present in 300 cases. Number of dys- | biasis. | jiverhe | entery. : Chinese 2222s saee oe eee ee 270 | 14 Tamils. 20 1 Malays 22.202. be ee eee Vy eae is bam MUTOPCANS: = s22 = tees ae 2), San se eee 2 Otherita ces eines ee ee ee 63 |S sk eee Totals ee eee 300 194 17 a These members correspond to about 15,000 cases in the hospitals. >The dysenteric condition in the seventeen cases was as follows: 6 advanced, 4 marked, 6 slight, 1 very slight. The small intestine was affected as well as the large in 4 out of the 17 cases. © Single abscess occurred 5 times; multiple abscess 12, the right lobe alone was affected 11 times; the left lobe alone 1 time; both lobes were affected 5 times. JoHN R. McD11t. ° THE FREE DISPENSARY OF THE PHILIPPINE MEDICAL SCHOOL. The free dispensary of the Philippine Medical School was organized in September, 1907, the necessary rooms, pending the construction of the new building in connection with the Philippine General Hospital, haying been furnished by the authorities of St. Paul’s Hospital, Manila. This clinic, from the beginning, has been markedly popular with the people and has furnished abundant material for the purposes of instruction. EDITORIAL. 353 The attendance for the nine months, up to and including June 30, 1908, is given in the following table: F ; : Obstet- | Eve; ear, Month. Medical. | Surgical. |Children. Tical, |20se and} Totals. throat. | =| 1907. September. 492 236 73 | 2 19 822 October === == 575 254 43 | 1 101 974 November ___-___ 587 281 56 | 1 155 1, 080 December ___---- 508 286 70 | 1 160 | 1,025 1908. | UM ye 573 324 45 0 221 1,163 February ___--___ 577 331 37 0 223 1,168 INE ROD oe | 605 361 43 0 265 1, 274 Nyoyalll = 494 326 43 0 251 1,114 IM ciyo= 822 er ol 413 301 44 0 179 937 UE ae es 620 388 83 0 221 1,312 Totals _____ 5, 444 3, 088 537 5} 1,795 | 10.869 The months of July and August have shown even a greater number of patients and, with careful records, this clinic should in a short time furnish valuable data for a more extended study of the diseases existing among the poorer classes in Manila and the provinces. Paun C. Frese. aie mee aires Bb. oath REVIEW. Pharmacology: The Action and Uses of Drugs. By Maurice Vejux Tyrode, M.D. Cloth. Pp. ix+255. Price, $1.50 net. Philadelphia: P. Blakiston’s Son & Co., 1908. It is to be presumed that this work is for the use of students of medicine and that consequently the author has endeavored to reduce the limits of the book so that it can be used for ready reference. In so doing he has omitted altogether the experimental side of pharmacology and so we are brought back to former times, when the knowledge of pharmacology possessed by beginning practitioners was based on the more or less positive statements of the text-books they had read and the lectures they had heard. It is our belief that the text-books of pharma- cology for beginners should be so constructed as to include experimental work and at least general laboratory directions, that they should handle but few drugs, and these well chosen and that the topic of materia medica had best be reserved for a separate volume. It is to be regretted, also, that the author has not included, so far as expedient and necessary, structural chemical formule. 'The mere name of a drug, even to those thoroughly conversant with the subject of pharmacology, often conveys no meaning, where the chemical formula does. This book, however, is a short. compendium which doubtless will find its place in the class room, although the student should be encouraged to do much collateral reading in connection with it. Io CG, 8 355 PREVIOUS PUBLICATIONS OF THE BUREAU OF GOVERNMENT LABORATORIES—Continued. (Concluded from second page of cover.) No. 32, 1905.—Biological Laboratory: I. Intestinal Hemorrhage as a Fatal Com- plication in Amcbic Dysentery and Its Association with Liver Abscess. By Richard P. Strong, M. D. IT. The Action of Various Chemical Substances upon Cultures of Amebe. By J. B. Thomas, M. D., Baguio, Benguet. Biological and Serum Laboratories: III. The Pathology of Intestinal Amebiasis. By Paul G. Woolley, M. D., and W. E. Musgrave, M. D. ‘ i Wo. 838, 1905, Biological Laboratory.—Further Observations on Fibrin Thrombosis in the Glomerular and in Other Renal Vessels in Bubonic Plague. By Maximilian Herzog, M. D. y 1No. 34, 1905——1. Birds from Mindoro and Small Adjacent Islands. II. Notes on Three Rare Luzon Birds. By Richard C. McGregor. No. 35, 1905.—I. New or Noteworthy Philippine Plants, IV. II. Notes on Cuming’s Philippine Plants in the Herbarium of the Bureau of Government Laboratories. III. Hackel, ‘“‘Notes on Philippine Grasses.’ IV. Ridley, “‘Scitiminez Philippinenses.”? V- Clarke, “Philippine Acanthacer.”” By Elmer D. Merrill, Botanist. No. 86, 1905.—A Hand-List of the Birds of the Philippine Islands. By Richard C. McGregor and Dean ©. Worcester. LIST OF PREVIOUS PUBLICATIONS OF THE MINING BUREAU (NOW DIVISION OF MINES OF THE BUREAU OF SCIENCE). 1890.—Descripeién fisica, geologica y minera en bosquejo de la Isla de Panay por D. Enrique Abella y Casariego, Inspector General de Minas del Archipiélago. 1890.—Memoria descriptiva de los manantiales minero-medicinales de la Isla de Luzon, estudiados por la comisién compuesta de los Sefores D. José Centeno, Ingeniero de Minas y Vocal Presidente, D. Anacleto del Rosario y Sales, Vocal Farmacéutico, y D. José de Vera y GOmez, Vocal Médico. i 1893.—Estudio descriptivo de algunos manantiales minerales de Filipinas ejecutado por la comisién formada por D. Enrique Abella y Casariego, Inspector General de Minas D. José de Vera y G6mez, Médico, y D. Anacleto del Rosario y Sales, Farmacéutico ; precedido de un prélogo escrito por el Excmo. Sr. D. Angel de Avilés, Director General de Administracién Civil. 1893.—Terremotos experimentados en la Isla de Luzén durante los meses de Marzo y Abril de 1892, especialmente desastrosos en Pangasinan, Unién y Benguet. Estudio ejecu- tado por D. Enrique Abella y Casariego, Inspector General de Minas del Archipiélago. 1901.—The Coal Measures of the Philippines. Charles H.) Burritt. fa 1902.— Abstract of the Mining Laws (in force in the Philippines, 1902). Charles H. urritt. 1902, Builetin No. 1.—Platinum and Associated Rare Metals in Placer Formations. H. D. McCaskey, B. 8. Pe Pelee aa of the Chief of the Mining Bureau of the Philippine Islands. Charles . Burritt. ¥ 1908, Bulletin No. 2.—Complete List of Spanish Mining Claims Recorded in the Mining Bureau. Charles H. Burritt. 1908, Bulletin No. 3—Report on a Geological Reconnoissance of the Iron Region of Angat, Bulacan. H. D. McCaskey, B. S. 1904.—¥Fifth Annual Report of the Mining Bureau. H. D. McCaskey. 1905.—Sixth Annual Report of the Chief of the Mining Bureau. H. D. McCaskey. 1905, Bulletin No. 4.—A Preliminary Reconnoissance of the Mancayan-Suyoc Mineral Region, Lepanto, P. I. A. J. Eveland, Geologist. 1905, Bulletin No. 5.—The Coal Deposits of Batan Island. Warren D, Smith, B. S., M+ A.,. Geologist. DIVISION OF MINES. 1908.—The Mineral Resources of the Philippine Islands, with a Statement of the Production of Commercial Mineral Products during the year 1907, issued by Warren D. Smith, Chief of the Division of Mines. LIST OF PREVIOUS PUBLICATIONS OF THE ETHNOLOGICAL SURVEY (NOW DIVI- SION OF ETHNOLOGY, BUREAU OF SCIENCE). Vol. 7.—The Bontoe Igorot, by Albert Ernest Jenks. Paper, ®2; half morocco, #3. Vol. II, Part 1.—Negritos of Zambales, by William Allen Reed. Paper, #0.50; half morocco, #1.50. ’ Vol. II, Part 2 and Part 3.—The Nabaloi Dialect, by Otto Scheerer. The Bataks of Palawan, by Edward Y. Miller. (Bound also in one volume with Part 1, Negritos of Zambales.) Paper, #0.50; half morocco, P1.50. Combined, half morocco, P3 1 Vol. I1J.—Relaciones Agustinianas de las razas del Norte de Luzon, by Pérez. Paper, P0.75 ; half morocco, 2. Vol. IV, Part 1.—Studies in Moro History, Law, and Religion, by Najeeb M. Saleeby. Paper, £0.50; half morocco, P1.50. DIVISION OF ETHNOLOGY. Vol. IV, Part 2.—The History of Sulu, by Najeeb M. Saleeby. Paper, 71.50. Vol. V, Part 1 and Part 2.—The Batam Dialect as a Member of the Philippine Group: of Malayan Languages, by Otto Scheerer. The F and V in the Philippine Languages, by C. E. Conant. Paper, P1.60. Directions for Ethnographic Observations and Collections, 1908. For free distribution. All the above publications which are for sale may be obtained from the Director of Printing, Manila, P. I. All publications for free distribution may be obtained from the Librarian, Bureau of Science, Manila, P. I. Correspondents will confer a favor by returning to the Library of the Bureau of Science any bulletins which they may have in duplicate, as there is a considerable demand for bulletins out of print. 1Qut of print. CONTENTS. WASHBURN, WILLIAM S. Health conditions in the Philippines CUE my ; Heyy ROGERS, LEONARD. The Prevention of Tropical Abscess of the Liver Bi : by the Early Diagnosis and Treatment of the Presuppurative Stage of ane Amosbici Hepatitis): 32 Aes 20s aed Ee Bee ie Re a ee) Aen ES ee ceed 285 By ea PHALEN, JAMES M., and NICHOLS, HENRY J. Filariasis and Ele- . phantiasis ‘in)Southern Luzon ses a ne Be ee ea eA PHALEN, JAMES M., and NICHOLS, HENRY J. Notes on the Distri- bution of Filaria Nocturna in the Philippine Islands __________________ 305 CASTELLANI, ALDO. Observations on a Palliative Treatment of Ele- phantiasisn (0d 0 Sch ye NSU OE SRE SNE ae Bee eres ae 3II RUEDIGER, E. H. Further Filtration Experiments with Virus of Cattle SPP Re gene ea EN LINAS ws JE ARC MOR Ty Ue tr Moa ay ea Ls WRC EOE REA CS OLD, EDWARD H.H. A Report of Several Cases with Unusual Symp- toms Caused by Contact with some Unknown Variety of Jelly-Fish (Seyphozoay)?. 2G ths iene ieee ers Sr Ne Gis IE LNB NAS sey Phe Ray BANKS, CHARLES S. A Mosquito which Breeds in Salt and Fresh Via beri ca NC! WSs NUN iad lee tay ace US Na ey SI SOI Aaeh geal IPED 28 OUD AL RRL 335 ALBERT, JOSE. A Case of Infantile Beriberi with Autopsy Report_____ 345 PD BEORVARACS uu UNG i) 2a atin OM TO Ses CUT ERIS 349 REVIEW DPBS SN RUAED CPatiy SAM IRS Ea Geko CG tetas ete Seis ARE MEN Rone gS Pty 355 The ‘‘Philippine Journal of Science’’ is issued as follows: Section A. General Science, $2, United States currency, per year. Section B. Medical Sciences, $8, United States currency, per year. Section C, Botany, $2, United States currency, per year. , The entire ‘‘Journal’’ $5, United States currency, per year. | Single numbers, 50 cents, United States currency. by Authors receive 100 copies of their papers free. © The numbers in each section will appear as rapidly as material is available. Each sec- tion will be separately paged and indexed. Subscriptions may be sent to the DIRECTOR OF PRINTING, Manila, P. I. FOREIGN AGENTS. THE MACMILLAN COMPANY, 64-66 Fifth Avenue, New York. Messrs. WM. WESLEY & SON, 28 Essex Street, Strand, London, W. C. 2 MARTINUS NIJHOFF, Nobelstraat 18, ’s Gravenhage, Holland. Messrs. MAYER & MULLER, Prinz Louis Ferdinandstrasse 2, Berlin, N. W. Messrs. KELLY & WALSH, LIMITED, 32 Raffles Place, Singapore, §. S. Messrs. A. M. & J, FERGUSON, 19 Baillie Street, Colombo, Ceylon. (Entered at the post- office at Manila, P. I., as second-class matter.) A limited number of complete copies of Volume I and Sup- plement to Volume I and Volume II, all sections, are still available for sale. Price of the complete volumes, unbound, $5, United States currency; of the Botanical Supplements to Volume I, unbound, $2.50, United States currency. Volume I was not divided into sections. a EDITED BY - PAUL C. FREER, M. me PH. ‘D. CO-EDITOR - RICHARD P. STRONG, Pu. B., M. D. WITH THE COLLABORATION OF VICTOR G. HEISER, M. D.; W. E. MUSGRAVE, M. D. JOHN R. McDILL, M. D.; FERNANDO CALDERON, M. D. JOSE ALBERT, M. D.; PHILIP K. GILMAN, A. B., M. D. eiusrsagl ae _ PHILIP E. GARRISON, B. A., M. D. ' PUBLISHED BY THE BUREAU OF SCIENCE OF THE GOVERNMENT OF THE PHILIPPINE ISLANDS -B. MEDICAL SCIENCES 3te, i, = Snsoaial ‘ng ifs ia, MANILA | ae En ees BUREAU OF PRINTING 1908 MAR 1 lgus Nationa ti i , PREVIOUS PUBLICATIONS OF THE BUREAU | OF GOVERNMENT LABORATORIES, 1No. 1, 1902, Biological Laboratory.—Preliminary Report of the Appearance in the Philippine’ Islands of a Disease Clinically Resembling Glanders. By R. P. Strong, M. D. No. 2, 1902, Chemical Laboratory.—The Preparation of Benzoyl-Acetyl Peroxide and ts Use as an Intestinal Antiseptic in Cholera and Dysentery. Preliminary Notes. By aul C. Freer, M. D., Ph. D. 1No. 3, 19038, Biological Laboratory.—A Preliminary Report on Trypanosomiasis of #e Horses in the Philippine Islands. By W. E. Musgrave, M. D.,and Norman B®. Williamson. 0) be 1No. 4, 1908, Serum Laboratory.—Preliminary Report on the Study of Rinderpest of ae Cattle and Garabaos in the Philippine Islands. By James W. Jobling, M. D. ‘ 1No. 5, 1908, Biological Laboratory.—Trypanosoma and Trypanosomiasis, with Special Reference to Surra in the Philippine Islands. By W. E. Musgave, M. D., and Moses T. Clegg. -¢ 1No. 6, 1908.—New and Noteworthy Plants, I. The American Element in the Philip- pine Flora. By Elmer D. Merrill, Botanist. (Issued January 20, 1904.) s 1No. 7, 1908, Chemical aboratory. —The Gutta Percha and Rubber of the Philippine Islands. By Penoyer L. Sherman, jr., Ph. D. 1No. 8, 1903.—A Dictionary of the Plant Names of the Philippine Islands. By Hlmer D. Merrill, Botanist. 1No, 9, 1908, Biological and Serum Laboratories —A Report on Hemorrhagic Septi- cemia eae in the Philippine Islands. By Paul G. Woolley, M. D., and J, W. vm Jobling, 1 No. 10, 1908, Biological Laboratory.—Two Cases of a Peculiar Form of Hand Infection See (Due to an Organism Resembling the Koch-Weeks Bacillus). By John R. McDill, M. D., and Wm. B. Wherry, M. D. 1No. 11, 1903, Biological Laboratory.—Entomological Division, Bulletin No. 1: Prelimi- nary Bulletin on Insects of the Cacao. (Prepared Hspecially for the Benefit of Farmers.) By (Charles 8. Banks, Entomologist. 1No. 12, 1903, Biological Laboratory.—Report on Some Pulmonary Lesions Produced by the Bacillus of Hemorrhagic Septicemia of Carabaos. By Paul G. Woolley, M. D. No. 18, 1904, Biological Laboratory.—A Fatal Infection by a Hitherto Undescribed. Chromogenic Bacterium: Bacillus Aureus Feetidus. By Maximilian Herzog, M. D. 1No. 14, 1904.—Serum Laboratory: Texas Fever in the Philippine Islands and the Far East. By J. W. Jobling, M. D., and Paul G. Woolley, M. D. Biological Laboratory: Entomological Division, Bulletin No, 2: The Australian Tick (Boophilus Australis Fuller) in the Philippine Islands. By Charles S. Banks, Entomologist. No..15, 1904, Biological and Serum Laboratories ——Report on Bacillus Violaceus Ma- nile: A Pathogenic Micro-Organism. By Paul G. Woolley, M. D. 1No. 16, 1904, Biological Laboratory.—Protective Inoculation Against Asiatic Cholera : An Experimental Study. By Richard P. Strong, M. D. No. 17, 1904.—New or Noteworthy Philippine Plants, If. By Elmer D. Merrill, Botanist: 1No. i8, 1904, Biological Laboratory.—!. Amebas: Their Cultivation and Btiologice Significance. By W. E. Musgrave, M. D., and Moses T. Clegg. II. The Treatment of Intestinal Amebiasis (Amebic Dysentery) in the Tropics. By W. E. Musgrave, M. D. year No, 19, 1904, Biologie Laboratory. Some Observations on the Biology of the Cholera we Spirilum. -By W. B. Wherry, M. D. r . 5 No. 20, 1904 — Biological Laboratory: I. Does Latent or Dormant Plague Hxist Where : the Disease is Endemic? By Maximilian Herzog, M. D., and Charles B. Hare. Serum Laboratory: I. Broncho-Pneumonia of Cattle: Its Association with B. Bovyisepticus. By Paul G. Woolley, M. D., and Walter Sorrell, D. V. S. III. Pinto (Pafio Blanco). By Paul G. Woolley, M. D. Chemical Laboratory: IV. Notes on Analysis of the Water from the Manila Water Supply. By Charles L. Bliss, M. S._ Serwm Laboratory: V. Frambeesia: Its Occurrence in Natives in the Philippine Islands. By Paul G@ Woolley, M. D. No. 21, 1904, Biological Laboratory—Some Questions Relating to the Virulence of } Micro-Organisms with Particular Reference to Their Immunizing Powers. By Richard > P. Strong, M. D. No. 22, 1904, Bureau of Government Laboratories.—I. A Description of the New Build- ings of the Bureau of Government Laboratories. By Paul C. Freer, M. D., Ph. D. ITA patel cane of the Library of the Bureau of Government Laboratories. By Mary Polk, ibrarian 1No. 28, 1904, Biological Laboratory.—Plague : Bacteriology, Morbid Anatomy, and Histopathology (Including a Consideration of Insects as Plague Carriers). By Maximilian erzog, M. D. No. 24, 1904, Biological Laboratory.—Glanders: Its Diagnosis and Prevention (Together with a Report on Two Cases of Human Glanders Occurring in Manila and Some Notes on the Bacteriology and Polymorphism of Bacterium Mallei). By William B. Wherry, M. D. No. 25, 1904.°—Birds from the Islands of Romblon, Sibuyan, and Cresta de Gallo. By Richard Kes McGregor. No. 26, 1904, Biological Laboratory——The Clinical and Pathological Significance of Balantidium Coli. By Richard P. Strong, M. D. No. 27, 1904.—A Review of the Identification of the Species Described in Blanco’s Flora de Filipinas. By Elmer D. Merrill, Botanist. No. 28, 1904.—1I. The Polypodiacex of the Philippine Islands. II. Edible Philippine Fungi. By Hdwin B. Copeland, Ph. D. No. 29, 1904.—I. New or Noteworthy Philippine Plants, il. II. The Source of Manila Elemi. By Elmer D, Merrill, Botanist. No. 30, i905, Chemical ‘Laboratory. —I. Autocalytic Decomposition of Silver Oxide. II. Hydration in Solution. By Gilbert N. Lewis, Ph. D. No. 81, 1905, Biological Laboratory.—I. Notes on a Case of Hematochyluria (Together with Some Observations on the Morphology of the Embryo Nematode, Filaria Noctr na). By William B. Wherry, M. D., and John R. McDill, M. D., Manila, P. I. II. A Search Into the Nitrate and Nitrite Content of Witte’s ‘‘Peptone,”’ with Special Reference to Its earueuee bes ihe Demonstration of the Indol and Cholera-Red Reactions. By William B. erry, M. D. + Out of print. 2 The first four bulletins in the ornithological series were published by the Ethnological Survey under the title ‘Bulletins of the Philippine Museum.” Later ornithological publications of the Government appeared as publications of the Bureau of Government Laboratories. (Concluded on third page of cover.) THE PHILIPPINE JOURNAL OF SCIENCE : B. MEDICAL SCIENCES Vou. III NOVEMBER, 1908 No. 5 A STUDY OF THE PRECIPITIN AND COMPLEMENT FIXATION REACTIONS. By Harry T. MarsHart and Oscar TEAGUE. (From the Biological Laboratory, Bureau of Science, Manila, P. I.) It is well known that if red corpuscles are treated with an inactivated, specifically hemolytic serum, together with a fresh serum containing complement, the corpuscles are dissolved. No hemolysis is produced if the fresh serum is not added, or if it contains no free complement. Any procedure which removes the free complement will therefore prevent hemolysis, and, conversely, we can determine whether any given treat- ment of a fresh serum removes free complement from it by performing the hemolysis test with it after such treatment. It is clear from this that the occurrence or non-oceurrence of haemolysis may be used as the indicator of the presence or absence of free complement in the fresh serum. If serum containing free complement is present when a bacterial ex- tract is mixed with the correspondimg antibacterial serum, among other changes occuring, some reaction takes place, in the course of which the free complement disappears. The nature of the reaction and what becomes of the complement is not Imown, but the indicator described above proves conclusively that there is no complement remaining free after the reaction has taken place. Tt has been found that this is a general reaction, which according to some observers, occurs whenever complement is present during the union of any specific antigen and antibody, or according to others, during the union of any specific antigen with its corresponding precipitin. There are also a number of other agencies which are not specific, but which lead to the disappearance of complement. T7851 357 358 MARSHALL AND TEAGUE. It can be seen from what has preceded, that for the specific comple- ment deflection phenomenon we require: 1. A hemolytie complex consisting of (a) specifically hemolytic serum, (6) corresponding homologous red blood corpuscles. 2. Fresh serum containing free complement. 3. An antigen. 4. An antibody specific for the antigen. If 2, 3, and 4 are brought together for an hour and are then added to 1, no hemolysis occurs as the complement in 2 has been “deflected” during the union of 3 and 4. JXnowing that this reaction always occurs, the phenomenon can be used for purposes of diagnosis, either of the antigen, (3), or of the antibody, (4). The deflection test has been applied to three main subjects: I. In the diagnosis of syphilis. II. To supplement the precipitin reaction in the forensic diagnosis of minute traces of blood, and in the differentiation of blood of various species and sub- species. III. In the diagnosis of bacteria and of bacterial diseases. In a former paper one of us (Marshall(1!)) traced the origin and development of the deflection method. The present article will deal in detail with (1) the technique and its modifications, (2) the inter- pretation of positive and negative results, (3) the range of application of the method, (4) its diagnostic value, and (5) lipoidal and non- specific deflections. We will also describe a comparative study of this and the precipitin method. I. TECHNIQUE FOR THE SERUM DIAGNOSIS OF SYPHILIS. 1, PREPARATION OF MATERIALS. A. THE H4MOLYTIC COMPLEX. a. The hemolytic serum.—All observers have used the serum of rabbits im- munized against the erythrocytes of sheep. Wassermann, Neisser, Bruck, and Schucht(2) recommend using a serum of which from 0.001 to 0.002 cubic centi- ineters dissolves 1 cubic centimeter of a 5 per cent suspension of sheep’s corpuscles when treated with 1 cubic centimeter of a 0.1 dilution of guinea pig serum. Of this he used twice the exact dissolving dose with each cubic centimeter of 5 per cent sheep’s corpuscles. Meier(3) and Michaelis and Lesser(4) use and recommend three times the exact dissolving dose of amboceptor. Wassermann(2) remarks that the limits of the hemolytic amboceptor must be determined from time to time. The avidity of complement for the amboceptor varies with the particular immune serum. When the serum grows old, it of itself causes deflection and under these circumstances it can only be used by treating the corpuscles with it and then centrifugating and suspending the corpuscles in fresh salt solution before adding complement. b. The red blood corpuscles—The authors quoted(2) note that the corpuscles must come from a healthy sheep which has not been bled too frequently. After frequent bleedings, the corpuscles become too fragile for use. The blood must be defibrinated, and the corpuscles washed and centrifugated until entirely free from serum, and a 5 per cent suspension made in 0.85 per cent salt solution. — c. The complement.—The complement, according to the same authors(2), must : i : 4 A STUDY OF FIXATION REACTIONS. 359 be serum obtained from guinea pigs on the day of the experiment; the serum must be free from hemoglobin and must be centrifugated until perfectly clear. b. ANTIGEN. Wassermann(2) uses extracts in salt solution from various organs of infants who have died of congenital syphilis, made by taking 1 gram of organ, grinding thoroughly in a mortar with 4 cubic centimeters of 0.85 per cent salt solution, plus 0.5 per cent carbolic acid, shaking for twenty-four hours, and centrifugating until the fluid is perfectly clear. He uses 1 cubic centimeter of a 0.1 dilution of this extract for each test tube. Meier(3) employs only extracts of livers from syphilitic fetuses, as other organs are less active. Morgenroth and Stertz(5) suggest that the luetic organs be frozen and kept solid until ready for use, and that from these frozen organs one gram be used for each experiment in preparing a fresh extract. Marie and Levaditi(6) thoroughly desiccate the fetal organs and make a powder which retains its strength for months, and for each experiment make up a fresh extract with a little of this powder and salt solution. The extract of Wassermann is fit for use for about six days, although Meier(3) finds that an ordinary aqueous extract retains its strength for four months if protected from heat, light and air, and if not too frequently centrifugated. Cc. THE ANTIBODY. The antibody is usually obtained from the serum of a patient suspected of suffering with the disease. In a large number of cases the cerebro-spinal fluid has been employed as antibody. Meier(3) draws 6 or 8 cubic centimeters of blood and as quickly as possible obtains at least 1.4 cubic centimeters of serum which is inactivated at once. In the case of children, less blood is drawn, also a smaller quantity of spinal fluid is used. He recommends that the serum or spinal fluid be used immediately because of the danger of rapid deterioration upon standing. In establishing the value of the sero-diagnosis of syphilis Wasser- mann(2) uses the serum of monkeys first inoculated with syphilis and subse- quently treated with subcutaneous inoculations of syphilitic material. He always clarifies the serums and extracts at as short an interval as possible before perform- ing the experiment. Meier finds also that the serum rapidly deteriorates and either loses its deflecting power, or, more usually, causes deflection even with extracts of normal organs. There are various precautions to be observed in regard to both antigen and antibody. Wassermann and his colleagues(2) make the following observations: 1. Many extracts and serums of themselves alone pick up complement, the amount of extract or serum required varying with the individual preparation and in the case of each, varying with age; 0.1 cubie centimeter of a serum may not block when it is fresh, but after standing it will do so. 2. Any extract or serum showing even the slightest trace of cloudiness or precipitation will deflect and is unfit for use until centrifugated. 3. Frequently a serum or extract which is perfectly clear, absorbs complement. This is especially true of those which have stood long before being clarified by centrifugation or before inactivation. To avoid this non-specific deflection of complement centrifugate and inactivate immediately after obtaining the serums and extracts; preserve carefully under aseptic precautions in completely filled tubes, closed by fusing the glass, and > keep at a constant freezing temperature away from light and air; centrifugate as frequently as is necessary; determine in each individual experiment the non- deflecting dose, and never use a large one. 360 MARSHALL AND TRAGUE. 4. Wassermann and Citron(7) have shown that albumoses, glycogen, fatty stuffs, and lecithin block complement in even small doses. The richer a fluid is in colloidal materials, the more it deflects and vice versi. Extracts of red blood corpuscles deflect most; spinal fluid, least. As a rule, fresh red blood corpuscle extract does not deflect in a dose of 0.5 cubic centimeter; old extracts deflect in doses no larger than 0.1 cubic centimeter. These various effects are distinct from the specific deflection. Michaelis and Lesser(4) find that occasionally an extract of syphilitic liver is itself hemolytic when added to corpuscles, amboceptors and complement. Fur- thermore, a definitely deflecting serum will often suddenly lose its power after standing. Meier(3) finds that antibody loses strength upon being kept even in completely filled, tightly sealed and blackened tubes in a cold place. Its action also varies with the age and condition of the complement and of the red blood corpuscles. Wassermann(2) notes that upon standing, even a perfectly clear serum or extract gradually develops a cloudiness or even a slight precipitation. It is very neces- sary to centrifugate both serum and extract until they are perfectly clear before performing the experiment. The slightest trace or precipitation in the serum makes it unavailable for the experiment. It must be remembered, however, that each centrifugation of a serum or extract decreases its strength, it appearing that the active constituents are carried down in the sediment. 2. PRELIMINARY EXPERIMENTS. A. COMPLEMENT. Most observers, including Wassermann(2), Michaelis(4), and Meier(3) recom- mend the use of 1 cubic centimeter of a 0.1 diision of guinea-pig serum, as the standard amount of complement for use in each test. B. VALUE OF HA2MOLYTIC AMBOCEPTOR. With each amboceptor a test must be made at the outset to determine ap- proximately its value. This value remains fairly constant, but shows gradual and progressive deterioration. Before each experiment make a preliminary test with 0.1 cubic centimeter of guinea-pig serum to determine whether the hemolytic amboceptor retains its strength. i Meier(3) simplifies this experiment as follows: He heats diluted fresh comple- ment for one hour at 37°, so that the results obtained will be comparable with those in the rest of the experiment; he then prepares three test tubes with: fixed amounts of corpuscles and the heated complement, and dilutions of 1.5, 2 and 3 of the amount of the hemolytic amboceptor which proved satisfactory in the previous experiments. Thus, if in a previous experiment 1: 200 of amboceptor gave a good deflection, the dilutions of hemolytic amboceptor tried out in the preliminary experiment will be 1: 300, 1: 400, and 1: 600. He examines this preliminary test after fifteen minutes, thirty minutes, one and two hours. In the first tube he expects to find lysis after thirty minutes, in the second in one hour at the latest, in the third it should be almost complete in two hours. After the first two tubes are positive, he estimates the dose of amboceptor which will be required and continues with the deflection experiment without delay. C. ANTIGEN. Meier (3) notes that it is very necessary to test the value of the antigen and to employ fresh serum from an unquestionably syphilitic patient in making the test. If the syphilitic serum is not fresh it may deflect with an extract of A STUDY OF FIXATION REACTIONS. 361 normal organs. Wassermann and Plaut(8) note that the aqueous extract under- goes sudden and rapid alterations in deflecting power. This is confirmed by others including Morgenroth and Stertz. D. FINAL PRECAUTIONS. In a preliminary test determine that the suspected serum does not cause deflection with normal extract. If there is enough serum available, test its action upon sheep’s corpuscles with complement. Human and monkey serum, normal or luetic is often quite strongly hemolytic for sheep’s corpuscles, at times 0.1 cubic centimeter producing hemolysis of 1.0 cubic centimeter of a 5 per cent suspension. The test tubes, glassware and other apparatus must be irreproachably clean, the extracts and serums must be collected and preserved under aseptic precautions, and the experiments must be conducted in such a way as to avoid contamination by bacteria, dust, ete. 3. DETAILS OF THE ACTUAL EXPERIMENT. a. Amounts of materials—Wassermann, Neisser, Bruck, and Schucht(2) use 0.1 cubie centimeter of each one of the ingredients, bringing the total volume in each test tube up to 5 cubic centimeters with normal salt solution. Meier(3) dilutes his materials so that he needs only to measure out 1 cubic centimeter of each ingredient, making the volume constant with salt solution. He uses two quantities, 0.2 and 0.1 of the antibody and also of the antigen. Michaelis(4) and others also use 0.2 or 0.1 of serum from the suspected case with 0.1 or 0.2 of extract of syphilitic organs. Landsteiner and Stankovic(9) use 10 parts of 0.8 per cent salt solution; 1 part of serum inactivated at 56° for one-half hour; 1 or 2 parts of extract and | part of guinea-pig complement. After one hour at 37° they add 1 part of 50 per cent sheep’s corpuscles suspension free from serum and previously treated with two dissolving doses of hemolytic serum, incubate for one hour and a half at 37°. Morgenroth and Stertz(5) recommend wider variations in the amounts of sub- stances employed, especially of the antigen. They show that the zone within which deflection occurs is narrow, in one experiment cited deflection occurring when 0.001 to 0.0025 of antigen was employed, but failing to occur with greater or less amounts. In most of the literature, 0.1 cubic centimeter of the extract of antigen was employed in each test tube. Meier(3) finds that this usually suffices when mixed with 0.1 cubic centimeter of the luetic serum, while it produces no deflection with 0.2 cubie centimeter of normal serum. If the extract of antigen is weaker he uses from 0.2 to 0.4 cubic centimeters with 0.1 cubic centimeter to 0.2 cubic centimeter of the luetic serum, always making a control to prove that the same dose of extract produces no deflection with even twice the dose of normal serum. Meier(3) notes that the antibody varies quantitatively in different cases and the quantitative test is necessary for exact scientific work. In practice, however, it is necessary to use only two dilutions, neither of which is so strong as a control with normal serum need be in order that the normal serum produces deflection. In practice Meier uses a dilution of one in five of antibody, that is 0.2 cubie centimeter for one quantity and for the other one-half of this, viz, one part in ten, or 0.1 cubic centimeter of antibody, but in a few of his cases 0.005 cubic centimeter (=1: 200) of serum, deflected completely when mixed with Iuetic extract, while even 20 times the amount (0:1 cubic centimeter) gave complete lysis, i. e., no deflection, when mixed with extract of normal organs. Michaelis and Lesser(4) also employ about 0.2 cubie centimeter of serum from the patient. 362 MARSHALL AND TEAGUE. It is generally customary among all authorities to use 1 cubic centimeter of a 0.1 dilution of complement as a standard dose. The total volume of fluid employed by different authorities varies from 2.5 to 10 cubie centimeters. b. Time and temperature—The general advice given by Wassermann with regard to time and temperature is to allow the antigen, antibody and com- plement to remain in contact for one hour at 37°, subsequently allowing this mixture to act upon the hemolytic complex for two hours at 37°. Some author- ities allow antibody, antigen and complement to remain at room temperature. The result may be observed upon removing the test tubes from the incubator, or they may be placed on ice and the result noted on the following morning. Meier(3) thinks it is very important to observe closely the experiment in the incubator and not let it run automatically for two hours. As soon as lysis is complete in all of the controls, remove the test tubes from the incubator and put them on ice without waiting for the expiration of two hours. Frequently from three-quarters to one hour suffices, especially if the corpuscles and hemolytic amboceptor have been previously mixed for one-quarter to one-half an hour. This is a great improvement, and does away to a large extent with the “Nachlés- ung” or hemolysis which develops in some test tubes after being removed from the incubator and placed upon ice. It is even better to bind haxmolytic amboceptor to the corpuscles by allowing them to stand in contact for one-half hour, and remove the excess of serum by centrifugation and suspend the laden corpuscles in fresh salt solution. ce. Controls —The controls which are required in conducting this experiment are numerous. In addition to the preliminary tests mentioned above, each experi- ment must be accompanied by the following controls. A parallel series of tests must be made— 1. With the serum under examination and normal extract. In these controls there should be no deflection; if deflection occurs, it is not specific and the experi- ment must be thrown out. 2. With standard fresh syphilitic serum and the extract of syphilitic liver. In this control there should be definite deflection, otherwise the extract is defective, and the experiment fails. 3. With standard fresh syphilitic serum and extract of normal liver. In this control there should be no deflection. If it occurs either the standard serum is deteriorating or the total quantity of colloids is sufficient to produce a non-specific deflection. 4. With serum which is certainly not syphilitic and the luetic extract. In this control there should be no deflection. If it occurs the experiment is valueless and a fresh luetic extract must be prepared. 5. With the antibody serum and complement alone. This test should give no deflection. 6. With the Iuetic extract and complement alone. This test should give no deflection. 7. With the red corpuscles, hemolytic amboceptor and complement, which has been previously heated to 37° for one hour. In this control there should be complete hemolysis. : 8. With blood corpuscles in salt solution alone. 9. With blood corpuscles and hemolytic amboceptor alone. 10. With blood corpuscles and complement alone. 11. With blood corpuscles and organ extract alone. In these controls there should be no hemolysis. Meier(3) remarks that as experience increases, it becomes less necessary to make daily controls of the standard luetic serum with extracts and of serums ES a oe A STUDY OF FIXATION REACTIONS. 363 without extracts, for fresh serum in 0.2 cubie centimeter quantities never deflects alone, but on the contrary, increases the rapidity of lysis because of the ambocep- tors for sheep’s corpuscles contained in normal and luetic human serum. The only exception to this rule is that the serum from an animal which has just had a hearty meal may cause deflection and under any circumstance this serum is not useful because of its milkiness. All authorities agree upon the necessity of having these various controls. d. Tables —The following tables from various authorities illustrate the manner of setting the deflection test for the determination of the antibody content of the suspected serum. Wassermann, Neisser, Bruck and Schucht(2) give the following summary of one of their experiments: Immune serum: Obtained from a monkey inoculated and subsequently immunized with syphilitic material. Antigen: 1. Extract of organs from an infant with congenital syphilis. 2. Extract of bone marrow of a monkey killed seven weeks after inoculation with syphilis. Antigen controls: 1. Extract of organs from a non-syphilitic foetus. 2. Extract of bone marrow of a monkey free from syphilis. TABLE I. 1| 0.1 immune | 0.1 extract Iue- | Fresh gui-} Union for | 0.002 rabbit | 1 ¢. e. of Block- serum. tie feetus. nea pig 1 hour serumh-| 5percent| ing of comple- at 37°. molytic | suspen- hee mo- ment0.1.| for sheep | sion of lysis. corpuscles sheep’s (2dissoly- | blood. | | ing doses). | DH | ele does 0.1 extract lue- |_____ do aes OO eens OO) ree | peel do -_--| Do. tic monkey. | Si eae doe 0.1 extract nor- | Complete mal foetus. hemo- | lysis. Gh ene (60) 0.1 extract nor- |..____ id. O}aees | pee dop==s|=——== does pee do ----| Do. mal monkey. | *| 5 | 0.1 normal | 0.1 extract lue- |_____ GO aa d|aone ot GD) aa GO ase (eer do ___ Do. monkey tie foetus. serum. @ a OO) a enne 0.1 extract lue- Do. tic monkey. 7 | 0.J immune | Salt solution____|_____ (so) == || 4 6 --= 4] ==! do eae Saar CKO) | Do. serum, 8 | 0.1 normal | Do. monkey serum. 9 | Salt solution) 0.1 extract lue- |_____ doe aa doets| Saas (lo) see ee do ____| Do. tic foetus. | 10 |_--_- do==aee 0.1 extract lue- |_____ GD eI a oye eres Oh) eel dopa Do. | tie monkey. | | 1 ee (610) <= | 0.1 extract nor- |__-__ (10) es CO seal ee OO aa IE does] Do. | mal fcetus. | | 1) | = | 0.1 extract nor- |_____ B10) oe CO) |e CO sae do ___-| Do. mal monkey. 364 MARSHALL AND TEAGUE. The other controls which are not tabulated are: (1) the hemolytic system alone; (2) blood corpuscles in salt solution; (3) blood corpuscles with comple- ment alone; (4) blood corpuscles with hemolytic amboceptor alone; (5) organ extract with blood corpuscles. The volume of fluid in each tube is brought up to 5 cubie centimeters with salt solution. In this table, numbers 1 and 2 are the only tubes showing the real experiment, all of the others, including the five noted below the table, being employed as controls. These two tubes demonstrate that there is specific luetic material in the organ extracts made from the syphilitic foetus and the syphilitic monkey, and that there are specific luetic antibodies in the serum of the immunized monkey. Wassermann, Neisser, Bruck and Schucht(2) also use a simple form of table indicating only the combinations which are brought together in the presence of complement serum, together with the final result upon hemolysis. TABLE II. [Wassermann, Neisser, Bruck and Schucht; Table I modified.*] Extract 2 Serum of|Serum of| of non- Hstrach | normal | luetic luetic | “Ghila’s Result. | monkey. | monkey. es liver | iver. ° | Pesseee st (yak Pee a 0.1 | Blocking of hemolysis. 0.1 | ee Pee) [ae ee eterte 0.1 | Complete solution. | Do. } Do. | Do. | Meier(3) uses the following table to indicate whether a suspected serum “A” contains antibodies, which will produce deflection with a syphilitic extract and with no other. In this table the actual experiment is shown in column I, numbers 1 and 2, while the other tests are controls. In the last column is recorded the degree of deflection. He does not tabulate the hemolytic system with its controls. TABLE III. | ik I. TI. | : ‘ E ag g Serum. i? 358 3 End result. + oO Result. oH Result. a Result. S| S O° Os 4 = = as an 5 iS) s A 2 5 m i =| (S| By a | = | Pe Nee ee ta 0.2 | 0.2) Complete | 0.2) Complete | 1.0] Complete | blocking. solution. solution. | DOz=2<5 eater i] On | COs) 0:2 Ieee Glee one | Standard syph-| 0,2] 0.2 |___ dona OO Nes do z | iliti | Spar ar ar ilitie serum. | | < : | | isasyph- Normal serum_____ } 0.2} 0.2} Complete |} 0.2 |---2- co TI (0) je 0) = Basa ilitie se- | | hemoly- | = Tum. 0} eee dope | 130) |= (lo) A=Serum to be tested. ‘Ztschr. f. Hyg. u. Infectionskrankh., Leipz. (1906), 55, 455. A STUDY OF FIXATION REACTIONS. 365 Instead of recording the presence or absence of hemolysis and its degree, Meier uses two quantities of antibody 0.1 and 0.2 cubic centimeter and follows Citron’s scheme of interpreting the result directly in terms of deflection without first noting hemolysis. The degree of deflection varies according to the combination of results obtained with these two quantities as follows: Serum. ’ i Designation of = = strength of 0.2 0.1 reaction. Complete blocking -_____ Complete blocking _____. t4a+4H4+ 10) eee | Incomplete blocking -__- db de ak JD YG) oes esr ee S| I[fliySis= sae aoe Eee we + 4 Incomplete ete ela Nu Te See ik 4. MISCELLANEOUS. Miihsam(10) notes that the negative test must be repeated after seyeral days as the complement binding substances are not always constant in amount, and Wassermann(2) states that amy specific serum, which of itself precipitates human albumen, is useless for the deflection test. This refers to the serum of monkeys previously immunized with luetie substances. Il. TECHNIQUE OF DEFLECTION TEST IN FORENSIC PRACTICE AND IN THE DIFFERENTIATION OF BLOOD. The application of the deflection test for this purpose is essentially the same as in the case just considered. The known quantities are usually the hemolytic complex, the complement serum, and the specific antibody obtained by immunizing a rabbit with human serum or other known material. The unknown quantity is the antigen, usually a blood clot or blood stain. Neisser and Sachs(11, 12, 13) adopted the following technique in diagnosing blood clot or blood stain. They employ as the hemolytic complex a 5 per cent suspension of sheep’s corpuscles freed from serum, and the serum of a rabbit immunized against ox corpuscles which is always strongly hemolytic for sheep’s corpuscles also. The serum is completely clarified by centrifugation and inactiy- ated by heating to 56° for half an hour. The antihuman serum should be of such a strength that 0.01 cubic centimeter will deflect when treated with 0.0001 of human serum. In general they recommend of such a serum the use of 0.02 cubic centimeter as a basic amount for future work and further(12) that the amount of human serum used in the test should be small, 0.0001 being a good dose for testing. In the deflection experiment,.they(11) use 1 cubie centimeter of a 5 per cent suspension of serum-free sheep’s corpuscles in 0.85 per cent salt solution treated previously with 0.0015 of hemolytic serum, which is just twice the lytic dose. In other test tubes quantities of human serum varying from 0.01 to 0.000001 are mixed 0.1 of antihuman serum and 0.05 of guinea-pig serum;? after standing for an hour these tubes are treated with the sheep’s corpuscles previously laden with -amboceptor. The mixture is placed in the incubator two hours, transferred to ice, and the results noted in the morning. *In a later report they use 0.1 cubic centimeter of guinea-pig serum. 366 MARSHALL AND TEAGUE. In testing blood stains in their three forensic cases, they(12) made extracts of the stain with normal salt solution using very small amounts of the solution. The work of Neisser and Sachs has been repeated and its value tested by Sehiitze(14), by Bruck(15, 16, 17) and by Bauer(18). _ The antisheep serum used by Schiitze(14) is of such a strength that 0.0005 to 0.00033 cubic centimeter dissolves 3 cubic centimeters of 5 per cent suspension of sheep’s corpuscles when treated with 0.1 cubic centimeter of fresh guinea-pig serum. He(14) immunizes rabbits either by intravenous inoculation of 3 cubic centimeters of human blood repeated three times or by subcutaneous inoculation of 8 or 10 cubic centimeters repeated five times. One week after the last inocula- tion the blood is drawn from the animal, the serum placed upon ice to clear, after which it is centrifugated and inactivated for one-half hour at 55°. ; He makes his various dilutions in such a manner that the required amount of each constituent is contained in the volume of 1 cubic centimeter, the total of volume in each test tube being brought up to 5 cubic centimeters with salt solution. Bruck(16) immunized rabbits by intravenous inoculations of 2 to 3 eubie centimeters of serum repeated after eight day intervals and the blood was drawn a week later. Of this serum 0.1 cubic centimeter usually precipitated the homologous antigen in a dilution of 0.1 or 0.05. With such a serum he could differentiate between the blood of the European, Chinaman, Arabian, Malay and monkey, by definite quantitative differences obtained in the reaction. In differentiating between the serums of various human races two inoculations of the rabbits gave such a strength that using 0.1 of the serum with 0.1 of com- plement, deflection was obtained with 0.001 of the tested serum. Stronger serums gave doubtful results. Bruck emphasizes particularly the importance of using small doses for inoculating and immunizing the rabbits, so that only very low im- munity is obtained. Acting upon this idea in a subsequent series of experiments, Bruck(16) immunized rabbits with 0.5 cubic centimeter every five days, giving three doses intravenously and ten days after the last dose withdrew the serum from the animal and tested it for its deflecting power. With this serum he could differentiate blood, pus and semen, from the same individual, using monkeys for obtaining the antigen for inoculation. In this test he used 0.1 of guinea-pig serum, 0.1 cubie centimeter of sheep’s corpuscles plus two dissolving doses of hemolytic serum, 0.1 cubie centimeter of antigen and a weak immune serum in dilutions varying from one-twenty-fifth to one-four hundredth. The controls which are used vary according to the purposes for which the test is performed. The general plan of the experiments of Neisser and Sachs, Bruck and Schiitze with the controls and results are shown in the appended tables. The following table, No. IV, of Neisser and Sachs(11) shows that the deflection is produced by human serum and that the reaction is specific, being given by no other serum except slightly by that of monkeys. 0.1 cubie centimeter of antihuman-rabbit serum-+0.05 cubic centimeter guinea pig-serum-+-varying amounts of various normal serums as possible antigens—- normal salt solution up to 1 cubic centimeter are brought together. After stand- i A STUDY OF FIXATION REACTIONS. 367 ing 1 hour at room temperature the mixtures are added to the hemolytic com- plex= (0.0015 antiox-rabbit-+-1 cubic centimeter 5 per cent sheep’s red blood corpuscle suspension) . TaBLe IV. Heemolysis produced with serum from— Amount of 7 7 | Semis Man. Monkey. Rat. Pig. Goat. Rabbit. Ox. Horse. Ne SCS 0 0 | Complete} Complete) Complete] Complete) Complete Complete| . 001 0 0 6 Ie | a OO | D2) We, | 0001. 0 | Moderate|___do ____ 60 |. Lo.) De, | .00001_} Trace____| Complete]____do -___|___.do __ |__-do aol eK) el [--a(CKo) =] IDO} | 000001) Complete;__-*do ____|____do -___|____do ____|____do 256 se I!) I, ODA OO I OO CO to | we, | | | | In this table the presence or absence of hemolysis is noted. It must be remembered that deflection is indicated by the absence of hemolysis, so that the first three or four tubes with human serum, and the first two with monkey serum are the only ones in which deflection has taken place. The table of Schiitze, No. V(14) shows deflection with human serum. The sheep’s corpuscles and hemolytic serum are mixed separately and not added until the other materials have been mixed and incubated for one hour at 37°. TABLE V. [Each ingredient—1.0 cubic centimeter, total volume 5 cubic centimeters. ] s os ; | | | Human ante i; piowekadi Antisheep | Sheep cor serum. human comple- serum. puscles, 5 Result. serum. ment. eT Ce nL: | 01 | 0.1 0.1 - 002 | 5 | Complete blocking of hzemolysis. 001 | 0.1 0.1 002 | Silos 0001 0.1 || 0.1 002 | 5 Do. | - 00001 0.1 0.1 - 002 | 5 | Appreciable blocking of hzemolysis. | | - 000001 | 0.1 0.1 - 002 | 5 | Heemolysis. | oOilaet Ge; |eea—a= 0.1 - 002 | 5 | Complete hemolysis. saltsol. |. | ! | 0.0 | 0.141 ce. 0.1 | 002 | || Do. | | salt sol. | | 0.0 | 0 0.1+2 ee. 002 | 5 | Do. | salt sol. | 0.0 0 | 0 | .002+-3 ce. | 5 | No hemolysis. | | | | salt sol. | } 0.0 0 | 0 | 0 || 5-F4! ce. Do. | | salt sol. | 1 1 368 MARSHALL AND TEAGUE. TasLp VI.—Comparison between fresh pig’s serum and pig’s blood dried on linen about three months. | | Sheep | Anti- Guinea-} Anti- cor- Pig’s serum, or pig’s blood spot. pig pig com-| sheep | puscles, Lysis. | serum. |plement.| serum. 5 per | | cent Serum: 501, = 2526--* == a: BAe 0.1 0.1 . 002 5 0 | Serum . 001 --- oe | 0.1 0.1- . 002 5 0 Serum . 0001 _ ihe 0.1 | 0.1 . 002 5 0 0.1} 0.1 - 002 5 0 | 0.1 | 0.1 002 5 Lysis. | 0.1 0.1 - 002 5 Lysis. 0 | 0.1! 008 5 | Complete. | 0 0.1 - 002 5 | Complete. 0.1 0.1 . 002 5 | Complete. 0 0.1 . 002 5 | Complete. Neisser and Sachs(13) and Schiitze(14) call attention to the fact that the very sensitiveness of the test lays it open to error, and in testing for the specificity of a drop of blood on a piece of cloth, error may arise from the fact that the cloth may be contaminated by sweat or nasal secretion, or some other organic body substance. They therefore use as one control a test made with éxtracts from the cloth adjacent to the blood clot but free from blood. Neisser and Sachs also used a control with boiled extract, as boiling removes the specific action of the serum deflection. All tests in which there is evidence of bacterial action must be discarded (14). Schiitze(14) (Table VI) dried pig’s blood on linen for three months and made a comparative test of this material with fresh pig serum with the deflection technique. One drop dried on a piece of cloth about 2 cubie centimeters in diameter dissolved in 2 cubic centimeters of salt solution and the extract cleared and filtered, had a deflecting strength of 0.01, while the fresh serum had a deflecting strength of 0.0001, the reaction being specific. It is seen that there is an abundance of experiments which prove that when carefully performed, the deflection test is just as reliable as the precipitin test in differentiating between blood from different species, and that Neisser and Sachs, Schiitze and Bruck, have found it possible to use it where the precipitin test is not available. - Neisser and Sachs recommend the adoption of the deflection test in forensic procedure, as a supplement to the precipitin reaction. They point out that it has certain advantages over the precipitin test which are: That it acts as a control for the precipitin method; that hemolysis is a much more definite index than minute precipitation; that an opalescent serum is available for use; that it is not necessary to have such high potency serum as is needed in the precipitin test and that it is not necessary to wait for the tlearing of the serum, which is so tedious in the older test. They recommend in every forensic case in which the diagnosis of blood must be undertaken that the precipitin test be performed and upon its completion fresh guinea-pig serum (1.0 cubie centimeter of 1:10 dilution) be added to each tube and the same materials be employed in making a deflection test. Schiitze agrees with Neisser and Sachs as to the value of the deflection test, while Bruck goes a step further. He recommends that the precipitin test be followed by a deflection test in which moderately strong immune serum is em- ee a A STUDY OF FIXATION REACTIONS. 369 ployed in order to obtain a racial differentiation, and thereafter a second deflec- tion test be performed with weak immune serum for more delicate differentiation between the various body tissues or secretions. INTERPRETATION OF RESULTS. Clear cut results with satisfactory controls are received as conclusive by almost all observers. However, a large measure of confusion has been caused by the fact that some one or more controls are often omitted or because the resulting deflection is not as absolute as could be desired. When Wassermann first put forward this method he advanced the opinion that a positive result could be obtained only in the event of antibody and antigen uniting. ‘The greater amount of work of this nature has been done in the investigation of suspected syphilitic serum, and up to the present time but few cases have been reported in which a positive result was obtained from a patient unquestionably free from infection. These few exceptions will be discussed later together with the change in the interpretation of the reaction which has been brought about by the rapid accumulation of fresh data. It may be stated that practically all investigators agree that the serum: diagnosis proves more quickly and more certainly than any other method whether syphilis is or has been present. However, there are a number of other causes which produce deflection of a non-specific character. Bruck(15) reports that serum can be modified in its action by heat. Treatment at 55 degrees for half an hour usually reduces the power so that it is rare to obtain deflection with less than 0.3 cubic centimeter of such a serum. Normal monkey serum when heated for half an hour to 60 degrees acquires strong powers of deflection so that 0.1 will bind four times the dissolving dose. of complement twice in succession, or in a single quantitative experiment will bind ten times the dissolving dose. Bruck compares this with the Pfeiffer-Friedberger reaction within the normal body. He finds that monkey serum is affected by heat in this manner with great regularity, guinea-pig serum less frequently, and rabbit serum still less. If the temperature is raised to 65° within 15 minutes the deflecting power is completely destroyed. He thinks it probable that the changes in deflec- tion are due to molecular changes comparable to those occurring on long standing. In the serum diagnosis of syphilis it has been frequently observed that a specific Iuetic serum will react with extracts of normal organs, particularly if a large amount of extract is employed. LHven in this case, however, it is always necessary to employ a luetic serum in the test. Wassermann(19) was at first inclined to believe that this was a peculiarity of old extracts, but this does not seem to be the case. A positive deflection may sometimes be observed in the control with an extract of liver itself, and Michaelis(4) also found that normal, non-deflecting serums may become deflecting after being kept frozen for a long time. 370 MARSHALL AND TEAGUE. Bruck(17) found that his strong immune serum alone would cause deflection in the amount of 0.05 cubic centimeters, and Uhlenhuth(20) gives us a long list of substances of diverse nature which will produce non-specific deflection. Selig- mann(21) concluded that absorption of complement is brought about by altering the molecular condition of the colloids in solution, even without causing precipi- tation. He states that his experiments do not explain the specific immunity reaction, but serve to show that there are other non-specific reactions of a similar nature. Landsteiner(22) noted deflection when the syphilitic serum was used with extracts from the organs of normal animals, for instance, guinea-pigs’ livers, or with alcoholic extracts of organs. We will describe below in more detail the nature of this process as well as the deflection with sodium oleate and lecithin. However, the positive reactions which are not specific are of such a nature that they do not prevent a careful worker from employing the deflection method with a degree of certainty that is at least comparable to that attaching to many generally accepted clinical methods. Although a positive fixation reaction with suitable controls give us certain evidence of the existence of syphilis, a negative reaction does not give the same proof of its non-existence. There are various possible sources of error which must be borne in mind in the interpretation of negative results. According to Michaelis and others, the syphilitic extract of liver is occasionally hemolytic itself. This function may more than compensate for any possible deflection; aqueous or alcoholic extracts of the liver are very unstable and it is not infrequent that a preparation which has proved satisfactory one day is per- fectly useless on the next, and almost all extracts deteriorate on standing. There are also other possible causes which may lead to a negative reaction. They may be summarized as follows: (a) the patient has no syphilis and has never had it; (0) the patient has been completely cured of previous disease; (c) the serum is obtained from a patient during a temporary absence of the specific complement-binding substances from the blood of the patient ; (d) there are certain refractory individuals whose serum always fails to deflect; (e) under energetic mercurial treatment it occasionally happens that the deflecting power disappears. It has also been observed that the reaction is less constant in the early stages and increases in regularity with the age of the disease. The preceding discussion shows that the particular value of the deflection methods in clinical medicine at present is in the diagnosis of syphilitic diseases. As Wassermann remarked(19) in December, 1907: “It is, up to the present time, more valuable than the Widal test was after an equal trial *~ * *. Probably as with the Widal test, some cases will be found which give a positive reaction, although there is conclusive reason to believe that syphilis is not present, but no such cases have been observed so far.” He summarizes about 1,500 cases in which the serum diagnosis of syphilis has been attempted, in the great majority of which results were eminently satisfactory. Citron notes that in the primary stages 90 per cent were positive, in the secondary stage between 98 and 100 per cent, in the late cases where the process is active the reaction is practically universal. a A STUDY OF FIXATION REACTIONS. 371 The diagnostic value of the test has already been very great to the clinician, the surgeon and neurologist, and to other specialists, and Proskauer professes to employ it as a routine autopsy procedure. The former article of Marshall(1) showed that there was considerable discussion over the theoretical interpretation of this reaction. Wasser- mann’s idea that it indicated the union of syphilitic antigen with syphilitic antibody at first found almost universal acceptance. However, Michaelis(23) very soon pointed out that the differences observed in the action of syphilitic serum toward syphilitic liver extract and toward normal liver extract were quantitative rather than qualitative. Then it was shown, as has been mentioned, that syphilitic serum gave positive reactions with extracts of normal organs, with lecithin and with sodium oleate and when comparative tests were made these substances yielded practically the same percentage of positive results as were obtained with the extracts of syphilitic liver. Hence the idea that the reaction was concerned with syphilitic antigen and antibody had to abandoned. Elias, Neubauer, Porges, and Salomon(24) regard the reac- tion as a precipitation reaction between colloids, the proteins of syphilitic serum having greater instability and yielding a wider flocculation zone than non- svphilitie serum with certain hydrophilic colloids, such as extracts of organs, lecithin, sodium oleate, and scdium glycocholate. Although the reaction is not specific in Hhrlich’s use of the term, yet almost all observers agree that it has a high degree of clinical specificity. Weil and Braun(25) report positive findings in pneumonia, typhoid, tuber- culosis, diabetes, and malignant growths, but their results have not been con- firmed by others. Much and Eichelberg(26) obtained positive reactions in 40 per cent of the scarlet fever patients subjected by them to the test. Seligmann and Klopstock(27), Hoehne(28), and Schliessner(29), however, report only neg- ative results in scarlet fever. Wechselmann and Meier(30) and Hitner(31) obtained positive results in two cases of leprosy. In contrast’ to the above exceptions, to which a few others could be added, the general verdict is that Wassermann’s sero-diagnosis of syphilis is clinically specific. We have thus far considered the application of the deflection of complement to the diagnosis of syphilis and to the differentiation of the blood of various species of animals. On treating the extract of bacteria with the serum of an animal immunized against the same bacteria, deflection of complement is likewise produced and the application of this principle bids fair to furnish an important addition to bacteriologic technique for the differentiation of closely related microorganisms. The attempts of Ballner and Reibmayr(32) to differentiate the capsule bacteria and of Gengou(33) to distinguish between the acid fast bacilli by this method were unsuccessful. Schiitze(34) concluded that the method was of no value in the study of cholera-like organisms, whereas Ruffner(35) claimed that it enabled him to differentiate between the strains of El] Tor and of true cholera and was hence more delicate than the agglutination test. Leuchs(36) could distinguish between typhoid, paratyphoid and the colon bacillus and Vannod(37) between 372 MARSHALL AND TEAGUE. the meningococcus and gonococcus. Wollstein(38) obtained results contradic- tory to those of Vannod(37), but Teague and Torrey(39) were able to confirm Vannod’s work and to show that furthermore differences such as Leuchs had found between typhoid and paratyphoid extracts exist between certain strains of gonococci. MKolle and Schatiloff(40) after having obtained negative results on using complement deflection in the study of experimental recurrent spiro- chetosis in mice and rats, finally obtained serum from a man suffering from the disease and with this were able to differentiate between the different varieties of spirocheti. Various attempts have been made to apply the method to the diagnosis of bacterial diseases by testing the serum of the patient against an extract of the bacterium in question. In gonorrhceal rheumatism positive results were obtained in a fair percentage of cases by Miiller and Opperheimer(41), Briick (42), and Mea- kins(43). Positive findings were also reported in typhoid and paratyphoid fevers by Leuchs(36). Except in its application to the diagnosis of syphilis, where the interpretation of the reaction has already been discussed, the original view of Bordet and Gengou that the method indicates the union of antigen and antibody has been very generally accepted and it is believed by most investigators that it is an antibody sui generis which is concerned here and not the precipitins, agglutinins or bacteriolytic amboceptors. PRECIPITIN TEST. The value of the precipitin test has been so thoroughly established by the work of Nuttall, Wassermann, Uhlenhuth and many others, that it is unnecessary to review the literature upon this subject. However, there are a few recent works that may be mentioned briefly. Carnwath(45) has of late described a modification of the technique by which he is enabled to obtain a positive result with very minute amounts of material. The essentials are that the minute blood stain is dissolved in a very small amount of salt solution; that very small glass tubes about 2 millimeters in diameter and 6 millimeters long are employed for the test; that the specific antiserum is introduced by means of a capillary pipette and upon this the suspected fluid is carefully placed in a separate layer. A positive reaction is shown in a few seconds at the zone of contact of the two fluids as a cloud, which gradually spreads upward. This method is very delicate and enables the observer to secure definite reactions with minute quantities of antiserum and of antigen. Carnwath was also able to apply the Neisser and Sachs method of following the precipitin test with the deflection test with these minute quantities, but he agrees with Uhlenhuth that this is unnecessary. Uhlenhuth in 1903 concluded that it is better in forensic cases to employ only such an antiserum as would produce a definite clouding within one or two minutes with a 1: 1000 dilution of the suspected material when there is one part of serum to 20 of the dilution. : Michaelis and Dehne(46) find that a specific precipitate is dissolved in the presence of an excess of undiluted homologous antigenetic serum. Dehne finds that this is particularly valuable to supplement the test with very minute quantities of antigen; the homologous serum from the known species being added in case of the positive reaction with the extract of suspected material. He also finds that when a specific antiserum produces clouding with the heterol- ogous serum, the precipitate is dissolved equally well by the addition of homol- ogous or heterologous serum. A STUDY OF FIXATION REACTIONS. 373 Weichardt(46) and Stranon(47) attempt to distinguish between individuals by obtaining a highly immune serum, determining its exact value, dissolving as much as possible of the antibody with the serum to be tested and finally adding serum from the homologous individual to determine how much antibody remains. Loele(48) finds he has satisfactory results with precipitin when the material used for inoculating his rabbits was preserved with two per cent for- malin in normal salt solution. EXPERIMENTAL WORK. In two cases we were called upon to determine the nature of suspected blood stains upon some clothing of natives accused of murder. In the first case the accused alleged that the stains were chicken blood. There were minute flecks upon the surface of a cheap khaki garment which had not been absorbed into the fiber. The stains were examined about five months after the murder, having been kept meanwhile in a safe at room “temperature. Extracts made with distilled water and subsequent addition of 1.7 per cent salt solution were colorless, the sediment having a dark, brown color. The hemin test, precipitin and fixation tests were all negative, and we concluded that the stains were not due to blood. The fixation and precipitin tests were conducted both with antihuman and antichicken serum. Tn the second case there was a stain on a cheap cotton garment, which measured about 1.5 by 1 centimeter. The stain had penetrated the fiber and gave an extract which was positive for hemin crystals, and which gave excellent precipitin and fixation reactions with antihuman serum. The accused claimed that the blood was from a carabao, but as neither precipitin nor fixation tests could be obtained by using anti- carabao serum with the stain, we made a diagnosis of human blood. In this latter case the precipitin test was eminently satisfactory and gave an excellent ring of precipitate in varying dilutions of the extract. The fixation test also yielded excellent results. Since in the Philippine Islands and particularly in Manila four races of men, Malay, Mongolian, Caucasian and Negro are represented, it would be of no small importance medico-legally, if we could distinguish between these bloods by means of biologic tests. Bruck(16) had already claimed that this could be done by means of the deflection method, before we undertook these experiments to determine whether either the deflection method or precipitin test furnished sufficiently reliable results for this purpose. At the same time a comparison of the two methods was made in the differentiation of the blood of the various species of cows to be found in Manila. : A number of rabbits were immunized, some against Caucasian blood, others against Filipino, monkey (Cynomolqus philippinensis Geoft.), chic- ken, and carabao serums. Of the antiserums obtained, one anticarabao 77851——2 374 MARSHALL AND TEAGUE. serum gave precipitation with normal salt and with all mammalian serums, though not with chicken and duck serum; another serum, an anti-Malay (Filipino) serum, gave some reaction with the serum of a rat; otherwise all of the antiserums were specific as is shown in the following table: TasLe VII.—Precipitin reactions. Serum of | Serum of | Serum of Serum of | Serum of Dilution of sora) cet an | on ance ae iii rabbit | bit No. rabbit | bit No. | rabbit No. 3168. 3167. No. 3195. 3008. | No. 1214. | | Caucasian _______| + + + | + | 0 Filipino + + + 205 || Monkeyes= aia + se = 0 Carabao _________ 0 0 (Oasys Ole et Oa a0) Ona wOreer mice 0 0 Ole as ike Ob oy eet OG | @ OSE McD | 0 0 0 aR 0 0 + 0 4 0 Pieces of filter paper were moistened with a drop or two each of various serums and were allowed to dry and remain at room temperature for from one to three months. They were then extracted with distilled water and an equal volume of 1.7 per cent salt solution was added to each preparation. These extracts were tested against each of the varieties of precipitin serum and it proved easy to differentiate the albumens in this way. By using an anti-Caucasian and antimonkey serum with varying dilutions of the extracts it was not difficult to distinguish even between monkey and human serum. The precipitin technique used throughout the experiments was the ring method. A drop of undiluted antiserum was placed in a small tube of from 3 millimeters to 6 millimeters in diameter; upon this a dilution of test material was placed with care to preserve the line of contact between the two fluids. A precipitin reaction became evident very quickly in a ving of precipitum at the junction of the two fluids, exactly resembling the albumen ring in the nitric acid test for albuminous urine. It was found that most accurate readings could be made in from 15 minutes to about one hour, the reaction being less distinct after mixing of the two fluids occurs. é The technique of the deflection method has already been discussed at length. A specimen of Caucasian blood was obtained from an American and specimens of blood were also obtained from a Negro, Chinese, Japanese, Negrito, Tagalog and monkey. Dilutions of these serums were prepared A STUDY OF FIXATION REACTIONS. 375 and simultaneous tests were conducted by the precipitin and fixation methods. The results were as follows: Precipitin limits of anti-Caucasian serum No. 3332. Monkey 1 to 1,000. Negro* 1 to 800. Negrito 1 to 1,000. Chinese 1 to 2,000. Tagalog 1 to 2,000. Caucasian 1 to 3,000. Japanese 1 to 3,000. Precipitin limits of anti-Filipino serum No. 3167. Tagalog 1 to 2,400. Negro 1 to 1,800. Chinese 1 to 2,400. Negrito 1 to 1,800. Japanese 1 to 2,400. Caucasian 1 to 1,200. Monkey 1 to 1,000. The limits here recorded indicate the greatest dilution of the serum which still gave a trace of reaction with the antiserums and, as it is extremely difficult to determine with certainty the exact position of these limits, it seems to us that the differences obtained can have but little, if any, practical value. However, the anti-Caucasian serum does precipitate Chinese, Japanese, Tagalog, and Caucasian serums at greater dilutions than it does monkey, Negro, and Negrito and likewise the anti-Filipino serum gives precipitation with greater dilutions of Filipino, Chinese, and Japanese serums than with those of the Negro, Negrito, Caucasian, and monkey. This last finding is especially interesting because it is directly contradictory to the rather remarkable conclusion arrived at by Bruck(16) from his deflection experiments. He found that anti-Cau- casian serum gave deflection with Caucasian serum 1 to 1,000, Arabian 1 to 900, Chinese 1 to 700, Malay 1 to 500; that anti-Chinese serum showed the same limits with Chinese and Caucasian serums, but required more of the Malay serum; that with anti-Malay serum the same limits were obtained for all three serums. He therefore concludes that the protein of the Caucasian contains all the groups of the Chinese and Malay proteins and in addition certain groups peculiar to itself; that the protein of the Chinese contains all the groups of the Malay and certain other groups not contained in the Malay protein. In deflection of complement tests conducted with dilutions as close together (600, 700, 800) as is indicated in Bruck’s tables, the difference in the degree of hemolysis in the adjacent tubes is so slight that it becomes very difficult to say where the limit of deflection lies and we believe that Bruck’s tables indicating a sharp dividing line between the blocking of haemolysis and hemolysis are misleading, although we As the Negro serum was cloudy, it was subjected to repeated centrifugation during the course of these tests and a not appreciable amount of proteid matter was thus removed, so that the dilution was probably really greater than 1 to 800. 376 MARSHALL AND TEAGUE. recognize the fact that in all probability his results were so tabulated simply for the sake of clearness in presentation. It would appear to us, therefore, that Bruck was not justified in assuming such a fundamental difference in the biological reaction on the basis of such slight experi- mental differences, and we are confirmed in this opinion by the fact that our precipitin experiments indicate that the established laws of the biological reaction hold also for very closely related serums. In our hands the deflection test with anti-Caucasian and anti-Filipmo serum showed differences between monkey and Negro on the one hand and Caucasian, Filipino, Japanese, and Chinese on the other, although we could not distinguish with certainty between Filipino, Caucasian, and Chinese as Bruck claimed he was able to do. Hence we conclude that neither the deflection of complement method nor the precipitin reaction can be used with safety in medico-legal cases to distinguish between the bloods of different races of men. A further comparison of the two methods was made with the serum of rabbits immunized to carabao serum, and the results are recorded below: Precipitin limits with anticarabao serum (average of three determinations) . Carabao, 1 to 3,000. Chinese cow, 1 to 900. Native cow, 1 to 900. American cow, 1 to 650. Goat, 1 to 150. The precipitin tests indicate that the native Filipino and Chinese cow are equally removed from the carabao, the American cow being further removed than either of these. The deflection tests gave less clearly defined results than the. precipitin reaction and showed the American and Chinese cows to be about equally removed from the carabao, the native being still further removed. It has been shown repeatedly that the antibody concerned in the deflection of complement is not identical with the precipitins, but nevertheless the lack of agreement in the instance cited is rather striking and indicates that the real nature of the deflection reaction has not yet been fathomed. REFERENCES. (1) Marshall, H. T.: This Journal, Sec. B. (1907), 2, 343. (2) Wassermann, Neisser, Bruck, and Schucht: Ztsehr. f. Hyg. wu. Infections- krankh. Leipz. (1906), 55, 451. (3) Meier, Georg.: Berl. Klin. Wehnsch. (1907), 44, 1636. (4) Michaelis, Leonor; Lesser, Fritz: Berl. Klin. Wehnsch. (1908), 45, 301. (5) Morgenroth and Stertz, Arch. f. path. Anat. Berl. (Virchow’s Arch.) (1907), 188, 166. (6) Marie and Levaditi: Ann. de L’ Inst. Pastewr (1907), 21, 138. (7) Wassermann and Citron: Deutsche med. Wehnsch. (1907), 33, 1165. (8) Wassermann and Plaut: Jbid (1906), 32, 1769. (9) Landsteiner and Stankovic: Centrbl. f. Bakteriol. Orig. (1907), 44, 353. (10) Miihsam, Hans: Berl. Klin. Wehnsch. (1908), 45, 14. a A STUDY OF FIXATION REACTIONS. BI (11) Neisser and Sachs: Jbid (1905), 42, 1388. (12) Neisser and Sachs: Jbid (1906), 43, 67. (13) Neisser and Sachs: Deutsche med. Wehnsch. (1906), 32, 1580. (14) Schutze, Albert: Berl. Alin. Wehnsch. (1906), 43, 1646. (15) Bruck, Carl: Zbid (1907), 44, 1510. (16) Bruck, Carl: Jbid, 793. (17) Bruck, Carl: Deutsche med. Wehnsch. (1906), 32, 945. (18) Bauer: Arbeiten aus d. koenigl. Inst. f. exp. Ther. zu Frankfurt, (1907), 71. (19) Wassermann, A.: Berl. Klin. Wehnsch. (1907), 44, 1599. (20) Uhlenhuth, Deutsche med. Wehnsch. (1906), 32, 1244. (21) Seligmann: Berl. Klin. Wehnsch. (1907), 44, 1013. (22) Landsteiner, K; Miiller, R; Pétzl, O: Wien. Klin. Wehnsch. (1907), (23) Michaelis: Berl. Klin. Wehnsch. (1907), 44, 1103. (24) Elias, Neubauer, Porges, and Salomon: Wien. Klin. Wehnsch. (1908), (25) Weil and Braun: Jbid, 938. (26) Much and Hichelberg: Med. Klinik (1908), No. 18, 671. (27) Seligmann and Klopstock: Berl. Klin. Wehnsch. (1908), 45, 1719. (28) Hoehne: Jbid, 1717. : (29) Schliessner: Wien Klin. Wehnsch. (1908), 21, 1375. (30) Wechselmann and Meier: Deutsche med. Wehnsch. (1908), 34, 1340. (31) Hitner: Wien. Klin. Wehnseh. (1908), 21, 729. (32) Ballmer and Reibmayr: Arch. f. Hyg. (1907), II, 64, 113-154. (33) Gengou: Berl. Klin. Wehnsch. (1906), 43, 1531. (34) Schiitze: Zbid (1907), 44, 800. (85) Ruffner, M. A.: Researches on the bacteriological diagnosis of cholera, Alexandria, (1907). (36) Leuchs: Berl. Klin. Wehnsch. (1907), Nos. 3 and 4. (37) Vannod: Centrbl. f. Bakteriol. Orig. (1907), 44, 10, 110. (38) Wollstein: J. Hap. Med. (1907), 9, 588. (39) Teague and Torrey: J. Med. Research (1907), 17, 223. Kolle and Schatiloff: Deutsche med. Wcehnsch. (1908), 34, 1176. Miiller and Oppenheim: Wien. Klin. Wehnsch. (1906), 29, 894. Bruck: Dewtsche med. Wehnsch. (1906), 32, 945. Meakins: Johns Hopkins Hosp. Bull. (1907), 18, 225. Carnwath: Arb. a. d. k. Gsndhtsamte, Berl. (1907), 27, 403. Michaelis and Dehne: Miinchen. med. Wehnsch. (1907), 54, 357. Weichardt: Hyg. Rundschau. (1903), 13, 756. Stranon: Verhandl. d. Naturforscher u. Aerzte, 77. Loele: Miinchen. med. Wehnsch. (1906), 53, 21. Cars eo BO SNS Ses ae Pes) ae eS een ars é bang) h Pe iane ra TUBERCULO-TOXOIDIN AND IMMUNIZATION SERUM.’ By T. IsHicamr.? One of the great misfortunes of mankind is that as yet there is no perfect scientific method of successfully combating man’s stubborn enemy, tuberculosis. In my belief, the only rational and promising cure for this disease in modern thereapy is the bacteriologic one. As Koch’s preparations prove efficacious on incipient tuberculous pa- tients in many instances only when administered with a careful avoidance of the reaction, the first and most natural step to be taken in our study of the cure is one toward methods of obviating the reaction. After continuous investigations for more than ten years, I have succeeded in preparing two remedial agents of comparatively great efficacy and free from any detrimental reaction. (1) The first is a chemical preparation from tubercle bacilli and is applicable to incipient and feverless patients. (2) The other is an immune serum and is applicable chiefly to patients in an advanced stage of the disease. I introduced these in the belief, based on my own experience of several years, that they were harmless and effective, although not absolutely infallible remedies for tuberculosis. I have since received the corrobora- tion of many practitioners who recognize their efficacy and harmlessness. In this paper I will attempt to describe them briefly. TUBERCULO-TOXOIDIN. This preparation is made by chemically dissolving the tubercle bacilli and modifying their toxic property, thus eliminating the reaction which is the common detriment of all other preparations made from tubercle bacilli. According to the aneders theory of immunization, a strong immunity can not be attained without employing strong toxin. Therefore, the question will naturally suggest itself as to whether immunization can be imparted by employing a chemically transformed and harmless toxin. My honored masters, Professors Kitasato and Behring, succeeded in 1Read at the Fifth Annual Meeting of the Philippine Islands Medical As- sociation, Manila, P. I., February 28, 1908. 2 Director of the Ishigami Institute for Infectious Diseases, Osaka, Japan. 379 380 ISHIGAMI. achieving their epoch-making discovery of the serum therapy of tetanus and diphtheria by first attenuating the virus by means of chemical reagents and then immunizing animals with it. Ehrlich’s tetanus-toxoid, which is obtained by chemically treating the virulent toxin until it is harmless to animals, still retains the power to immunize them and to neutralize the anti-toxin. Considering these facts, it is quite a natural step to apply the same principle to the subject of tuberculosis and to expect a successful solution of the problem. From my own experience of many years, I find that for the purpose of curing tuberculosis, bacterial immunization is neces- sary and that, as the absorption of the tubercle bacilli from the sub- cutaneous tissue of man and animals is extremely difficult, they must first be chemically dissolved and thus made absorbable. METHODS OF PREPARING TUBERCULO-TOXOIDIN. The culture of the tubercle bacilli is well soaked and washed with water to remove the soluble toxin. It is then thoroughly dried and weighed, and, after washing again with water, it is treated with strong sulphuric acid in order to disintegrate the bacterial body and thus extract the inner-toxin and change its toxicity. Then, after adding a large amount of water, stirring and allowing to stand for some time, the fats and aromatic oil rise to the surface, leaving the active substance in the bottom in the form of a precipitate. This precipitate is gathered on a filter paper and well washed with distilled water until it becomes neutral. Five-tenths gram of the dried product is dissolved in 100 cubic centi- meters of a solution of weak alkali to form a brown, clear liquid. Although the preparation of tuberculo-toxoidin is such a simple matter, the duration of soaking in the sulphuric acid must be carefully regulated according to the virulence of the bacilli; otherwise the toxicity may still remain too great, or the whole may be rendered useless by carbonization. Therefore, more or less skill in manipulation is required in preparing the toxoidin. ; This substance when injected subcutaneously in man or animals is easily absorbed without local irritation, and, as the toxic property is already changed, comparatively large doses can be injected without harm; yet while it is harmless, it is as effective in immunizing man and animals as Hhrlch’s so-called tetanus-toxoid. Hence the name “tuberculo- toxoidin.” _ = The following experiments on animals demonstrate the efficacy and harmlessness of the preparation : (1) Test of toxicity—No reaction was obtained by the injection of 10.0 cubic centimeters of the tuberculo-toxoidin into the peritoneal cavity of a tuberculous guinea pig, which would have succumbed in twenty-four hours to an injection of 0.1 cubie centimeter of Koch’s old tuberculin. TUBERCULO-TOXOIDIN AND IMMUNIZATION SERUM. 381 (2) Prophylactic test—Guinea pigs injected subcutaneously with 1.0 cubic centimeter of the toxoidin are generally found to be immune against the inocula- tion of tubercle bacilli from the fourth until the fourteenth day after the operation. (3) Therapeutic experiments.—If the treatment of a guinea pig subcutaneously inoculated with tubercle bacilli commences within one week of the inoculation, and 0.5 to 1.0 cubic centimeter of the toxoidin is injected subcutaneously about ten times, the disease will either be cured or prevented from making further progress. If, two or three weeks after the inoculation of bacilli, the injection of the above doses is made into an animal with greatly swollen glands, the swelling subsides, the body weight increases, and the fatal period is postponed; whereas a control animal dies in three months, the test animal receiving injection treat- ment lives over a year. When such an animal is killed, autopsy demonstrates that the tuberculous lesions of the organs are not entirely healed. This is due to the fact that guinea pigs are too susceptible to tubercle bacilli to allow of a complete cure. A noteworthy fact is that in the guinea pigs treated with the toxoidin, the visceral tubercles generally show a tendency to heal and the number of cells containing bacilli is much greater than in those which have not been thus treated. Moreover, the bacilli in the cells are small and short, evidently representing a degenerate form. CLINICAL APPLICATION. From my own experience and the reports of other practitioners who have tried the preparation, the following conclusions may be drawn: (1) By injecting the preparation in a gradually increasing dose into tuber- culous patients without fever, almost every one of them increases in body weight and vital capacity, and becomes conscious of the alleviation of the symptoms. (2) The bacilli in the sputum are gradually broken up and agglutinated and finally disappear, although in some rare cases small amount of expectoration containing bacilli are found for a long time. (3) The quantity of opsonin in the patients’ blood is found gradually to increase by the injection treatment. ; (4) The incipient and feverless tuberculous patients, almost without excep- tion, can be completely cured from within three to six months by injection of this preparation. (5) In patients in a more or less advanced stage, if nutrition is good, similar results can be obtained. In feverish patients, a satisfactory result is often obtained by means of the injection used side by side with antipyretics. In more serious cases, beyond a certain degree, the treatment is quite useless. (6) Those patients who are once cured or alleviated by this treatment only very seldom suffer from a second attack. (7) Out of a total of 772 tuberculous patients, each of whom had received more than fifteen injections of tuberculo-toxoidin in my clinic within the past few years, there were 274 who were completely cured and 258 who were partially cured. These last two figures added together make 532, being 68.91 per cent of the total number of patients. Those who for various reasons discontinued the treatment numbered 107; those who died numbered 29; the remainder, 104. (8) Out of a total of 778 patients treated with the tuberculo-toxoidin (injected oxen ISHIGA MI. more than fifteen times) by other practitioners, there were 232 who were com- pletely cured and 228 who were partially cured. These last two figures com- bined make 460, equal to 59.13 per cent of the total number of patients. Those who discontinued the treatment for various reasons numbered 162; the deaths 63; and the remainder, 93. IMMUNE SERUM. The results of previous investigators on the problem of the serum therapy of tuberculosis, although undoubtedly very valuable, have not yet reached a stage to permit of the general application of serum therapy to patients. My own investigations of previous years have also failed, because of the difficulty im immunizing animals agaist tuberculosis and of the characteristic detrimental reaction of the animal serum upon tuberculous patients. I have finally succeeded, however, by means of the injection of the tuberculo-toxoidin, in preparing an immune serum of a comparatively strong efficacy. I have also succeeded in removing the characteristic reaction of animal serum upon tuberculous patients in the manner mentioned below. When an animal serum is injected subcutaneously into tuberculous patients, there are often noticed characteristic violent reactions such as acute urticaria about the injected area, redness of the face, palpitation of the heart, increased respiration, itching of the entire surface of the skin and, though rarely, pain in the joints. All these symptoms, which disappear in from five to thirty minutes, are doubtless due, as maintained by Dr. 5. Ogata, to the agglutination of the red blood corpuscles. 8 When the serum of a goat, a cow or a horse is treated with from 2 to 3 per cent of sodium chloride, kept at 50° C. for thirty minutes, and then filtered through a Chamberland filter, it can be clearly shown under the microscope to have entirely lost the power of agelutinating the blood of tuberculous patients or of healthy people, and, usually it no longer causes any reaction, either local or general, on injection into a patient. EXPERIMENTS ON ANIMALS. When 0.1 cubic centimeter of Koch’s old tuberculin, which is the fatal dose to a tuberculous guinea pig, is mixed with 0.025 cubic centimeter of the immune serum, and the mixture after ten minutes’ standing is injected subcutaneously into a tuberculous guinea pig, there is’ not the slightest disturbance noticed in the animal. When the phagocytic phenomena are examined according to Dr. Wright’s method, my immunization serum presents decidedly more marked phagocytic activity than other sera. When 0.5 cubic centimeter of the immune ‘serum diluted to four times its volume is injected subcutaneously eyery other day into a tuberculous guinea pig with markedly swollen lymphatic glands, the swelling of the glands is ‘ereatly reduced after about ten injections. By further continuing this treatment, the course of the disease is arrested in spite of the fact that the tuberculous lesions of the organs are not yet completed healed. The microscopic sections show the bacilli engulfed in the cells becoming smaller and smaller, thus in- dicating the degeneration produced by the serum. TUBERCULO-TOXOIDIN AND IMMUNIZATION SERUM. 383 CLINICAL APPLICATION. Generally speaking, as has already been stated above, my immune serum does not when injected subcutaneously cause any local or general reaction ; still, in some exceptional cases of idiosyncrasy, a reaction may be noticed. When, however, the immune serum is administered internally as described elsewhere, it produces nearly the same results as by subcutaneous injec- tion, but without any reaction. Hence, except for cases demanding quick or local results, it will be found safer and more convenient to administer it internally. The following cases require subcutaneous injection : (1) The cases of acute tubercular cerebral meningitis in which the exudation is not yet marked. I have three records of satisfactory cures attained by injecting the serum into children who had fallen into stupor from tubercular cerebral meningitis. I have also several records of much alleviation by the serum injection of cases of cerebral meningitis appearing in the course of pulmonary tuberculosis. (2) The cases of tubercular peritonitis having painful indurations. (3) The cases of painful tubercular arthritis. In the following instances, either the injection or the internal admin- istration is employed, as the circumstances demand : ‘In eases of pulmonary tuberculosis with high fever or with disordered nutrition, when the patients are unfit for the tuberculo-toxoidin treat- ment, the serum injection is first to be resorted to. When the symptoms are alleviated and the fever disappears and nutrition is restored, the tuberculo-toxoidin is injected in the usual manner. According to the results of the serum treatment performed in my sanatarium, out of a total of 189 patients, 43 were completely cured and 63 partially cured. These last two figures added together give 106, being 56.08 per cent of the total number of patients. Those who, for various reasons, discontinued the treatment, numbered 37; those who died, 24; and the remainder, 22. (1) The average number of injections for those who were completely or par- tially cured was 55 per capita. (2) The increase and decrease of opsonins were greater during this treatment than in the tuberculo-toxoidin treatment. (3) The body weight and vital capacity generally increase as a result of the serum treatment. (4) The phenomena of agglutination, degeneration, and diminution of the bacilli are similar to those of patients under the toxoidin treatment. Judging from the percentage results summarized in the figures above, the result of the serum treatment appears to be somewhat inferior to that obtained with tuberculo-toxoidin. As, howeyer, the serum is employed generally in the more serious cases, while the tuberculo-toxoidin usually 384 ISHIGAMI. is injected in less advanced cases, the above figures are not strictly comparable with each other. If the advanced patients are first treated with the serum until the symptoms are alleviated and are then injected with tuberculo-toxoidin, a much better result is obtained. INTERNAL ADMINISTRATION OF TUBERCULO-TOXOIDIN AND IMMUNE SERUM. The subcutaneous injection of the tuberculo-toxoidin is, as stated above, the safest and most efficacious of all modern therapeutic methods for the alleviation of tuberculosis. However, as this form of injection always requires proper precautions, there are many patients who are prevented thereby from receiving the treatment. Moreover, sometimes, though rarely, there are encountered patients of constitutional idiosyn- erasy in whom the injection of the serum causes a reaction. For such cases we are necessarily obliged to resort to a simpler method of admin- istering these cures. I have ascertaimed by experiments on animals that the internal admin- istration of the tubereulo-toxoidin and immune serum is harmless and efficacious. Consequently, I have tried the same method on patients for the past few years and found it comparatively efficacious and free from any reaction. It is difficult to obtain results by administering the tuberculo-toxoidin and the immune serum in liquid form. If administered in the form of pills, however, they are partially absorbed without change, as is seen from the following facts: (1) Those patients in whom the injection of tuberculo-toxoidin causes fever are also subject to the rise of temperature by the internal administration of the toxoidin pills in comparatively large doses. (2) Those patients in whom urticaria is produced by the injection of the serum also develop the same symptoms on administration of the serum. pills in comparatively large doses. When patients in an advanced stage receive the toxoidin injection, [ administer the pills at the same time in the following manner: The serum pills are given first until all the symptoms are sufficiently alleviated. The toxoidin pills are then substituted and, in the meantime, the number of injections is gradually diminished. The administration of the pills is maintained for a long time after stopping the injections in order to prevent the diminution of the immunity attained. This particular method of treatment has proved itself to be most effectual. In the liquid state, the efficacy of the tuberculo-toxoidin and of the im- mune serum is uncertain, probably because of changes due to the action of the gastric juice. Im the form of pills they seen partially to escape the action of the digestive juices and to be absorbed from the intestinal wall. : ‘ A NEW INTESTINAL TREMATODE OF MAN. (FASCIOLETTA ILOCANA, gen. noy., sp. nov.) By Purr E. Garrison.t (From the Biological Laboratory; Bureau of Science, Manila, P. I.) In April, 1907, during routine examination of feces, at Bilibid Prison, Manila, P. I., an oyum was found about 100 microns long, oval in form with one end more sharply rounded; shell, light brown in color and of medium thickness, with an operculum at the sharper end; contents rather refractile, colorless, and composed of a mass of yolk-cells, among which the germ-cell could in some cases be distinguished. In May, and again in September of the same year, eggs of the same description were found in the faeces of two other natives prisoners and in April of the present year still two other prisoners showed the same ovum. One of the first three patients was discharged without treatment, two were treated for other parasites and the stools examined for the worms which were the source of the eggs in question, none being found. The two cases of April of the present year (prisoners Nos. 6667-D and 6612-D) arrived at the prison during the same week. The first was treated for a rather heavy infection with Ascaris lwmbricoides. Several of these parasites were passed, but no other worms were found, although upon subsequent examinations the undetermined ova had disappeared from the stools. Treatment with male-fern was advised in the case of prisoner No. 6612-D upon the supposition that we might be dealing with an intestinal trematode* and this treatment was administered by Dr. H. CO. Shattuck, resident physician of the prison. The stools passed after treatment were examined by my student assistants, Mr. Ricardo Leynes and Mr. Rosendo 1 Assistant surgeon, United States Navy; detailed medical zoélogist to the Biological Laboratory, Bureau of Science, Manila, P. I. * The use of male-fern in infections with intestinal trematodes was first sug- gested to us by Dr. Ch. Wardell Stiles in his lectures at The United States Naval Medical School, upon the theoretical ground that a drug which is effective for cestodes might be also for other plathelminthic parasites. 385 386 GARRISON. Llamas, of the Philippine Medical School, who found 21 small trematode worms. Superficial examination of the parasites showed that they were Mas- ciolide, but did not belong to any species reported for man, and after study of stained specimens I was unable to ascribe them to any recognized genus of this family. On May 4, 1908, a preliminary report of the parasite was made before the regular monthly meeting of the Manila Medical Society, giving a brief description, but without definitely deter- mining the systematic position of the worms.* The further study of stained and sectioned specimens has furnished the data for the following more complete description. DESCRIPTION OF TYPE SPECIMENS. In addition to the diminutive size of the parasites, they are remark- able for the size and prominence of the ventral acetabulum and for the general contour of the body, which is broadest in the region of the aceta- bulum and tapers posteriorly throughout fully two-thirds its length. In its anterior third, the body appears almost round, but becomes increas- ingly flattened dorso-yentrally toward the caudal end. A cephalic cone is absent, but the extreme anterior portion of the body (about one-eighth) is more or less distinctly marked off from the remainder by the prominence of the acetabulum itself and the rapid lessening of the transverse and “The following extract is taken from the proceedings of the monthly meeting of the Manila Medical Society of May 4, 1908: “Doctor P. E. Garrison.—aA new trematode parasite of man. “Author’s abstract.—Ova found five times in native prisoners at Bilibid during the past year; 2] worms obtained from last case after dose of male-fern. Patient complained of no symptoms; physical examination negative, except a slight anemia. Hookworms and whipworms also present. Morphology of parasites: Small Trematoda, of the family Fasciolide; 4, 5 to 6 millimeters long by about 1 millimeter broad; broadest at junction of anterior and median thirds; skin without spines; acetabulum near and much larger than oral sucker; pharynx globular; cesophagus very short; intestinal caeca unbranched and extend to postericr extremity; male and female genital pores open separately between acetabulum and oral sucker, slightly to left of median line; testicles posterior, median, one directly behind the other, each divided into anterior and posterior lobe by median transverse constriction; ovary anterior to testicles; shell gland between testicles and ovary; uterus moderately developed; vitellogene glands highly developed, extending from plane midway between acetabulum and ovary to posterior extremity, meeting in median line ventrally and encroaching upon median field dorsally after they pass caudad of the testicles; posterior excretory tract divides just behind testicles into two lateral excretory canals. Ova average 107 uw long by 63 wu broad, with prominent operculum at one end, unsegmented at oviposition, develop ciliated embryo, which hatches in about one week. Specific and generic position of parasite not yet difinitely determined, the indications being that it may be necessary to create a new species and perhaps a new genus also. (Specimens and photographs demonstrated.) ” A NEW INTESTINAL TREMATODE OF MAN. 387 dorso-yentral diameters anterior to the acetabulum, and also by a more or less distinct transverse depression in the ventral surface slightly anterior to the acetabulum. The anterior portion thus marked off appears in some specimens almost like a cephalic appendage, an ap- pearance which is heightened by the fact that after preservation this anterior part of the worm is frequently bent sharply dorsad out of line with the longitudinal axis of the remainder of the body. The posterior extremity (about one-fifth) of the body also is more or less distinctly differentiated from the remainder by a slight, but rather abrupt shortening of both the transverse and dorso-ventral diameters and also by its darker color, due to the extension of the vitellaria across the median field in this portion of the worm. The remaining, middle portion of the body, comprising something over three-fifths of its length, contains anteriorly the large and prominent yentral acetabulum, behind which this portion of the body is more or less distinctly marked off into five longitudinal tracts or fields, namely, two lateral fields along each lateral margin, containing the intestinal ceca and the vitellaria, a median field containing anteriorly the coils of the uterus, and posteriorly, the ovary, shell-gland and testicles, and two light colored sub-lateral fields separating the median from the two lateral fields and marking the course of the two main branches of the excretory tracts. Dimensions.—Fifteen specimens gaye the following measurements in millimeters : Maximum Maximum Maximum Maximum Length. breadth. thickness. 5 Length. breadth. thickness. 4.25 1.00 0.70 | 5.00 1.00 0.80 4.00 0.80 0.60 | 6.00 1.35 1.00 4.50 1.00 0.70 5.25 1.00 0.80 5.50 1.25 0.80 4.00 1.00 ~ 0.60 5.00 1.00 0.75 4.50 0.80 0.60 5.00 1.20 0.80 5.80 1.00 0.70 4.00 0.75 00 | — 400 0.75 0.50 4.25 1.00 0.70 Maximum, 6 millimeters long, 1.35 millimeters broad, 1 millimeter thick; minimum, 4 millimeters long, 0.75 millimeter broad, 0.50 muilli- meter thick; average, 4.74+- millimeters long, 0.99-+ millimeter broad, 0.70 millimeter thick. Cuticle is smooth and without spines. Pigmentation is slight and evenly distributed; the fresh specimens were of a semi-transparent red-gray color and the testicles, ovary, vitellaria and uterus were distinctly visible under a hand lens. Ventral acetabulum.—The acetabulum measures from 480 to 520 p in diameter (about half the maximum transverse diameter of the body) and is situated with its center at just about the junction of the first and second anterior fifths of the body. 388 GARRISON. Alimentary tracts—The oral sucker is terminal or slightly ventro- subterminal, the greater development of its dorsal side giving the oral opening a more or less marked inclination toward the ventral surface. It measures from 130 to 200 » transversely and dorso-vyentrally by from 75 to 130 » antero-posteriorly (about one-third the size of acetabulum). From the oral sucker to the pharynx extends a short, rather broad pre- pharynx which in some specimens appears almost obliterated by the close approximation of these two organs, while in others it is considerably extended, its length in different specimens varying from 10 to 63 up. The pharynx is globular and measures from 150 to 190 » in diameter. The wsophagus is very short (50 to 100 »), its bifurcation occurring just anterior to the plane of the genital pores. The thin walled intestinal ceca pass rather sharply outward toward the lateral margins and then follow these margins rather closely to near the posterior extremity of the body, one cecum sometimes reaching a slightly more posterior position than the other. Before they reach the equator of the body the ceca become bounded laterally, and also to some extent ventrally and dorsally, by the vitellogen glands. Hacretory tracts.—In the posterior fifth of the body the excretory tract is single and dilated into a cavity of considerable size with irregular, ill-defined walls (“excretory bladder”). On reaching the posterior border of the caudal testicle the tract divides into two lateral branches which pass cephalad between the median and lateral fields above noted to a position dorsad of the acetabulum where approaching the median line, they are separated by only a thin septum. (Im some sections the two tracts appear actually to joi anteriorly.) Male organs.—The testicles occupy the posterior part of the median field of the middle portion of the body and he one immediately and directly behind the other in the median line. They are bounded pos- teriorly and laterally by the excretory tracts. Hach testicle is more or less distinctly divided by a transverse circular constriction into an anterior and posterior lobe. Im some specimens, this constriction is very slight and the testicle appears almost oval, while in others it is well marked and there may be even slight indentations at other parts of the surface, marking off four or five poorly defined lobules. From each tetsicle the vas deferens passes forward through the lateral (marginal) fields to a position dorsad of the acetabulum where the two enter the posterior end of the cirrus pouch. The cirrus pouch measures from 560 to 608 » in length by from 240 to 280 p» in breadth and is situated dorso- anterior of the acetabulum, with its axis directed forward and ventrad, and also slightly to the left side. Posteriorly it contains a large vesicula seminalis which receives the vasa deferentia and which as seen in different specimens appears to be capable of considerable distention. Within the A NEW INTESTINAL TREMATODEP OF MAN. 389 cirrus pouch the cirrws is more or less coiled or looped and provided with a well developed musculature and a glandular envelope (pars prostatica). In each of the specimens, the cirrus is extruded through the male genital pore and externally is curved in from one to two spiral turns. Female organs.—The ovary is globular and situated at just about the center of the body length, slightly to the right of the median line. Pos- terior to the ovary, and filling the space between it and the anterior testicle is a well developed, globular shell gland. The vitellaria extend anteriorly to or shghtly behind the junction of the anterior with the middle third of the body length or to a plane about midway between the proximal | borders of the ovary and acetabulum. Passing posteriorly, they conform closely to the lateral margins and extend slightly upon the ventral and dorsal surfaces, so that on cross section they give the form of a crescent, in the convexity of which lie the intestinal ceca. After passing caudad of the testicles the vitellaria quickly spread across the dorsal surface and meet in the median line, at the same time encroaching more gradually upon the ventral surface until, in the extreme posterior portion of the body they meet in the median line ventrally also and completely encircle the body, enclosing the extremities of the ceca and excretory tract. The transverse vitello-ducts cross the sub-lateral fields (excretory tracts) at the level of the anterior border of the anterior testicle, almost at right angles to the longitudinal axis of the body and enter the postero-lateral borders of the shell gland. Jauwrer’s canal present. Receptaculum senumis absent. The coils of the wterus are fairly developed, extend on the left side as far back as the shell gland, and fill the median field between the ovary and acetabulum, being bounded laterally and separated ' from the ceca by the broad excretory tracts. The anterior extremity of the uterus continues into the well developed vagina which passes forward dorsad of the acetabulum directed slightly toward the left and opens at the female genital pore, separate from and, situated just to the left of the male pore, the two pores being about midway between planes passed through the anterior border of the acetabulum and the posterior border of the pharynx respectively and just behind the bifurcating intestinal ceca. The site of the genital pores is marked by the transverse depression in the ventral surface above mentioned as more or less distinctly sepa- rating the cephalic extremity from the remainder of the body. Ova.—The oya are not very numerous. The shell is thin, hght brown in color, with an operculum at the smaller end. Im the feces the egg- contents are colorless and composed of a number of ill-defined vitellogen cells among which the ovie cell could, with difficulty, be detected in some eggs. The ova, in fresh feeces, vary considerably in size and also in their relative length and breath, some being shorter and thicker than 77851——3 390 GARRISON. others. The careful measurement of fifty ova in the fresh stool gave the following results, in microns: 99.9 X59.2 92.5 X 62.9 99.9X 55.5 92.5 X 66.6 96.2X59.2 103.6 X59.2 96.259.2 92.5 X 66.6 99.9X74. 103.6 X 59.2 99.9 X59.2 92.5 X53.5 103.6 X 62.9 103.6 X 62.9 103.6 X 62.9 103.6 X 62.9 114.7 X55.5 99.9 X59.2 99.9 X59.2 98.0 X 59.2 92.5 X55.5 96.2X74.0 - 103.6 X 62.9 103. 60. 99.9 X 66.6 111.0X 62.9 96.2 X 62.9 103. 62.9 103.6 X 62.9 114.7 x 66.6 92.5 X59.2 103.6 53.5 88.8X62.9 99.9X 62.9 96.2 62.9 107.3 X59.2 107.3 X59.2 96.2 X59.2 111.0 81.9 96.2X57.4 99.9X 55.5 99.9X81.9 99.9X59.2 94.3 53.5 96.2 X 62.9 92.5X 62.9 92.5 59.2 96.2 X59.2 96.2 X59.2 92.5 X59.2 Maximum dimensions: Length, 114.7; breadth, 81.9 p. Minimum dimensions: Length, 88.8 ; breadth, 53.5 p. Average dimensions: Length, 99.58; breadth, 53.5 p.° When the stools, were repeatedly sedimented until their fecal charac- ter was destroyed, the ova, in about 10 days, developed ciliated mira- cidia which, raising the operculum, escaped from the shell and swam free in the water. Attempts were made to infect several varieties of snails and one variety of fish with the free miracidia, but without success. Upon the basis of the characters above described, it is proposed to establish a new genus and species in the family Fasciolide, of which these specimens shall be the type and for which we propose the names /ascio- letta vlocana. FASCIOLETTA gen. nov. GENERIC DIAGNOSIS.—Fasciolide: Body small, elongate, broader anteriorly than posteriorly. Acetabulum near and much larger than oral sucker. ' Intestinal tract with short, broad prepharynx, highly developed pharynx, short csophagus, and long, unbranched ceca, which pass along lateral margins and extend to near the caudal extremity of worm. Hxcretory system cqnsists of a posterior median stem which, posterior to the testicles, divides into two laterally placed canals which extend anteriorly, separating the testicles, shell gland, ovary and uterus from the ceca and vitellaria. Genital pores anterior to acetabulum. Male organs: Testicles massive and compact situated one directly behind the other, in the median line, in posterior portion of body, both caudad of transverse vitello- duct. Cirrus and cirrus pouch highly developed. Female organs: Ovary com- pact, unbranched, situated slightly to right of median line at about the equator of body. Receptaculum seminis absent, Laurer’s canal present. Witellaria most highly developed, in posterior one-fifth where superficially. they spread over the dorsal and ventral surfaces, more or less completely encircling the body. Anterior to the caudal border of the posterior testicle they are confined to the lateral fields, conforming closely to the lateral margins of the body, external to the intestinal cxca, and reach a position considerably cephalad of the ovary. * Measurements made with Zeiss objective D D (9237), correction collar at 20, micrometer ocular No. 3, tube length 145. a er A NEW INTESTINAL TREMATODE OF MAN. 391 Shell gland well developed, situated between ovary and anterior testicle. Uterus coiled in the space bounded laterally by excretory channels, anteriorly by aceta- bulum and posteriorly by ovary and shell gland. Ova large, operculated, not very numerous, and develop ciliated miracidium after leaving body of host. Host OF TYPE SPECIES.—Homo sapiens: Habitat; intestine. TYPE SPECIES.—lascioletta ilocana. : Fascioletta ilocana sp. nov. SPECIFIC DIAGNOSIS.—/ascioletta: Length, 4 to 6 millimeters; maximum breadth, 0.75 to 1.35 millimeters; maximum thickness, 0.50 to 1 millimeter; greatest breadth and thickness a little posterior to the caudal border of the acetabulum. Posteriorly, the body attenuates gradually throughout two-thirds its length to a rounded caudal. extremity; anteriorly, for about one-third its length, to a rather sharper cephalic extremity. In the posterior half the body becomes increasingly flattened toward the caudal end. Oral sucker terminal or slightly ventro-subterminal, small (130 to 200 w transversely by 75 to 130 p deep) ; dorsal lip much larger than ventral, giving the sucker a ventral inclina- tion. Ventral acetabulum about three times as large as oral sucker (nearly globular, 480 to 518 w in diameter), situated with its center at about the junc- tion of the first and second anterior fifths of the body length. Skin smooth and without spines. Pigmentation slight and evenly distributed. Prepharynx from 10 to 63 w long. Pharynx globular, from 150 to 190 mw in diameter. (sophagus short (50 to 100 mw). Intestinal bifurcation immediately anterior of plane passed through genital pore. Intestinal ceca thin-walled; follow rather closely the lateral margins of body to near its posterior end, being partly inclosed by the vitellaria throughout considerably more than the posterior half of their course. Genital pores open upon the surface separately to the left of the median line and slightly posterior of a plane midway between posterior border of pharynx and anterior border of acetabulum. Male organs: The cirrus pouch is from 560 to 608 w long by from 240 to 280 w broad; situated antero- dorsad of the acetabulum, with its longitudinal axis directed antero-yentrally and slightly to the left. Posteriorly it contains a bladder-like vesicula seminalis which receives the vasa deferentia and gives origin to a well developed cirrus which takes a more or less coiled course to the male genital pore through which it may protrude in from one to two spiral turns. Vasa deferentia divergent. The testicles lie one immediately and directly behind the other, occupying the median field just caudad of the transverse vitello-ducts. Hach testicle is more or less distinctly divided into an anterior and posterior lobe by a transverse, circular constriction, and other slight indentations of the surface may indicate ill-defined secondary lobules. Female organs: Ovary globular, situated at equator of body, slightly to right of median line. Vitellaria highly developed, extending antero-posteriorly from the caudal extremity to a plane midway between proximal borders of ovary and acetabulum. Cephalad of the posterior border of the tes- ticles they lie along the extreme lateral margins, filling the space between margins and ceca and extending somewhat upon the dorsal and ventral surfaces, thus inclosing the ceca dorsally and ventrally between the two superficially placed vitellogen layers. Caudad of the testicles, the vitellaria spread over the dorsal surface and meet in the median line, at the same time gradually encroaching upon the median field ventrally. In the extreme posterior portion of the worm (about one-tenth of its total length) they may meet in the median line ventrally as well as dorsally, thus completely inclosing the caudal extremities of the ceca and excretory tract. At the anterior border of the anterior testicle the trans- verse vitello-ducts pass inward and slightly forward to the well-developed, 392 GARRISON. globular shell gland which fills the space between the anterior testicle and the oyary. Uterus fairly well developed; its coils filling the median fields between the excretory tracts from the acetabulum to the ovary on the right side and extending caudad of the ovary on the left to the border of the anterior testicle. Its anterior extremity is continued into a well developed vagina which passes diagonally across the median line dorsad of the acetabulum to reach the female genital pore, which is situated just to the outer side of the male pore. Ova from 88.8 to 114.7 w long by from 53.5 to 81.9 wu broad, averaging 99.58 by 56.04 ; develop miracidium in about 10 days after leaving host. Further development unknown. HasiratT.—Intestine of man. TYPE LOCALITY.—ILocos Sur, Northern Luzon, Philippine Islands. Type SPECIMEN.—Number 240-A (co-types number 240), Helminthological Collection, Bureau of Science, Manila, P. I. FREQUENCY, LOCALITY, AND PATHOGENISIS. Over 5,000 native Filipinos, representing all parts of the Islands, have been examined for intestinal worms during 1907 and the first three months of 1908. That only five infections with Fascioletta have been encountered would seem to indicate a very low frequency with regard to the population of the Islands as a whole. However, all five of the infected prisoners came thom the north- western provinces of Luzon, and two of them, including the one from whom the worms were obtained, had lived all their lives in the Province of Ilocos Sur. Accordingly, there is some indication that the parasite may not be equally distributed throughout the Islands. Only the two cases which appeared in April of the present year were examined clinically. Questions and answers had to be passed through two interpreters (Tagalog and Ilocano) and only fragmentary and rather uncertain information could be secured. Both prisoners had lived in Ilocos Sur all their lives. They had worked bare legged in fields over- flowed with water; fish was an important part of their diet; they had not suffered from any sickness except “fever”’—which facts, excepting possibly the last, would apply to the great majority of the population. At the present time neither complained of any illness nor would either admit having or having had any intestinal trouble. Physical examination was negative with the exception that one of the prisoners was somewhat anemic, the hemoglobin registering about 85 per cent. In this case in- fections with hookworms and whipworms also were present. oe ILLUSTRATIONS. ac. =acetabulum. L.c. =Laurer’s canal. t. =testicles. cir. =cirrus. m. =mouth. trs. vy.d.—transverse vitello- cir. p. =cirrus pouch. m. g. p.=male genital pore. duct. exc. p. =excretory pore. oes. =cesophagus. ut. =uterus. exc. tr.=excretory tract. ov. =ovary. va. =vagina. f. g. p. =female genital pore. p. =pharynx. vd. =vas deferens. g.p. =genital pores. pp. =pre-pharynx. V. &- =vitellogen glands. int. =intestinal ceca. Sg. =shell gland. v.S. =vesicula seminalis. (Photographs by Charles Martin, Bureau of Science.) PLATE I. * Fic. 1. Photograph. A group of eight specimens of Fascioletta ilocana, natural size, 2. Photomicrograph of type specimen from ventral surface. Stained with carmine and picric acid. Enlargement about 18. 3. Semi-diagrammatie drawing showing anatomy. 4. Photomicrograph of longitudinal section in median line. Stained with carmine and picric acid. Enlargement about 20. 5. Semi-diagrammatic drawing showing apparent structure and relations of cirrus and cirrus pouch. Prats II. Fies. 6, 7, 8, 9. Semi-diagrammatic drawings of transverse sections through (6) cirrus pouch just caudad of genital pores; (7) ovary; (8) posterior testicle; (9) plane midway between testicle and caudal extremity. Fic. 10. Photomicrograph of ova of Facioletta ilocana and Trichuris trichiura. Fies. 11, 12, 13. Photomicrographs of ova (11) in fresh feces; (12) showing developed miracidium; (13) showing operculum lifted after escape of miracidium. Enlargement about 320. 393 GARRISON: New INTESTINAL TREMATODE OF MAN.] [PHIL. Journ. Scr., Vou. III, No. 5. GARRISON: NEW INTESTINAL TREMATODE oF MAN.] [PHrIn. Journ. Scr., Vou. III, No. at inl BLASTOMYCOSIS OF THE SKIN IN THE PHILIPPINE ISLANDS.* By James M. PHALEN and Henry J. NicHOLS.* I. [xrropuction. Il. PREVALENCE. iI. Dirrzrent Forms. IV. ORGANISMS AND CULTURES. V. OTHER Kinps or BLASTOMYCOSIS. I. INTRODUCTION. Our instructions from the Surgeon-General of the Army state that “narasitic diseases of the skin deserve further study and attempts should be made to isolate and cultivate the fungi causing them.” Blastomy- cosis we have found to be a particularly suitable subject for such a study because of its prevalence and lack of recognition. Blastomycotic infec- tion of the skin was first described in 1894 by Gilchrist and generalized blastomycosis by Busse in the same year. Since then a considerable literature has been produced, in large part by American authors, as is shown by reviews by Hyde and Montgomery, Hektoen and others. The term blastomycosis is a general one and is used here for convenience to designate pathologic conditions produced by double contoured, budding bodies. The botanical relations of these forms to yeasts and fungi, their relations to each other and to such bodies as those of coccidioidal granu- loma have not been sufficiently worked out to permit of exact classification. Accordingly, we shall simply call attention to the clinical peculiarities of the disease as we have seen it, to the nature of the organisms and of the cultures obtained and to the presence here of other forms of blasto- mycosis. II, PREVALENCE. We believe that cutaneous blastomycosis is one of the common para- sitic skin diseases among both natives and white men in the Philippine Islands. The dispensary clinic of the University Hospital, in Manila, is a rich field for observing these cases among natives. Through the 1Read by abstract at the Fifth Annual Meeting of the Philippine Islands Medical Association, Manila, P. I., February 27, 1908. -* Captain, Medical Corps, United States Army, and first lieutenant, Medical Corps, United States Army, constituting the United States Army Board for the Study of Tropical Diseases, as they occur in the Philippine Islands. 395 396 PHALEN AND NICHOLS. kindness of Doctors Saleeby and Winsor we have been able to study a number of patients at the Dispensary and usually have been able to find without previous arrangement one or more cases. The physicians in charge say that at least one new case of this form of disease apples for treatment each week. Among 50 natives examined on one morning we found 5 cases. In the last eight months we have seen 7 officers with various degrees of the disease and have ceased to keep track of the exact number of enlisted men affected. The infection has been seen in Min- danao, Jolo, Cebu, Panay, Samar, and Luzon, and there is every reason to believe it to be widespread throughout the group of Islands. This is somewhat surprising because among skin diseases common in the Tropics, no mention is made of this condition by Manson, Scheube, Mense, Macleod in Albutt’s System or Jackson, nor is the term found im special articles on the skin diseases of different tropical countries. The only account of this form of infection in the Tropics, which we have found, is by Ashburn and Craig. They had a white patient, age 40, with five lesions of two years’ duration on his face, resembling ring-worm. Serapings stained by the modified Gram method showed round, double- contoured bodies lying in and between the epithelial cells. The patient stated that the disease was common among natives, but rare among whites: He improyed under potassium iodide internally. No cultures were obtained. There are several references to blastomycotic ulcerations in the East by Sakurane and Okugawa, Japan, 1905; Lukis, India, 1907; Strong, Philippine Islands, 1906, and Shattuck, Philippine Islands, 1907, but the lesions described seem to be different from those with which we are now concerned. Ill. DIFFERENT FORMS. Clinically the disease appears in three distinct forms, although there are intermediate types from the mildest to the most severe. A. The mild cases somewhat resemble the commonly observed skin infections with ordinary fungi. ‘The lesions are elevated little, if at all, above the surrounding skin, are irregular in outline, and the surface when freed from scales presents a smooth, reddish surface. The lesions itch considerably, but otherwise give no discomfort. The couse is toward a progressive extension of the patches, with marked induration of the affected skin. The tendency to appear in unusual locations, and the frequency of a symmetrical distribution are the features which distinguish it clinically from ring-worm, with which it has many features in common. It has been observed to occur on the back of the hands, the forearm, shoulder, face, front of the leg, and the toes. Case I—In fig. 1 is given an illustration of a lesion of this class. This patient, a sergeant of an Infantry regiment, first came to the Philippine Islands in 1904 and went to Camp Jossman, Island of Guimaras, for station. In the spring of 1905, while cutting a clump of bamboo at that post, he scratched his BLASTOMYCOSIS OF THE SKIN. 397 right wrist on a thorn. The cut bled a little and he sucked it. A little later the spot became reddened, and itched greatly, and it gradually spread around the wrist. A similar spot appeared upon the palm of his right hand. These spots were treated with various antiseptic ointments and lotions for nearly two years, without much effect until, while at Mount Gretna encampment in 1906, they were healed by the application of a strong alcoholic solution of mercuric chloride. Shortly after, small spots of a similar character appeared upon the left wrist and left leg, and these have persisted and have continued to spread ever since, more rapidly since his return to the Philippines in July, 1907. He came to us in March 1908, somewhat anxious about his condition as he had been told by a Spanish physician that the disease was likely to affect his internal organs. ‘The lesions present at that time were situated on the outer side of the left leg near the knee and on the back of the left wrist. There were several areas, each 5 to 8 centimeters in diameter, irregular in outline, slightly raised, with a well-defined edge and covered with scales which, when removed, left a pink, glistening surface. The surface feels rough and indurated. No crusts nor exudate are present. The scales, when removed, treated with a potassium hydrate solution and ex- amined under a high-power lens, show in abundance the organisms illustrated in figs. 6 and 7, a more detailed description of which will be given later. Attempts to cultivate the organism from this group of cases proved unsuccessful. A picture of a section of the skin is shown in fig. 8. From a study of the sections, the process appears to be twofold. On the one hand there is an overgrowth and widening of the papillary layers. The papillae show a definite downward growth and often include a small island of connective tissue which appears somewhat like a miliary abscess, but contains no polynuclear cells. On the other hand, the corium in places infiltrates the epithelium, producing a fibrosis and degeneration of the epithelium so that as the section is moved across the field, one part will show an excess of epithelial elements and the next a loss with an increase of connective tissue. A marked infiltration with round cells appears in the deeper layers of the corium. The majority of these cases are of many months’, or even of years’ standing. ‘The mildest yield to strong local antiseptics, others only to potassium iodide internally. These infections are usually passed over as a variety of “dhobie itch” and even on microscopic examination of the scales often nothing is seen unless the oil immersion lens is used. B. The second type of the disease is the one most frequently encoun- tered. In these cases the lesions are in quite large areas, sharply cir- cumscribed and considerably elevated above the surrounding, healthy skin. They are frequently observed to have a border raised above the rest of the patch, this ridge being beset with “miliary” abscesses covered with crusts. The remainder of the area has a red, smooth surface covered with scales. Case II.—The patient is a Filipino girl, 8 years of age, from the Tondo district of Manila. No history as to the beginning of or the duration of the disease is obtainable. The lesion shown is irregularly circular in outline, about 7.5 centimeters in diameter, situated back of the left axilla. It presents a 398 PHALEN AND NICHOLS. erescentic ridge 3 to 6 millimeters high and 13 to 20 millimeters wide, with a concavity upward extending along the lower edge and sides of the patch. This ridge has a number of small pustules opening upon its surface, and is covered by a crust made up of the dried discharge. The center and the upper part of the affected area is oceupied by indurated tissue, with a smooth surface covered by fine scales. A smaller area, 4 by 5 centimeters, of a similar character occupies the outer side of the right elbow. This area has a ridge along the posterior border, with some superficial erosion. The rest of the lesion is made up of indurated tissue of a like character to the larger lesion. The scales and crusts show a great quantity of blastomycetes. ‘ Case III.—This patient is an officer in a Scout organization, and presents the following history: In the early part of 1904, while stationed at Camp Connell, Samar, he noticed a small papule near the middle of his left cheek. He con- sidered it of no consequence, and so does not remember much of its early characters, except that it itched considerably. He does not recollect any injury or abrasion of the face previously. From this beginning the present lesion has extended, at first Gownward, then forward and upward; at first it was quite superficial and the earlier places were healed by the local application of nitrate of silver. As is customary in these cases, the eruption recurred almost immediately and the patient has never been free from it since. When first seen by us, in April, 1908, there was present on the left cheek a large, crescentic patch extending parallel to the lower jaw, presenting an indurated ridge along the convexity of the patch and induration of a less degree inside. : The whole area is red and shining, except where covered with scales. Along the ridge, a number of more indurated spots exist, lighter in color, which upon opening exude a small drop of white pus. There are some crusts covering small cavities also containing pus. Examination of the scales and pus in this case reyeals in large numbers the same organisms found in the others. Casr IV.—C. C., Chinaman, 40 years old, a shopkeeper in the Santa Cruz district of Manila, seen at St. Iuke’s Dispensary. No history is obtainable, except that the lesions present are of eight months’ duration, came on grad- ually and were still extending. This patient has a circular patch, 5 centimeters in diameter, over the center of the back of his neck. This patch has a raised, indurated border and a central portion, indurate, but apparently healed, on the level with the rest of the skin. The surface of the raised border is smooth, glossy and of a dark red color. This patient has also a round, elevated spot, 12 millimeters in diameter at each angle of the mouth and on the right side of the lower lip a patch extending laterally from the angle of the mouth to the median line, and reaching downward for about 25 millimeters, the lower border being scalloped and raised in a sharp ridge. The lesions are bright red and glossy. The scales show a large number of organisms which are indis- tinguishable from those found in the other cases; a culture was obtained from this case, which will be described later. A number of other cases of this class have been observed (fig. 2). They all give a history of a long, chronic course, and of resistance to treatment. ‘They have been diagnosed as syphilis, leprosy, tuberculosis and other diseases. However, with the exception of tuberculosis, there is little resemblance to these infections. The case of cutaneous blastomy- cosis, reported by Ashburn and Craig in 1906, belongs to this second BLASTOMYCOSIS OF THE SKIN. 399 class. Both im appearance and in microscopic findings their description coincides with those that we have given. The histologic picture of type B is intermediate between those of A and C. The papille show more marked overgrowth and the upward growth of the connective tissue reaches the surface of the skin and thus accounts for the formation of crusts. There is a greater infiltration in the deeper layers of the corium. The infiltrating cells are almost entirely of connective tissue in various stages of growth, but there are some unusual cells, large and round, which when stained by hematoxylin and eosin, have a deep black nucleus and a rim of pink protoplasm. C. This form answers clinically quite closely to the descriptions of cases of cutaneous blastomycosis reported from the United States. One well-marked case of this class has been under observation for the past three months, and one other was seen at St. Luke’s Dispensary. (Figs. 4 and 5.) Casi V.—B. C., male Filipino, 34 years old, a resident of Pasay, and a coachman by occupation. He was born in Pasay and has lived there all his life. He has been married for twenty years, had five children, two of whom died of smallpox, two of intestinal trouble and one, 11 years old, is alive and well. Ten years ago he acquired a small venereal sore which healed in a week. He has no further symptoms to indicate that the sore was syphilitic. There is no evidence of tubercular infection. Two years ago a sore appeared on the right buttock, near the anus, on the site, the patient thinks, of an abrasion due to horseback riding. This healed after three months of dispensary treatment. One year ago, it reappeared on the right buttock, since which time it has spread gradually to its present dimensions. : Present condition (fig. 3).—The lesions occupy nearly the whole of the right buttock, and extend several inches over on to the left. They reach downward on to the back and inner side of the right thigh and up into the groin in front on the right side. The greater part of this area is occupied by scar tissue, but the process: is still active in a ridge 5 centimeters wide along the left border of the patch, in an oval area 5 by 7.5 centimeters in the median line above, in the extreme right edge, in the lower part of the right side and in the right groin. Over these areas the surface is raised 3 to 6 millimeters above the surface of the skin. In places there is a fine, papilliform growth with deep fissures intervening and in others broad, warty surfaces, dry or covered with large scales. The papilliform elevations are frequently covered by a large, yellow crust, and the intervening fissures contain pus loaded with blastomycetes. - The patient was put on ascending doses of potassium iodide, and within a week the papille began to contract and became smoothed over and ceased to secrete an exudate. In two months the disease was apparently entirely cured, although some induration remained. A culture was obtained from this case. A section (fig. 8) from a lesion of this form shows a great overgrowth of epithelium, which superficially resembles an epithelioma. However, the cells are more regular in size, shape, and arrangment. Pearls are occasionally seen. The increase of connective tissue is also very marked and it reaches the surface in wide processes, showing a great deal of exudation of blood cells. The epi- thelium in its growth incloses a great many small areas of connective tissue. The hair and sweat glands are apparently not involved in the overgrowth. 400 PHALEN AND NICHOLS. . Clinically it seems as if the milder forms did not develop into the more severe. This can only be decided by further observation, especially of cultures obtained. The diagnosis depends on finding blastomycetes in the lesions con- stantly and in such number that they can not be regarded as accidental. Control examinations of scales, crusts and pus from other lesions have shown occasional blastomycetes, but these are not constantly present nor in such numbers as are seen in the lesions described. Of course, sections and cultures are desirable, but in our experience the latter are difficult to obtain and are unnecessary hefore starting treatment. After seeing a number-of cases we have been able to pick out others from their clinical appearance. In the milder forms the presence of blastomycetes and absence of any fungi in a manifestly parasitic disease differentiate the affection from ring-worm, Tinea imbricata, etc. The severe forms may be taken for tuberculosis or syphilis. If tuberculous they will not heal up in one to two months of treatment with potassium iodide. The history and clinical appearance differentiate the affection from syphilis, as in the latter disease there is no such overgrowth of the epithelial structures. In tertiary yaws the lesions are ulcerative, while in this form of blastomycosis of the skin no definite ulcerations have been seen. IV. ORGANISM AND CULTURES. We have been unable morphologically to distinguish any difference in the organisms from the various cases. If a scale is taken from type A, or a crust or some pus from either B or C and macerated thoroughly in a ten to twenty per cent solution of potassium hydroxide, the organisms become very distinct. Their most striking feature is a double contour, usually less than 1 p» thick, but occasionally:-some are seen in which it is 2 w. There is a great variety of forms; the most frequent is the round, measuring 5 to 10 ~; many minute ones of the same kind are seen, 2 to 3 » in diameter, often in clusters; budding forms are frequent and others making a figure of 8. Another frequent appearance is the rod-like one with rounded ends. Some forms are elongated and in phantastic shapes. ‘These organisms stain with difficulty, a faint rim of blue being often all that can be seen with the modified Gram’s stain. No internal structures have been made out, nor is any eyidence of sporulation seen except in cultures. Im sections the organisms are found in small numbers in the types A and B, in the more superficial layers of epithelium between the cells. We have found no differential stain for them. With hematoxylin and eosin they stain to a light brown and often have a halo about them. They are most readily demonstrated (fig. 10) in unstained sections treated with potassium hydroxide and mounted in glycerin. The double Nets BLASTOMYCOSIS OF THE SKIN. 401 contour is then fully brought out and this, with buds, makes identification certain. In type © they are found more deeply in the section, but always among the epithelial elements. : Scales from type A failed to yield a culture although when incubated for a week and examined they showed a great increase, with elongation and segmen- tation of the organisms which approached the cultural forms seen in fig. 12. Scales from type B were washed in water, soaked in absolute alcohol one hour, washed in salt solution and put on plates and slants of maltose and glucose agar. Many remained sterile, a few showed a subtilis-like organism; one on glucose agar, after four days’ incubation, gave a filamentous growth in pure culture. This culture on being transplanted grew more readily on sugar media and potato, but showed only a slight filamentous growth on plain and glycerin agar either at room or body temperatures. The organism grows on potato, at room temperature, in prominent, light brown folds (fig. 10). At body temperature the folds are black. Microscop- ically (fig. 11) the growth consists of short, blunt branching and segmented processes and in round forms, 20 to 30u in diameter filled with a number of small, round spores. The growth on glucose-agar is abundant, forming brown folds in the center and lighter filamentous processes at the edges. No aérial spore-bearing hyphe are seen. Microscopically (fig. 13) the processes are longer, more slender and no sporulating forms are seen. The development on maltose-agar is less marked and consists of a brown film on the surface and a white growth penetrating deeply into the medium (fig. 13). In glucose-bouillon a floculent white ball is found at the bottom of the tube; the fluid above is clear. Co- EDITOR | "RICHARD Ee STRONG, Pu. Be M. D. WITH THE COLLABORATION OF VICTOR G. HEISER, M. D.; W. E. MUSGRAVH, M. D. JOHN R. McDILL, M. D.; FERNANDO CALDERON, M. D. JOSE ALBERT, M. ‘D.; PHILIP K. GILMAN, A. B., M. D. aa PHILIP E. GARRISON, B. A., M. D. & a Mik AURAL OF SCIENCE _\ . OF THE GOVERNMENT OF THE PHILIPPINE ISLANDS * B. MEDICAL SCIENCES “MANILA BUREAU OF PRINTING : a ; 1908 fi Jobling, M. D. PREVIOUS PUBLICATIONS OF THE BUREAU OF GOVERNMENT Sy LABORATORIES, She “ies ui 1No. 1, 1902, Biological Laboratory. —Preliminary Report of the Appearance in the Philippine Islands of a Disease Clinically Resembling Glanders. By R. P. Strong, M. D. No. 2, 1902, Chemical Laboratory.—The Preparation of Benzoyl-Acetyl Peroxide and Its Use as an "Intestinal Antiseptic in Cholera and Dysentery. Preliminary Notes, Byrn Paul C. Freer, M. D., Ph. D. 1No. 3, 1908, Biological Laboratory.—A Preliminary Report on Trypanosomiasis of Horses in the Philippine Islands. By W. E. Musgrave, M. D., and Norman EB. Williamson. — 1No. 4, 19038, Serum Laboratory.—Preliminary Report on the Study of Rinderpest of Cattle and Garabaos in the Philippine Islands. By James W. Jobling, M. D. 1No. 5, 1903, Biological Laboratory.—Trypanosoma and Trypanosomiasis, with Special — pete ube fo Surra in the Philippine Islands. By W. E. Musgave, M. D., and Moses T. Clegg. Rea 1No. 6, 1903.—New and Noteworthy Plants, I. The American Element in the Philip- as pine Plora. By Elmer D. Merrill, Botanist. (Issued January 20, 1904.) 1No. 7, 19038, Chemical Laboratory. —The Gutta Percha and Rubber of the Philippine Islands. By Penoyer L. Sherman, jr., Ph. D. 1No. 8, 1903.—A Dictionary of the Plant Names of the Philippine Islands. By Elmer D. Merrill, Botanist. No. 9, 1903, Biological and Serum Laboratories.—A Report on Hemorrhagic ‘Septi- cemia in Animals in the Philippine Islands. By Paul G. Woolley, M. D., and J. W. 1No. 10, 1908, Biological Laboratory.——Two Cases of a Peculiar Form of Hand Infection (Due to an Organism Resembling the Koch- ‘Weeks Bacillus). By John R. McDill, M. D., and Wm. B. Wherry, M. D. ' 1No. 11, 1903, Biological Laboratory.—Entomological Division, Bulletin No. 1: Prelimi- nary Bulletin on Insects of the Cacao. (Prepared Especially for the Benefit of Farmers. ) By Charles S. Banks, Entomologist. 1 No. 12, 1903, Biological Laboratory.—Report on Some Pulmonary Lesions Produced by the Bacillus of Hemorrhagic Septicemia of Carabaos. By Paul G. Woolley, M. D. No. 18, 1904, Biological Laboratory.—A Fatal Infection by a Hitherto Undescribed. Chromogenic Bacterium: Bacillus Aureus Fetidus. By Maximilian Herzog, M. D. 1No. 14, 1904.—Serum Laboratory: Texas Fever in the Philippine Islands and the Far East. By "J, Ww. Jobling, M. D., and Paul G. Woolley, M. D. Biological Laboratory: Entomological Division, Bulletin No. 2: The Australian Tick (Boophilus Australis Fuller) — in the Philippine Islands. By Charles $. Banks, Entomologist. No. 15, 1904, Biological and Serwm_ Laboratories. —Report on Bacillus Violaceus Ma- nile: A Pathogenic Micro-Organism. By Paul G. Woolley, M. D. , 1No. 16, 1904, Biological Laboratory.—Protective Inoculation Against Asiatic Cholera: An Experimental Study. By Richard P. Strong, M. D. No. 17, 1904.—New or Noteworthy Philippine Plants, II. By Elmer D. Merrill, Botanist. 1No. 18, 1904, Biological Laboratory.—I. Amebas: Their Cultivation and BEtiologie Significance. By W. E. Musgrave, M. D., and Moses T. Cleg: II. The Treatment of - Intestinal Amebiasis (Amcebic Dysentery) in the Tropics. By Ww. E. Musgrave, M. D. No, 19, 1904, Bnplg ical Laboratory.—Some Obseryations on the Biology of the Cholera Spirillum. By W. Vherry, M. D. No. 20, 1904. Tana Laboratory: I.. Does Latent or Dormant Plague Exist Where the DiseaSe is Endemic? By Maximilian Herzog, M. D., and Charles B. Hare. Serum Laboratory: II. Broncho-Pneumonia of Cattle: Its Association with 5. Bovisepticus. By Paul G. Woolley, M. D., and Walter Sorrell, D. V. S. III. Pinto (Pato Blanco). By Paul G. Woolley, M. D. Chemical Laboratory: IV. Notes on Analysis of the Water from the Manila Water Supply. By Charles L. Bliss, M.S. Serum Laboratory: V. Frambesia> Its Occurrence in Natives in the Philippine Islands. By Paul G. Woolley, M. D. No. 21, 1904, Biological Laboratory.—Some Questions Relating to the Virulence of Micro- Organisms with Particular Reference to Their Immunizing Powers. By Richard P. Strong, M. No. 22, 1904, Bureau of Government Laboratories —I. A.Description of the New Build- ings of the Bureau of Government Laboratories. By Paul GC. Freer, M. D., Ph. D. IT, A eeloere! of the Library of the Bureau of Government Laboratories. By Mary ‘Polk, ibrarian 1No. 238, 1904, Biological Laboratory. —Plague: Bacteriology, Morbid Anatomy, and Histopathology (Including a Consideration of Insects as Plague Carriers). By Maximilian Herzog, M. D. No. 24, 1904, Biological Laboratory.—Glanders: Its Diagnosis and Prevention (Together with a Report on Two Cases of Human Glanders Occurring in Manila and Some Notes on the Bacteriology and Polymorphism of Bacterium Mallei). By William B. Wherry, M. D. No. 25, 1904.2—Birds from the Islands of Romblon, Sibuyan, and Cresta Ae Gallo. By: Richard C. McGregor. No. 26, 1904, Biological Laboratory.—The Clinical and Pathological Significance of Balantidium Coli. By Richard P. Strong, M. D. No. 27, 1904.—A_ Review of the Identification of the Species Described in Blanco’s Flora de Filipinas. By Elmer D. Merrill, Botanist. No. 28, 1904.—I. The Polypodiaceze of the Philippine Islands. II. Edible Philippine Fungi. By Edwin B. Copeland, Ph. D. No. 29, 1904.—I. New or Noteworthy Philippine Plants, III. II, The Source of Manila Blemi. By Elmer D. Merrill, Botanist. No. 30, 1905, Chemical_Laboratory.—I. Autocalytic Decomposition of Silver Oxide. Il. Hydration in Solution. By Gilbert N. Lewis, Ph. D. No. 81, 1905, Biological Laboratory.—I. Notes on a Case of Hematochyluria (Together with Some Observations on the Morphology of the Embryo Nematode, Filaria Nocturna). By William B. Wherry, M. D., and John R. McDill, M. D., Manila, SPL Toe TD As Search Into the Nitrate and Nitrite Content of Witte’s ‘‘Peptone,’’ with Special Reference to Its ninenige ba “the Demonstration of the Indol and Cholera- Red Reactions. By William B. Wherry, 1 Out of print. 2 The first four bulletins in the ornithological series were published by the Hthnological Survey under the title ‘“‘Bulletins of the Philippine Museum.” Later ornithological publications of the Government appeared as publications of the Bureau of Goyernment Laboratories. é (Concluded on third page of cover.) THE PEMVEICPINE JOURNAL OF SCIENCE B. MEDICAL SCIENCES Vou. IIT DECEMBER, 1908. No. 6 STREPTOTHRICOSIS WITH SPECIAL REFERENCE TO THE ETIOLOGY AND CLASSIFICATION OF MYCETOMA.'* By W. E. Muserave and M. T. Creee, with a bibliography by Mary Pork. (Prom the Biological Laboratory and the Library, Bureaw of Science, Manila, P. I. OUTLINE. INTRODUCTION. Part I. ORIGINAL WORK. Material (cultures of streptothrice). General consideration. REVIEW OF THE LITERATURE. General. As to genus determination. Morphology. As to species and varieties. Biology. GENERAL DISCUSSION. Pathogenesis. CONCLUSIONS. Animal experiments. Part IT. STREPTOTHRICOSIS. SYMPTOMATOLOGY. Synonyms (actinomycosis—nocardiosis). General. Definition. CLINICAL TYPES. History. Generalized streptothricosis. Etiology. Thoracic streptothricosis. Contributing causes. Lungs; pleure ; heart. Streptothrice. Abdominal streptothricosis. Synonyms. Liver; intestine; mesentery; kid- Diagnosis. neys; pelvic viscera; appendix, Morphology. ete. Biology. Cerebral streptothricosis, Pathogenicity. Brain; cord. Transmission; infection. External streptothricosis. Species or varieties. Streptothricosis of the jaw, mouth, S. Actinomyces, types of: Bos- ete. (Lumpy jaw.) trem; Wolff and Israel; Streptothricosis pedis (mycetoma, Wright. Madura foot). S. Nocardii. Miscellaneous streptothricosis. S. Eppingeri. DIAGNOSIS OF STREPTOTHRICOSIS. S. Madure. PROGNOSIS. S. Canis. COMPLICATIONS. S. Capre. PROPHYLAXIS. PATHOLOGY. TREATMENT. General. BIBLIOGRAPHY. Special. ILLUSTRATIONS. 1To be read in abstract at the Bombay Medical Congress, February 23, 1909. 79284 447 448 MUSGRAVE, CLEGG, AND POLK. ? ’ INTRODUCTION. Before entering on a study of the etiology of mycetoma, it is necessary to define the disease. This is exceedingly difficult, either from a clinical or an etiologic standpoint. Formerly the diagnosis was based upon a clinical picture the essentials of which were a chronically enlarged foct with sinusses from which were discharged small granules of various colors and consistency, accompanied by a peculiar, oily degeneration of the tissues. Further classification was made principally upon the color of the granules; black, ochroid, white, red and mixed varieties being recognized. However, when bacteriologic studies began to show the multiplicity of the organisms concerned in the production of Madura foot it became necessary either to consider it a clinical entity of multiple etiology or to attempt an etiologic classification. This was made still more imperative by the discovery that the organisms causing this symptom complex were found.also producing lesions in other parts of the body. A number of authors have continued to use a clinical classification, while others have attempted to give one based upon etiologic findings. The result is great confusion in the nomen- clature of the disease. As a prerequisite to an etiologic classification and definition of myce- toma it is necessary first to know and to be able to classify the etiologic factors concerned. So far this has not been done satisfactorily. The botanists are hopelessly confused in their grouping of the organisms and im consequence medical men have been unable properly to identify them. In the first place, authorities differ as to where the group of organisms belongs in the vegetable kingdom, some placing it among the bacteria and others higher up among the fungi. Practically all the latest writers upon the subject agree as to the great similarity between the various species of these organisms and the majority have placed them as species of a single genus, or as parts of two or even three closely allied genera. In order to establish a uniform and clear conception, and after carefully studying all phases of the question we have decided tentatively to accept Streptothric Cohn 1875 as the generic name of the group of organisms under discussion. The result of this decision is that the other names given to the ten- tative genus, such as Actinomyces, Nocardia, Oodspora, ete., become synonyms, the disease streptothricosis beg limited to infection with parasites properly belonging to the genus, the various species of which will be considered presently. Adopting such an interpretation, we have a fairly definite group of organisms with reasonably uniform pathologic and clinical manifesta- tions, connected with other groups of closely related organisms giving somewhat similar manifestations. For example, the Oidia or Blasto- myces cn the one hand and the tubercle bacilli on the other, may some- STREPTOTHRICOSIS. 449 what closely resemble the Streptothrice in their action in certain parts of the body. Mycetoma may be defined and classified in one of three ways, if Streptothrix is accepted as the most available generic name. (1) It may be considered as a clinical disease of multiple etiology (which may or may not be limited to Streptothrix infections; (2) the term may appropriately be made synonymous with streptothricosis, actinomycosis, nocardiosis, etc.; (3) it may be made a clinical type (foot infection) by a Streptothria (Actinomyces or Nocardia). Hach of these classifications has something in its favor and also may be criticised. The first would make diagnosis easy, for all forms of foot enlargement giving certain clinical manifestations regardless of the etiology, known or unknown, might be included, but it is open to the objection of not being definite and does not conform to our present methods of etiologic classification. The second method has much in its favor and is practically adopted by Manson. The objections to it are that it adds a new significance to a term which does not clearly express the conditions and also adds a further synonym to a group of infections already rendered confusing by the number of its synonyms. The difficulty can more satisfactorily be met by the third method. We have therefore decided to follow the third classification making mycetoma a clinical type or variety of streptothricosis—Streptothricosis pedis—and to define it as follows: A disease consisting of a Streptothiix infection of the foot (Streptothri- cosis pedis, Actinomycosis pedis), characterized by a chronic course, swelling and deformity of the part, a peculiar, oily degeneration of the tissues with cavity and sinus formations and the discharge through the fistulous openings of mycotic aggregations containing the microor- ganisms. Mycetoma, with this definition, becomes so intimate a part of strep- tothricosis that a balanced conception of it can only be obtained by a study of the whole subject of streptothricosis and a classification of the organisms concerned. For this reason, the scope of this paper has been enlarged to include a diseussion in two parts of the whole subject of Streptothria or Nocarida infections. ; Parr I. ORIGINAL WORK. MATERIAL. The material for this paper consists of the following cultures: 1. S. freeri Musgrave & Clegg, This Journal Sec. B. (1907), 2, 477. 2. S. madure Vincent. (This culture was sent to us by Professor Foulerton who writes as follows concerning it: “This culture has been in my hands for the last ten years; it corresponds with Vincent’s description of his organism, and 450 MUSGRAVE, CLEGG, AND POLK. is apparently of the same stock as that from which all the cultures in the London laboratories are derived.” ) 3. 8S. madure Vincent. (This culture was sent to us by Professor Binot of the Pasteur Institute in Paris.) 4. S. madure Vincent. (This organism was isolated by Dr. R. P. Strong from a case of the pink variety of mycetoma in India, and the culture has been given by him to us, for study. 5. Streptothriz of human actinomyces. (From Binot of the Pasteur Institute in Paris.) 6. Streptothrix of “farcin de boeuf’ “A”. (From the late Professor Nocard through Binot.) 7. S. nocardii. (From Foulerton who writes that “this culture was given to me by Nocard some six years ago.”’) 8. S. eppingeri “A”. 9. S. eppingeri “B”. (Both of these cultures are from Foulerton who writes as follows: “*A’ is a descendant of what I believe to have been Eppinger’s original culture, “B’ a culture isolated by myself from a case which has not yet been published in detail. I have examined also a third culture of this species obtained by Dr. McDonald from a third case (The Scottish Medical and Surgical Journal, 1904). All three strains evidently belong to the same species.” 10. 8. capre Silberschmidt. (Received from Professor Silberschmidt of Ziirich through Binot.) 11. S. canis Levy. (From Professor Levy of Strassburg through Binot.) 12. S. chaleea Foulerton. (Received from Foulerton who writes that this is a saprophytic species isolated by him from the air.) The following cultures have also been received, but failed to develop on transplantation : S. madure Vincent. (Furnished by Professor Vincent of the Val du Grace, Paris.) S. madure. (From Legrain de Bougie through Binot.) Streptothrix of bovine Actinomyces. (From Binot.) Streptothrix of “farcin de boeuf” “N”. (From the late Professor Nocard through Binot.) Streptothric of Eppinger (“A”) and (KI). (From Binot.) : Streptothri« of Deci. (From Binot who writes regarding this culture that “it was isolated by Deci in the Argentine Republic from a human case resembling tuberculous meningitis.” Binot further states in his letter that all the cultures which he has forwarded to us were received by him directly from their authors). Streptothriz ‘32’. (Received from Foulerton who writes that this or- ganism was isolated by him from a kidney removed from the living patient by operation; the organism was demonstrable in sections of the kidney and was present in large quantity. It is briefly referred to as 8. hominis III in the Lancet (1906), 1, 970. ‘“‘This organism resembles closely some of the apparently purely saprophytic species, and the infection in the case was probably primary in the lungs.” Streptothria isolated from a case of mycetoma by Dr. Chaterjee of India. Dr. Homer Wright states, in reply to a letter regarding cultures of Actino- myces and his “Hyphomycete,’ that he no longer has cultures of these organisms. A comparative study under conditions as nearly alike as possible has been made of all these strains, with due consideration of their morphol- ogy, biology, and pathogenic character. All of them, to obviate as STREPTOTHRICOSIS. 451 much as possible any influence of long cultural environment were, where feasible, first passed through animals and the studies then made from the reclaimed cultures taken from the experimental lesions. All the cultural and other biologic properties have so far as we have been able to do so, been studied under the same conditions in regard to media, temperature, and generation from animal lesions. Our results and consequent descriptions show some variation from previous descriptions of some of these organisms, but in general the picture is very much as given by the original authors. We have failed entirely to obtain a culture of the Wolf and Israel and Wright type of Actinomyces, but, because of the great importance of this organism in the discussion, we have, for comparative purposes, taken James Homer Wright’s description of it from his classical mono- graph. We have also failed to secure a definite culture of Bostroem’s Actinomyces, although the one sent by Professor Binot from the Pasteur Institute is probably of this species. However, in view of a possible mistake we have used both the description given by Bostroem as well as the Pasteur Institute culture im our comparative work. ‘The impor- tant characteristics of our cultures are shown in the following descriptions and are summarized in the attached table. No. 1. Streptothriz freeri. This organism was isolated by us from a case of the ochroid variety of mycetoma and has already been fully described (This Journal, Sec. B (1907), 2, 477). It is identical with Eppinger’s organism which will be discussed subsequently in this paper, and the name given by us in the first publication should fall as a synonym for S. eppingeri, the latter having priority. Other described organisms of the group which are probably identical with this are those of Stokes, Aoyama and Miyamoto, MacCallum, Sabrezes and Riviére, and possibly several others. No, 2. Streptothrix madure. This organism has been carefully described by Vincent, Foulerton, and others. A summary of its characteristics are given both in the text and table and in our first report and are again shown in the table attached to this paper. Our work with cultures of this species has been in the main confirmatory of the published results of others. We have worked with three cultures received respectively from Foulerton, Binot, and Strong. These strains are identical in every particular except that the one from Binot is less pathogenic for monkeys than either of the other two. Morphologically this species gives very constant results. The colonies are made up of intertwining, long filaments which may, or may not, be radially placed at the periphery. There is true branching, but no club formation in cultures and none in experimental lesions in monkeys up to fourteen days. The organism takes the usual aniline stains; it is Gram positive, but is neither acid nor alcohol fast. Culturally it is a facultative aérobe with strong oxygen requirements. It grows well in the incubator and at tropical room temperature. Positive trans- plants on artificial media are readily made, but some difficulty is often en- countered in securing growth from experimental lesions. This difficulty is greatest when large quantities of the material are transferred to the media, probably because of an inhibiting material in the contents of the lesions. This hypothesis is supported by the fact that development is much more easily secured if the 452 MUSGRAVE, CLEGG, AND POLK. granules from the lesions are washed in sterile salt solution before transferring them to artificial media. Growth on satisfactory media becomes apparent in from two to four days; development gradually continues for several weeks, depending somewhat upon the quantity of medium present. The principal characteristics of growth on various types of media are shown in the table. Pathogenicity: Several monkeys have been successfully infected with the Foul- erton and Strong strains of this organism, but results with the one from the Pasteur Institute were all negative. Intra-abdominal inoculation has proved the most satisfactory and under similar conditions the character of the lesions produced varies but little. The lesions consist of nodular, tubercle-like processes in the omentum, abdominal wall, and contiguous tissues. These lesions break down and become surrounded by pockets and channels containing a peculiar, pus-like material in which may be found the microdrganisms. (See also animal experiments. ) No. 3. Streptothrix madure. (Pasteur Institute culture.) This is identical in all essentials with S. Vincent except that it is not pathogenic for monkeys. This may be due in part at least to its long cultivation on artificial media. No. 4. Streptothriz madure. (Strong’s culture.) This organism is identical with Vincent’s species and its description has been included in the above. No. 5. Streptothrix actinomyces. This culture was received from Professor Binot of the Pasteur Institute as human Actinomyces. It is quite different from the Wright type and it also appears to have slight distinctions from the Bostroem type of Actinomyces. Morphologically it appears in the tissues as a fungus of the ray type, but without clubs in young experimental lesions. In colonies the cultures are dark, almost black in color, are made up of the branching filaments and transforma- tion products, generally with radial arrangement of the terminals at the margins of the colonies. “ The. organism stains poorly by the usual laboratory methods; it is Gram positive and neither acid nor alcohol fast. Culturally it is a facultative aérobe and grows on the majority of the usual media. In reclaiming cultures from experimental lesions this organism acts very much like S. madurae mentioned above; however, if the colonies are first washed in distilled water and then transplanted to artificial media, growth takes place without difficulty. Da This type, like the majority of the species examined, grows better in media containing sugar or glycerine. Pigment is produced in all media and the body of the medium is generally darkened to a considerable extent by the culture. The pigment varies from an ochre-yellow in ordinary agar to a dark, almost black color in glycerine-agar and on potato. The characteristics on varous media are shown in the table. Pathogenicity: This species is pathogenic for monkeys by intraperitoneal in- oculation. It produces the usual actinomycotic lesion like those seen in the clinical disease in man and animals. The organisms are found in the broken- down mass discharged from the sinusses. : No. 6. Streptothrix of farcin du boeuf “A,” and No. 7. Streptothrix nocardii. These two strains are identical in all essential particulars and may therefore be described together under the correct name of S. nocardu. Noeard’s original description of this organism was not very complete, but several other observers have studied his and other strains and a number of good descriptions have been given. Foulerton has devoted careful study to this species and our work is in general confirmatory of his description. We haye STREPTOTHRICOSIS. 453 already noted the principal characteristics of this organism in both the text and table in our first report and a summary is also shown in the table in this one. Photomicrographic illustrations of its appearance in cultures are also submitted. Morphologically this parasite shows marked variation under different environ- ment. In young cultures and early lesions the hyphal forms are prevalent and quite uniform in appearance, but in older cultures and in colonies from lesions, irregularities are encountered. Coccus and bacillus-like forms predominate and very old cultures may almost have the appearance of mixed culture of bacteria. The filaments may or may not be radially placed at the periphery of the colonies. There is true branching, but no true clubs have been seen in cultures or in experimental lesions up to fifteen days of age. The Gram-Weigert method of staining gives good results and portions acid fast to the Ziehl-Neelsen-Gabbett method of staining are very numerous. The organism is also alcohol fast. Culturally this species is a facultative aérobe. It grows on the majority of laboratory media at incubator or tropical room temperature; development becomes apparent in from two to four days after inoculation. The difficulty of securing transplants from experimental lesions, mentioned in connection with S. madure does not obtain with this organism. The principal cultural characteristics on various media are shown in the table and may briefly be summarized as follows: Small, white, irregular, round, raised, opaque colonies develop on ordinary agar after two to three days. Growth is slow and not abundant and no pigment is produced. Glycerine-agar after three days shows discrete colonies which coalesce later and become heaped up, presenting a moist, meal-like growth. No pigment is produced. On potato, growth appears after 48 hours as a buff-yellow, granular, raised mass without pigmentation or erosion of this medium. - In bouillon growth appears after 48 hours as a grayish, flocculent mass at the bottom of the tube, later a few grayish granules appear on the surface of the medium and in some instances “puffball” formations occur at the bottom of the tube. The fluid remains clear. In ascitic fluid a very slight growth slowly develops at the bottom of the tube. _In litmus-milk growth appears only at the bottom of the tube. The milk is not coagulated and its color is not changed. Pathogenicity: This species is an exquisite tissue parasite for monkeys, and is pathogenic to a less extent for some other animals. Monkeys inoculated in the abdominal cavity and killed after five to fifteen days show characteristic lesions. In the majority of instances the early lesions are tubercle-like formations scat- tered through the mesentery and other tissues contiguous to the point of inoculation. In some cases pus pockets and channels are formed, surrounded by adhesions and containing granules made up of the microérganisms in the pus-like material. Guinea pigs inoculated in a manner similar to the monkeys give parallel results. : No. 8. Streptothrix eppingeri “A,” and No. 9. 8S. eppingeri “B.” These strains are identical in all essential particulars and may be described under the correct name of S. eppingeri. This is one of the most important species of this group of organisms and has been well de- seribed several times. It has been isolated from anatomical lesions of such varying character as those from meningitis, by Eppinger and others, to Madura foot, as has been published in our first report. Foulerton has described this species and we have fully discussed its characteristics in our first report and summarized them in the table in this paper. Our work has demonstrated fully 454 MUSGRAVE, CLEGG, AND POLK. the identity of S. freeri with this species and it is probable that several of the varieties described in the literature also must be classified with it. Its characteristics may be summarized as follows: Morphologically a variety of forms exist varying from small, oval, coceus and bacillus-like bodies, to long branching filaments, depending upon the lesion or the age of the culture and the media used. In tissues the branching filaments are not seen by the ordinary method of staining, the growth occurring as a skein of thread-like filaments and with colony formation. The threads present a beaded appearance by using Gram-Weigert’s stain. In cultures portions of the filaments are acid-fast by the Ziehl-Neelsen-Gabbett method, and they are also Gram positive. The entire mass from experimental lesions is often acid-fast. Culturally the species is a facultative aérobe and grows on the majority of media. Growth becomes apparent on ordinary agar after two days, consisting of a smooth, adherent membrane which at first is porcelain-white, later it develops a delicate, orange-pink color. The medium remains moist and is not colored in its depth. Glycerine-agar, after about three days, shows a growth consisting of small, whitish colonies, which gradually develop a delicate pink color. Later, as the colonies progress, they become umbilicated and coalesce, forming a heaped-up growth and producing a bright, orange color. The medium becomes slightly darkened. On potato the growth appears after about four days as a granular layer, at first white, later becoming yellowish and gradually assuming a brick-red color. As the colonies develop they become umbilicated then coalesce and finally produce a moist, meal-like growth on the surface of the medium. The colonies can be lifted in heaps from the medium by the platinum loop, and when immersed in salt solution or distilled water readily disintegrate into fine, flat particles which float on the surface. : In bouillon growth appears after 48 hours in the form of small, flat particles, which at first are white, but later assume an orange tint on the surface of the medium. As growth progresses, the colonies coalesce and produce a membrane on the surface of the liquid. Portions of this membrane fall to the bottom of the tube. In ascitic fluid a very slight growth occurs after six day’s incubation. Litmus-milk shows growth on the surface of the medium in the form of fine, white particles which in time becomes pink in color. A film is gradually formed on the surface of the milk, which is neither coagulated nor changed in color. Pathogenicity: The three cultures of this species, including the two strains from Foulerton as well as our own, are pathogenic for monkeys, producing on inoculation characteristic progressive lesions. (See animal experiments.) Typ- ical Madura foot may be produced by inoculation into the feet of monkeys. Subcutaneous inoculation produces abscess-like pockets, containing a thick, viscid pus in which the colonies of the organism may be observed as small, white granules. Intra-abdominal inoculation results in tubercle-like formations with adhesions, breaking down of tissue with abscess and sinus formation. Granules made up of the colonies are present in the abscess contents. No. 10. 8. capre. A study of this species from the culture sent us by Fouler- ton confirms in general the findings of Silberschmidt and of Foulerton. It shows characteristics which differentiate it specifically from any of the others with which we have worked. Morphologically this organism more closely resembles the bacteria than the others and in its action on monkeys it also resembles the tubercle bacillus quite closely. The filaments show true branching without club formation and they are shorter than with most of the other species. Bacillus- and coccus-like forms STREPTOTHRICOSIS. 455 predominate in cultures and are also very prevalent in experimental lesions. It stains by the stronger aniline dyes in a somewhat irregular manner, is Gram positive and largely and strongly acid and alcohol fast. Culturally it is a facultative aérobe and grows on most of the laboratory media. Growth first becomes apparent in from two to four days and progresses slowly. The cultural characteristics are shown in the accompanying table and need not be repeated here. Pathogenicity: This organism is pathogenic for monkeys and guinea pigs and by intraperitoneal injection for rabbits. The lesions differ somewhat from some of the other members of the group in that there is much less tendency to sup- puration or other form of tissue necrosis. The lesion is essentially a tubercle- like formation which spreads from the point of inoculation by the formation of other small granules. When studied microscopically these lesions resemble the tubercle quite closely, always contain the microédrganism and occasionally giant cells are encountered. The tubercle-like granules occasionally break down and form small pockets of thick granular pus-like material, but this is the exception and granules made up of colonies of the parasite have not been encountered as in the other species. No. 11. S. canis. This organism is probably identical with S. capre of Sil- berschmidt. The only important points of difference in the cultures which we have are shown in the table, and consist principally in the difference in reaction in litmus milk. Morphologically and in its pathogenic action S. canis gives very similar results to S. capre. The same tubercle-like lesions are formed in experimental animals and the close similarity in other respects has led to the conclusion that the two belong to a single species. No. 12. 8. chalcea. This is a nonpathogenic species reported by Foulerton and carried along in this work principally as a control. It is distinguished specifically from the other species by morphologic and cultural characteristics, and parti- cularly by its being nonpathogenic for monkeys. ANIMAL EXPERIMENTS. The following are summaries of our animal experiments. The general results are placed under the discussion of the characteristics of the various species of the microdrganisms. A complete summary will be found in the chapter on general discussion and conclusions. S. nocardi: Monkey No. 3635, inoculated in the abdominal cavity with one loop of a two months’ culture and the animal killed 12 days later. Autopsy shows numerous miliary tubercle-like granules extending over the entire surface of the omentum and mesentery with an occasional suppurative process. The pus when pressed out contains small, yellowish-white granules made up almost entirely of the microérganism. Monkeys numbered 3722, 3726, 8714 were inoculated in a similar manner to the above. All showed similar lesions with the exception of monkey No. 3722 which gave a negative result. Guinea pigs and rabbits inoculated in the abdonimal cavity for the greater part developed similar lesions. Intravenous inoculation in rabbits gave negative results. S. eppingeri: Monkey No. 3665 was inoculated in the abdominal cavity with one loop of a ten days’ culture and the animal was killed thirteen days later. Autopsy shows numerous, tubercle-like granules in the lower portion of the mesentery, 456 MUSGRAVE, CLEGG, AND POLK. with extensive adhesions of the mesentery to the abdominal wall. On separating the adhesions, or on section through them, numerous sinusses are exposed; these hold a thick, viscid, pus-like substance containing numerous small grayish-white granules composed principally of Streptothria. Monkeys numbered 3664, 3633, 3622 were inoculated in a similar manner to monkey No. 3665 and the lesions produced were in all essentials similar to those found in that animal. Foulerton’s strain of S. eppingeri. Monkey No. 3725 was inoculated in the abdominal cavity with one loop of a ten days’ culture and the lesions produced are similar to those found in animals inoculated with S. eppingeri of the original strain. S. madure. Monkey No. 3854 was inoculated by opening the abdominal cavity and burying a loop of the material from a two weeks’ culture of Strong’s strain of the organism, Ten days later the animal presented a distended abdomen with a marked tympanites and was killed on this date. Autopsy shows numerous miliary tubercle-like processes in the omentum and mesentery and adhesions surrounding the inoculated material. The adhesions are easily separated and show small, pinkish-white granules adhering to the mesentery. Rabbits and guinea pigs inoculated subcutaneously, intravenously, and intra- peritoneally with this organism gave negative results. Monkey No. 3856 was inoculated in the abdominal cavity with one loop of a two weeks’ culture of Fullerton’s strain of this organism and killed two weeks later. Autopsy shows a small, tumor-like mass made up largely of adhesions confined to the coils of the intestine, omentum, and abdominal wall. On section the tumor shows several small abscesses from which can be expressed a thick pus containing small, white granules composed almost entirely of the organisms. The latter are present in large numbers. Monkey No. 3724 was inoculated in a manner similar to the above with negative results. Guinea pig No. 3856 was inoculated into the abdominal cavity with one loop of a two weeks’ culture and killed after 10 days. Autopsy shows slight adhesions of the omentum to the abdominal wall and intestine, but no other lesions are present. - ee Subeutaneous and intravenous inoculations of monkeys, rabbits, and guinea pigs gave negative results in every case. Monkeys numbered 3719, 3627, 3668 were inoculated with one loop of a two weeks’ culture of Vincent’s original strain of this organism. The inoculations were made subcutaneously and intraperitoneally and in no instance were progres- sive lesions produced. Guinea pigs and rabbits inoculated subcutaneously, intravenously, and by in- traperitoneal injections also gaye negative results. Actinomyces (from the Pasteur Institute) : Monkey No. 3864 was inoculated into the abdominal cavity with one loop of a two weeks’ culture. The animal died three weeks later. Autopsy shows small abseesses in the abdominal wall at the site of inoculation and numerous miliary, tubercle-like granules in the omentum and mesentery. The pus from the abscesses contains many minute, hard, black granules which by microscopic examination are seen to be made up of a net-work of mycelia and transformation products of the microérganism. Monkeys numbered 3622 and 3623 were inoculated in a similar manner and presented similar lesions to the above. Intravenous, subcutaneous, and intraperi- toneal inoculation of rabbits and guinea pigs gave negative results in each case. STREPTOTHRICOSIS. 457 S. capre: Monkey No. 3858 was inoculated into the abdominal cavity with one loop of a two weeks’ culture and ten days later the animal was killed. Autopsy shows numerous miliary, tubercle-like bodies on the mesentery, diaphragm, and on the surface of the liver. There is slight adhesion of the omentum to the abdominal wall at the site of the inoculation. Monkey No. 3625 was inoculated into the subcutaneous tissue and into the peritoneal cavity with a suspension of this organism. The animal died three weeks later. Autopsy shows extensive adhesions around the site of inoculation and there is a large abcess in the abdominal wall. On section the abcess contains a heavy, creamy, pus-like material in which are numerous, minute, grayish- white granules. These granules are composed of microérganisms and a pure culture is easily obtained by transplanting the granules to artificial media. Guinea pig No. 3859 was inoculated in a similar manner as were monkeys numbered 3858 and 3625 and the lesions produced were similar to those described for the monkeys. Intravenous inoculations of rabbits gave negative results in the animals used. S. canis: Monkeys numbered 3633 and 3626 were inoculated in the abdominal cavity with one loop of a two weeks’ culture and a two months’ culture of this organism’ respectively, and both animals were killed two weeks later. Autopsy shows slight adhesions near the site of inoculation. The omentum and mesentery are intensely congested and contain numerous miliary, tubercle-like granules. Monkeys, guinea pigs, and rabbits inoculated subcutaneously showed no pro- gressive lesions at autopsy. Intravenous inoculation of rabbits gave negative results. Intraperitoneal inoculation of guinea pigs in two instances produced lesions similar to those described for intraabdominal inoculations in monkeys. NS. chalcea. Monkeys, guinea pigs, and rabbits when inoculated subcutaneously and intra- peritoneally gave negative results. LITERATURE. A review of the literature of this subject may for convenience be divided into two divisions (1) genus and (2) species determinations. Several of the generic names which have been introduced are clearly descriptive of organisms belonging to other genera such as Cladothrix or Leptothriz, and some refer to organisms properly belonging to the classes Oidia or Bacteria. GENUS. a The generic names which appear to have some claim for consideration are as follows: STREPTOTHRIX. Corda named this genus, giving, according to Saccardo (Sylloge Fungorum (1886), 4, 282) the following generic diagnosis: “Hyphe fertiles erecte, virgato-ramosz, ramis ramulisque spiraliter tortis. Conidia globosa vy. ovoidea, in ramulis solitarie acrogena, subinde pleurogena, sessilia vy. stipitellata, fusca.” Cohn (Untersuchungen iiber Bacterien, I1—Beitriige zur Biologie der Pflanzen (1875), 1, 186) used the name Streptothric in a new sense in describing an 458 MUSGRAVE, CLEGG, AND POLK. organism Streptothrix fosteri, which he found in the lachrymal ducts of a patient. The definition for this organism as given by De Toni and Trevisan (Saccardo’s Sylloge Fungorum (1889), 8, 928) is as follows: “Wilamentis tenuissimis, hyalinis, parallele insimul stratiformi-coalitis vel fasciculatis, rectis vel incurvis, sparse irregulariterque ramosis, in fragmenta inaequilia secedentibus.” CLADOTHRIX. Cohn (loc. cit., 185) wnder the name Cladothrix dichotama described an organism which was later included as the type species of a genus established by Marehand (Botanique cryptogamique, Paris (1883)) of which De Toni and Trevisan (Saccardo, (1889), 8, 927) give the following generic diagnosis: “Filamenta basi ab apice superiore distincta, vagina crassa obducta cylindrica, wtate provecta a basi ad apicem magis magisque incrassata, articulata, pseudo- ramosa. Arthrosporae binae in singulis microbaculis ellipsoideis ortae.” However Mace (Compt. rend. acad. sci. (1888), 106) in a careful study of Cladothrix dichotoma Cohn showed that it did not have the supposed property of dichotomous division of the filaments, but that this appearance was simulated by a lateral branching process. ACTINOMYCES. Meyen (inten (1827) 2, 433) described a fungus under the name Actino- myces horkelii. Bollinger (Centrabl. f. d. med. Wiss. (1877), 15, 481) pub- lished an account of a disease in cattle caused by a vegetable organism which was carefully described and named Actinomyces by Harz (Jahresb. d. k. Central- Thierarzneischule, Miinchen (1877-78), who at this time probably did not know of the previous occupation of the name by Meyen. The work of Bollinger and Harz attracted much attention and was rapidly, followed by a number of important contributions to the subject. For example, James Israel (Vireh. Arch. (1878), 74, 15; 50) described a similar organism as the cause of a similar disease in man and Ponfick (Breslauer drtzliche Zeitschrift, May, 1879, and in subsequent publications) established the generic identity of the microdrganisms in man and animals. The work of several writers showed that there existed varieties of this organism, but for a con- siderable time Actinomyces remained unquestioned as a generic name for the organisms. Botanists classified the organisms in various ways, the most noteworthy being that of De Toni and Trevisan who created a new genus Nocardia (Saccardo, 8, 927) and placed Actinomyces (Saccardo, 8, 928) as a species with the following diagnosis: “Glomerulis subglobulosis e filamentis densissime intertextis, fasciculos in- numeros apice valde incrassato clavatos, a puncto centrali communi undique irradiantes constitutis.” OOSPORA. : This generic name was introduced by Sauvageau and Radais (Ann. Inst. Pasteur (1892), 6) to include the organisms previously described as Actinomyces, Cladothriz, and Streptothriz. This term never was seriously considered in the literature and needs no further notice. — oe STREPTOTHRICOSIS. 459 NOCARDIA. De Toni and Trevisan (Saccardo, 8, 927) introduced Nocardia as the generic name and included as synonyms, Streptothrix Actinomyces, and in part Dis- comyces. ‘The generic diagnosis given by them is as follows: - “Wilamenta tenuissima, evaginata, articulata, Cladotricis more pseudoramosa, nune e nucleo firmo radialiter expansa, nunc varie coalita. Arthrosporae in filamentis normalibus obvenientes, transformatione cocci singuli orte.—Hst Cladothrig sine vaginis. SPHAEROTILUS. Engler (Syllabus der Pflanzenfamilien (1907), 5 ed., 5) places all the above- described organisms in the family Chlamydobacteriaceae of the Schizomycetes. He reduces the above-mentioned genera including Actinomyces to Sphaerotilus Kuetz (1833) the generic definition of which as given by De Toni and Trevisan (Saccardo, 8, 926) is as follows: “Filamenta premitus affixa, basi ab apice superiori distincta, initio simplicia, dein Cladotricis more pseudoramosa a basi ad apicem subzquilata, articulata, vagina gelatinosa obducta, in fasciculos crassos floccosos varie divisos consociata. Multiplicatio fragmentis filamentorum secedentibus, quae filamenta et fasciculos novos efficiunt. Arthrosporae numerosissimae, articulorum divisiones in tres directiones ort.” The above review shows the confusion which exists regarding the botany of the group of organisms which are variously recognized as Streptothriz, Cladothria, Actinomyces, Nocardia, ete., and this seems to have been still further emphasized by workers in medicine and by other recent writers upon the subject. Some of the more important contributions are as follows: Petruschky (Handbuch der Microérganismen, Kolle and Wassermann (1903), 2, 832) classifies Actinomyces, Streptothrix, Cladothrix and Leptothrix as species of Trichomyceta of the hyphomycetes. He recognizes Streptothria as the generic name of the parasites of mycetoma. } _ From the standpoint of an investigator in medicine, whatever may be the criticisms of botanists, the work of L. Gedoelst (Les Champignons parasites de Vhomme et des animaux domestique, Paris, 1902) is particularly satisfactory, because of its simplicity of arrangement and attention to details. His classifi- cation places the organism under discussion among the Fungi imperfecti and in the genus Discomyces Rivolta (1878), with Streptothriz Cohn (1875); Actino- myces Harz (1877); Nocardia Trevisan (1889) ; Odspora Sauvageau et Radais (1892) and Discomyces Blanchard (1900) as synonyms. Foulerten (Allbutt’s System of Medicine (1906), 2, pt. 1, 302) who has been interested in this subject and has made many most important contributions to it, maintains Streptothrix Cohn to be the generic name. Foulerton gives four reasons for using Streptothria in preference to any of the other terms. 1. He does not consider that Corda’s indefinite use of the term in 1833 should make Streptothrix Cohn (1875) untenable. 2. This being acceptable, Streptothria becomes the correct botanical name by priority of description. 3. Streptothrix was adopted by the committee of the Pathological Society. 4. It is by far the most generally used name. 460 MUSGRAVE, CLEGG, AND POLK. James Homer Wright (Osler’s Modern Medicine (1907), 1, 327; 340) who has made valuable contributions to the study of Actinomycosis recognized No- cardia as the correct generic name, but raises Actinomyces from species, as given by Trevisan, to generic rank and thus converts what most authors have included in a single genus, into two genera. Sir Patrick Manson (Tropical Diseases (1907), 4 ed., 759) in his recent discussion of mycetoma has adopted a liberal etiologic classification, both by his definition and his classification of the varieties of mycetoma. He classes actinomycosis as one variety of mycetoma, designating it as actinomycotic my- cetoma, and the other names under discussion here might also be included in this category, if we adopt this definition. This eminent author in his definition of mycetoma terms it “a fungus disease of warm climates, affecting principally the foot, occasionally the hand, rarely the internal organs or other parts of the body.” Manson in this classification follows Brumpt (Arch. Parasit. (1906), 10, 489) who in turn apparently adopts his classification of the parasites from Gedoelst (loc. cit.). The diverse forms of the disease recognized are: J. Actinomycotic mycetoma caused by Discomyces bovis (Harz 1877). I. Vineent’s white mycetoma produced by Discomyces madure (Vincent 1894). III. Nicolle’s white mycetoma the result of Aspergillus nidulans (Hidam 1883). IV. Buffard’s black mycetoma caused by Aspergillus bouffardi (Brumpt 1906). V. Classie black mycetoma from Madurella mycetomi (Laveran 1902). VI. Brumpt’s white mycetoma from Indiella mansoni (Brumpt 1906). VII. Reynier’s white mycetoma resulting from Indiella reynieri (Brumpt 1906). VIII. Bouf- fard’s white mycetoma from Jndiella somaliensis (Brumpt 1906). SPECIES CONSIDERATION. Following the generic name of the entire group of organisms under consideration, the next logical step. of the problem is a discussion of the Species properly belonging to the genus. The classification of species is a more difficult problem than the generic determination, largely because of the imperfect description of many of the so-called species or varieties. In fact, but few have been described with sufficient clearness to make determination possible. It is not possible to state who first recognized this group of organisms. It may have been Corda, 1842; Mayen, 1827; Von Langenbeck, 1845 (Acland in Allbutt’s System (1906), 2, pt. 1, 325); Sir T. Smith, 1855 (ibid) ; Lebert (1857) (Traité d’anatomie pathologique, 1, 54) ; Ballingal, 1855; or any one of several other writers, some of whom undoubtedly saw these parasites in lesions of the human body. However, Henry Vandyke Carter, working from 1859 to 1874, first established the pathogenic role of the streptothrices in human pathology. While Carter did not cultivate his organism on artificial media and his descriptions are insufficient for species determination, a study of his publications leaves no doubt but that he was working with a clinical type of Streptothrix infection and his observations as to the specific etiology were quite satisfactory. Erye 1860, Collas 1861, Biddie 1862, Coquerel 1866 Moxon and Hogg (Trans. Path. Soc., London (1870)), Bristowe (Trans. Path. Soc., London (1871)), Hogg (Med. Times & Gaz.) (1871), all recognized fungus-like bodies in cases of foot infection, which were clinically mycetoma or Madura foot. Berkeley (Med. Press & Circ., (1876) ) states that he had cultivated one of STREPTOTHRICOSIS. 461 these organisms from a case of Madura foot which had been forwarded to him by Vandyke Carter. He named the organism Chionyphe carteri. Rivolta (Med. Vet. (1868) ) probably saw these organisms in pus taken from an abscess on the jaw of a cow. Rivolta (1868-1875) also found disc-like bodies in nodular masses from the tongue of a cow. He named the disease sarcomycosis. Robin (Traité de Microscopie, Paris (1871), 575) gives a brief description of yellowish granules from two abscesses which were probably due to Strepto- thriz infection. Heller (about 1872, completed a work which he published in Deutsch. Arch f. klin. Med (1885), 37, 372) and from his description and drawing probably saw these organisms in the discharges from a case which he later considered to be acute actinomycosis. Perroncito (1875) evidently saw and described species of this organism taken from a pseudosarcoma of the jaw of a cow. Cohn (Beitr. Biol. d. Pflanzen. (1875)) 1, 148, described an organism which he obtained from concretions in the lachrymal canals of a patient, terming it Cladothria fosteri. Bollinger (Deutsche Ztsch. f. Thiermed., Leipz. (1877), 3, 334) noted the constant occurrence of a branching organism in lumpy-jaw of cattle; Harz (ibid, (1878) ) described it, naming the organism Actinomyces bovis and Bollinger termed the disease actinomycosis. Israel (Virch. Arch (1878), 74, 15) described a disease in, man similar to actinomycosis in cattle and detailed the microscopic appearances of the causative Streptothriz. Ponfick (Breslau. drztl. Ztschr. (1879) furnished strong evidence of the etiologic identity of the diseases of man as described by Israel and of cattle as given by Bollinger and Havrz. Corre (Arch. méd. Nav., Par. (1883)) in reporting the notes of Dr. Collas called attention to the probable identity of actinomycosis with the earlier de- scribed mycetoma, and many other authors since that time have come to the conclusion that the diseases are probably the same. Mandareau (Bull. acad. méd. (1887), 18, 555) gave a morphologic descrip- tion of a species of Streptothriz. Nocard (Ann. Inst. Pasteur (1888), 2, 293) described and cultivated a Streptothriz from the lesions of a disease known as farcin du boeuf which was very prevalent among cattle in Guadeloupe. Organisms which agree with Nocard’s description have repeatedly been isolated from pathologic lesions by other authors. Nocard’s work was epoch making in that he was the first satisfactorily to cultivate a Streptothrix in pure culture. Affanassiew and Schultz (Miinchener med. Wehnsch. (1889), 36, 418) briefly described a Streptothrix obtained from pus and sputum. Cultures were patho- genic for guinea pigs. Protopopoff and Hammer (Ztschr. f. Heilk. (1890, 11, 255) reported incomplete studies of the cultures of Affanassiew’s and Schultz’s organism. Kischensky (Arch. f. exp. Path. wu. Pharm. (1889), 26, 79) partially described and probably cultivated a Streptothriz which may have been identical with that cultivated later by Wolff and Israel from a human case of actino- mycosis of the lungs. Bujwid (Centrbl. f. Bakt., etc. Abth. 1 (1889), 6, 630) cultivated and briefly described a Streptothrix which was a facultative anaérobe taken from a human case of actinomycosis. Eppinger (Wien klin. Wehnsch. (1890), 3, 321) cultivated a Streptothrix from a brain abscess and a “pseudo tuberculosis of the lungs”, the patient having manifested the clinical symptoms of meningitis during life. This organism was Gram positive, acid-fast and a facultative aérobe. Growth occurred on the ordinary laboratory media and the organism was pathogenic for laboratory 462 MUSGRAVE, CLEGG, AND POLK. animals. Eppinger’s publication, like that of Nocard, forms a landmark in the history of the disease. His work has been confirmed by MacCallum and others and his organism, which is a different species from that of Nocard, will be more fully considered in this paper. Almquist (Ztschr. f. Hyg. (1890), 8, 189) cultivated species of Streptothria from three different sources. The first was discovered as a contamination in a gelatin culture tube, the second was cultivated from pus taken from the base of the brain from a human case and the third culture was isolated from water. Liebman (Arch. per le sci. med. (1890), 14, 361) discussed the cultivation of Streptothrix in pure ‘culture. Bostroem (Beitr. 2. path. Anat., etc. (1891), 9, 1 to 240) cultivated a single species of Streptothrix from eleven cases of actinomycosis. His organism was Gram positive and in part acid-fast and was a facultative aérobe in cultures. Growth was obtained with difficulty directly from the lesions, but the later trans- plants were more satisfactory in artificial media. Bostroem’s article was the first published exhaustive consideration of the cultivation of Streptothria. Wolff and Israel 1891 (Vireh Arch. (1891), 126, 11) cultivated a Streptothrix from two cases of clinical actinomycosis in man. In one case the lesion was a retro- maxillary tumor and the other was actinomycosis of the lungs. This organism was acid-fast and a facultative anaérobe. Gruber (Zr. VII Intern. Cong. Hyg. «& Demog., Lond. (1891), 2, 65) discovered (as an accidental contamination of culture media) an organism which he described as Micromyces hofmanm. This organism produced pyemia in animals and “ray fungus” types were present in the lesions. The articles by Doyen (Tr. VII Intern. Cong. Hyg. & Demog., Lond. (1891), 3) and Roussel (These, Paris, 1891) are not available to us. Hesse (Deutsche Ztschr. f. Chir. (1892), 34, 274) obtained a Streptothrix by culture from an abscess in the groin, which when opened was found to com- municate by a sinus with the intestine. Autopsy on the patient, who died after more than a year’s illness, showed a rectal fistula communicating with multiple abscesses in and around the pelvis. There was bronchitis, but the organisms were not found in the sputum. The organism was Gram positive and aérobic in culture media. Growth occurred on the majority of media and serum media were liquefied. No positive results were obtained from intravenous, intraperi- toneal, or subcutaneous injections of cultures into rabbits, guinea pigs or white mice. Sauvageau and Radais (Ann. Inst. Pasteur (1892), 6, 242) studied a number of streptothrices which had already been isolated by other authors. They made a classification of Streptothricae in general, based upon cultural characteristics. The articles by Lanz (Cor. Bl. f. sechwéiz. Aerete (1892), 307; 339) ; Ebermann (Inaug. Diss. St. Petersburg (1893); Dor (Gaz. hebd. de med. (1893) 2 s., 30, 40) and of Dor and Bérard (Prov. méd. (1893) are not available to us. Vincent (Ann. Inst. Pasteur (1894), 8, 129) cultivated a Streptothrix which was pathogenic for laboratory animals from a case of ochroid variety of myce- toma. We have already noticed this organism somewhat in detail and it will be considered further. Vincent’s work is very important because he was the first satisfactorily to cultivate a Streptothrix from the Madura foot type of the disease and because his organism is specifically different from any of those described before his paper appeared. Boyce and Surveyor (see bibliography) in a series of articles, described streptothrices which they were able to isolate from cultures made by friends in India, taken from cases of mycetoma. and forwarded to the authors in England. The brief description given by these authors renders it probable that this organism was identical with that of Vincent. Karg (Ref. Diims’ Deutsche mil-drztl. Ztschr. (1894), 23, 145) cultivated a Streptothri« STREPTOTHRICOSIS. 463 from a case of actinomycosis in man. Karg considered his organism to be identical with that of Bostroem. This author also reported a second case of the disease with results similar to those obtained with the first one. Leith (Edinb. Hosp. Rep. (1894), 2, 121) and Newjadomsky (Ref. Lubarsch and Oster- tag Ergb. (1898), 5, 665) each isolated by culture a Streptothrix from a human ease of actinomycosis. The article of Kitchensky (Arch. f. exper. Path. wu. Phar- makol. (1890), 26, 79) is not available to us. Sabrazés and Riviére (Presse méd. (1894), Sept. 22) reported the cultivation of a Streptothrix from abscesses in the brain, lungs, and kidneys of a human case. This organism only grew anaérobically. In their second case (Mercredi méd. (1895), 485) an aérobic Streptothrie was cultivated from the sputum and subcutaneous abscesses of a patient. Both these organisms are reported as being pathogenic for small animals, the latter one, however, only producing lesions when injected together with dilute acetic acid. Aschoff (Ber. klin. Wehnsch. (1895), 32, 738) cultivated a Streptothria from a case of human actinomycosis and stated that he had produced actino- mycotic lesions in animals by inoculating cultures of the organism. Du Bois Saint-Sevrin (Semaine méd. (1895)) cultivated a Streptothria from a case of ulcer of the cornea in a human patient with a pseudomembranous conjunctivitis. Ferré and Faguet (Mercredi méd. (1895), 441) did the same from an abscess in the centrum ovale of the brain. The authors considered this organism to be identical with that of Eppinger. Rullmann (Ref. Centralbl. f. Bakt., ete. (1895), 17, 884) cultivated a Streptothriz from soil and again in 1898 the same author (Miinchener med. Wehnsch. (1898), 45, 919) cultivated what he apparently considered to be the same organism from a case of disease of the lung. It was a Streptothria# positive to Gram’s stain, which grew on ordinary media as a facultative aérobe. Positive local lesions were produced in rabbits, guinea pigs, and mice when these animals were inoculated with cultures. Garten (Deutsche Ztschr. f. Chir. (1895), 41, 257) cultivated a Streptothriz from lesions in a human case. There was necrosis of the vertebrae and ribs, with abscesses, sinus formation and empyema. This organism grew on laboratory media and was pathogenic for three out of thirty-seven rabbits and guinea pigs. Dor (Gaz. hebd. d. méd. (1896), 43, 553) obtained a Streptothrix from an actinomycosis-like abscess at the angle of the jaw. The pus contained granules with long, beaded filaments which did not stain by Gram’s method. The organism grew aérobically on liquid media only. Sawtschenko (Baumgarten’s Jahresb. (1896), 12, 613) cultivated an organism from a case which he termed pseudoactinomycosis. It formed long threads which did not stain by Gram’s method and which grew only under anaérobic conditions. Jurinka (Mitth. a. d. Grenzgeb. d. Med. u. Chir. (1896), 1, 139) cultivated a Streptothrix from a human -case of actinomycosis which he considered identical with that of Wolff and Israel. The article by Kozerski (Ref. Jahresb. d. ges. Med. (1896), 2, 223) is not available to us. 5 Scheele and Petruschky (Verhandl. d. Con. f. innere Med. (1897), 15, 550) cultivated a Streptothrix which was acid-fast by the Ziehl-Neelsen method from the sputum and subcutaneous abscesses of a case of pyzemia, pleuro-pneumonia, cystitis, and pyelitis. It grew on agar, gelatin, and broth. Its pathogenic character for animals apparently was not determined. Buchholtz (Ztschr. f. Hyg. (1897), 24, 470) described a Streptothrix found in the lung of a patient suffering from a disease which, both clinically and pathologically, very closely resembled tuberculosis of the lungs. The organism was Gram positive and acid-fast, but did not grow on artificial media. Urban (Miinchener med. 792842 464 MUSGRAVE, CLEGG, AND POLK. Wehnsch. (1897), 44, 124) cultivated a Streptothrix from a case of human actinomycosis. Berestnew (Aktinomykose und ihre Erreger (Dissert), Moskau (1897) reported several cases. A Streptothriv was cultivated from a sub- periostial abscess of the lower jaw of a woman (Case I). This clinically was a case of “lumpy jaw.” This organism was a Streptothrix, facultative anaé- robic, Gram positive, dying after three generations on artificial media. It was not pathogenic for rabbits, guinea pigs, or tame mice. The organism from his Case II] was cultivated from an abscess under the right nipple of a 16-year-old patient who had symptoms of disease of both lungs. The organism differed from that of Case I in that it grew somewhat better in the presence of oxygen. The cultures in Case IIT were from sputum and chest sinuses in a patient forty-four years of age, who died after an illness of about one year. The organism was Gram positive, facultative aérobic, and grew best in bouillon. It was neither fatal for rabbits nor guinea pigs when injected either intraperi- toneally or subcutaneously; a temporary infiltration of the tissues resulted by the latter method. Abel (Miinchener med. Wehnsch. (1897), 44, 124; 149) made brief reports of a pathogenic Streptothriz from sputum. Van Neissen (Vireh. Arch. (1897), 150, 482) worked with an organism which was not differentiated from that of Wolff and Israel. z Berestnew in another case (Ztsehr. f. Hyg. w. Infeetionskrankh. (1898), 29, 94) obtained a Streptothrix in pure culture from the lesions in a child suffering from an abscess of the ling and pyemia. This organism was negative to Gram, grew anaérobically on media and was pathogenic for animals. Petruschky (Deut- sche med. Wehnsch. (1898), 24, Ver.-Beil. 78) cultivated an organism similar to that of Scheele and Petruschky (loc. cit.) from the sputum obtained from a second case of streptothricosis. Alissow and Skworzow (ref. Lubarsch and Ostertag (1898), 5, 664) studied two cases of streptothricosis in man. They obtained two organisms in bouillon cultures, a bacillus and a Streptothrix grow- ing in symbiosis. Pure cultures of the Streptothria developed only clubs and rods, but when bacteria were again mixed in the cultures, long fungus threads were produced. The authors consider the lesions to be due to the mixed infec- tion. Schtscheglow (1898) (ibid.), also secured mixed cultures and the bacteria present influenced the morphology of the Actinomyces. Newjadomsky (1898) (ibid) reported one case in. man in which a NStreptothriz was obtained in pure culture from a subdiaphragmatic abscess. The author considered the organism to belong to a new species. It was not pathogenic for guinea pigs. Rull- man (Miinchener med. Wehnsch. (1898), 45, 919) cultivated a Steptothrix from the sputum of a patient with a localized lesion near the root of the right lung. This organism was Gram positive and grew on all media. It was pathogenic for mice, rabbits and guinea pigs, and could be reclaimed by culture from lesions in these animals. Grillo (Reforma Medica (1898), 14, 301) cultivated a Strepto- thric from a case of human actinomycosis and from the bovine infection and reproduced the disease by animal inoculation with cultures of the organism. Har- bitz (Norsk Mag. f. Legevidensk (1898), 13, 1) obtained a Streptothrix by culture from five cases of human actinomycosis. Flexner (Journ. Hap. Med. (1898), 3, 435) reports a case of human infection with a Streptothrix, but his organism did not grow on artificial media. The article by Marwedel (Beit. ¢. klin. Chir. (1898), 21, 561) is not available to us. Foulerton (Lancet (1899), 2, 779) cultivated his Streptothria hominis from abscesses of the chest with deep sinuses in a patient showing symptoms of a severe lung involyent with pyemie symptoms. This author (see bibliography) has also made numerous other contributions to the morphology of the subject and has probably done more than any other toward clearing up the confusion which STREPTOTHRICOSIS. 465 exists regarding this group of organisms. Levy (Centralbl. f. Bakt., ete. (1899), 26, 1) cultivated a Streptothria from five cases of clinical actinomycosis in man. He considers his organism to be identical with that of Wolf and Israel. Paul Krause (Centralbl. f. Bakt., etc. (1899), 26, 209) obtained a Streptothria from an abscess of the lower jaw. It was Gram positive but not acid-fast, a facultative aérobe and grew on ordinary laboratory media. No positive results were obtained by intraperitoneal or subcutaneous injection of cultures into rab- bits, guinea pigs, or white mice. Hayo Bruns (Centralbl. f. Bakt., etc. (1899), 26, 11) cultivated a Streptothria from a lesion which according to the diagnosis was an actinomycotic abscess of the abdominal wall. The organism was Gram positive, but not acid-fast and did not stain well with the ordinary aniline dyes. Growth occurred on ordinary media, best under aérobic conditions. No lesions were produced by intravenous, intraperitoneal, nor subcutaneous injections of cultures in rabbits, guinea pigs, or mice. Silberschmidt (Ann. Inst. Pasteur (1899), 13, 841) obtained a Streptothrix by culture from the lungs of a goat which had a disease closely resembling tuberculosis. This organism was carefully described by the author and later by Feulerton and Jones, (Tr. Path. Soc. (1902), 53, 99) who considered it to be a new species and our work is in accord with this conclusion. ; Brault (Arch. d. parasit. (1899), 2, 535) observed two human cases of actino- mycosis. He cultivated a Streptothrix, at first in symbiosis with bacteria and later in pure cultures. His organism grew on ordinary media and was path- ogenic for animals. Norris and Larkin (Jowrn. Dap. Med. (1900), 5, 155) obtained a Streptothrix by culture from two cases of bronchopneumonia and bronchiectiasis. Both cases proved fatal. This organism was Gram positive, but not acid-fast by the Ziehl- Neelsen method. The authors consider it probably to be identical with Israel's Streptothrix. Local lesions were produced in both rabbits and guinea pigs by in- jection of the cultures. Cozzolino (Ztschr. f. Hyg. u. Infectionskranfh. (1900), 33, 36) reports a human case of Streptothrix infection of the ear. He cultivated an organism from the lesion which was pathogenic for mice and guinea pigs and described it very well. It was a facultative aérobe, but branching was not observed. Dean (Zr. Path. Soc. (1900),-51, 25) cultivated a Streptothriw from the lesions in a horse which clinically was considered his organism to be a new species, differing in certain particulars from any described previously. This organism was a facultative aérobe, Gram positive, and grew very poorly on the majority of media and not at all on others. It was pathogenic for animals, producing lesions which contained organisms resembling Actinomyces, with club-shaped ends. However, in cultures no club formations were observed. Tusini (Arch. f. klin. Chir. (1900), 62, 249) observed four cases of Streptothrix infection in man. The one reported in detail was an infection which clinically was Madura foot. From this case, he cultivated a Streptothrix which was pathogenic for guinea pigs and which in cultural characteristics closely resembled the organism of Vincent. Sternburge (Wien. klin Wehnsch. (1900), 13, 548) cultivated a Streptothrix resembling that of Wolff and Israel from three cases of human actinomycosis. Aoyoma and Miyamoto (IMitth. a. d. med. Fac. d. k. jap. Univ. a. Tokio (1901), 4, 231 to 276) obtained a Streptothrix in pure culture from an abscess of the lung. This was Gram positive, acid-fast, and a facultative aérobe; pathogenic for rabbits, white mice, and hens. The authors believed their organism to be very closely related to or identical with S. eppingert. Mertens (Centralbl. f. Bakt., etc. (1901), 29, 649) reported one human case and cultivated a Streptothrix suffering from actinomycosis. He 466 MUSGRAVE, CLEGG, AND POLK. from the lesions. Cultures at first only grew in bouillon, but gradually growth on other media was successful. The anaérobic tendencies of his organism were changed so that it grew aérobically after a considerable time on artificial media. This organism produced lesions in the eyes of rabbits. Silberschmidt (Ztschr. f. Hyg. u. Infectionskrankh. (1901), 37, 345) studied eight cases of Streptothria infections in man. He cultivated the organism and believed he had isolated three different species. In six of his eight cases the organisms closely resembled those of Wolff and Israel. The others more closely approximate Bostroem’s organism, Jelenewski (Ref. Baumgarten’s Jahresb. (1901), 17, 495) studied fifty cases of actinomycosis occurring in the mouths of animals. He cultivated the fungus first with B. subtilis. Later he obtained pure cultures both aérobically and anaérobically. Cultures of the organisms were pathogenic for calves, but not for rabbits and guinea pigs. The author concluded that his Streptothrix was a new species, basing his decision upon both its cultural and pathogenic properties. Foulerton and Jones (Z'7. Path. Soc. (1902), 53, 56) studied the group extensively and described some new species. The tentative classification by these authors was the most satisfactory which had been made up to the time of its publication. } They also cultivated a Streptothria ( (ibid), 75, 93) which they believed to be the cause of the disease, from a conjunctivitis and keratitis in a twelve year old girl. The organism was Gram positive, but not acid-fast; a facultative aérobe growing on all media. It was not pathogenic for rabbits, guinea pigs, or white mice. The same authors (ibid, 100) isolated a Streptothric from “a case of pulmonary infection in a woman.” This organism was Gram positive, not acid- fast, grew on the usual laboratory media, and was not pathogenic for rabbits. MacCallum (Centralbl. f. Bakt., ete. orig. (1902), 31, 529) cultivated a Strep- tothric which he considered to be identical with that of Eppinger from the peritoneal exudate in the body of a child dead of subacute purulent peritonitis which followed a surgical operation for relief of stricture of the oesophagus: Birt and Leishman (Journ. Hyg. (1902), 2, 120) studied a Streptothrix which was obtained from a fatal human case. Empyema, pericarditis, and “cirrhotic nodules in the lungs” were present at autopsy. The organism was isolated from the pleure, pericardium, and lung. It was Gram positive and acid-fast and showed strong aérobic tendencies. It grew on the majority of media, producing a coral-pink color. This organism was pathogenic for guinea pigs and is probably identical with Eppinger’s Streptothriz. Schukewitsch (Ref. Jahresb. d. ges. Med. (1902), 1, 711) cultivated a Streptothric somewhat resembling that of Wolff and Israel from twenty-two out of twenty-five cases of human actinomycosis. Von Baracz (Arch. f. klin. Chir. (1902), 68, 1050) reports on fifty-two cases of actinomycosis. The article is a splendid monograph, but does not go extensively into the question of the etiology of the disease. Welleminsky (Deutsche med. Wehnsch. (1902), 28, Ver.-Beil. 196) cultivated a Streptothriz-like organism, nonpathogenic for animals, from lesions in one ease. Trolldenier (Ztschr. f. Thiermed. (1903), n. s. 7, 81) reports a case of acti- nomycosis in a dog. He cultivated a Streptothri« which he considered to be a new species from the lesions. The organism was pathogenic for mice and guinea pigs, rabbits, dogs, and calves. Doepke (Miinchener med. Wehnsch. (1903), 50, II, 2245) studied several human cases and cultivated organisms which where similar to that of Wolff and Israel. Ligniéres and Spitz (Arch. d. parasitol. (1903), 7, 428; Centralbl. f. Bakt., etc. (1904), 35, 294; 452) cultivated a Streptothri« from a calf suffering from actinomycosis which they considered similar to that of Wolff and Israel. The article by Horst (Ztschr. f. Heilk., Abt. f. path. anat. (1903), 24, 157) is not available to us. ee ee re ae a STREPTOTHRICOSIS. 467 James Homer Wright (Journ. Med. Research (1904), 13, 349) cultivated what he believes to be a single species of Actinomyces from 13 cases of human actinomy- cosis and two cases of the bovine disease. He considers his organism to be of the same species, if not identical, with that of Wolff and Israel. This article is the most thorough study of one species of this group of organisms that has yet been made. Stokes (Am. Journ. Med. Sci. (1904), n. s. 128, 861) obtained a Streptothriz from an abscess of the lung. This organism was acid-fast, grew aérobically and was pathogenic for laboratory animals. Schabad (Ztschr. f. Hyg. (1904), 47, 41) considers the true Actinomyces and the organisms of Bostroem or Eppinger to be different species. _He cultivated from the sputum and abscess of the breast in one human case an organism which he considered to be identical with that of Eppinger in its morphology, biology, and pathogenicity. Hartman (7'r. Chicago Path. Soc. (1904), 6, 157) cultivated a Streptothrix from one human case. The articles by Tuttle (Med. and Surg. Rep. Presbyterian Hosp. N. Y. (1904), 6, 147) and Me- Donald (Scot. Med. & Surg. Journ. (1904), 14, 305) are not available to us. Pinoy (Comp. rend. acad. sci. (1906), 143, 1175) isolated a Streptothriz and claimed to have experimentally reproduced the black granules by inoculation of cultures into a pigeon’s foot. His organism was a facultative anaérobe. Nicolle and Pinoy (Arch. d. parasitol. (1906), 10, 437) cultivated a Streptothriz from a case of mycetoma in an Arab. Musgrave and Clegg (This Jurnal, Sec. B. (1907), 2, 477) obtained a culture from the sinuses in a case of the ochroid variety of mycetoma occurring in a Filipino woman in Manila. The cultural characteristics have already been described and will be further discussed. Poppenheimer and Satchwell (Journ. Infect. Dis. (1907), 4, 617) report a case of endocarditis and isolation of a pleomorphic bac- terium resembling somewhat closely the Streptothrice. They review the literature of Streptothriz infections in man and tentatively classify their organism as a Cladothriz. The report of these authors is thorough and complete and from their description it does not seem as if their organism could properly be considered under Streptothrice. Strong cultivated a Streptothriz from a case of mycetoma in India. ‘This organism is undoubtedly identical with that of Vincent. OTHER STREPTOTHRICA. In addition to the pathogenic organisms of the group under discussion and which have been isolated from pathologic lesions in man and animals, others have been cultivated from sputum, pus, or other human excreta under circumstances which make their exact source questionable; there are still others which have only been described as being obtained from animals; and some have been cultivated only from air, water, soil, and other outside sources. The following may be men- tioned: S. rubra of Ruiz-Casabé (ref. Centralbl. f. Bakt., etc. (1895), 17, 466) isolated from sputum; Cladothrix mordoré of Thiry (Arch. d. physiol. (1897), 29, 284) obtained from an anginal exudate; the Streptothrix of Dean (Tr. Path. Soc. (1900), 51, 26) isolated from an abscess of the jaw in a horse; and NS. lacerte of Terni (ref. Centralbl. f. Bakt. etc. (1896), 19, 953) isolated from nodules in the liver of a lizard. Rossi-Doria (Ann. d. I’Ist. Wig. sper. d. Univ. di Roma (1891), 1) cultivated a Streptothria from a case of bovine actinomycosis. Sanfelice (Centralbl. f. Bakt. etc., orig. (1904), 36, 355; and Arch. f. wiss. u. prakt. Thierheil, (1896), 22, 153) obtained Streptothrice from several minor cases of bovine actinomycosis. He considered his organisms to be similar to those of Gasperini and Doria. Gasperini (Proc.-verb. Soc. Tose. di Sci. Nat. (1895), 9, 64; 292) isolated and described two strains of Streptothrix from actinomycosis in cattle. He (Ann. d. VIst. dig. sper. d. Univ. di Roma (1892), 2, 167; Proc.-verb. Soc. 468 MUSGRAVE, CLEGG, AND POLK. Tose. de. Sci. Nat., July 5, (1896) also worked with a number of cultures obtained from other authors including that of Dessy (loc. cit.). With this latter organism, he stated that he had produced typical actinomycosis by injection into the jaw of a cow. : Lange and Manasse (ref. Levy. Centralbl. f. Bakt. ete. (1899), 25, 5) isolated a Streptothriz somewhat resembling that of Wolff and Israel from actinomycosis inadog. Bahr (Ztschr. f. Thiermed. (1904), n.s. 8, 47) cultivated a Streptothrix from an actinomycosis-like disease in a dog. Dean (Vr. Jenner Inst. Prevent. Med. (1899), 2, 17) did the same with an organism resembling that of Wolff and Israel, obtained from an abscess in the jaw of a horse and this Streptothrix was pathogenic for animals. Mosselmann and Liénaux (Ann. d. méd. vet. (1890), 39, 409) obtained a Streptothrix from a case of bovine actinomycosis. Ligniéres and Spitz (Bull. Soc. centr. d. méd. vet., Paris (1902), 56, 487) cultivated a bacillus from cases of clinical actinomycosis in cattle. They state they produced true actinomycosis, the organism showing the club-shaped Strep- tothrix granules, with cultures of this organism, by inoculation of their cultures into cattle. The Streptothrix of Caminiti (Centralbl. f. Bakt. etc., orig. (1907), 44, 193) is one of the most important of the organisms cultivated from the air, because of its pathogenic properties and close cultural resemblances to the Streptothrice which produce clinical actinomycosis. This organism is Gram positive, acid-fast in part, a facultative aérobe with anaérobic preferences, liquefies gelatin and produces pigment in varying amount and color in artificial media. It is pathogenic for all animals experimented upon, producing circumscribed local lesions by in- jection of cultures. Other organisms of this class which may be mentioned are S. lewcea Foulerton (Tr. Path. Soc. (1902), 53, 101) isolated from sewage and water; S. alpha Jones (ibid, 102) ; NS. erythrea Foulerton (Ibid, 107) from culture tubes prepared with horse serum; S. beta Jones (ibid, 109); Cladothrix invulnerabilis of Acosta and Grande Rossi (ref. Centralbl. f. Bakt, ete. (1893), 14, 14); the Streplothri« of Kedzior (Arch. f. Hyg. (1896), 27, 328) isolated from sewage and water; SN. albido-flava, S. carnea, and S. auwrantiaca of Rossi-Doria (Ann. @Ist. Wig. d. Roma (1891), 1) isolated from air; Wicromyces hoffmanni described by Gruber (ref. Centralbl. f. Bakt., etc. (1891), 10, 648) isolated from air. Several other brief descriptions of Streptothrice from pathologic lesions might be noticed, but the principal ones have been mentioned above. The technical descriptions have for the greater part been omitted in this review of the literature, but it may be stated that a classification of this material which will be satisfactory to all is scarcely possible. However, several authors have attemped an arrangement of species and varieties. Foulerton worked with a large collection of cultures obtained from various sources. He redescribed and renamed several species, both pathogenic and non- pathogenic, the classification being based largely upon morphologic and cultural characteristics. Rossi-Doria occupied himself for the greater part with Strep- tothrice cultivated from extraneous sources and his classification is based upon the character of the cultures obtained. Gaspereni gave a classification based upon cultural characteristics. Brumpt (Arch. d. parasitol. (1906), 10, 489) recognized several species and more than one genus. Wright worked with one species and gave the most complete description of that organism to be found in literature. His “Hyphomycete” cultivated from a ease of the “black variety” of mycetoma evidently was not a Streptothrix and therefore is not included in STREPTOTHRICOSIS. 469 the discussion in this paper. Caminiti recognizes forty-one species based upon his own work and a review of the literature. Manson’s classification refers particularly to mycetoma and has already been noticed. If we carefully study the literature of species determination, it will be found in greater part to be only of historic interest and value. The work is generally too incomplete to be final for species determinations, and in cases even the generic position of the described parasites is doubtful. For this reason we have considered only the technical descrip- tions of the organisms which have been cultivated and described with sufficient accuracy and completeness to make them available for com- parative purposes. Much of the work of the older writers was well done when due consideration is given to the technique developed at the ' time of publication, and this work should always be kept before us in giving historical summaries. However, for purposes of further study and for comparison, having in view the harmonizing of our ideas regard- ing these infections, it seems to us that the following are the principal publications regarding Streptothrice, which have been isolated from pathologic lesions of man or animals. 1. Nocard (1888); 2. Eppinger (1890); 3. Almquist (1890); 4. Bostroem (1891); 5. Wolff and Israel (1891); 6. Hesse (1892); 7. Vincent (1894); 8. Boyce and Surveyor (1894); 9. Aschoff (1895); 10. Du Bois Saint-Sevrin (1895); 11. Sabrazés and Riviére (1894) (A and B); 12. Rullmann (1895) ; 13. Dor (1896); 14. Sawtschenko (1896); 15. Scheele and Petruschky (1897) ; 16. Bucholtz (1897); 17. Berestnew (1897); 18. Rullmann (1898); 19. Silbers- chmidt (1899); 20. Brault (1899); 21. Cozzolino (1900); 22. Dean (1900) ; 23. Aoyoma and Miyamoto (1901) ; 24. Jelenewski (1901) ; 25. Foulerton (1902) (3° or more species) ; 26. Trolldenier (1903); 27. Pinoy (1906). The work of Musgrave and Clegg (1907) might also be included in this list. The twenty-eight species or varieties to be taken from this list are considered with due regard to the manner in which they are described by the authors. It is certain that they do not all represent different species and it is probable that some of the other organisms not included do belong to new species. Many of the articles in the literature are incomplete, and a careful study of such descriptions as are given convinces us that not more than ten different species are represented in the group. Several of the varieties may show slight morphologic and biologic differences, but these are not sufficient to warrant their being classed as separate species. GENERAL DISCUSSION AND CONCLUSIONS. The subject of streptothricosis or nocardiosis becomes somewhat sim- plified if the results of our own work are combined with those taken from the literature, but we realize fully that after considering all pos- sible evidence, points must still remain open for discussion, and complete harmony regarding this subject can only be obtained by common adop- tion of a somewhat arbitrary classification. 470 MUSGRAVE, CLEGG, AND POLK. DETERMINATION OF GENUS. It is difficult to determine upon the correct name of the diseases, because of the botanical confusion regarding the position and designa- tion of the group of organisms concerned, and of the lack of clearness of definition specifying definite limitations for the organisms to be included as the etiologic factor. Both Streptothriz and Actinomyces are untenable as generic names if we strictly follow the rules of nomenclature, because they are not entitled to priority in the literature which belongs to Nocardia; besides both Streptothriz and Actinomyces are open to the objection that they have not received a sufficiently clear botanical definition and both names have been used in too uncertain a sense in the past. Actinomyces has also, unfortunately, been taken into recent literature with practically two definitions. The objections to Nocardia are as follows: (1) The published definition erroneously states that the branching is “false branching ;” (2) the name has not been sufficiently accepted by bota- nists to insure permanency and (3) usage is very much against it, particularly as in some of the recent writings its meaning has been limited to include only a portion of the organisms which surely belong in the genus. Considering the confusion in botanical literature and the uncertainty, and therefore the liability to change which pertains to this nomenclature, we have, as stated in the introduction, chiefly because of usage, and therefore somewhat arbitrarily, tentatively accepted Strep- tothriz as the generic name of the organisms concerned, and streptothri- cosis as the designation of the disease caused by this group of branching. filamentous organisms. In making this decision we are fully aware of the rights of those who favor Actinomyces or Nocardia, and under the circumstances are tempted to introduce a new name (Carteri) for the genus, together with a full and complete definition. Whatever the nomenclature, it is a fact that we have here a group of closely allied vegetable parasites of man and animals, which have the following principal characteristics : Branching, filamentous organisms which Serelp into colonies made up of the organisms and “transformation products.” The terminal hyphe may or may not be radially placed on the surface of the colony and they may or may not develop “clubs.” The group in general take Gram’s stain and several members show acid-fast properties in a varying degree. The organisms grow on artifical media, differing in their requirements for oxygen and in pigment production. ‘To a less degree they show other variations in appearance on artificial media. The majority of the organisms produce lesions in monkeys, which histologically resemble those found in the human infections and in those of other animal diseases caused by members of this genus. This group or genus is closely allied to other genera of somewhat STREPTOTHRICOSIS. 471 similar characters, the latter ranging from the branching bacteria through the nonbranching filamentous Leptothrix and the pseudo-branching Cladothria, to the budding Oidia or Blastomyces. The only question of doubt regarding the expediency of our generic classification is raised by the very thorough and exhaustive work of James Homer Wright, who has brought forward some strong arguments in favor of making two genera out of the group of organisms under discussion. As may be remembered, Wright separates this group into two genera ; Actinomyces and Nocardia. He defines Actinomyces accurately and places all the organisms which he thinks do not come within this defini- tion into the genus Nocardia. Actinomycosis is defined as: “A suppurative process combined with granulation tissue formation, the pus of which contains characteristic granules of ‘drusen’’/composed of dense aggregates of branched filamentous microérganisms and their transformation of degenera- tion products. In the term transformation products are included the charac- teristic, refrangent, club-shaped bodies radially disposed at the periphery of the granule, for these bodies have long since been clearly shown to arise by a trans- formation of the peripheral filaments. They may or may not be present at the periphery of the granule.” Wright, in his further discussion of the organisms, emphasizes the following points as being characteristic of Actinomyces. Club formation in tissues, anaérobism, granule formation, peculiarities in culture media, morphology and action when injected into laboratory animals. However, some of these distinctions were not constant even in the author’s series of cases. If we accept Wright’s definition of actinomycosis, some of the organ- isms termed Nocardia by the author must be included as etiologic factors in actinomycosis, because the requirements are fulfilled by microérganisms not included in his description of the organism which he considers the specific cause of the disease, and furthermore, if his definition and description of Actinomyces be accepted as sufficient for genus determination, other genera could be removed from the group with almost, if not with equally good cause. However, some of the principal characteristics given for Actinomyces are not peculiar to his organisms. Most of these are differences in degree only from other members of the group, and are not specific, and in some instances, as we have demonstrated by work with original cultures, Wright’s conclu- sions, based upon a study of the literature, are wrong. His observations regarding S. capre Silberschmidt, and 8. madure Vincent are examples of this. Wright states that Vincent’s case was probably one of actino- mycosis, and that Silberschmidt worked with mixed cultures. We have had cultures from the original strains of both these organisms in our hands and are able to state positively that the bacillus- and coccus-like 472 MUSGRAVE, CLEGG, AND POLK. forms of S. capre described by Silberschmidt are forms of the pure culture and not bacterial contamination. As to Vinecent’s case, the organism is distinctive and can not possibly be included in Wright’s definition of Actinomyces; indeed, it forms one end of the Streptothrix group, while the Actinomyces of Wright forms the other. SPECIES DETERMINATION. Species determination in this genus is made extremely difficult, and classification of all the forms which have been given in the literature is impossible, because of the incomplete and imperfect descriptions which are given. Several of these descriptions are old, have not been repeated or confirmed, and are lacking in the elucidation of important points which are now recognized as essential for diagnosis. Our correspondence has elicited the fact that cultures of several of these species are no longer obtainable, and therefore, no further study of them can be made. Fortunately, we have been able to secure cultures of the most important members of the group and by comparative morphologic and biologic studies, particularly with reference to their pathogenic character, we have been able somewhat to simplify the classification by showing that some of the described species are identical. This includes S. freeri, which from a study of the literature we thought to be a new species, but after comparative study found to be identical with S. eppingeri in all essential particulars. Another difficulty in establishing species or yarieties is encountered in attempting to fix the amount of variation necessary to constitute a new species. ‘he differences between various members of the group are practically in every instances those of degree only. For example; in the requirements for oxygen we have variations from facultative anaéro- bism with strong tendencies toward being negative to oxygen, as exempli- fied by the Wolf, Israel and Wright type of Actinomyces, to facultative aérobism with strong oxygen requirements, as exemplified in S. eppingeri; while other strains show intermediate stages of aérobiosis. Although strict anaérobes and equally strict aérobes have been mentioned, the con- clusions probably are based upon errors in technique. Certainly this is true with the organisms with which we have worked, for in no instance have we encountered either a strict anaérobic, or an equally strict aérobic Streptothriz, although some of the cultures under our hands have had such properties ascribed to them by others. Staining reactions—The terminal filaments in lesions and young cul- tures usually stain very well by the usual aniline dyes, but in older colonies the central detritus does not stain and the filaments give irregular staining reactions often showing irregular, including coccus- and ba- cillus-like, forms. The reaction to Gram/’s solution is somewhat varia- ble, depending upon the age of the colonies and there is some variation STREPTOTHRICOSIS. 473 between the different species or varieties. However, in general, all strains are Gram positive to a greater or less degree. Differences in acid fast properties have been used as being diagnostic in a number of described species, while unfortunately in others they have not been mentioned. ‘These are important points in differentiation, but unfortunately such properties are a somewhat variable manifestation, depending in part upon the age and environment of the parasite and perhaps also upon other conditions, the nature of which is not clear. As with the oxygen requirements, degrees from the marked acid fast prop- erties of S. eppingeri through those organisms showing the tendency only in certain portions, to S. madure@ which has no such properties are noted. S. eppingeri, often when taken from animal lesions and sometimes for example in cultures, will show acid fast properties which involve the entire organism, while in other cultures only portions of the organism will retain the fuchsin when decolorized and counter stained with Gabbet’s stain. Pigment production under certain circumstances is a property of most of the organisms of this group, as the cause of this is unknown and the result is variable, its diagnostic importance is lessened. Under like conditions, the color and general appearance of the pigment in any of these strains is usually fairly constant, but sometimes, particularly in animal tissues, it may show a more intense color. For example, ¥. madure, which usually produces a reddish-pink pigment in cultures, may, when inoculated into monkeys, at one time give a similarly colored pigment or again one considerable darker; so dark in fact as to appear almost black to the naked eye. The pigment of Actinomyces in our ciultures shows but little color other than black. On media the color develops slowly and gradually to a dark gray, almost black. Some of the phenomena of pigment production and color may be explained, but in gen- eral the process is still obscure. For example, a darker pigment usually results in animals from the inoculation of fresh material from another animal than is the case if cultures are used. ‘The next lighter shade is produced by inoculation with old, pigmented cultures, but color produc- tion is slower when young, unpigmented cultures are used for inocula- tion. Harly pathologic lesions due to these parasites, like young cultures, rarely show pigment. The later in both instances is produced and grows more marked with age. Concentration undoubtedly has something to do with the apparent color of the pigment, for the harder the granule the darker the pigment appears to be. Granule formation both in tissues and to a less extent, in cultures, is a property of all the pathogenic Streptothrice with which we have worked. These granules vary considerably in consistency and color in the several species, but in the majority of instances they are made up of branching filaments with transformation products, which consist in irregular forms, 474 MUSGRAVE, CLEGG, AND POLK. crystals and unstainable detritus. The arrangement of the peripheral filaments may or may not be radial and there are various degrees of density of the mass. In two of our cultures (S. canis and S. caprae) there is less tendency to suppuration after inoculation in animals and the individual colonies have more the appearance of tubercles than in our other cultures. This difference has been pointed out by other observers. However, the lesions in our experimental animals were small ; in the older lesions the type of the granule is not known, if we except the knowledge gained from the statements of the authors who described the parasites, the description being taken from the original lesions. The granules or colonies produced by the other cultures were in the majority of cases free in the necrosed, liguefied substance found in the various channels produced by these infections. Club formation, in the lesions, in tissues and less frequently in cultures, is used as one of the points of differentiation between species of the organisms of this group. No doubt there is considerable variation in this respect under certain conditions, but the circumstances reported as surrounding club development are sufficiently varied and confusing to detract somewhat from what would otherwise be valuable for purposes of distinction. Wright found club formation to be rather constant in original lesions, and observed it occasionally in certain cultures. In experimental lesions, it was also fairly constant, except in early lesions where clubs were some- times absent. Bostroem and others, working with species differing somewhat from Wright’s organism in other particulars, also observed clubs both in lesions in animals and occasionally in cultures. None of our cultures show definite clubs in culture or in experimental lesions in animals, although in several the terminal branches show some enlargement suggesting club formation (see illustrations). Our experi- mental animals were all killed within a shorter time after inoculation than were those of Wright, in which clubs were found. Branching is similar in all of our cultures and is also similar to that recorded by most observers who have worked with this group of micro- organisms. The cultural characteristics of all of our strains have already been described. While there are variations in the reactions between some of these strains, they all appear to belong to one group of organisms, and if we analyze the literature carefully others, including the organisms of Wright and of Bostroem, may also be included in the group. The following may be noticed if we take up the principal cultural characteristics comparatively as well as somewhat more in detail. Surface growth is considered to be poor in Wright’s organism and is not very profuse in some of our strains, but in Bostroem’s organism and in most of ours, while it may be slow, it does occur in a satisfactory manner and in some strains s STREPTOTHRICOSIS. 475 it may be luxuriant. There is but little tendency for surface growth to spread in any of the cultures, but on the other hand, it heaps up, as it were, giving raised colonies sometimes 1 centimeter above the surface of the media. (See plates.) This is also true with Wright’s organism, where surface growth appears. Wright first called particular attention to the character of growth in glucose- agar suspension cultures. In this medium with his organism, there is a narrow zone 5 to 10 millimeters below the surface where the colonies are very numerous but small, while lower down they are less numerous, but ot larger growth. Surface growth is the rule in our cultures in this medium, and only occassionally a colony may develop in its depth. Stab cultures in sugar-agar.—Growth with Wright's organism occurred in small nodules along the course of the needle, it did not penetrate the medium to any extent and did not grow on or near its surface. The growth in our cultures occurs mainly upon the surface and upper portion of the track of the needle. Anaérobiosis.—Wright considers his organism as an obligate anaérobe, a statement which is somewhat qualified in the details of his work. For example, in discussing the growth upon glucose-agar suspension media he states that the most profuse growth of the organism is in a narrow zone 5 to 10 millimeters below the surface of the medium and that this way may be “explained as the result of a stimulating action exerted upon the growth of the microédrganisms by the presence of a small amount of oxygen which has penetrated into the medium from the surface.” This oxygen requirement is further illustrated by the author when he states that “in sugar-agar suspension cultures, placed under anaérobie conditions, there is little or no tendency to form colonies on the surface.” Growth occurred along the course of the needle only in stab cultures on glucose-agar. It did not penetrate the medium and, on the other hand, did not grow on the surface. However, when discussing growth upon surface inoculations in slanted solid media, Wright found that surface growth was not luxuriant and in some of his strains no growth occurred even under anaérobic conditions. Again, Wright observed that “in general, growth appears to be as luxuriant in bouillon either under aérobic or anaérobic conditions.” To judge from the above and other statements which might be taken from Wright’s excellent monograph and according to the standards used in this report for the other members of the group, Wright’s organism must be considered to be a facultative anaérobe. In bowillon media there is some variation between the manner of growth of our cultures, but little which may be considered of value in the differentiation of species. The tendency in some of our cultures is toward a surface growth which may gradually separate and fall to the bottom, or settle on the sides of the tube. In other instances, the majority or all of the growth may occur at the bottom of the tube. The medium is not clouded, but in some cases it becomes darker, apparently because of the absorption of pigment from the organisms. There are no essential differences between our cultures in bouillon and those reported by Wright. Potato, as is well recognized, is not a very satisfactory medium for compara- tive studies, excepting where the same set of media is used. Fairly luxuriant growth was obtained in every instance with our cultures on potato slants.? *The potato slants employed in this laboratory are made from selected potatoes treated and prepared according to the rules laid down by the committee of the American Public Health Association. 476 MUSGRAVE, CLEGG, AND POLK. There was not much variation between the different cultures except in the color of the pigment and the appearances which have already been described. Potato proved itself to be a very unsatisfactory medium for Wright’s organism. Most of his strains grow on it very poorly, and some of them not at all. Litmus-milk is not a favorable medium for the differentiation of species. Growth takes place slowly, and with two strains the color is slowly discharged. No other appreciable changes occur in the medium excepting with cultures of “chaleea,” in which a slightly acid reaction is produced. The favorable influence of sugar and glycerine upon cultures of all strains of the group of organisms has been noted repeatedly. Sugar or glycerine containing media not only are the best in securing growth, but with all our species pigment production is more active in these media. Pathogenic characters—The pathogenic character of many varieties of this group of organisms in the human and animal economy is well established. However, experimental inoculations in animals have not given constant results in the hands of other investigators, and our experiments have been uncertain with all animals except monkeys. The details have already been described and it only remains to state here that lesions similar in their gross and histologic appearances to the original ones produced by these organisms, have resulted with each of the strains which we have studied, except with one of the strains of S. Madurae which has already been mentioned in this discussion. CONCLUSIONS. There is, in human pathology, a very important group of branching, filamentous microdrganisms which logically belong to a single genus. The generic name is yariously given as Streptothrix, Actinomyces or Nocardia; the last of these names is probably scientifically the most correct, but because of the present botanical confusion and uncertainty the first is here employed, because of its more general acceptance. The following species to judge from our work and from a study of the literature are the most important and may be recognized as estab- lished. There are probably a number of others but the description of many of them are too imperfect to allow of their recognition. S. actinomyces Bostroem, 1890. S. actinomyces Wolff & Israel, 1891 and Wright, 1905. S. nocardu. S. eppingerr. S. madure Vincent. S. capre Silberschmidt. The disease caused by infection with these parasites is properly named streptothricosis, with actinomycosis and nocardiosis as synonyms. Other names, such as lumpy-jaw, madura foot, mycetoma, etc., should be considered more as describing anatomic location rather than as designa- tions relating to any special or specific cause of infection. Mycetoma might well be taken as the correct name for the group of infections if a strict interpretation of rules of nomenclature is followed, but usage renders it perhaps more desirable to retain the name as representing STREPTOTHRICOSIS. 47 Streptothricosis pedis. If mycetoma is to be considered in any more comprehensive light than this, it should become another synonym for streptothricosis. It should not be considered a disease caused by organ- isms other than Streptothrice. Parr If. STREPTOTHRICOSIS. Synonyms.—Actinomiycosis, Nocardiosis. Derrinition.—An infectious disease of man and animals caused by one or more species of Streptothriz. It is characterized anatomically by a peculiar, low grade of inflammation, usually confined to one part of the body, but im rare instances assuming the proportions of a general in- fection. The inflammatory process usually is accompanied by suppura- tion of a certain kind; the discharges contain granules made up princi- pally of colonies of Streptothrix. The general picture of chronic inflammatory disturbance is seen clinically, and enlargement, suppuration and the presence of the causative organism in the lesions is observed locally. History.—The history of Streptothrix infection is shown in the review of the literature given in Part I. In general it may be stated that the disease has probably long been recognized and frequent references are made in older medical literature to conditions which presumably were due to infection with these microorganisms. According to Rivolta, Trutto discussed the condition among cattle in Italy in 1785 under the name of “Krotenkrankheit.” The colonies of the organisms were more or less accurately described by Langenbeck (1845), Sir T. Smith (1855), Lebert (1848), Rivolta (1868), Robin (1871), Heller (1872), Perroncito (1875), and others (see Ackland). Mention of the anatomical form of the disease generally described as mycetoma or Madura foot are also quite old, the principal authors being: Kampfer (1712), Heynes (1806), Brett (1840), Gill (1842), Godfrey (1844), Colebrook (1844), Gunther (1844), Hyre (1848), Bollmgol (1855), Eyre (1860), Collos (1861), Bidie (1862), Hirsch (1868 and 1886), Coquerel (1866), and many others (see This Journal, Sec. B. (1907), 2, 487). Of these observers Colebrook (1850), Bollingol (1855), Coquerel (1866), Maxon and Hogg (1870), Bristowe (1871), Berkeley (1876), and others probably saw and in a few instances partially described the organisms present in the lesions. However, the really important history of Streptothria in- fections dates from Vandyke Carter’s work (1859-1874). This author deseribed and illustrated the parasites in many cases of the foot (Ma- dura foot) type of the infection. Bollinger and Marz (1876) first ac- curately described and named one of the parasites causing the disease known as lumpy-jaw in cattle. The next epoch in the history was due to an article by J. Israel (1878) who was the first to describe the disease and parasite in man in locations other than the foot (Madura foot) and 478 MUSGRAVE, CLEGG, AND POLK. hand, the infection in these places already having been described by Carter and others. Israel’s work was followed by that of Ponfick (1879) with strong evidence as to the identity of the disease in man and animals. From the year 1876 the literature accumulated rapidly and the infection was reported for man and animals from widely varying locations and countries. Bostroem (1890) contributed the first thorough and exhaustive labo- ratory study of the microdrganisms and this work was followed a year later by an equally exhaustive treatise on the same subject by Wolf and Israel. The organisms described by Bostroem on the one hand and by Wolf and Israel on the other, although isolated from apparently similar diseases, showed certain morphologic and biologie differences which led to much discussion during the next few years. Organisms corresponding to the descriptions of both these pioneer observers continued to be men- tioned in the literature, each investigator maintaining his organism to be the true cause of the disease. In 1888 Nocard cultivated and quite accurately described a Strepto- thriz as the cause of a disease locally termed farcin de boeuf of cattle in Guadalupe; Nocard’s organism seemed to be of a different species from either Bostroem’s or Wolf and Israel’s. Eppinger (1890) cultivated and accurately described another species of Streptothrix as the cause of a brain abscess and “psuedotuberculosis” in a man. Vincent (1894) first satisfactorily cultivated and described a Streptothriz as the cause of mycetoma or Madura foot and his organism seemed to have certain characteristics showing it to be specifically different from any of those previously described. Foulerton (1899-1907) gave descriptions of several new species of the parasites and has brought out the most thorough and exhaustive considera- tion of the whole subject with which we are familar. Wright (1905) contributed a most complete and exhaustive study of the biology of the Wolf and Israel variety of this organism. ‘The work of bringing all this group of similar organisms together in a single genus is largely due to the researches of Rossi Doria, Petruschky, Foulerton and several other recent writers, particularly of the German and French observers. In this article we have shown conclusively that Eppinger’s organism isolated from clinical actinomyces on several occasions is identical with S. freert, which is one cause of Madura foot in the Philippine Islands. Very little is known regarding Streptothrix infections in this Archipelago. Our records show two cases in which Actinomyces was the etiologic factor in human disease, and several infections of cattle have been observed in the islands. One case of the Madura foot type of the disease has been seen. ErtioLocy.—Predisposing causes, for this disease, except in a few in- stances, have not been sufficiently studied to make a satisfactory estimate of their influence. "v2 STREPTOTHRICOSIS. 479 The geographic distribution is very wide, but no very large series of cases have been studied by any one observer. Collections of such series have been made in America, Germany, France, England, Russia, Swit- zerland, and in the British colonial possessions. The most frequent incidence is found in certain parts of the Tropics, particularly in India, but, as has been pointed out by Ackland, the disease may be overlooked in a community for a long time until special attention is called to its prevalence. According to available statistics the infection is more frequent during young, adult life, but cases have been reported in children and in old people. Males are much more frequently affected than females—295 males to 110 females being given in Leith’s statistics, and 65 males to 36 females in Ackland’s. Race, nationality, residence, overcrowding, climate, occupation, and physical condition, to judge from available statistics, seem to exert but a minor influence on the spread of the disease, although a more careful study of a large material may show some of these to have greater signif- icance. General environment and mode of living would naturally be expected to have considerable influence as predisposing factors, particularly in determining the part of the body involved. For example, the Madura foot type of infection is most common among people who go barefoot, it being largely a wound infection. Streptothrice are the specific, causative agents of the infection. They haye already been considered in Part I of this report, and only a brief summary will here be given. Synonyms.—Actinomyces, Nocardia, Odspona, Chenaphe cartert. Draenosts of these organisms is made from morphologic and biologic considerations. ‘They are branching, filamentous organisms, which de- velop slowly into colonies made up of the branches and their “transforma- tion products.” These colonies vary in color, size and consistency, and when stained show various changes in different portions. The filaments at the periphery are usually intact, with or without club formation, and the terminals may or may not be radially placed. Toward the center of the colony, or granule, irregular forms, such as coccus- and bacillus- like ones, are found, together with crystals and nonstaining detritus. The majority of these organisms may be cultivated on artificial media, where they show various but characteristic biologic properties. That some of them are pathogenic tissue parasites 1s shown by their action on laboratory animals. Morphologically these parasites are rather closely related to some of the branching bacteria. ‘The young filaments vary in width from 0.5 to 1 » and in length from 5 to 20 » or more. They usually stain homoge- neously, and in some strains taken from lesions they are acid-fast to the 79284 —3 480 MUSGRAVE, CLEGG, AND POLK. Ziehl-Neelsen-Gabbett method. In older forms the segments are often broken, the sheath-like substance not showing either in fresh or stained specimens. The breaking up of the filaments produces great variety and size of irregular forms; some of these may appear to be very much like bacteria, but their true nature is easily established by laboratory methods. The majority of these organisms may be stained by the aniline dyes, all show Gram positive characteristics to a greater or less degree, and several are as acid-fast-as is the tubercle bacillus. Biologically certain species—both saprophytic and pathogenic—are widely distributed in nature. They have been found on food stuffs—par- ticularly cereals—in water, air, soil, etc. Zodlogically they are found in some insects and several animals, and in man. Cattle are the most fre- quently infected of the animals, but rarer instances of the disease have been reported for other species. Cultivation of these organisms is probably possible with all species, although several authors have reported failures, and all observers have noted the difficulty of obtaining a culture from the lesions in animals. However, when adaptability to artificial media has once been secured, no very great difficulty is found in keeping the culture. In general, it may be stated that these organisms grow slowly on artificial media, but that the cultures show most positive characteristics in the majority of instances. In all there is a tendency to “pile up” on the medium rather than spread over the surface. Pigment production of various shades is a very common property, and this is more marked as a rule in glycerine or glucose containing media. Resistance to physical, chemical, and other agents by these organisms is rather great if we consider them to be non-spore bearing parasites, but this resistance is not sufficient to permit us to consider that true spore formation is present as it is understood for bacteria. PATHOGENIC CHARACTER.—The pathogenicity of several species of Streptothnia has recently been demonstrated by different workers, accord- ing to the accepted bacteriologic rules governing such decisions. Other members of the group appear to be saprophytes in that they do not produce lesions in animals by the usual methods of procedure. There is also considerable lack of uniformity in the results of animal experiments with nearly all the pathogenic strains. However, working with monkeys, our results have been more uniformly successful than those reported by other observers, or than our own results with other laboratory animals. The pathogenicity of this group of organisms seems to be influenced to a certain extent by the same conditions which produce changes in the virulence of bacteria. Not only may the virulence of some of these species be increased by passage through susceptible animals, but with the inereased virulence differences in cultural results may be noticed. These are shown principally in greater difficulty in securing growth, in STREPTOTHRICOSIS. 481 a slower growth on artificial media and sometimes in slight changes in the color and quantity of pigment production. Some of the so-called saprophytic species may in reality be found to be pathogenic, when improved technique is used. Modes of transmission.—Although experimental evidence is still far from satisfactory regarding modes of transmission, it seems to be entirely reasonable to assume from the known biology and the available evidence, that transmission may take place both directly and indirectly. So far as we are aware, no positive examples of direct transmission from person to person have been reported, but that such infection does not take place’ in localities with high incidence of the disease, seems probable. Rather convincing evidence of indirect transmission through the agency of food- stuffs, water, etc., has been furnished by several observers. Several authors whose work has already been reviewed, have shown that patho- genic species may be isolated from water, air, soil, and food-stuffs and the history of many of the reported cases indicates infection from some such source. The frequent presence of the infection in the lower animals must not be forgotten in considering the manner of transmission of the parasites. . Infection probably takes place in two general ways, first, by direct or wound infection, as is shown in many cases by the history of injury before the development of the symptoms of the external forms; and secondly, infection by way of the respiratory or gastro-intestinal tracts, which is shown in many of the internal forms of the disease. Species ——The number of species important in this disease is probably a considerable one. Those which we have been able to recognize from the literature and our own work are given in Part I. It seems probable that all the species have not, as yet, been discovered and that some, which have been described, are specifically different from the ones mentioned here. ParHoLtogy.—tIn general the morbid changes found in this disease are those of a peculiar, low-grade, chronic infective process. Anemia, atrophy of tissues, and mild, chronic degenerations of parenchymatous organs are present. ‘The special pathology depends somewhat on the part of the body involved and on the extent of this involvement. ‘The strep- tothritic unit, as it were, is a granule which is usually surrounded by a zone of peculiarly appearing suppuration, and this in turn by an area of inflammation characterized by connective tissue proliferation and cell infiltration. Cells of the usual character are found, with a relative in- crease of fixed tissue cells and occasionally a giant cell. In other instances the suppurative zone is absent and the streptothritic unit takes on more the general and histologic appearance of a tubercle. In fact, the whole morbid process of Streptothria infections resembles more or less closely that produced by Bacillus tuberculosis. Tissue destruction often spreads 482 MUSGRAVE, CLEGG, AND POLK. by means of continuity, but more usually by intercommunicating channels running in various directions. These channels contain the broken down tissue and granules made up of colonies of the infecting organism. Few tissues escape the destructiveness of the Streptothrix, but it appears to be more active in the connective tissues, bones, and mucous membranes. However, practically every organ and tissue of the body has been involved. The disease spreads through the body in at least two ways, by directly continuing along the tissues, in which case the area involved is rarely great, and by metastases through the blood vessels, when the infection may be so great as fairly to be considered a general infection. The character of the morbid process suggests that the minute action is toxic in character, although if such is the case, the toxin must act very slowly. ‘The lymphatics near a diseased process may be enlarged, but are rarely found to be broken town or to contain the microérganism. Symproms.—The clinical manifestations of Streptothriz infections are essentially those of a slowly developing, chronic inflammatory process. They vary much with the location of the lesions and further complications are secured by the presence of mixed infections which are frequent when the disease attacks regions of the body exposed to bacterial invasion. In many instances, where the lesions are located in the internal organs such as the liver, definite clinical manifestations do not occur and unless the infection spreads, its nature in all likelihood is not recognized during life. : When the lesions are located externally, or in places where the dis- _ charges reach the surface of the body, the nature of the infection should be suspected from the appearance of the wound and the character of the discharges ; on the other hand, it may be generalized, manifest itself in an acute course and be difficult to distinguish from a pyzemia of other etiology. The incubation period varies between wide limits, and as given by authors may be from a few days to more than two years. The onset is usually gradual, by the slow development of the lesions. The following clinical varieties may be recognized: Generalized streptothricosis—This form of infection has been noted by several observers. It occurred 9 times in Ackland’s 109 cases. This type usually begins in a local lesion and is transmitted through the blood vessels. In the majority of instances, it occurs in mixed infections with bacteria, but cases in which no bacteria were present have also been reported. Several species of the organisms causing these general infec- tions have been found. ‘This type is generally acute or subacute clinically and the symptoms as given by various authors are similar to septicemia or pyemia from other causes. LExtensive lesions may occur in practically every organ and tissue of the body. The diagnosis is only made by laboratory methods, the prognosis is bad and treatment unsatisfactory. Thoracic streptothricosis—The organs of the chest, particularly the a STREPTOTHRICOSIS. 483 lungs and pleuree are most frequently involved in this disease. It occur- red 65 times in 257 cases reported by Duvan and 29 times in Ackland’s 109 cases. The clinical symptoms in the lungs and the physical signs may resemble a chronic tuberculosis or severe bronchitis and the pleural involvement may consist of chronic, adhesive pleuritis or more often of empyema. Unless there is perforation of the chest wall or metastases, the clinical manifestations in these types show nothing characteristic of the disease and the true nature of the infection can only be determined by laboratory methods. Streptothricosis of the heart and mediastinum have been reported, and Ackland notes nine: cases involving the cesoph- agus. Abdominal streptothricosis, including all the organs of the abdominal and pelvic cavities, have been reported by various observers. The liver and gall bladder suffer most often. Involvement of these viscera occurred forty times in Duvan’s series and thirty-three in Ackland’s. The ap- pendix is quite frequently involved and in some instances is the primary seat of the lesions. : Other lesions are found in the mesentery, intestine, rectum, spleen, bladder, prostate, testicle, kidneys, and abdominal wall. In none of these types are there any characteristic clinical manifestations which differentiate this infection from other chronic inflammatory conditions of tuberculous or other etiology in the same locations. Cerebral streptothricosis includes involvement of the brain, cord, men- inges, and nerves, as well as the other tissues in these organs. The central nervous system was involved 19 times in Duvan’s 257 and 5 in Ackland’s 109 cases. Several different species of the organisms have been found in these lesions, that of Eppinger being the principal one. This species, as has been shown in Part I of this report, is identical with S. freert which caused the mycetoma in our case. The reported cases show no characteristic symptoms in these types of infection. External streptothricosis may involve any of the external or contiguous tissues, including the mouth and jaw, neck, skin, and subcutaneous tissues, conjunctiva, nose, and extremities. “Lumpy-jaw” or “big-jaw” ig one of the most frequent of these various types; mycetoma, Madura foot or streptothricosis pedis is a very common tropical type and others involving many anatomical locations are frequently encountered. Prac- tically all described species of the genus of the organism have been found at one time or another in external streptothricosis, and there does not appear to be much variation in the clinical picture because of any special species or variety. The clinical manifestations of external streptothri- cosis are rather characteristic. The peculiar, crater-like skin lesions of a chronic character leading through ramifying channels, through which is discharged the peculiar, oily, pus-lke substance containing granules, makes a rather constant and characteristic picture. As we have already stated, mycetoma or Madura foot is best classified here as the clinical 484 MUSGRAVE, CLEGG, AND POLK. type of Streptothricosis pedis, because it may be caused by several if not any of the species of this genus and the clinical manifestations are practically the same in all cases. The special symptoms of this. type are well known and have already been discussed in this report. Miscellaneous types of streptothricosis may be mentioned, such as in- volvement of the conjunctiva, bones, ear, nose, intercostal spaces, ete. Their only peculiarities are in the anatomical locations of the lesions. Draenosis.—The diagnosis of Streptothrix infections is made clinically by the character of the exposed lesions and discharges and by laboratory methods. Obviously, the common and frequent involvement of internal organs is rarely recognized except by microscopic examinations at opera- tions or at autopsy. The thoracic types may be determined by microscopic and bacteriologic studies of the sputum or aspirated fluid from the pleural cavities. It is generally stated by competent observers that these types are frequently overlooked, even in sputum examinations and it is not improbable because of the acid-fast properties of some of the organisms that they may occasionally be mistaken for the tubercle bacilli. The resemblance may, at times, be quite close. In some of our experimental lesions the similarity has been striking. ‘The microscopic examination of material from exposed lesions often requires some patience and care to enable the observer to find the organisms ; unless a granule is encountered, when, of course, the determination is easy. Inasmuch as some other closely related organisms such as Oidia, Leptothriz, and Cladothrix may cause somewhat similar lesions, Streptothrice should not be diagnosed positively without careful microscopic study of the organisms present in the lesions. PROPHYLAXIS.—From what we know of the distribution of the organ- isms of this disease and the mode of transmission and the prevalence of certain anatomical types, prophylaxis should consist in guarding against wound infection and generally by care in food and drink. Im the Tropics most of the types consist in local foot or other skin wound infections, which should be guarded against by wearing shoes and by promptly treating skin wounds and abrasions according to antiseptic methods. Prognosis.—The prognosis depends to a considerable extent upon the location and extent of the lesions. The general infections and those of the internal organs almost always end fatally. The external types are much more amenable to treatment and the mortality is small. According to the statistics of Duvan, and Poncet and Berard who analyzed 257 cases, the mortality was as follows: Skin, 2.3 per cent; face and neck, 10; jaw and temporal region, 30; abdominal cavity and intestine, 65; thoracic, 85; liver, 100, and brain and spinal cord, 100 per cent. The mortality in mycetoma, under proper treatment, is very small. The course of the disease is usually chronic, but it may be general otothrix capre Silberschmidt. Streptothrix freeri. Our culture) ; | Short filaments resembling ba coid forms; occasionally lon ing branching but no club faq Cultures from 2 weeks to 2 m Ziehl-Neelsen method show tions,. giving the organism short, plump bacilli. Gra: staining. Growth appears in 2 or 3 day colonies ; medium remains [ so well nor does it at medium that it does on tH media. --| Growth appears after 2 days ¢, white colonies which later growth a moist, mealy appeg brownish color. --| Similar to glycerine-agar......... . which soon assume a light-bro Colonies develop on the surfac| and later form a surface m¢ forms at the bottom of the mains clear. Pe Very slight growth; no pigme}] 3 | Pathogenic for guinea pigs an| - cutaneous and intraperitone Our culture. Appear after 3 days as sligh: Long, branching filaments, 2 to 7 y in diameter. Transverse segments are shown of various length from coccoid to10 winlength. Branch- ing occurs as lateral hyphe developing from the segments. The filaments have a definite wall. Spores have not been observed. Coc- coid and club-like forms present in certain medium, Culture from 5 days to 2 months stained by Ziehl-Neelsen method show many acid-fast portions. The organism is Gram-positive. From 2 to 3 days’ growth appears as smooth, glistening colonies which later coalesce and produce a delicate pink pigment; medium remains moist. Growth after 3 to 4 days at first as small, whitish colonies; these gradually take on a delicate pink color; later as the colonies develop they become umbilicated and coalesce forming a heaped-up growth and produce a burnt-ocher color. Similar to glycerine-agar.. Growth appears after 3 days as flat particles on the surface of the medium; these produce in time a delicate pink color; as growth proceeds a granular mass collects in the bottom of the tube; this mass is more or less coherent. Very slight growth; no pigment; no clubs. Pathogenic for guinea pigs and monkeys by in- traperitoneal injections. Oultural characteristics of various types of Streptothrix and of Actinomyces. o. _ color. 7 ely, Growth appesrs after 4S hours as a granular layer, at | Brat white, becoming yellow to brick-red. This In later covered by @ fine. white, powdery eMorescence, culture “resembling a sugar almond. Offs Sorcsta = paticle’ and adhering to siden/of taba; some |] Portions fal1 to the bottom. No pixmentatfon of me- ‘ delicate orange color; medium small whitish colonies which graduali & delicate pink color. Later as th develop they become umbilicated and forming = heaped up growth and prodi orange color. Similar to glycerine-agar____..._.. Growth appears after 45 hours as o Tnyer at frat white, becoming yollow red. Similar to literature. ot pathogenle for white mic % rabbits Inoculated subcutaneously recovered after developing temporary Swelling. 1 rabbit Inoculated In anterlor chamber re developed = nodule on the iris but no general | Infection. 1 rabbit {noculated intravenously and an- | other fn the kidney died on the fifth and seventh days ctirely. Two xuinea pigs inoculated intraperito- After 6 days yery slight growth occurs, surface of the medium; no pigment; n Pathogenic for rabbits guinea pigs and « by Intraperitoneal Injection. brane-lIike Heben, pinger'sorig- inal Similar to Bp- pingsr'sorlg- inal, Growth appears after 48 hours ax a buf-yellow granular growth; no pigmentation or erosion of medium. Growth appears after 24 hours ss m graylih, Hoceulent mass at the bottom of the tubs, Rabbits, dogs, cals, horses, and oxen are not affected by Intraperitoneal or {ntrayenous in- Sections. In guinea pigs {otraperitoneal or in- trayenous Injections cause constantly within 20 Ways, @ miliary tubereuiosis similar to that produced by Hacillus fubereuloris. growth slow and not abundant on this medium ; no pigment. Appeara after 3 daya as discrete colontea; later the colontes coalesce and become heaped up, Presenting a molst, mealy growth. This or- ‘anism does not produce plement. Similar to glycerine-agar, Growth appears after 48 hours as a buff-yellow kranular growth Growth nppears after 24 hours ax a graylih, Aocculent mass at the bottom ot the tube; later a fow grayish granules appear on the surface end {8 some fnstances puifeall formation occirs At the bottom of the medium, Very slight growth at the 1 the tubs; 0 pinmeot; no clubs, Pathogenic for guinea ples and snus monkeys by 1! peritoneal Injectione ment Js produced. <= Growth appears after 5 days as small pinkish-white colon{ea, Inter the col- onies deyelop a heaped up growth and Assume o wrinkled appearance with a eep-pink color. Similar to glycerine-agar. Growth appears after 3 days as small, pinkish-white colonies; these later de- Yelop & dark pink, ralsed growth. == Growth appears after 5 days as a cober- ent mass at the botiom of the tubo, murface growth rare. >| Very sllxht growth; no plement... Pathogenic for monkey by Sntraperito- neal Injection. which slowly take on a rose color; they show unmbilfcation in the center and become confluent and adherent to the medium. Growth appears afler § days ns small, discreto, White colonies with waxy, wrinkled liter often dereloping pink pigment. Growth appears Opaque-whilo, granular, more or Tesi eohering colonies ut the bottom of the tube; surface Krowth rare; no pigmentation of medium. ‘The Inoculation of cats, rabbits, guinea pigs, and mice produced nothing more than a small nodule At the site of injection and theao disappeared (Vincent). Nocard carried out intraporitoneal, Tntravenous and subcutaneous inoculations of dogs, wheep, rabbits, guinea pigs, fowls and Dikeons; Lis results were negative in overy lu ‘whilisb-yellow colontes elop. after 4 days small, doy- Growth appears after 5 days as mall, pinkiab granules and Vater nerumes a dark-pinke color. Similar to glycerino-agai Growth appears after 3 days as mall, pinkiah-wbite colonii which Tater develop a dark pink, round, granular growth, Similar to Iiterature..... Very slight growth; no pigment] Negative results in monkeys by {ntraperitoneal inoculation. Growth appears after 72 hours ax a beaped-up, irregular mass of a creamy-yollowish-white color, offen showing patches of pink coloration; no pikmentation or erosfon of medium. ) Similar to Streptothriz madurm of Vincent. Similar {o Streplothris madura of Vincent. Similar to Stroptothriz mmodure of with that its pigment ts a more with a pale peripb- ery. Similar agar Similar to Streptothri= madura of Vincent. do Honea monkeys; leafon con~ tain granules organism similar to thove seen eled, brownlsb-white col- onies appear which form fan adherent, brown, irreg- War membrane Sn from 3 to 15 days. Vincent the exception delicate pink to glycerine Colonies in 4 to 8 days which form a dry, brown, raised growth Colontes develop on surface fu concave, fine, dry, pale luke which Tatter form surface membrane; fuld clear but a doposlt forms {h the bottom of the tubs | Very alight growth; no | te pigment. Extenalye lesions were produced by Intraper- Pathogenic for guinea pigs by subcutaneous and tn- {njectfon fn] traperitoneal InJoctions. with and aro colonies; medium remutns molt; does not grow 0 well nor doss It produce the plement on this medium that {t does on the sugar-containing media. '} Growth appears after 2 days as small, brownlsh- white colonies which later coalesce giving the | growth a moist, mealy appearance with a light brownlih color. Similar to glycorine-aea Appear after 8 days ox slightly ralsed colonfex which soon assumo a light-brown color. Colonies develop on the surface ax fine, dry disks and later form a aurfaco membrano; a depoalt forms at the bottom of the tube; medium re- malo clear. Very slight growth; no plement. Pathogenic for guinea pigs and monkeys by sub- cutaneous and Intraperitoneal Injections. Ws on sugar-containing media. ‘Appeara after 2 days ox small brownish-white volonies. These later assume an ocher color. ‘Tho colontes woon coalesce giving culture mojst, mealy appearance. Similar to glycerine-agar..... Growth appears aftor 2 fo 4 days as slightly ralied, white colonies; these Inter asume a light brown color. Growth occurs ai a (hin, white membrane on the surface of the medium; a deposit forma but the medium remains clear. Very slight growth; no pigment: no clubs Totraperitoneal Injections In monkeys produced numerous milfary tubercie-like bodies {n the peritoneum and mesentery. +) Similar Grows an a dark-brown, adhering membrane. to glycerine agar. Grows ax « dark-brown, adbering mombrane. Growth from the planted material io the bot~ (om of the tuber no surface growth. Very slight Krowth; no pigment; no clube NeKAthye eee appearance and which coalesce {nto an adherent, wrinkled, Hehen-like mem= brane ‘Opaque, granular, like grape seeds, which coalesce to a Joss, flaky sediment; no surface membrane forma. ,} Similar to glseerine-agar; medium be- bright yellow membrane; the me- lum becomes dark. Small, opaque colonies which later coalesce, developing = tough, black membrane; os growth proceeds a. bright yellow pigment [x produced on the surface of the mombrane; the medium also takes On a dark color Similar to plycerine-agar comes molat. Growth occura In the bottom of the tube as a film contatning many black granules; no growth ou the surface of the mediutn. Very slight growth; no plement; no |. clube Intraperitoneal Injection In monkeys | produces extensive suppurative Jeafons containing many amall, black granule ony scribed. de. | Streptothrix eppingerl from Foulerton “A.~ Streptothrix epplnger! trom rn . Foulerton "B."" Streptothrix nocardl, Streptothrix madurm from Strong. Streptothrix madurm from Vincent. Streptothrix madurm from Foulerton. “ Streptothrix caprm Stiberachmiat Actinomyces from Pasteur Tnstitute. Stroptothrix freerl Literature. Oar culture. ioe occa) See > Streptothrix canis, our culture. pobtfeptotnrix chalea sae TGs Gee ee Se eee s Our cultare Literature. Our culture. Literature. Our culture, Literature. Our culture. Literature. Our culture. Literature. Our culture Literature. Our culture jotlced, depending upon Foulerton has | Similai - ‘appearance and also showing clubbed ends. the culture and media, from small o} Seal Geaie ee beatae 1h masses showing many | Muny coccold forms; short plump Alaments with | Thin oganism | Long, thin, Mlaments with true branch-| Many twisted filaments showing (rue branching| Long, thin flamenta with true | Similar to Streptothris madur@ of | Similar to Strepfothrie | Twisted, branching Mlamonts | Short Dlaments resembling bacilli and many eoe- | Short, plump, Mlamenta; many resembling bacilli; | Long, thin, filaments | Ray fungus cona(sting of a | Radiating mycelium containing maby ) Similar to) Long branching flamonts, 2 fn diam Drauchloig disments The diame Sea Lal eae hort branching hypba ocear, In young evl-| ox mot) ing; no club forms. forms, the mycollum shows a ray-llke growth | branching; no club forms,| Vincent modurce of Vincent. whieh break off at the ord || cold forma; occaslonally longer filaments show- | oval and coccold forms. rh Brasggiiy= [fax wnt oe. mareeln cba epee say boda oaalar lieve) | ator hall erent ean feed eh era ise eariaed constant. No sbeath observed and ASTateS (ures; tn older cultures oreld forms predom- | previously at the periphery but no true club forms; some These hyphm may or may not {nto forms resembling bas- | Ing branching but no elub forms. pba. taining many spores In| branching occurs. ony do- | leaeih frou oecsld 1640 4 falength.. Hranche aeerie foate. becn de- F of ths byphic abow an enlargement along thelr|| bo radially placed at tho pe- : HIM or cocch Al fow! ot center; branching forms ierites, . MmtipeertsiesTatsral rua ieee as ae scribed. courses, riphery of the granule. the shorter forma shaw Present. V) he sermeate, Tie tlameate\have x Seal clubbed ends. . i wall, Spores have not Been observed. Coc it old aod club-Iike forma present Portions of lament acid-fast by Zieh Similar to Ep-| Cultures from 9 days to 3 months ofd stain o 7 ; Tete Bee method; ovold forma ware Gecolorised ge SO ae Poa Nae months old stained by | Cultures stained by Zlehl-Neelsen method show —_ Cultures stained by Zichl-Neslsen method | Culture 1 week old stalned by ZlohI-Neolwen me-} Cultures stainod by Zlobl-Neel- “| A Trrvgular suibing <..| cultures trom 2 weeks to 2 months old atained by | Culturo stained by Zlebl-Neclsen method mhows | No acid-fast portions | Cuituro stained by Ziebl- | Culture stained by Blebl-Nesleen | Culture from 5 days fo 2 monthe stained by ike bodies and portions of mycelium are inal. spe. ‘hans method show many acid-fast por- | many acid-fast portions The organism {8 whowed no acid-fast portions. Gram-| thod showed no acid-fast portions. nen method showed no acid- ‘Ziehl-Neelsen mothod slow many acid-fast por many acid-fast portions The organism js} by Ziehl-Neelsen Neelsen method shows no | method shows no acid-fast portions Ziebl-Noolssn method abow many acid-fast pealtivel jese are also alcobol-fast. Gram-pasitive posltive with Irregular staloing. fast portions, Gram-positive tlons, giving the organfsm tho appearance of | Gram-positive In portions, giving It the appear- | method of staining. | acid-fast portions This | This organimn stains well’ by the Portions The organism {9 Gram-positive. ‘ with irregular staining. short, plump bscllll, Gram-positive, irregular | tice of corel and short bacitlt. Gram-positive for | organism stalns well by | Gram mothod, I tall whitish colonies which coalesce Into a thick adherent | Growth appears after 2 days as smooth, adben = staining. P portions: tiie] Ciramajmgthod? Grembrane with elevations and Gepresslons of aa crange || membrane at frst a porodain-whltellaey do Small, while, Irregular, round, opaque colonies | Small, white, Irregular, round, opaque colonies; <———} Grows very slowly and yery Wttle pik- | Small projecting, round, whitish-yelfow colonies | Grow very slowly on this me- }..nd0 .. x In 2 or 3 daya varicose, shriy- | Growth appears in 2 or 2 days as amall brownlan | Grows ax a smooth, glistening, brownlsh-white | Grows as dark-brown, | Smal}, opaque colonies which | Small, opaque colonies wbich later be-| Similar to) From # fo 3 days’ growth appears ax amooth, which form on adhervnt, thick, wrinkled mem- colony; does not grow so well on this medium | gdherent membrany. Tater show a white, downy || come Black andi{nitime produces'm| morphol=|) gilstnlag colonies which \later’ coalesce (and produce nm delleate pink pigment remains molst, medium’ Growth after 8 (> 4 days nt Orat ns small, shitiih colonies; thesa gradually take on m Welleste pink color; Inter ax the colonies Gevelop they become umbilicated and coalesce forming a heaped-ap growth and produce a burat-ocber color, Similar to glycerine-axar, Growth appears after 3 days as flat particles on the wurface of the medium; these produce In Ume a delioate pink color; as Krowth proceeds ‘a qranular mass collects In the bottom of the tube; (his mas ls more of lems cohervnt. ‘Vers allght growth; uo plement; no clubs, ‘| pathopeale for guinea pli and monkeya by In- don the efgbteenth and twenty-fourth day. cane. fn madura foot. STREPTOTHRICOSIS. 485 and acute and general infection may take place during the course of a chronic localized type of the infection. CompiicaTions.—While streptothricosis may be found together with a number of other diseases, or may develop its symptoms as sequel of other diseases, the principal direct complications are those due to mixed infections of bacteria. Several of the pathogenic bacteria have been found associated with Streptothrice in lesions and the course and outcome of the disease is influenced accordingly. Tuberculosis, because of its close clinical relation to streptothricosis and the frequent lung involvement of both organisms, has led to confu- sion in some of the reported cases. TREATMENT.—The varieties of treatment most useful in this disease are general, as well as local surgical intervention if cause is indicated and a combination of all of these methods may be necessary. Potassium iodide administered in large doses over a long period of time is generally admitted to have a favorable influence on the course of the disease and complete cures have been reported from this method of treatment. Local measures consist in antiseptic dressings and the use of the Roentgen rays. Surgical measures consist in drainage, removal, or amputation according to the location and extent of the lesions. A combination of all three forms of treatment would suggest itself as offermg the most favorable opportunity for recovery. BIBLIOGRAPHY. * Appott, A. C., and GILDERSLEEVE, N. The etiological significance of the acid- resisting group of bacteria, and the evidence in favour of their botanical relationship to bacillus tuberculosis. Univ. Penna. Med. Bull. (1902), 15, 106-125.—On the actinomyces-like development of some of the acid-resisting bacilli (Streptothrices?). Centralbl. f. Bakt. etc., (1902), Orig., 31, 547-550, 1 pl. ApBkE, ConrAp. Drei Faille von tédtlich verlaufener Actinomycose. Beitr. 2. path. Anat. u. z. allg. Path., (1897), 22, 132-171. AxseL. Demonstration von Sporozoen und pathogenen Hefen. Miinchener med. Wehnsch., (1897), 44, 124.—Fettgehalt von Scolices und Coccidien. Ibid, 149-150.—Zur Bakteriologie der stomatitis und angina ulcerosa. Centralbl. f. Bakt. etc., (1898), Abt. 1., 24, 1-7. * Actanp, T. D. Actinomycosis hominis. Trans. Path. Soc. London, (1885-6), 37, 545-549, 1 pl—Actinomycosis hominis. Brit. Med. Journ., (1886), 1, 1159-60.—Htiology and pathology of actinomykosis. Lancet, (1886), 1, 973-74. + Acosta, E. Nueva propiedad del Cladothrix invulnerabilis. Crénica médico- quirtrgica de la Habana, (1894), no. 18; Ref.: Centralbl. f. Bakt. etc., (1895), Abt. 1. 17, 465.—} and GranpE Rossi, F. Descripcién de un nuevo clado- thrix invulnerabilis. Ordénica médico-quirtrgica de la Habana, (1893), no. 3; Ref.: Centralbl. f. Bakt. etc., (1893), Abt. 1., 14, 14-16. ’Unmarked references have been verified in the Library of the Bureau of Science; in references marked + in most cases the original is not available, but reviews and abstracts have been verified as cited; references marked * have not been verified. 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Med. & Phys. Soc., Bombay, (1862), n. s., 7 (app.), 3-7.—* On mycetoma, or the fungus-disease of India; including notes of recent cases and new observations on the structure, ete., of the entophytic growth. Jbid., 206-221, 2 pl—* Memoranda accompanying a specimen of mycetoma. Trans. Path. Soc. London, (1863-4), 15, 251-253, 1 pl.—* Note on mycetoma, the fungus disease of India. Trans. Med. & Phys. Soc., Bombay, (1863), n. s., 8, (app.), 26-28——* On mycetoma. Brit. € For. Med.-Chir. Rev., (1863), 32, 198-203.—* Brief notes of two cases of mycetoma, or the fungus disease of India, with sketches. Trans. Med. & Phys. Soc., Bombay, (1869), n. s., 9, (app.), 47-49.—* The parasitic fungus of mycetoma, or the fungus of India. rans. Path. Soc. London, (1872-3), 24, 260-263.—* The etiology of Madura-foot. Indian Med. Gaz., Caleutta, (1874), 9, 220.—; On mycetoma, or the fungus disease of India, London, (1874), 113 pp., 11 pl; rev.: Lancet, (1874), 2, 591—7 On the nature of mycetoma, or the fungus disease of India. Lancet, (1874), 2, 44; 113; also (translation): Arch. méd. nav., (1875), 24, 157-170.—* The so-called fungus-foot of India. Indian Med. Gaz., (1875), 10.—y Note on the apparent similarity between mycetoma and actinomyces. Trans. Med. & Phys. Soc., Bombay, (1886), III, 9, 86-90; also abstr: Lancet, (1886), 1, 321.—* Trans. Path. Soc. London, (1886). _* CASAGRANDI. Sulle relazioni tra batteri proto, meta, paratrofi. Questi Ann., (1901-3) . * CatTERINA, A. Contributo alla cura dell’actinomicosi con alte dosi di joduro di potassio. Clin. chir., (1898), 6, 49-56. *CazaLis, C. A. Streptothrix Foersteri symbiosé avee un micrococcus recontré dans la secrétion de la conjonctivite granuleuse pseudotuberculose expéri- mentale. Nowveaw Montpel. méd., (1896), 5, 309; 331; 351, 1 pl. *Crcr, A. Mucormicosi in mano affeta da osteocondroma (mano di Madura). Contribuzione allo studio delle infezioni ifomicetiche, Genova, (1887) . * CHABANELX, J. A., and BourrarD. Pied de Madura, observés 4 Djibouti. Ann. hyg. et méd. colon., (1901), 452.—See also Brumpt, Bouffard, and Chabaneix. * CHarMoy. ‘Trois cas dactinomycose. Réflexions a leur sujet. Bull. Soc. méd. Yonne, (1901), 42, 63-74. . Curari, H. Ueber primiire Darmactinomycose des Menschen. Prager med. Wehn- sch., (1884), 9, 93-94. * Curari, O. De la “pharyngomycosis leptotricca.” Rev. mens. de laryngol. etc., (1887). * CHIAROLANZA, R. Ricerche sperimentali sulla emolisina di wna _ streptotrix. Med. ital., (1907), 5, 425. CuitpE, F. L. A remarkable case of mycetoma. Lancet, (1894), 2, 1271--1273.— See Hatch and Childe. 792844 496 MUSGRAVE, CLEGG, AND POLK. Cnipman, W. W. The clinical aspect of actinomycosis. Montreal Med. Journ., (1905), 34, 93-98. * CHoux. Un eas d’actinomycose. Arch. méd. et pharm. mil., (1891), 18, 490- 494.—#tude clinique et thérapeutique de l’actinomycose. Arch. gen. méd., (1895), 1, 401-421; 565-588; 664-697. * CyreTIEN, E. De lactinomycose humaine. Sem. méd., (1895), 15, 17-24; also transl.: Med. Week, Paris, (1895), 3, 37; 49.—* Des manifestations buccofa- ciales de l’actinomycose chez Vhomme. Odontologie, (1895), II., 2, 65-74. * CrpenkowskI, L. Zur Morphologie der Bacterien. Mém. Acad. imp. sci. St. Petersbourg, (1877), VII., 25, 18 pp., 2 pl. CIECHANOWSKI, STANISLAW. Zur Aktinomycesfiirbung in Schnitten; technische Notiz. Centralbl. f. Bakt. ete., (1903), Abt. 1., Orig., 33, 238-239. * CLAISSE. De Jlactinomycose linguale primitive. Presse méd., (1897); ref: Centralbl. f. Chir., (1898), no. 10. Criaus, Epuarp. Ueber die Localisation und geographische Verbreitung der Aktinomykose beim Rind in Bayern. Deutsche Ztschr. f. Thiermed., (1888). 13, 290-300. *CrausseN. Aktinomykose der Zunge beim Rind. Witt. f. Tierérete, 3. * CLEGHORN, J. Case of Madura foot. Indian Med. Gaz., Calcutta, (1874), 9, 260. CrLemow, FRANK G. Mycetoma (Madura foot) in the Yemen. Brit. Med. Journ., (1906), 1, 918-919. ; * CLERC. Actinomycose de ’amygdale. Thése, Lyon, (1905). * CLEVELAND, R. A. A case of mycetoma in Cyprus. Journ. Trop. Med., (1907), 10, 223. * CopMAN, E. A. A case of actinomycosis. Boston Med. & Surg. Journ., (1898); 139, 134. * Conn, Ferp. Biologische Mitteilungen iiber Bakterien. Jahresb. d. schles. Ges. f. vaterl. Kult., (1874), 51, 116-119—* Untersuchungen iiber Bacterien, II. Beitr. z. Biol. d. Pflanz., (1875), 1, 141-208, 2 pl. *GoIcNeT. Actinomycose du maxillaire supérieur. Mém. et compt.-rend. Soc. sci. méd. Lyon, (1893), 33, 94-96. * CoLEBROOK. Indian Army Med. Rep., (1844) —* Med. Rep. by Med. Board, Madras, (1850).—WSee also Godfrey and Colebrook. *Cornas. Lecon str la dégénération endémique des os du pied, Pondichery, (1861); also: Arch, méd. nav., (1883), $1, 204. Coxe, J. See Arquembourg and Colle. * ComInaciInI. Un cas di actinomicosi umana. Gazz. osp., (1893), 14, 922. *Contr, P. L’actinomicosi bronco-polmonare primitiva nell’uomo. Riv. ven. sei. med:, (1885), 3, 105; 231, 1 pl. CoorEr, Luprorp. cultivated from commercial vaccine virus. Jowrn. Med. Research, (1903-4), 10, 493-512. 510 MUSGRAVE, CLEGG, AND POLK. *De La Hoz, E. Champignons pathogénes et mycoses du continent américain. Paris, 1905, 125 pp. *Hupson, W. H. A case of actinomycosis hominis, involving the tissues of the back and lungs. Ann. Swrg., (1897), 26, 626-633. * Hug, F. Actinomycose cervico-faciale? Normandie méd., (1907), 22, 9-12. *HumMEL, E. Zur Entstehung der Aktinomykose durch eingedrungene Fremd- kérper. Beitr. z. klin. Chir., (1895), 13, 534-544. *Huntiy, W. Case of Madura in its initial stage. Glasgow Med. Journ., (1889), 32, 344; (1890), 33, 339. : *Wurn. Ein Fall von Actinomykose des Auges. Centralbl. f. prak. Augenh., (1894), 18, 106-109. *Huryra. Jodkalium bei Aktinomykose. Ungar. Veterinirber., (1896), 38. - * HyYpdE, JAMES N. A contribution to the study of mycetoma of the foot as it occurs in America. Trans. Am. Dermat. Ass., N. Y., (1896), 19, 74-90, 1 pl. * Senn, NicHoLas, and Bisnor, D. D. aoitete al ab Yada & adgarmosy ,r20l .F jslovimgs isamangisans'l ob fo Sup JOll & steicatod woirme 2) ORT! & sielaolons 2ue aS ee ee ees dhvebtiratuus ents tang ol ab: tutge: spiel aula ob Meliabdl. a lbp), soaoittia shies ob sup iatis eyeltsT eh sanivord sf sb do tihsgA'b z xis odldersezer teo’s ,AUMARSVRM-TIDA 413ivoa sl ab, aoltsoqrosg 6b al 9b slaicubiane sitieq sl umeoted Iniods'b to d8@f linve Ef al fi ~siq jo sbeinert) xuseisly sh eagsid xueb-sb sSarco? Inantells atrowiyire gal adsequorg 335 tuo tnonreviezovon& stom el emndegle enmtiyns esb eteifdo xuneisig esl aiug ; snisiov stéo al Jo ome! jmsenere 8 aeninties inob eodanst eaoiseonqhb sebnoloig ob abyer, tua jo tem sl ob uesvitt ub ayoeesh-us ot ob eontasib expel ob, sitimeex moigs: el eitry i (2onndased) colidom t9 eavir esnnity ni mila psipigoloid smv ae tniog wa orloiz edit ,(obsensO-olsen) a sa o1sitGo goinot olds olol .edivodA ob enotivas xvas imate oh soneloiv si seq drovuoo Jaemalatsmsg Isis oo wsq doonmatonm < titefisrag iyoest oz sa ivp 93velS oupisdqeonds Sibimudl ony xe wuplazp 9b aoitqeoxe'l & .stst vo staseda i2o wel ; anoils aisy uoevet stivena $29 soiaeior al .sdise Sasemanienibro at sh sdarsol jesnivorg el of sletasito sitmq sf taeetsverd a9 so: tiosly ob adeogmos aetioltos. 2syiel sb to estismiag.. fis adose onidgeonis sau encsh zotientsteup, zlsivulls sespsielunarecaaie) x teo-bue ub to bie ub: eanshadse yqoigés 42h. ollse, egetaayae, Seirovat eect sit imp 25ans apalionl 289) ob Beadtins eW abner al oh socaiom stnettogmi say illisvest @ solesios sl eaupigoloid ¢ moitsciidug eau'b teido'l imotst alalluedr 29D .estbro avot ob axsvib eal asl zsq adgibd: evbesr-estqotos asl, eSldensgest inte YIOU 4 ‘ cn GEE ee SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles = 1961, n° 6) M, ANTOINE: Notes d’entomologie marocaine. LXVII. — Description de deux nouveaux Sphodrides cavernicoles du Rif central. Pristonychus (Antisphodrus) Ambroggii nov. spec. Long.: 15 - 16,5 mm. — Apteére, déprimé, remarquablement svelte (presque quatre fois plus long que large), entiérement roux obscur, le tégument micros- culpté, trés finement sur lavant-corps qui demeure brillant, trés fortement sur les élytres qui sont mats, voire subchagrinés aux forts grossissements. Il n’y a aucune trace de ponctuation, si fine soit-elle. Téte forte, sans exces, yeux peu convexes, petits, deux fois et demie plus courts que les tempes, celles-ci subrectilignes derriére les yeux puis convergentes, séparées du cou par un trés profond sillon qui s’efface complétement sur l’occi- put ; carénes oculaires légérement convergentes et laissant A découvert l’extréme base des antennes, Corselet déprimé, trapézoidal, un soupcon plus large que long, bord anté- rieur rectiligne, les angles latéraux étroitement saillants, le maximum de largeur au quart antérieur, les cétés peu arqués en avant, rectilignes en arriére (1), sans sinuosité prébasilaire, les angles postérieurs droits. Champ postangulaire largement déprimé avec une vague impression linéaire dans le fond ; base concave, non rebordée. Elytres trés plans, trés paralléles et trés étroits (environ deux fois plus longs que larges) le maximum de largeur au tiers postérieur, peu et progres- sivement rétrécis vers la base, celle-ci, entre le pédoncule mésothoracique et Yépaule, légerement tombanite, l’angle huméral par suite un peu obtus, émoussé, situé dans l’axe de la huitiéme strie, Stries extrémement fines, les intervalles plans. 4 - r r r Dessous absolument glabre, imponctué ; mésosternum denté. Antennes gréles atteignant presque le milieu de l’élytre (¢), le troisiéme article sans impression, les suivants un peu comprimés. Pattes gréles, face antérieure des protibias densément pubescente sur sa moitié distale ; face inférieure des profémurs convexe, unicarénée ; brosse métatibiale longue mais peu fournie, se continuant sur la face inférieure du premier article des méta- tarses, la face supérieure de ce dernier couverte d’une ponctuation allongée, peu strioliforme mais dont chaque élément est précédé d’une aspérité subépineuse donnant a Vorgane l’aspect d’une petite rape. Ongles lisses. Chétotaxie normale du genre: 2 pores frontaux, 2 pronotaux, 1 scutellaire, 2 subapicaux, pas d’apical, pas de dorsaux, série ombiliquée continue. Chez les femelles les antennes sont 2 BRS courtes et les tempes fortement convexes, presque tuméfiées. (1) Chez un de nos exemplaires ces cétés sont méme trés légérement. convexes. — 117 — SCCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) Organe copulateur (fig, 1) relativement svelte, l’apex, vu de profil, assez effilé, vu de face au contraire largement tronqué. Style gauche quadrangulaire dépourvu d’apophyse a l’angle terminal interne. Il existe une armature interne compliquée dans laquelle on distingue une grande plaque de squames épineuses et, vers apex, quelques tractus allongés. Fig. 1. — Pristonychus (Antisphodrus) Amgroggii. — Edéage : 1. profil droit ; 2. apex vu de face ; 3. paramere gauche vue de face. Localité. — Grotte du Kef sur le jbel Laghchlab (Speleo-club de Rabat), 3 ex, dont un ¢ ; grotte de Toghobeit prés Bab-Taza (A. Camus), 2 2 9 ; Aven de Moulay Abd-el-Kader Serafa (M™° Penor), une 2°. Tres différent des deux cavernicoles franes décrits jusqu’ici du Maroc. 1 est inutile de le comparer au P. Villardi ANToINE qui est un Cephalosphodrus (abdomen micropubescent, 3° article des antennes impressionné). Quant 4 P. (Antisphodrus) Malhommei ANTOINE, c’est un insecte a microphtalmie beaucoup plus prononcée, a corselet distinctement microponctué, a stries plus fortement gravées, A premier article des antennes plus gréle et a ponctua- tion du premier article des métatarses plus nettement strioliforme ; l’organe copulateur est autrement conformé. C’est certainement du Ledereri ScHauruss andalou qu’il se rapproche le plus. Une comparaison détaillée nous est malheureusement impossible car nous ne possédons pas cette espeéce, mais MaTevu (1) en a donné une silhouette d’en- semble avec croquis de l’édéage. Ambroggii est nettement plus étroit (surtout de Yarriére-corps), le pénis, vu de profil, est plus gréle et le style gauche a une forme tout autre. La tuméfaction des tempes de toutes nos femelles semble lapparenter A la forme d2 la « Sima de las Palomas » connue par un seul exemplaire du méme sexe et dont Matreu pense qu’elle appartient « a uma raza caracterizada por sus mejillas enormemente abultadas y salientes ». A la demande des membres de l’actif Spéléo-Club de Rabat, nous avons dédié cette belle esp2ce a Monsieur Amprocel, président honoraire du Speléo- (1) matEv, 1953, Revision de los Ceuthosphodrus (s. str.) cavernicolas de la penin- sula iberica. Premier Congr. Intern. de Spéléologie, III, p. 117. — 118 — aie SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) Club de Rabat, ancien chef du centre des études hydrogéologiques du Maroc, et actuellement chef du Service de la Division des ressources en eau A la Food Agricultural Organisation (F.A.O.) a Rome. Pristonychus (Antisphodrus) vagabundus nov, spec. Long.: 13 mm. — Apteére, svelte sans excés (une fois et demie plus long que large environ), entiérement brun roux, la microsculpture presque effacée sur lavant-corps, plus développée sur les élytres qui cependant sont assez brillants ; entiérement lisse, sans ponctuation. Téte assez forte, yeux peu convexes, petits, leur diamétre antéro-postérieur contenu deux fois et demi dans la longueur des tempes, celles-ci non tuméfiées, subparalléles, le sinus collaire net mais peu profond; carénes sus-oculaires convergentes, sillons frontaux évasés. Corselet déprimé, trapézoidal, un peu plus large que long, le bord antérieur concave, les angles latéraux trés saillants, cOtés peu arqués en avant, assez fortement rétrécis en ligne droite vers l’arriére, les angles postérieurs droits, vifs, tombant au milieu du sixiéme intervalle, base absolument rectiligne ; fossettes basilaires larges, avec, dans le fond, une impression linéaire qui se pro- longe vers l’avant en une gouttiére marginale peu profonde. Elytres longuement elliptiques, le maximum de largeur au tiers postérieur, longuement rétrécis en avant, la base, entre le pédoncule et l’épaule, légérement oblique sur le grand axe, l’anglo huméral par suite obtus, émoussé, tombant en face du septiéme intervalle. Disque légérement convexe, stries bien creusées, intervalles convexes, les pairs: 2-4-6-8 peu mais visiblement plus larges que les impairs. Antennes fines, le troisiéme article un peu arqué, les suivants subtilement comprimés, l’extrémité atteignant le tiers antérieur des élytres, Pattes moyenne- ment gréles, face antérieure des protibias pubescente, face inférieure des profé- murs convexe, a peine unicarénée, brosse métatibiale peu fournie mais prolongée sur la face inférieure du premier article des métatarses qui montre, au dessus, une ponctuation strioliforme peu rapeuse. Ongles lissas. Dessous sans micropubescence, mésosternum sans dent. — Chétotaxie normale. Localité. — Rif central: Ketama, 1650 m., un seul exemplaire (9) trouvé sous une petite pierre plate, en pleine cédraie, loin de toute anfractuosité visible, le 10 mars 1961 ! P. vagabundus est indubitablement un cavernicole (1) et sa présence dans le domaine épigé doit étre tenue pour accidentelle. Bien que géographiquement tras voisin du précédent il en diffsre profondément par sa taille, ses élytres plus courts, elliptiques, convexes, brillants, le sinus collaire moins profond le corselet plus larg2 plus rétréci vers la base, l’absence de dent mésoternale etc... Malhommei Antoine qui a les mémes dimensions a les yeux beaucoup plus petits et plus plans, les élytres paralléles, tras mats, les intervalles plans. Quant a V’élargissement des intervalles pairs, il convient d’attendre d’autres captures pour savoir si le caractére est spécifique ou individuel (2). (1) Ce que démontre au surplus la totale dépigmentation des Laboulbéniales qui le parsément. (2) Il est spécifique chez P. (Sphodroides) anomostriatus Antoine de la grotte du plateau de Kik. — 119 — 33 2enel wb, 29: "Be froif (OP Srtd les wpigalodgarbid. BORE, Sha GUA PCE rat" hake ah Oph vee.a Ta f COTES. acted fane'| gue. 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SiPRABHOMeS pithor swe repsepaenc ie penta caged cD ee | £ : ‘ ier his ge ele ei a aldiety P Bicoradetas it Ze S nndalo oti & 2S i) anth SitedMigne 745 ey isnidiaeonas; Presa rapa aRaRat clon a costae hoRMapideswesy 4eb ec vicad OMB D ISIS Sridd SHereY SEN HOES Bue oe Sia nea ‘gress Dre bony lar eS neo Hi Sechaos st Undtoty" Briont Stiles” euitie ah picatead 4 {SoReVitod © tz here: 8S" sfgirrefosint ish 3B ss oave | [Siind eto fetay insHST ech Sater ard gttstesd ‘xvetr eho h Bholeadtih Marit SF e™inp SRHEAPE tren satis lo calf nae sof alent ater alilavegresabys cobalt tigad esees'b -sthaatic boiesivirosnlihtiag Bllerssint an foawsset <8) fouhivibsi wo | supitiasae, jea ppptogisa, ol. iz = : y < r squr ST coer Ofer aire. . ito exlnledelivenin® ah cubetimaatonts Stated at pra 5 us siiomesb sup oD aT) Ace tort ab SH alter R RussEtebrnidaet es Ry BAE AY % Suitl, fipeeeosee nis Be ATA ob used: — i= SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) K.B. SACANTANIS (Meknés): Elevage au laboratoire de la cochenille noire Saissetia oleae Bernard (Homopiera - Coccidae). 1, — L’un des plus grands ennemis de Joléiculture méditerranéenne, !a cochenille noire, cataloguée sous le nom Saissetia oleae Bernard, des Coccidae- Lecaniinae, constitue aussi un obstacle sérieux au développement de J’olivier au Maroc, surtout dans le Nord du pays. Liintérét que présente l’étude biologique de Vinsecte, qui doit aboutir a Vélaboration d’une méthode de lutte, est done évident. Saissetia oleae Bernard est un ravageur extrémement polyphage. Plus de 140 hotes réguliers ou occasionnels ont été déja rapportés dans la bibliographie mondiale. Parmi eux se trouvent des plantes appartenant a des familles bota- niques trés éloignées. Nous citons l’Olivier, ’Oranger, le Pin, le Pistacier, le Peuplier, le Poirier, la Robinie, le Grenadier, les Solanum (jasminoides, nigra, melongena), le Laurier-rose, le Romarin, le Cycas, l’Ipomée, le Bananier etc... I est done important d’étudier de pres l’écologie de cette cochenille pour com- prendre son mode de propagation et la physiologie de sa nutrition qui lui per- met de profiter de la save de plantes trés différentes. 2. — Pour commencer |]’étude approfondie d’un insecte, l’établissement d’une méthode d’élevage au laboratoire est indispensable. Cette étude réalisée dans un lieu ou tout facteur est contrélé et faite de pair avec l’étude de l’évolution de V’insecte dans la nature, peut donner des précisions quelquefois étonnantes et inattendues sur l’écologie, le cycle biologique du ravageur et découvrir son point faible, qu’on utilisera pour lutter contre lui. L’élevage d’un insecte au laboratoire se révéle souvent difficile 4 réaliser, On ne comprend pas toujours bien les particularités et les secrets de la vie naturelle. Il faut combiner d’une facon satisfaisante les conditions de milieu comme la température, ’humidité, l’éclairage, les cages, les manipulations mini- ma mais quelquefois astucieuses et surtout il faut trouver le milieu nutritif convenable et indispensable. Nous avons essayé avee succés l’élevage de la Cochenille noire sur ses hétes préférés dans la région de Meknés qui sont l’Olivier, ’Oranger et le Lau- rier-rose. Nous continuons l’élevage sur des plantes cultivées en pot. Cet élevage nous aidera dans une étude comparative de l’influence de V’héte sur l’évolution de Vinsecte. Le besoin d’un élevage en masse et surtout d’une manipulation facile nous a amené au choix des tiges de pommes de terre (Solanum tubero- sum) comme héte-milieu nutritif de la cochenille noire. A ce choix nous sommes guidés par l’exemple des entomologistes américains qui ont élevé d’autres cochenilles sur les tiges de pommes de terre (1). L’utilisation de la pomme de terre comme support et milieu nutritif de !a cochenille s’est démontrée efficace. Jusqu’A ce moment on a élevé cinq géné- rations consécutives de l’insecte, issues d’une souche initiale de quelques coche- nilles enlevées @ un olivier, (@) Situ and ArmiracE : The biological control of Mealybugs. Calif. Exp. Sta. Bul. 509, 1931. (1) matEeu, 1953, Revision de los Ceuthosphodrus (s. str.) cavernicolas de la penin- sula iberica. Premier Congr. Intern. de Speleologie, 111, p. 117. — 121 — SCCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6), 3. — On applique la technique de la germination en clayette pour avoir des tiges vigoureuses en abondance. Dés que la germination se réalise on « plante » les tubercules germés sur une couche de terre placée dans des plats en tole de dimensions choisies (46x32 p. ex.) pour permettre leur placement sur les étageres d’élevage ou dans les cages d’élevage des parasites ou des prédateurs de la cochenille. Pour contaminer les tiges on utilise les larves de cochenille sorties d’ceufs prelevés des pontes controlées, pour éviter l’infection de V’élevage par les aca- riens ou d’autres parasites, prédateurs ou symbiotes indésirables. L’éclosion des ceufs se réalise dans des boites de Petri mise dans une étuve a la température de 25°C pour Vincubation. A l’aide d’un pinceau sec on attrape les larves et on les pose sur les tiges. La fixation se réalise assez rapidement si la température varie entre 22° a 24°C et A une demi obscurité. Chaque série de tiges peut supporter deux ou trois générations de chenilles c, a. d. peut rester plus au moins en bon état de végétation pendant 5 a 7 mois. La variété de la pomme de terre choisie joue un role important a Ja durée de chaque série. Mais il est convenable d’élever une génération seulement sur chaque série de tiges, 4, — Les premiéres observations faites sur les cochenilles noires élevées au laboratoire par la méthode prescrite montrent que nos connaissances ac- tuelles sur la biologie de la cochenille noire sont élémentaires. On mentionne par exemple que l’insecte ne peut produire que deux ou trois générations par an dans la nature. L’élevage du laboratoire démontre qu’A la température de 24°C on peut avoir continuellement une génération tous les 70 jours. L’insecte ne présente de diapause 4 aucun de ses stades évolutifs. Par l’élevage on observe aussi que les larves fixées méme au début du 3° stade larvaire peuvent se déplacer si le lieu ou le milieu ne leur conviennent pas. A un Age plus avancé tout déplacement est impossible. Gn constate aussi trés facilement qu’A des températures inférieures 4 18°C la fixation devient de plus en plus difficile. Ce fait explique la diminution massive des colonies de l’insecte pendant la période dautomne et d’hiver. Mais les observations systématiques viennent seulement de commencer, et une étude profonde et détaillée de ce grand ravageur est a espérer. Laboratoire des Parasites de lOlivier Station Centrale de Phytidtrie Service de la Recherche Agronomique et de V’Enseignement Agricole — 122 — SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) Discussion : La communication est suivie de la visite commentée des laboratoires et ea particulier des salles d’élevage de la station de phytiatrie, visite qui améne les auditeurs a se faire préciser quelques points. A des questions de M. SapHore, M, Sacanranis répond en soulignant l’intérét local du probleme, La cochenille cause dans le Zerhoun d’importants dommages. Par contre le défeuillage 4 peu prés total observé dans certaines olivettes en Février est dQ & un champignon (Cycloconium). M. Dectoirre, qui étudie une maladie de la pomme de terre, demande les réactions de la pomme de terre observées dans les élevages, M. SacantTanis répond qu’il existe effectivement des malformations et en particulier des tubé- risations sur les tiges aériennes, sans qu'il puisse affirmer que le parasite en soit la cause. M. SaPHorE s’étonne que l’intérét national d’une lutte contre la cochenille noire ne semble pas envisagé par les pouvoirs publics. MM. Sacanranis et DECLOITRE citent des exemples qui prouvent qu’une lutte antiparasitaire, en- gagée sans une connaissance suffisante de la biologie du parasite peut aboutir a des résultats néfastes, par exemple en supprimant les prédateurs de ce para- site. Il faut d’abord étudier la vie de la cochenille et les travaux ne sont pas encore assez poussés pour pouvoir envisager une lutte sur une grande échelle. — 123 — ie all 4 -~ On suplique, la technique.de ta aesmination ena clayets ce tines vigduretses en abondaucs Dbe que ta. pes: 5 + plante > les whereales germés sar one couche de terre ritatda-sodbi atedal rahi obinakaempa, stinks: al, ban eh, aol sniram, ip otitiyoaibitvrcai aby: mnitete, eh 29 lee prddateurs de Is egchemnilie. "| .ttmiog eourpfoup wetes racy oink sidmnill imanwibuea maybongha encoawmagae jell Gamomge, paoRaosnols, afrahwect arith oscuro, ob eal 9 ligand meg 80: eabdpeilo,. paige 2agb) oxzaede, Jake) amasag 6.8) 3 guts 39, realise clus des bed “wee ane { a8 det S inate SHON Sin ote RE ob Sige PbS ‘ateRPMi oe Be Seb yihes ! [Seta 25 rad 6" bird BSS, wadise we ral oan AS Od BRR REE beetle ob insmevilootis oleixa rite oh viektatian ett atti: Has whSsdadle asa neve Nee FAKED Sitp Wactilt, pat “en weer ateh nner, NEES ating! aaloveRiie? et lel agazivey” way? SIERR Eta eieAtkGis SHY onu'ip tnovirere itp 2oigenoxe 2sh testi ‘ituocia ‘Ineg aires tag ub pe igoloigt nl ab ainagitiag, Sageeataniios 2 ~SR 92 ab ats! psig, taf dnsrtttiqay 19 “glasses weg g BS: phi, dito ape "AVON Boe ia 5 Lligarinen al ob ay. ply weulbale biodg, sllads > ‘ghana, afi tHe alt ut heete ete iia je PS, 4400 4 Mag "élavage en aa de‘ Inrvaire peaweat Bs a. tin age ee moi niet tay aihay f iene i SCCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) G. VARIN (Joinville-le-Pont) : Fabriciana auresiana Frithstorfer et sa sous- espece marocaine Buckwelli Varin nova. (Lépidoptéres-Nymphalidae). Fabriciana auresiana a été décrit d’Algérie par Friistorfer. Cette espéce appartient au méme genre que niobe L. et qu’elisa Gopart, C’est une belle Argynne qui vole dans les montagnes d’Afrique du Nord, Voici la description de la forme nominale : Cette esp3ce ressemble beaucoup a F. Niobe auquel elle avait été momen- tanément rattachée. Male: Envergure de Vaile antérieure: 25/30 mm; dessus des ailes d’un fauve plus ou moins clair, les petites taches noires submarginales en forme d’accent circonflexe sont bien marquées. Le revers des postérieures est d’une couleur vert foncé teintée de marron, Femelle: Env. de Vaile ant.: 30 mm env. dessus légsrement plus pale que le male. Au revers des postérieures la teinte marron domine sur le fond vert foncé. Quelques localités de vol: Massif des Aurés, Lambéze, Tala-Rana (Kabylie) ete. Ce papillon parait en juin-juillet. F. auresiana vole également au Maroc dans les montagnes du Moyen et du Haut Atlas. Les F. auresiana marocains constituent une forme qui, dans le Moyen Atlas, est plus grande et plus vigoureuse que celle d’Algérie et se présente par ses caractéres comme une sous-espéce différente de la race nominale. Je dédie cette belle race marocaine 4 mon ami le Docteur Buckwet. de Meknés en la nommant buckwelli ssp. nova. En voici la diagnose : Male: Env, de Vaile ant.: 29/30 mm. La teinte du dessus des ailes est plus rougeatre que celle des exemplaires d’Algérie avec les petites taches submar- ginales en accent circonflexe le plus souvent plus réduites. Mais c’est surtout le dessous des ailes postérieures qui tranche d’une facon remarquable, Le lavis est d’un vert brillant avec un léger reflet métallique trés rarement nuancé de marron, Femelle: Env. de Vaile ant.: 30/32 mm. Légérement plus pale que le male avec le lavis des ailes postérieures d’une teinte un peu plus soutenue. Holotype, male: Ifrane (Maroc) 1.600 m. 20-6-53. Dans ma collection. Allotype, femelle: Ifrane (Maroc), 1.600 m. 20-6-53. Dans ma collection. Paratypes males et femelles répartis dans la Collection du Muséum d’His- toire Naturelle de Paris, dans celle du Docteur Buckwett et dans la mienne, SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) Localités des paratypes: Moyen Atlas: Environs d’Ifrane, Région d’Ifrane : Mont Koudiat, Forét de Jaba, Dayet-Achlef, Ain-Leuh, Afraou-des-Beni-Ab- dahlah (2.550 m), Ras-el-Ma, Grand Atlas: Vallée de Imminem, Camp de Villaye de Tachdert (2.400 m). Les exemplaires du Grand Atlas présentent les mémes caractéres de colo- ration que ceux du Moyen Atlas, mais paraissent d’une taille plus réduite, certains spécimens des hautes altitudes sont méme plus petits que les auresiana d’Algérie. Au Maroc, Fab. auresiana parait en juin, les exemplaires qui volent encore en juillet sont défraichis. — 126 — ——————————— SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles - 1961, n° 6) A. CAMUS: Insectes des eaux salées de la région du Bas Ouerrha. Du point de vue géographique, la région qui fait l’objet de ce bref exposé est située dans le Bas Ouerrha, affluent du Sebou. Deux zones ont attiré particuliérement notre attention. Tout d’abord, au NE de Khenichet sur Ouerrha, le Jbel El Moghra, ensuite la riviere souterraine de Hairat Bou Amira, sur le flanc Nord-Ouest du Jbel Bou Jmana au SE de Souk El Tnine Jorf El Mellah. Du point de vue géologique, le secteur étudié appartient a la nappe pré- rifaine, I] s’agit d’une nappe de charriage composée de terrains d’age triasique, jurassique, crétacé, nummulitique et miocéne inférieur, qui s’est répandue vers le Sud. Dans ce complexe il n’y a pas de succession stratigraphique continue. L’importance des terrains saliféres doit étre soulignée. Le terme de salifére utilisé par les géologues se rapporte a des marnes rouges comprenant des niveaux lagunaires de sel et de gypse. Les affleurements sont d’importance variable. Le sel forme quelquefois des amas considérables comme a Tissa. Dans le secteur étudié il faut citer la mine de sel de l’oued El Moudina (versant Nord du Jbel Moghra) et le déme de sel que traverse sur une longueur de 100 métres la riviére de Hairat Bou Amira. Il est évident que les eaux qui sont associées A ce terrain salifére ont une concentration élevée. Au cours de prélévements d’échantillons d’eau en vue de lJ’analyse chimique, notre attention a été attirée par la présence d’organismes animaux vivants dans des conditions de salure anormale, Les analyses chimiques ont été effectuées par M™° Fizator, du laboratoire du Service géologique, et les déterminations entomologiques sont dues a M. Kocuer, de l'Institut Scientifique Chérifien, Les points ot ont été reconnus les organismes sont: 1° L’oued El Akreuch du Moghra x = 469,300 y = 430,250 z = 38 m environ 2° Le Bir Nasser (puits - source) x = 470,600 y = 429,150 Zz = 90 m environ 3° La riviére souterraine Hairat-Bou-Amira, ~ x = 487,800 y = 424,750 z = 80 m environ (feuille au 1/50000 de Khenichet S/Ouerrha) Du point de vue entomologique les espéces recueillies sont: 1° Eaux de VOued-El-Akreuch-du-Moghra : Ochthebius notabilis Rooch. (coléoptere Hydraenidae), en nombre: aucun renseignement particulier, espéce banale. 2° Eaux du Bir Nasser (Puits-Source) Coléoptéres : 4 espéces (banales) Hemiptéres: 2 espéces (dont I indéterminée) Odonates Anisoptéres : 2 larves (Orthetrum sp.) ; Diptéres: 1 larve de Stratiomyiinae (trés probablement Hirtea longicornis Scop). — 127 — SOCIETE DES SCIENCES NATURELLES ET PHYSIQUES DU MAROC (Comptes-rendus des séances mensuelles = 1961, n° 6) La larve de cette espace se trouve dans les marécages d’eau douce, parfois dans les eaux saumatres ou salées (selon Smcuy, in Faune de France, 1926). 3° Eaux de Hairat-Bou-Amira (riviére souterraine). Potamonectes sp. aff. Cerisyi Aubé (coléoptére, Dysticidae), 3 exemplaires. P. Cerisyi est connu (Guicuor, etc) comme une2 espéce spéciale aux eaux salées (remarquer le dépot de sel sur les jointures). Le présent insecte en est voisin, mais notablement différent quand méme, il ne peut pas étre rapporté non plus aux autres espéces signalées du Maroc, peut-étre est-ce 1A une espéce nouvelle. Du point de vue chimie des eaux: Il est intéressant de comparer a l’eau de mer, l’eau de la riviére souterraine Hairat Bou Amira. La représentation en diagramme logarithmique met en relief les ressemblances et les différences. Les deux échantillons ont 4 peu prés la méme concentration. Eau de mer Eau de Hairat Bou Amira 36 226 mg/l 35000 mg/1 Mais la différence en magnésium est trés importante. Eau de mer Eau de Hairat Bou Amira 1405 mg/l 205 mg/1 Quant a l’eau de l’oued El Akreuch du Mogra, sa qualité chimique excep- tionnelle rend toute comparaison difficile, sa concentration (250 g/l) est sept fois celle de la mer. Ces eaux sent salines, riches en chlorure, sulfate de soude, magnésie, chaux. Eau de mer plage de Mehdya Hairat Bou Amira Oued Akreuch du Mogra Ca 390. 1120 1 760 Mg 1405 205 560 Na 11 256 11 808 92 083 Cl 19 560 19 250 144 400 SO, 3 360 2014 3990 CO; 120 60 = 60 RS 36 226 35 900 250 000 DH 676 364 670 Les résultats présentés sont des faits d’observation et c’est le spécialiste qui doit tirer des conclusions. Il ne faut voir ici qu’une modeste contribution a la recherche scientifique. Il y a lieu de rappeler ici le travail de J. Marcat sur les eaux salines (1) récemment présenté a la Société des Sciences Naturelles (séance du 4 avril) qui constitue un document de base du plus haut intérét scientifique, (1) sg. marcat Répartition des eaux salées au Maroc. Atlas du Maroc, Section V, Hydrogéologie planche 14 B. — 128 — RAI SMITHSONIAN INSTITUTION LIB! “TTT 3 9088 0130 7 665 RIES 8