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Mice, C57Bl/6N (B6) and BALB/cAnN (BALB), infected with Schistosoma mansoni were examined 8-26 weeks postinfection (PI) to estimate the fecundity of the worms and the contribution of death of worms and the death of heavily infected mice to the decrease in worm numbers in chronic infections. Portal worms were recovered by perfusion and the lungs were examined for parasites shunted from the portal circulation. Animals that died were more heavily infected than those that survived. Between eight and 12 weeks PI, this loss of worms resulted in a net decrease of approximately 19% of worm pairs in surviving BALB mice, but of only 4% in B6 mice. Loss of portal worms to the lungs after the eighth week of infection was 9-13% of portal worms in BALB mice and 3-4% in B6 mice. The estimated rates of egg production by S. mansoni decreased slightly with time in both strains of mice. At 12 and 20 weeks PI, tissue eggs per worm pair and eggs passed in the feces per worm pair often decreased as the intensity of infection increased. We do not consider the loss of worms in the murine host relevant to most infections in humans because of the high intensity of infection relative to body size in mice and the high frequency of severe portal obstruction in murine infections.

In 1971 we estimated that Schistosoma mansoni eggs in the tissues of mice were destroyed with an approximate half-life of four weeks. Our present results of five experiments suggest that egg destruction is not as rapid, and no significant destruction of eggs was detected for up to 26 weeks after treatment. However, in these experiments, a mean of 60% of the eggs in intestinal tissues were found in the feces at the time of treatment. In previously reported experiments, only 15% of gut eggs were passed in the feces. We now believe that underestimation of the number of eggs passed in the feces led to an overestimation of the number of eggs destroyed in the tissues. We analyzed liver eggs separately because eggs lost from this site are unaffected by eggs passed in the feces. No significant decrease in liver eggs occurred in the present experiments, but reanalysis of previously published data showed significant egg destruction in the liver in several experiments, although at a much slower rate than previously estimated. However, inspection of the data in the previously published and present experiments does not show a convincing difference in the number of eggs in the liver after treatment. The persistence of egg shells is probably not important in the pathogenesis of disease, but is of concern in calculating worm fecundity. Hepatic collagen levels increased markedly two weeks after treatment and subsequently decreased significantly in some, but not all, experiments.

Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.

Experimental infections with Schistosoma mansoni and S. japonicum differ in several aspects and post-treatment resorption of fibrosis might be one of them. To investigate this point, mice infected with each of these schistosome species were treated with praziquantel and the evolution of hepatic lesions was sequentially followed for five months. Parasitologic data showing destruction of worms and eggs and biochemical findings of progressively decreased collagen concentration after cure indicated that the lesions caused by S. mansoni and S. japonicum involuted in a similar fashion following chemotherapy. The time sequence of the histologic changes indicative of decreasing inflammation and progressive matrix degradation and resorption was also similar in both cases.

Schistosoma mansoni and S. japonicum infections in nude mice (nu/nu) were compared with infections in nu/+ heterozygotes or intact mice. Seven to 12 weeks after exposure to S. mansoni, the responses of Swiss NCR, C3H, BALB/c and C57B1/6 nude mice did not differ substantially. Nude mice of all these strains showed minute granulomas around eggs in the liver and minimal hepatic fibrosis. Microvesicular and necrotizing changes in hepatocytes were similar in all mouse strains, and S. mansoni infections were frequently lethal to nude, but not to intact mice between the seventh and ninth weeks of infection. Nude mice that survived the ninth week of infection generally lived until the 12th week. The number of eggs per mature worm pair in the tissues of S. mansoni-infected nude mice was similar to the number in intact mice, but nude mice passed fewer eggs in the feces. Nude mice that received serum from infected intact mice excreted eggs in the stool in numbers equivalent to intact mice, but continued to form minute granulomas around S. mansoni eggs. Reconstitution with fetal thymus or with splenocytes from normal or S. mansoni-infected mice partially or completely restored hepatic granuloma size, granuloma eosinophils, hepatic fibrosis, and excretion of eggs in the feces. In contrast to S. mansoni infection, S. japonicum infections in nude mice did not cause necrosis of hepatocytes or excessive mortality, and S. japonicum eggs were passed in the feces in numbers equivalent to those passed by infected intact mice.

Individual male and female schistosomes approximately three weeks of age were implanted into the portal venous system of C57Bl/6 mice to produce infections with a single pair of Schistosoma mansoni or S. japonicum. Mice were killed between seven and 54 weeks after infection. Worm fecundity was measured by counting eggs accumulating in the tissues and eggs passed in the feces. Schistosoma mansoni worm pairs laid approximately 350 eggs per day with no change in the apparent rate of egg laying between eight and 52 weeks after infection and approximately one-third of the eggs were passed in the feces. Schistosoma japonicum worm pairs laid approximately 2,200 eggs per day initially and this decreased to 1,000 eggs per day by the end of the experiment, with one-third to one-half of the eggs being passed in the feces. There was marked variability in the fecundity of individual worm pairs, but the number of eggs passed in the feces of individual mice correlated well with the number of eggs in the intestines at all time points in S. mansoni-infected mice and at the seventh and tenth week of S. japonicum infection.

Rabbits were infected with Schistosoma japonicum of Japanese origin between 1973 and 1979. The distribution of lesions and eggs in the small intestine and colon changed significantly twice during that period, and the number of eggs per worm pair passed in the feces changed at least once. The shift in egg distribution and that in egg passage occurred at different times and appeared not to be causally related. The number of eggs per worm pair retained in the tissues of chronically infected rabbits was consistently greater in rabbits with colonic bilharziomas. We postulate that differences in the schistosome population were responsible for the alterations in worm behavior. These differences may have been caused by the introduction of new isolates from the field, or by selection during laboratory passage.

Mice of several strains were exposed to Schistosoma japonicum cercariae and killed 6, 7, 10, or 15 weeks later. Hepatic fibrosis was consistently most marked in ICR mice and least marked in C57BL/6, A and C57BL/Ks mice. Intermediate degrees of fibrosis were present in C3H, CBA and Nmri mice. The size of circumoval granulomas also varied greatly among mouse strains but the degree of hepatic fibrosis was unrelated to granuloma size, indicating that the mechanisms regulating granuloma size may not be relevant to other important parameters of pathology induced by schistosome infection. The degree of fibrosis in S. japonicum-infected ICR mice is similar to that measured in S. japonicum-infected rabbits but is less than that in S. mansoni-infected mice.

Groups of 6 to 8 grivet monkeys (Cercopithecus aethiops aethiops), each of which had been exposed to 600 cercariae of Schistosoma mansoni, were killed 3, 6, and 31 months after exposure. Other groups of monkeys were repeatedly challenged with cercariae beginning 4 or 23 months after the initial infection, and were killed 31 months after the first exposure. Peripheral blood leukocytes, eosinophiles, and schistosome eggs passed in the feces were determined during the course of the infection. At autopsy, gross and histopathologic observations were made, worms were recovered by perfusion, and the number of eggs in the tissues was determined by digestion. Monkeys became acutely ill about 8 weeks after the initial exposure, and death was attributed to acute “toxemic” schistosomiasis in 4 of 46 infected animals. The symptoms and signs of the acute phase did not recur with reinfection. Most subsequent natural deaths were caused by Klebsiella infection, which occurred in both infected and control monkeys and did not appear to be related to the schistosome infection. Relatively stable infections were found after a single exposure to cercariae, with only a slight decrease in worm numbers and moderate decrease in egg passage after 31 months. With repeated reinfection, only 19% of challenge cercariae developed into adult worms. Oviposition by these worms was delayed and the rate of oviposition was substantially less than in monkeys infected only once. Eggs deposited in the tissues were rapidly destroyed. The calculated rate of oviposition varied from 658 eggs/day per female 3 months after a single infection to 299 eggs/day per female 31 months after repeated infections. Although very heavy infections were present in repeatedly infected monkeys, only slight hepatic fibrosis was seen and no portal hypertension or portal-systemic collateral circulation developed. Severe intestinal disease was present in only two monkeys. The remaining animals had little diarrhea after the acute phase, and there was only slight loss of plasma protein into the feces 31 months after exposure.

Four hundred consecutive autopsy cases were examined in Cairo, Egypt. Sixty percent of cases had Schistosoma haematobium eggs in the tissues and 25% also were infected with S. mansoni. Only a quarter of S. haematobium infections were active, while nearly two-thirds of S. mansoni cases remained active. Adult S. haematobium and S. mansoni were effectively recovered from the mesenteric circulation by a combination of perfusion and dissection. Quantitative recovery from the genitourinary system was reasonably complete, although small numbers of worms were missed in the dissection of these organs.

Groups of mice infected with Schistosoma japonicum were killed 7, 10 or 15 weeks after infection. The size of hepatic granulomas and degree of hepatic fibrosis in individual mice were examined in relation to the number of worm pairs present using regression analysis. Mice with heavy S. japonicum infections had smaller circumoval granulomas in their livers than did mice with lighter infections. Hepatic fibrosis per unit infection, i.e., per worm pair or per egg, also decreased as the intensity of infection increased. These trends were similar in 8 strains of mice examined. No clear trends were found in rabbits or monkeys infected with S. japonicum. Hepatic fibrosis in S. haematobium-infected mice decreased with increasing intensity of infection, although this trend was significant only in infections of 1 year duration. C57BL/6 mice infected with S. mansoni often showed trends similar to those in S. japonicum-infected mice; however the findings in C3H and ICR mice infected with S. mansoni were more variable. Most of the data for the present report were from animals also described in previous publications. The relevance of these findings to schistosome infections in humans is unknown but the results are clearly pertinent to the analysis of hepatic pathology in experimental infections. Overall egg production by the worms was not affected and the number of eggs per worm pair recovered from the tissues was not generally influenced by the number of worm pairs present.

A Japanese strain of Schistosoma japonicum produced segmental circumferential lesions 15-40 cm in length in the proximal jejuum of infected rabbits, while a Philippine strain of the parasite produced small numbers of focal nodular lesions (bilharziomas) in the colon. Sequestration of large numbers of schistosome eggs in these latter lesions apparently accounted for the small and erratic number of S. japonicum eggs passed in the feces of rabbits infected with the Philippine strain. These focal masses also illustrate dramatically the gregarious nature of schistosome worm pairs, all of which concentrated in two or three focal lesions, leaving essentially normal bowel elsewhere. Sandy patches were frequently seen in the bowel in sites of heavy egg deposition, and calcified eggs were evident radiologically. The fibrotic response to schistosome egg deposition was marked in the liver. In contrast, the collagen content of the intestine was nearly normal in animals infected with the Philippine strain and only moderately increased in rabbits infected with the Japanese strain. Numerous eggs and granulomas were present in the lungs, but fibrosis of pulmonary granulomas was minimal.

Thirty patients infected with Schistosoma mekongi, S. mansoni or S. japonicum had cell-mediated immune responses assessed by lymphocyte transformation in vitro (LT), immediate hypersensitivity responses determined by basophil histamine release in vitro (HR) and IgG antibody responses evaluated in an enzyme-linked immunosorbent assay (ELISA). Species specificity was evaluated with antigens obtained from adult worms or eggs of the three schistosome species. Though cross-reactivity was present in all tests, homologous antigens elicited responses significantly greater than those to heterologous antigens in all comparisons of parasite specific IgG and IgE antibody in these groups of patients. A similar generalization could be made for the lymphocyte responses to the same antigen preparations, but statistically significant differences were achieved only in certain comparisons.

Sixty-seven rabbits were killed 8-66 weeks after infection with a Japanese strain of Schistosoma japonicum and 22 were killed 12-55 weeks after infection with a Philippine strain. Worm numbers decreased moderately over the course of infection and the number of eggs laid by each worm pair also decreased, as evidenced by decreasing numbers of mature (viable) eggs per worm pair in the tissues and, for the Japanese strain, by decreasing numbers of eggs per worm pair passed in the feces. Many eggs calcified in the tissues and the number of eggs per worm pair found in the tissues increased with time in a nearly linear fashion. For both schistosome strains, the total number of eggs in the tissues was proportional to the number of worms present at any given time. The number of eggs passed in the feces correlated well with the number of worm pairs present in rabbits infected with the Japanese strain, but in rabbits infected with the Philippine strain the few eggs passed in the feces correlated poorly with the intensity of infection. Worms of the Japanese strain were located primarily in venules of the proximal jejunum and those of the Philippine strain primarily in venules of the colon.

A gibbon was repeatedly exposed to Schistosoma haematobium infection and was followed for 68 months after the first exposure. Severe obstructive uropathy and calcification of the bladder and ureters were found despite the fact that the mean excretion of eggs in the urine averaged 167 eggs per day and never exceeded 400 eggs per day.

Eight of 10 young chimpanzees were infected with the Japanese strain of Schistosoma japonicum. In 6 of these, and in 1 normal chimpanzee, a surgical end-to-side portacaval shunt was constructed during the 8th week of infection. One additional infected chimpanzee was treated successfully with the nitrovinylfuran, SQ 18,506. In the four animals surviving both infection and shunting hepatic portal fibrosis was either absent or mild. In the 7-month survivors and in the drug-treated control animal there was evidence of healed portal endophlebitis and arterialization, but no active schistosomal liver lesion was found. Nevertheless, three of these animals showed variable degrees of active schistosomal glomerulopathy, similar to that seen in the unshunted infected control and to that described in earlier studies. There was a shift of the egg burden from the liver to the lungs, as well as evidence that the number of surviving adult worms had decreased following portacaval shunting. These observations suggest that schistosomal nephropathy in chimpanzees is more closely related to infection intensity per se than to the degree of liver damage caused by infection.

Adult Schistosoma hematobium and S. mansoni were recovered at autospy. The number of eggs of both species present in the tissues and passed in the excreta was related to the number of female worms (worm pairs) recovered. Only 26% of the S. hematobium infections were active at the time of necropsy. 47% of S. hematobium females were in the mesenteric circulation and 52% were in the genitourinary organs. S. hematobium worm pairs were sedentary laying eggs in single sites for prolonged periods. In addition the worm pairs seemed to be clustered in active genitourinary lesions. S. hematobium eggs calcified and accumulated in the tissues and a geometric mean of 600000 eggs/worm pair was found. Large numbers of eggs remained in inactive cases. There was a significant increase in eggs/female worm in older persons. The relative contribution of egg accumulation (increasing the numerator) and worm death (decreasing the denominator) to this phenomenon are not known. In contrast S. mansoni eggs were not retained in the tissues to the degree exhibited by S. hematobium. There was an apparent equilibrium between egg deposition and egg excretion or destruction. A geometric mean of 15900 eggs/worm pair was present and did not change with age. The total number of eggs/female worm and the relative proportion of eggs in the lungs liver and intestines were similar to those seen in Brazilian cases of S. mansoni infection. The number of eggs/female worm found in feces was lower than that noted in Brazil. S. hematobium infections were much heavier in cases also infected with S. mansoni than in those with pure S. hematobium infection. No pure S. mansoni infections were seen. S. mansoni infection appeared unaffected by S. hematobium infection except for calcification and accumulation of S. mansoni eggs in the genitourinary system. (authors)

Symmers' clay pipestem fibrosis of the liver was produced by Schistosoma japonicum infection in the rabbit. Gross and microscopic portal fibrosis and portal vascular lesions resembled those in hepatosplenic schistosomiasis in man. Portal obstruction caused dilation of portal-systemic collateral veins but only minimal portal hypertension. The rapidity of development and prevalence of Symmers' fibrosis were related to the intensity of the schistosome infection. A mixed macronudular and micronodular cirrhosis of the liver was also present in most animals with Symmers' fibrosis, and other differences from the disease in man were present as well. Hepatic fibrosis regressed after the 30th week of infection, as judged from gross and microscopic observations and from measurement of hepatic collagen. The prevalence of Symmers' fibrosis and cirrhosis also decreased after the 30th week in the less heavily infected rabbits. The S. japonicum-infected rabbit is an imperfect model of human Symmers' fibrosis, but the rabbit is the only experimental model available other than the schistosome infected chimpanzee. The rapid production of severe fibrosis without the use of hepatotoxic agents, and the reversibility of the lesions, make this model of general interest for the study of hepatic fibrosis.

The maturation of female Schistosoma japonicum was found to vary greatly within each of two Philippine strains of this parasite and some females did not contain uterine eggs 7 to 15 weeks after infection while others contained numerous eggs before the fifth week of infection. It was found that female worms containing less than 20 uterine eggs contributed little to the accumulation of eggs in the tissues of infected mice. Such worms also generally appeared to be immature. The variable rate of maturation of worms is likely to have profound effects on the immune reactions of mice as well as on the pathologic response to infection. Systematic delay in oviposition was serendipitously found in worms from mice which had been irradiated for other purposes prior to exposure to S. japonicum, and from the fourth to the sixth week after infection egg production by worms in irradiated mice lagged well behind that in intact mice. Seven to 10 weeks after infection these worms were laying normal numbers of eggs, as judged by egg passage per worm pair in the feces and the accumulation of eggs in the tissues. S. mansoni developed normally in irradiated mice.

Specific IgM and IgG antibody to a polysaccharide present in the epithelial cells of the gut of adult schistosomes was measured in four groups of infected patients: I) patients with documented acute schistosomiasis; II) Americans exposed to schistosomiasis within the preceding 0--4 years; III) chronically and heavily infected patients, mostly from Puerto Rico, without hepatomegaly or hepatosplenomegaly; and IV) heavily infected Brazilian children with hepatic or hepatosplenic schistosomiasis. Specific IgM and IgG titers were both highest in the acute Group I patients and lowest in the chronically infected Groups III and IV. Total IgG and IgM levels were compared to specific antibody titers. Immunoglobulin levels tended to follow specific antibody titers except in the chronically infected Groups III and IV in which total IgG rose to high levels. The decrease in specific antigen titers over the course of time occurred despite continued antigenic stimulation and suggests a modulation of the humoral response. The mechanism remains obscure.

A cerebral cyst 5 cm in diameter and 60 ml in volume was found to be as large as a racemose cysticercus. Because this cyst bore necrotic remnants of a scolex and its hooks, it was presumed to be a cysticercus of Taenia solium. This case demonstrates that in contrast with the unusual presentation of cerebral cysticercosis, cysts of the Taenia solium type can be very large, and when such cyst is encountered, a special search should be made for evidence of a scolex.

Symmers' periportal fibrosis of the liver is the major cause of morbidity and mortality in Schistosoma mansoni infection. The diagnosis is best established definitively by a wedge biopsy of the liver. The ability of abdominal ultrasonography to diagnose this condition was prospectively compared with two independent pathological examinations of wedge biopsies of the liver. Both pathologists and the ultrasonographer were unaware of the clinical diagnosis and each other's findings. Twenty-eight of 41 patients had Symmers' fibrosis by pathological examination and all were diagnosed correctly by ultrasonography prior to surgery. Symmers' fibrosis was not diagnosed by ultrasound in any of 10 patients without Symmers' fibrosis on biopsy. In 3 patients the diagnosis of Symmers' fibrosis was uncertain because the pathologists disagreed as to its presence. These results confirm the findings of previous studies and establish that ultrasonography is at least as sensitive as wedge biopsy in diagnosing Symmers' fibrosis.

Praziquantel is a newly developed drug effective in the treatment of schistosomiasis. In order to assess the efficacy and toxicity of praziquantel in the treatment of Schistosoma mekongi, 11 infected Laotian refugees, all belonging to a single extended family, were treated in a double-blind crossover trial with praziquantel and placebo. Initially, one group of five received praziquantel 60 mg/kg body weight in three divided doses orally while the remainder received an identically appearing placebo. Patients were evaluated clinically before, during and following therapy for 2 days. After 2.5 months the patients were re-evaluated and subjected to the opposite treatment, and final follow-up took place 5–7 months later. Three other patients were treated using an open protocol. All but one person was cured (91%). This patient failed to show a decrease in egg excretion 2.5 weeks after praziquantel therapy and was lost to follow-up thereafter. Side effects were common and consisted primarily of abdominal pain, malaise, and fever. These were generally mild and transient. No abnormal laboratory findings were associated with praziquantel therapy. At the final evaluation 6/6 patients with initial hepatomegaly showed a decrease in liver size.

Summary and Conclusions 1. It seems reasonable to suspect the existence of beri-beri wherever pellagra and scurvy are found, because all three diseases develop on a basis of faulty nutrition and because beri-beri probably may be combined with either pellagra or scurvy. 2. In the Far East a number of important factors are recognized which may predispose or contribute to the development of beriberi. Among them are chronic malaria, pregnancy, climatic heat and moisture, bad hygiene and various other debilitating conditions. 3. In the United States there are various forms of disease which are debilitating and which may interfere seriously with nutrition as well. Polyneuritis, moreover, appears occasionally with these diseases. Among them may be mentioned chronic alcoholism, including Korsakoff's syndrome, diabetes, cancer, tuberculosis, syphilis, pregnancy, and the marasmus of infants. 4. Some of the cases of polyneuritis developing with the above mentioned conditions might, perhaps, be properly regarded as true beri-beri and not merely as complications or sequelae of the other diseases. But, because polyneuritis is not a common disease in the United States, it is not likely that beri-beri is common here. 5. Inasmuch as there are no known criteria which are satisfactory for the diagnosis of beri-beri the therapeutic test should be applied in doubtful cases. The usual course of polyneuritis is gradual, the convalescence requiring weeks or months. On the other hand, early cases of beri-beri respond quickly to treatment and this is particularly true of infants. Chronic cases of beriberi, in which extensive degeneration of nerves and muscles has taken place, cannot respond quickly to any form of treatment so that the therapeutic test would be of little value in these cases. 6. Circulatory disorders with cardiac hypertrophy and dilatation in a case of polyneuritis suggest the diagnosis of beri-beri but may be due to other causes. 7. Conditions due to faulty nutrition are particularly common in infants. Even breast-fed infants may suffer from them. The beri-beri of infants in the Far East is said to develop, as a rule, in breast-fed infants, and its occurrence is explained by deficiency in the diet of the nursing mother, even though she may not herself show definite symptoms of beri-beri. A polyneuritis appearing in a nursing infant in this country might, perhaps, be due to beri-beri.

Previous studies have affirmed and denied the importance of obstructive vascular lesions in the pathogenesis of portal hypertension in hepatosplenic schistosomiasis. In addition, the relation between anatomic and hemodynamic alterations has not been adequately explained. In this study, vinylite casts of intrahepatic vessels of cadavers with hepatosplenic schistosomiasis were made and compared with those of cadavers with normal livers and with cirrhosis of the liver. Extensive distortion and obstruction of small portal branches was noted with hepatosplenic schistosomiasis mansoni. These lesions were especially marked in the periphery of the liver, and histological sections from the periphery frequently showed portal tracts in which the portal vein branches were occluded or apparently absent. The rich network of anastamosing venules in the portal spaces was apparently derived from the peribiliary venous plexus. An increase in number and size of intrahepatic arterial branches was marked in cases of hepatosplenic schistosomiasis. Increased arterial supply explains the observed maintenance of normal hepatic blood flow in many patients with this disease. Although the cause of portal hypertension is evident, the pathogenesis of Symmers' clay-pipestem fibrosis of the liver is not. The nearly constant association of Symmers' fibrosis and portal hypertension in schistosomiasis indicates a common, or interrelated, pathogenesis for the obstructive lesions and Symmers' fibrosis.

Resumen Se refiere en detalle un caso de “rat-bite disease” (enfermedad producida por la mordedura de ratas; denominada “Sodoku” por los japoneses). Se trata de un nino de tres meses y medio de edad. El dia 13 de octubre del 1923 noto la madre una herida sobre el ojo izquierdo. Debido a la abundancia de ratas en el lugar supuso seguido que una rata lo habia mordido. El nino parecia estar bien y la herida aparentemente empezo a sanar pero dos semanas despues aparecio un enrojecimiento acompanado de hinchazon en la region de la herida. Se llevo a un consultorio endonde se practico una incision pero no se observo ningun pus. La temperatura era de 103°F (39.5°C). La incision cerro bien pero 28 dias despues (nov. 10) la temperatura subio a 101°F. (38.2°C.) Dos dias despues el paciente presento una erupcion del tronco y las extremidades. El ojo izquierdo aparecia cerrado por la hinchazon que se extendia como 5 cm. en todas direcciones. Una de las glandulas linfaticas de la region auricular anterior presentaba induracion y tamano de 1 cm. Cuatro glandulas mas se hacian palpables al lado izquierdo debajo del agulo de la quijada. El higado y el bazo se hacian palpables, el primero 5 cm., y el segundo 3 cm., por debajo del reborde del margen costal. Nuevo examen en noviembre 12 demostro: Temp. 101°F. (38.2°C.). Conteo globular blanco 12,600. Conteo diferencial 38 porciento polimorfonucleares y 68 porciento linfocitos. Globulos rojos normales. Puncion del contenido del area edematosa y de las glandulas afectadas con tenido Giemsa, dio negativo microscopicamente. Wasserman negativo. El 20 de noviembre, un dia despues del segundo paroxismo se obtuvieron aproximadamente 5 cc. de sangre la que fue diluida en una solucion al 2 perciento de citrato de sodio. Tres cuartos de hora despues se inyecto esta sangre en el peritoneo de tres ratones blancos y dos conejillos. La sangre fui examinada muy cuidadosamente al ultra-microscopio para espiroquetos. Este examen y muestras tenidas al metodo Giemsa resultaron negativos. El 5 de diciembre, 15 dias despues, todos los animales temian espiroquetos en la sangre. La morfolgia de este espiroqueto es identica con la ya descrita por Futaki y colaboradores.

Summary The reasons for trying tartar emetic in clonorchiasis, the various methods of preparation of the drug, dosage, administration, the untoward effects, precautions to be observed and the results obtained by others in the treatment of schistosomiasis have been dealth with. Application of the treatment to three cases of clonorchiasis has been described and full reports of the cases are appended. Treatment with tartar emetic alone appears to have been completely successful in 1 case of clonorchiasis and to have failed in 2 others. One of these cases was apparently cured by a course of tartar emetic followed by a few small doses of arsphenamine. Trial of this method in the third case was unavoidably interrupted. No change in the appearance of the ova was observed. They did not shrivel or turn black as do the ova of the Schistosoma when tartar emetic is used. Other points of interest in connection with the cases have been touched upon.

Parasitologic, serologic, pathologic, biochemical, and clinical studies were conducted in 15 chimpanzees exposed to Schistosoma japonicum cercariae. Numerous viable eggs were passed in the feces after a prepatent period of 5 to 8 weeks. Worm recoveries at autopsy varied considerably, but not evidence was found of a reduction in worm burdens with infections up to 17 months' duration. No consistent difference was observed in the percent recovery and location of worms in animals exposed only once or in those exposed repeatedly. Most eggs in tissues were found in the liver and large intestine, but numerous eggs were also present in the small intestine and lungs of heavily infected animals. Nearly normal hepatic blood flow was maintained via the hepatic artery even in animals with completely obstructed intrahepatic portal branches. Well-developed portasystemic collateral venous channels effectively decompressed the portal system. Hepatomegaly and severe portal fibrosis were common gross findings; variable degrees of pipe-stem fibrosis consistent with infection intensity were found. The development of pipe-stem fibrosis was particularly rapid and destructive, and hepatic lesions were more inflammatory and polymorphous with S. japonicum than has been reported with Schistosoma mansoni. Marked intestinal lesions were present in a variable and patchy segmental distribution. Glomerular lesions occurred in most chimpanzees with pipe-stem fibrosis, and the prothrombin time was abnormal in several of the more severely diseased animals. Marked hypoalbuminemia and hypergammaglobulinemia were frequent. Hypoglycemia and uremia appeared to be important factors in some infected animals. The chimpanzee was a particularly valuable model for studies on the pathogenesis of schistosomiasis japonica.

Summary The results of treating 6 cases of clonorchiasis are discussed and compared. The first 3 cases were more fully reported in an earlier paper. Details of the others are appended. Four of the 6 cases appear to have been cured. In favor of this view are the following facts: 1. Rapid disappearance of the ova from the feces during a course of medication when previously the ova had been found with considerable regularity. 2. Repeated negative results of the examination of concentrated specimens of feces during a period of a month or more before discharge from the hospital. Case 6 was an exception to the extent that a single ovum, which showed well-marked signs of degeneration, was seen ten days before discharge. 3. Repeated negative examinations during a period of another month at the United States Immigration Station in East Boston where this work was skilfully handled under the direction of Dr. Albert J. Nute of the United States Public Health Service. In 2 cases disappearance of the ova took place during a course of intravenous injections of tartar emetic alone. In 1 case the ova disappeared suddenly after the intravenous use of a few doses of arsphenamin which had been preceded by an intensive course of tartar emetic. In another case a like result occurred after a few doses of tartar emetic which had been preceded by an intensive course of sulph-arsphenamin intramuscularly. The facts seem to indicate, first, that both tartar emetic and arsphenamins are somewhat poisonous to Clonorchis; and, second, that it may be advantageous to give them in successive courses. For the treatment of clonorchiasis in the future it may prove desirable to administer an antimonial and an arsenical alternately, or in alternating intensive courses. Some of the newer antimonials, which seem to be less toxic than tartar emetic but equally potent medicinally, can probably be substituted advantageously for tartar emetic. Similarly, it might prove advantageous to use atoxyl or some other arsenical instead of arsphenamin. By some such modifications of method it seems likely that permanent cures can be more quickly and more surely attained. It seems not improbable that good results might have been obtained in the two cases in which treatment failed had there been opportunity to follow up with arsphenamin the intensive treatment with antimony which these patients received.

Detailed parasitologic, serologic, clinical, and pathologic observations of Schistosoma mansoni infections in the chimpanzee were made over a period of 3 years. Six animals were exposed once to 250, 1,000, or 2,000 cercariae and necropsy was performed after 7 to 36 months. Four other chimpanzees were exposed monthly to 100 or 250 cercariae and necropsy was performed 24 to 36 months after the first exposure. Viable eggs were found in the feces 6 to 8 weeks after exposure and without significant reduction in number for the duration of the experiment. Recovery of worms revealed no evidence of acquired immunity with time or repeated exposures. Although the relation of recovery of worms to fecal egg counts and tissue egg assays was variable, there was a direct relation between the severity of clinical and pathologic involvement and the magnitude of egg deposition in tissues. Pathologic changes in the liver of the chimpanzee were remarkably similar to those reported for heavily infected human beings. In one animal characteristic pipe-stem fibrosis and extensive portal-systemic collateral circulation developed, with esophageal varices. Fibrosis of distal portal fields occurred around granulomata and egg-related inflammatory infiltrates. In middle-sized and larger portal fields, stage 3 pipe-stem fibrosis was found to precede local egg deposition and is of uncertain pathogenesis. Severe pathology of the colon with extensive development of inflammatory pseudopolyps was also seen. These experimental infections in chimpanzees closely resembled Manson's schistosomiasis in man as regards the course of the disease and the number and location of worms and eggs.

Summary Systolic blood-pressures have been recorded for the two races of Guatemala; namely, the mixed Spanish-Indian and the pure Indian. The data have been compared with normal standards for North Americans at home, with similar data from Yucatan, and with blood-pressure levels from various other countries and various other races. It was thus determined that Guatemalan systolic blood-pressure levels average about 10 mm. lower than those of North Americans living in the United States of America and that the levels for Yucatecans occupy an intermediate position. The data were then discussed with reference to the possible influences of age, sex, race, weight and height, psychogenic influences, nutrition and diet, climate, season, and altitude. It is extremely difficult to evaluate the possible effects of so many variables. The following inferences were, therefore, drawn tentatively. The low systolic blood-pressures in Guatemala and in Yucatan seem to be more characteristic of the Indian population than of the Spanish-Indian mixed race. The low pressures seem not to be attributable to sex, weight or height, season or altitude, and perhaps not to climate. The low levels of systolic pressure may perhaps be caused by racial characteristics, slow tempo of life, and a possibly deficient diet. Data on diastolic pressure and on pulse-pressures have been presented. These indicate that diastolic pressures are nearer the standards for Americans in the United States of America than are the systolic pressures; the pulse-pressures tend to be correspondingly low.

Summary Review of the comparative pathology of the Hoeppli phenomenon shows that it is correlated with substantial egg loads, appears during the later part of the acute primary state of infection, arises around mature eggs, occurs selectively in organs with large egg loads and affects a fraction of eggs not exceeding 10 percent at any time. Immunofluorescent studies in Mastomys coucha show that the Hoeppli corona contains both egg antigen and fixed host globulin, and is therefore an antigen-antibody complex. Within the complex, there is a gradient of antigen-antibody concentration, with antibody excess in the periphery. The precipitate pursues a sequence of maturation and degradation concomitant with the evolution of the pseudotubercle, during which additional host and parasite components may be incorporated into it. The characteristics of the Hoeppli phenomenon in three schistosome species, its relationship to the in vitro circumoval precipitate, and to stellate precipitates in other granulomatous diseases are discussed, and it is postulated that the Hoeppli phenomenon is an auxiliary mechanism of antigen sequestration invoked by the heavily infected host when antigen production against certain egg fractions attains a critical concentration and ratio resulting in precipitation of an antigen-antibody complex in vivo.

Summary Data are presented which throw light on the frequency and source of such tropical diseases as are found commonly in Massachusetts. The incidence only is shown for tropical diseases less common or rare in Massachusetts. When interpreting the figures a distinction must be drawn between reportable diseases regarding which both state and hospital data are available and the diseases which are not reportable. Information about diseases not reportable was obtained only from the larger hospitals in or near Boston. Among the reportable diseases it seems very probable that amoebic dysentery and pellagra are decidedly more common than the figures indicate. The same doubtless is the case for the rarer diseases which are not reportable. The figures for all the diseases listed above should be regarded as minimal. It is a pleasure to express thanks particularly to the members of the Statistical Division of the Massachusetts State Department of Health and to the record-room personnel of the hospitals for cordial co-operation and assistance in obtaining the data desired. Grateful acknowledgments are extended to the authorities of the hospitals listed below for permission to examine and to make use of their records. Boston City Hospital Carney Hospital Massachusetts General Hospital Massachusetts Homeopathic Hospital Peter Bent Brigham Hospital United States Marine Hospital United States Naval Hospital

My part in this Symposium on Vitamin Deficiencies is limited to the clinical manifestations of B1 hypovitaminosis. Beri-beri has long been regarded as the classical example of B1 hypovitaminosis. It would, therefore, be logical to discuss the prominent groups of symptoms associated with beri-beri. But, because it is difficult, even under experimental conditions, to exclude a single ingredient from the diet of man and, at the same time, to supply all other necessary food factors in abundance, it is to be expected, in any particular case of beri-beri, that the conditions which have caused this syndrome have also brought about more or less deficiency of substances other than B1. Therefore, it cannot be confidently asserted that all the symptoms which occur commonly in beri-beri are due to lack of vitamin B1. Still less is it possible to be sure that symptoms of less regular occurrence in beri-beri are attributable to lack of vitamin B1.

Summary A technique for the quantitative recovery of S. mansoni from human cadavers was presented. Analysis of the data from 197 autopsies indicated that nearly all worm pairs were recovered. The procedure is moderately time-consuming but not difficult, and can be performed with simple equipment and with little interference in the autopsy routine. Evidence of heavy infection was most common in cases of Symmers' clay-pipestem fibrosis of the liver. In over half of untreated cases of Symmers' fibrosis there were more than 160 worm pairs, whereas in only half of those without Symmers' fibrosis were there more than 10 worm pairs. It is postulated that a heavy infection is a prerequisite for the development of Symmers' fibrosis. Schistosomal pulmonary arteritis and cor pulmonale, when present, were associated with Symmers' fibrosis. The only other gross evidence of disease attributable to S. mansoni infection was a single case of ulcerative colitis in a massively infected child (1,608 worm pairs). Cadavers with portal or postnecrotic cirrhosis had light infections. When Symmers' fibrosis was not present, liver and spleen weights were not increased, nor were they related to the intensity of infection. The number of eggs in the feces reflected the worm burden in the absence of Symmers' fibrosis, although there was great individual variation. In cases of Symmers' fibrosis, and apparently in those of cirrhosis, fewer eggs per worm pair were found in the feces than in other cases. This, together with the mixture of lightly and heavily infected instances of Symmers' fibrosis, would make difficult ante-mortem estimation of the intensity of infection. The number of eggs per gram of feces per worm pair did not change significantly with age or intensity of infection. Routine ante-mortem fecal examinations had been frequently positive in cadavers harboring fewer than 10 worm pairs. The number of eggs in the tissues was related to the intensity of infection, but showed changes related to age and worm burden. The number of tissue eggs per worm pair increased in older persons, but decreased with increasing intensity of infection; the latter apparently reflected more rapid destruction of eggs in the tissues in heavy infection. The distribution of worms did not vary greatly with age or intensity of infection. In cases of Symmers' fibrosis, and in those of cirrhosis, an increased proportion of worms and eggs was found in the small intestine, and there was a striking decrease in the proportion of eggs in the rectosigmoid colon, the most frequent site of oviposition in subjects without Symmers' fibrosis or cirrhosis. The ratio of male to female worms recovered was slightly greater than one and showed no change with age or intensity of infection. In rare instances, male worms only were recovered; in these, few worms were found, and a small number of dead eggs was generally found in the tissues, indicating previous bisexual infection. The post-mortem data suggest that light S. mansoni infections, including those of many years' duration, are of little consequence, although obviously they do not exclude the possibility that they produce significant disease not evident at autopsy.