The American Journal of Tropical Medicine and Hygiene - Volume 10, Issue 6, November 1961

An epidemic of malaria, covering about 100,000 square miles in four central provinces in the highlands of Ethiopia and portions of the highlands of five other provinces, was observed in Ethiopia between June and December of 1958. The altitudinal limits of the epidemic ranged approximately between 1,600 to 2,150 meters elevation, in which area the communal immunity of the habitants is low for the most part. The estimate of the number of malaria cases attributed to the epidemic is estimated to be not less than three million cases. Deaths from malaria may have exceeded 150,000.

Anopheles gambiae was the only vector involved. Plasmodium falciparum was the predominant malaria parasite. It accounted for the severe acute illness which characterized the clinical syndrome of most cases and the high mortality observed in many districts. Food shortages in 1958, due to 1957 crop failures in some areas, also indirectly contributed to high mortality.

The main precipitating cause of the 1958 epidemic appears to have been unusual weather conditions in the highland areas of Ethiopia. Rainfall exceeded all other previous years on record, and abnormally high atmospheric temperature and relative humidity prevailed.

In an effort to elucidate the state of immunity acquired by mice given curative treatment for a malaria infection, white mice infected with Plasmodium berghei were treated with primaquine diphosphate and subsequently exposed to various infectivity procedures for determining whether plasmodia had been completely eradicated or merely reduced to subpatent, chronic levels. Test of cure procedures included: (a) serial blood smears continuing at intervals for 5 weeks; (b) subinoculation of blood into recipients; (c) splenectomy of donors with subinoculation of spleens into recipient mice; and (d) sacrifice of donors with subinoculation of total organ content into recipients.

Blood examination was an adequate criterion for demonstrating radical cure in mice following primaquine therapy since all mice presumed cured on the basis of post-treatment blood smears failed to transmit the infection to recipients inoculated with their blood or organs. Splenectomy did not produce relapses in any of the cured mice.

An apparent attenuation of the infection was noted in recipients of blood and organs from treated animals.

One group of mice, with parasitemias on one or more occasions following therapy, apparently underwent spontaneous cure since they failed to transmit the infection to recipients by any infectivity procedure employed. Furthermore, splenectomy did not evoke relapses in these animals. Therefore, although serial blood smears taken after treatment are adequate for selection of mice uncured by drug therapy, the parasitemia state of such mice cannot be relied on for prognosticating the ultimate infection status of the animal and its consequent immune response to challenge infections.

In three experiments the character of the feces and the condition of the colon and cecum were observed in 34 young adult dogs that had been placed on either a normal or salmon diet and, after 2 weeks, either inoculated orally with cysts of Entamoeba histolytica or not inoculated.

During the 34 to 96 days of observation, most of the dogs lost weight, those on the salmon diet to a greater extent than the others. No signs of vitamin deficiencies were observed. Twelve dogs on normal diet passed normal stools and displayed no intestinal lesions not attributable to worms; one of nine inoculated with E. histolytica acquired infection.

After 5 to 29 days, among 22 dogs on salmon diet, 12 regularly passed blood and mucus in fluid, often dysenteric, stools. Five of these dogs had been inoculated with E. histolytica, seven had not. In two of the salmon-fed dogs the stools were consistently normal and the intestinal mucosa also appeared to be normal; in the others, the mucosa was in some degree hemorrhagic and friable, with masses of sloughed epithelial cells in the covering mucus. E. histolytica infection was demonstrated in 5 of 9 inoculated dogs, but pathological changes seen in the colon and cecum were essentially the same irrespective of amebic infection. Bloody stools and bowel lesions in some cases apparently were in part due to hookworms, and amebae might have contributed to some of the changes seen; in most instances, however, the salmon diet appeared to have provided the chief causative factor. Thus, the results from earlier studies of amebic colitis in salmon-fed dogs may require reinterpretation.

A method for the isolation and purification of two distinct complement fixing antigens from dried Trichinella spiralis was described. It consisted of an initial extraction with 0.15 M sodium chloride followed by fractionation with ethanol under conditions of controlled pH and ionic strength. Each antigen was purified further by physicochemical methods. The purified antigens, ethanol soluble (ES) and ethanol insoluble (EI), were shown to differ by their ultra-violet absorption spectra, in serologic tests, and by absorption studies.

The ES and EI antigens were evaluated in complement fixation tests against sera from both trichinella and non-trichinella infections. The ES antigen was shown to be quite specific for trichinosis. The EI antigen, on the other hand, lacked specificity, but proved to be extremely sensitive for the detection of trichinosis. The use of both antigens was suggested for the diagnosis of trichinosis in complement fixation tests. Evidence for cross-reactivity between trichinella antisera and typhoid antigens was shown with agglutination reactions.

The chemical structure of the ethanol soluble (ES) and ethanol insoluble (EI) antigens isolated from Trichinella spiralis larvae was determined. The ES antigen was found to be a glycoprotein averaging 75% protein and 15% carbohydrate. The polysaccharide consisted entirely of glucose units. The EI antigen, on the other hand, was found to be a nucleoprotein averaging 60% nucleic acid and 14% protein. The nucleic acid portion analyzed to be deoxyribonucleic acid. Studies on the enzymatic breakdown of the antigenic substances inferred that the protein portion of each antigen was needed for activity in complement fixation tests.

A case of splenic granulomata in a male Chinese in Thailand is described. The lesion is believed to be caused by microfilariae of Wucheria bancrofti. It is assumed that the granulomatous process occurred as the microfilariae migrated out of the vascular channels and were destroyed in the spleen. The low incidence of the observed lesion is probably due to the reversibility of the process.

Nine patients with filarial lymphoedema or elephantiasis were investigated by lymphangiography. In Kenya x-ray lymphangiograms made in patients with filarial lymphoedema show a typical pattern of varicosities which clearly differentiate this condition from lymphostatic verrucosis, the prevalent form of non-filarial lymphoedema. Microfilariae are absent from the blood even when there is no obstruction to the flow of lymph in the affected leg. In advanced cases there is total obliteration of the lymphatic system of the leg.

Prednisone in ordinary dosage has been found to increase significantly the number of Wuchereria bancrofti microfilariae that persist in the night blood during treatment with diethylcarbamazine. This effect ceases when the prednisone is discontinued. The implications of this on theories concerning host-parasite relationships in filariasis and the microfilaricidal action of diethylcarbamazine are discussed.

The anthelmintic effect of the phloroglucinol derivative desaspidin in the treatment of fish tapeworm (Diphyllobothrium latum) infection was studied. The drug was used in doses of 200 and 400 mg. Thirty grams of castor oil emulsion was given as a purgative. The 200 mg dose of desaspidin was effective. A total of 2,368 persons received treatment. A significant side effect was observed in only one subject.

Observations have been made on the protective mechanisms which appear to be involved in conferring a high degree of acquired resistance on Macaca mulatta within 2 years after initial exposure to Schistosoma mansoni. It has been shown that the resistant monkey develops marked cellular responses in the skin and lung during transit of schistosomula, and that many of these larvae are trapped and destroyed in the lung, where they elicit inflammatory foci of distinctive morphology which are described here in detail and named “tuft-like foci”. Both the skin and the lung reactions of the resistant monkey are indicative of hypersensitivity, but only the latter appears to retain schistosomula in considerable number. In spite of lung trapping, a considerable proportion of infective larvae survives the lung stage and reaches the hepatic portal blood, but these parasites are stunted and die within 60 days after challenge without further cellular reaction except that which occurs after their death in the liver. Circumlarval precipitates were not seen around any of the multiple trapped larvae examined. The findings are discussed in the light of the literature, and it is suggested, as a working hypothesis, that (a) both humoral and cellular factors are involved in acquired resistance and (b) schistosomes may be capable of partially blocking host antibodies, possibly through absorptive control.

Several factors may be involved in the pathogenesis of hepato-splenic schistosomiasis mansoni, but their relative importance has not been convincingly demonstrated. It has been postulated that malnutrition, toxic products of worms, dead worms, eggs produced by the worms or any combination of these factors may be the cause of this disease. Studies of this problem in the past have been hampered by the lack of a suitable experimental animal. Recently, the occurrence in mice of a syndrome resembling hepato-splenic schistosomiasis in humans has been reported. With the development of this syndrome in mice used as a criterion of significant disease, the effect of each of the above factors was studied. On the basis of the results obtained it is felt that eggs are the prime factor in the development of hepato-splenic schistosomiasis in the mouse, that toxins produced by the worms or an allergic reaction to their presence may be a contributing factor in the early stages, and that dead worms and malnutrition are probably only of ancillary importance.

The first known case of cervico-facial actinomycosis on the Isthmus of Panama was confirmed by recovery of the organism Actinomyces bovis.

The fungus was found to be sensitive to penicillin and oxytetracycline and the patient made an uneventful recovery.

Young adult rats given a combined infection with Trichinella spiralis and encephalomyocarditis (EMC) virus experienced a high incidence of crippling and death while control rats which received the nematode alone remained free of disease. Rats given the virus alone had a much lower incidence of crippling than did those with the combined infection.

Rats which received T. spiralis and EMC virus were also distinguishable by a sharp and sustained loss of weight, presence of virus in skeletal muscle and by some differences in muscle histology.

The synergistic effect of T. spiralis on EMC virus infection was demonstrable over a period of 10 to 28 days after inoculation with the nematode.

The results of this inquiry indicated that illnesses reported as encephalitis to health departments in the Central Valley of California covered a broad spectrum of syndromes ranging from frank severe encephalitis to mild meningitic illness with no definite signs of cerebral involvement. Of 153 illnesses observed during three consecutive summers and recorded as cases of encephalitis in official morbidity records, unequivocal encephalitic manifestations were noted in approximately 30%, and borderline encephalitic signs in an additional 22%. In the entire group of reported encephalitis cases, group B Coxsackie virus and WEE virus infections were encountered with equal frequency, although each virus was associated with only 14% of the cases. Mumps, ECHO, SLE, and herpes simplex viruses, in declining order of frequency, were each associated with a lesser number of illnesses, but in 40% of the cases no viral infection was established. When only the illnesses classified unequivocally as encephalitis were considered, however, the proportion attributed to WEE virus increased to 35%; Coxsackie virus infection was associated with 13%, and other virus infections were encountered in less than 10% of the cases. In the cases of doubtful encephalitis, the mumps virus was implicated most frequently (25%) followed by Coxsackie B virus (11%), WEE virus (8%), and SLE virus (3%). In illnesses classified as aseptic meningitis with no signs of encephalitic involvement, group B Coxsackie and polioviruses were the agents most frequently encountered (each in 16%) followed by ECHO (10%), mumps (7%) and WEE (4%). In each clinical category, no viral infection was established in 35 to 45% of the cases. There was appreciable variation in these proportions from year to year, but in each year the arthropod-borne viruses, WEE and SLE together, were implicated most often in cases classified as frank encephalitis, and Coxsackie group B viruses equaled or exceeded the mumps virus in such illnesses. Of the other enteroviruses, an ECHO virus (type undetermined) was associated in only one instance, and poliovirus not at all, with frank encephalitis. Inasmuch as the role of group B Coxsackie viruses as causal agents of aseptic meningitis is well established,7,9 the association of these viruses with 12 to 19% of such illnesses each year is believed to be a reasonable approximation of their relative etiologic importance in the endemic occurrence of this syndrome in the particular localities and seasons represented in this study.

While the frank encephalitic illness observed in association with group B Coxsackie viruses in this study could reflect the occurrence of coincidental infections in persons whose illness was due to other unrecognized causes, the probability of an etiologic association may be supported on several grounds: (1) the frequency of association of group B Coxsackie viruses with encephalitic illness equaled or exceeded that of other commonly recognized encephalitogenic viruses including mumps and herpes simplex, and was exceeded only by WEE virus; (2) the consistency of such association over three consecutive summer periods; (3) the lack of a similar association of poliovirus or ECHO viruses with encephalitis, although both of the latter were associated with other illnesses in the areas under study and could have been present in coincidental alimentary infections; (4) the occurrence of rises in titer of neutralising antibody to Coxsackie virus, indicating a temporal relationship of the infection to the encephalitic illness; and (5) the concentration in infants and young children of encephalitic illness associated with Coxsackie viruses.

It appears reasonable to conclude that perhaps 10 to 15% or more of the incidence of summer illnesses reported as encephalitis from the California Central Valley in recent years may have been attributable to Coxsackie group B viruses. Although the majority of the reported cases of encephalitis found to be associated with a Coxsackie virus infection could more appropriately be classified as an aseptic meningitis syndrome, group B Coxsackie viruses may also have accounted for possibly 10 to 15% of the frank encephalitic illnesses. Poliovirus and ECHO viruses were also implicated in about 15% of the cases reported as encephalitis, but on review these cases were almost uniformly classified clinically as aseptic meningitis or doubtful encephalitis. Despite the implication of enteroviruses in over one-fourth of the cases of reported encephalitis, there still remained roughly one-fourth of the cases in which both virus isolation attempts and serologic tests failed to establish a possible viral etiology.

Mosquito pool suspensions were inoculated in parallel into embryonated hens' eggs, mice, chick embryo tissue cultures and hamster kidney tissue cultures for a comparison of the sensitivity of these four host systems for the isolation of St. Louis encephalitis, Western equine encephalomyelitis and Turlock viruses. Mice and hamster kidney tissue cultures were the most sensitive hosts for the recovery of SLE virus, and approximately the same number of isolates were recovered in each of these systems. Embryonated eggs were slightly more sensitive than the other three host systems for the isolation of WEE virus. The only satisfactory host system for the isolation of Turlock virus from the mosquito pools tested was the embryonated egg.

The facility of identification of the isolates in the different host systems is discussed.

Under the conditions of tropical rain forest and secondary forest in Liberia it was found that surveys of the tsetse fly Glossina palpalis, the vector of Gambian sleeping sickness, could be more efficiently carried out by traps than by the conventional method of hand catching with fly-collectors.

Unbaited traps, 2 feet high and 2 feet long, covered with natural burlap, were adopted because they gave a uniform rate of sampling. Traps twice as large caught more tsetse but were difficult to standardize. Folding traps, more easily carried than the rigid standard type, were equally effective in a short trial.

In direct comparisons, four traps caught as well as two collectors in low densities of G. palpalis, with a marked superiority during the dry season, when their catches gave a truer index of the numbers of tsetse present. In high densities of this species, traps gave a better performance than men, since their rate of catching was unaffected by the numbers of tsetse to be caught. It is economical to employ traps, but not men, for detecting flies at very low densities.

Traps can be used to measure the factor “man-fly contact.” Comparability requires a standard procedure in visiting traps. The catches obtained with daily visits are nearly doubled with visits twice a day, and fall to 70% with visits on alternate days and to below 40% when visited twice a week. These differences are due both to the escape of flies between visits and to the attraction of tsetse to the traps by hosts each time a trap is visited.

These traps could be used also for surveys of tabanids and other insects.

A case of cholera with acute tubular necrosis and metabolic alkalosis is reported. The etiology and mechanisms of metabolic alkalosis are discussed.

In Thailand, bladder stone is a highly endemic disease in children in two of four distinct geographic regions of the country, the North and Northeast. Vesical stones occur early in life; a median age of 5 years has been reported in Ubon Province, and they are seen 8 times more frequently in males than in females. Preliminary observations suggest that bladder stones are more common in rural than in urban areas and that recurrence rates are low (less than 1%). No adequate hypothesis for the pathogenesis of bladder stone exists, although extended observations of this condition in Thailand and elsewhere strongly implicate a deficiency or excess of some human nutritional factor(s). The early age of onset of bladder stone suggests the possibility of the transmission of a lithogenic factor in human milk. This hypothesis may serve as a departure for the additional epidemiological and clinical studies which are needed to clarify our understanding of this problem.

Listeriosis, by Privatdozent Dr. med. H. P. R. Seeliger, Hygiene - Institut, Rhenische Friedrich - Wilhelms - Universität, Bonn Rh. (Germany; foreword by Dr. Dr. h. c. K. F. Meyer, Hooper Foundation for Medical Research, San Francisco, California; with an introduction to the 2nd German edition by Prof. Dr. Dr. H. Eyer, o. ö. Professor für Hygiene und Medizinische Mikrobiologie, Max v. Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie der Ludwig-Maximilians - Universität, München (Germany). 308 pages, illustrated (67 illustrations, 5 of them colored). New York, Hafner Publishing Company, Inc., 1961. $14.25.

The Chemotherapy of Tropical Diseases, by Sit Philip Manson - Bahr, M.D., F.R.C.P, D.T.M.&H. (Cantab), Consulting Physician to the Hospital for Tropical Diseases, London, and John H. Walters, M.D., F.R.C.P., Lt. Colonel I.M.S. (ret.), Physician, The Hospital for Tropical Diseases, London.

This text has become a classic reference in tropical medicine in the English language. It was first published in 1898 and the present 15th edition by Sir Philip H. Manson-Bahr is the ninth in his experience with this book. The previous edition appeared in 1954 and in the interval between then and the present edition considerable progress has been made in a number of clinical areas in the field of parasitism and tropical medicine, particularly the anemias, leprosy, insecticides and chemotherapy. In these various areas major revisions and additions have been incorporated in the text and the previous material which has been basically excellent has been revised wherever indicated. The table of drugs, particularly in Chapter LIII, is extremely up to date and a very valuable and convenient reference. The sections on Medical Zoology in the Appendix contains more than 200 pages and can easily serve as a useful text in medical parasitology, including entomology, for students.