The American Journal of Tropical Medicine and Hygiene - Volume 24, Issue 4, 1975

The three members of this year's Craig Lecture Committee were spaced as widely apart as national geography allows: Dr. von Lichtenberg in Boston, Dr. Schwartzwelder in New Orleans, and myself in Honolulu. It was then by a process that can be described as postal triangulation that we navigated to today's speaker, Dr. Leonardo J. Mata. It is, I believe, a tribute to Dr. Mata's excellence that the unanimous nomination of a Craig Lecturer associated with the field of nutrition was made by a committee composed entirely of self-confessed medical parasitologists. Perhaps this was a response to the dietary etymological roots of our calling but, more importantly, it reflects the concern of all of us with one of the great issues of our times, the starvation of the poor peoples of the tropical world.

Mr. President Dr. Rozeboom, Officers and Members of the Society, ladies and gentlemen:

I begin with a word of appreciation to Dr. Desowitz and Members of the Charles Franklin Craig Lectureship Committee for having invited me to speak on the problem of malnutrition and infection in the less developed areas of the world. I accept this invitation because it gives me an opportunity to express to this distinguished Society some views on the nature and origin of malnutrition and infection interactions in the poor nations of the world.

Countries can be divided into the highly industrialized and the less developed or preindustrial. The industrialized societies generally have larger natural resources, better developed science and technology, efficient food production and higher levels of education and health than the less developed nations. There is evidence to indicate that the gap is widening.

Biological factors have had more emphasis than socioeconomic factors in attempted derivation of causality in health problems in tropics and subtropics.

Amodiaquine cured 38% (13/34) of patients with falciparum malaria in Southeast Thailand. Chloroquine cured 0% (0/13). The cure rates with amodiaquine were the same whether a 1.5 g or 2.0 g course was used. Most patients were resistant to amodiaquine at the RI level and to chloroquine at the RII level. In hospital, amodiaquine cleared parasitemia more frequently than did chloroquine. With the 2.0 g course of amodiaquine, the parasite clearance time was 77 hours; the fever clearance time of 36 hours was low and suggests that amodiaquine does not cause a drug fever. Because of resistance, chloroquine should not be used for falciparum malaria in Thailand. Routine use of amodiaquine is not indicated because more effective drugs are available.

During field studies carried out in 1971, 1972 and 1973 in a highly malarious coastal area of El Salvador, it was possible to collect information on the patterns of Plasmodium vivax parasite occurrence in a large number of infected individuals. In most of the persons who had experienced a marlaria attack during the high transmission period in June, July, August and September, renewed activity occurred 5 to 8 months later, during the low transmission season the next year. Subsequent activity in these same cases occurred after intervals of about 4 to 9 weeks in duration. On epidemiologic grounds, and on the basis of the life patterns of the El Salvador P. vivax strains demonstrated in previous studies in volunteers, this renewal of activity probably represents the occurrence of relapses rather than new infections. This pattern is similar to the “temperate zone” strains of P. vivax, where initial relapses occur after prolonged periods, followed by subsequent relapses after much shorter intervals of inactivity. This type of relapse pattern in a tropical area may enhance the survival of the parasite through a prolonged period of vector inactivity, such as the long dry season experienced in El Salvador.

A slide flocculation test for Chagas' disease is described, which uses a lyophilized, stable antigen obtained by formalin and ultrasonic treatment of culture forms of Trypanosoma cruzi. The test was compared with other tests for the serodiagnosis of American trypanosomiasis and showed a high sensitivity, positive results being obtained in every case of acute or chronic Chagas' disease. In sera from blood donors and from normal individuals with negative T. cruzi antigen complement fixation tests a specificity of 96% was found. False positive flocculation tests were seen, especially in cases of South American blastomycosis and in a few cases of acute toxoplasmosis. Since it is easy and quick to perform, the slide flocculation test can be recommended as a screening procedure, especially for blood banks.

The prevalence of protozoan and helminth parasites of the intestinal tract in a Papua New Guinea island with a population of 16,800 was assessed by surveys of a series of randomly selected villages. There were significant differences in the severity of infection with these parasites between the two linguistic groups inhabiting the eastern and western halves of the island. Blood examinations for malaria and microfilariae also differed. It is thought that these differences reflect obscure microenvironmental factors in what would appear to be an epidemiologically homogeneous population.

A gravid female nematode was found in histopathologic sections of an appendix in a postmortem examination. This parasite was identified as Rictularia, a genus of small intestinal parasites in numerous mammals. The parasites of this genus have not previously been identified in man.

In a controlled field trial of treatment for dracontiasis, mebendazole (Vermox®) was found to be effective in eliminating the adult worm and preventing clinical relapses, but it did not achieve significant amelioration of symptoms, subsidence of inflammation, or healing of ulcers. The failure is attributed to poor absorption and lack of anti-inflammatory action of the drug. Mebendazole was well tolerated and although two patients reported mild gastro-intestinal disturbances, which may be attributed to the drug, the study confirms that mebendazole is one of the safest anthelmintics in current use and is in that respect ideal for mass therapy.

Four species of primates, baboon (Papio anubis), patas monkey (Erythrocebus patas), green monkey (Cercopithecus aethiops) and chimpanzee (Pan troglodytes) were inoculated with third-stage larvae of a human strain of Loa loa from Cameroon, West Africa. The baboon and patas monkeys developed patent infections after 135 to 148 days; the green monkeys and chimpanzee did not. In each animal which became patent, microfilaremia rose rapidly to high levels. In the baboon, but not in the patas monkeys, there was a suppression of microfilaremia during the 4th month of patency. After splenectomy, microfilariae reappeared in the peripheral blood in large numbers. In both baboon and patas monkeys, the microfilariae of Loa loa maintain the diurnal periodicity so characteristic of their behavior in man.

Chrysops atlanticus, an American species of deerfly collected along the Missisippi Gulf Coast, will support the development of the microfilaria of human Loa loa to the infective stage. Development takes place in the fat body of the fly and requires 9 to 10 days in flies maintained at a temperature of 80°F and 60% to 80% relative humidity. The site of development and pattern of morphogenesis of the parasite in C. atlanticus is virtually identical to that described in natural African vectors. Chrysops atlanticus will support the development of large numbers of L. loa to the infective stage without apparent ill effects. Two uninfected patas monkeys each were given 75 third-stage larvae obtained from experimentally infected C. atlanticus. Both animals developed patent infections in approximately 5 months, clearly demonstrating that the entire life cycle of Loa loa can be maintained in the laboratory outside endemic areas.

The association of Schistosoma mansoni infection and proteinuria was investigated by measuring quantitative urinary protein in a defined population in an endemic area in northeastern Brazil. Persons with schistosomiasis had higher mean urinary protein than those without. Two of 162 persons with schistosomiasis had clear evidence of renal disease (pathologic proteinuria, abnormal urinary sediment). These results seemed to be related neither to the intensity of S. mansoni infection as measured by fecal egg excretion nor to the presence of hepatic and splenic enlargement in schistosomiasis.

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.

The development of anti-immunoglobulin (Ig) antibodies in rhesus monkeys repeatedly exposed to Schistosoma japonicum cercariae was studied. Anti-Ig developed in all 8 monkeys exposed 5 times to cercariae of the Formosan strain, while none of 4 monkeys exposed once to the Philippine strain developed such antibodies in the same period. All monkeys developing anti-Ig had specificities for IgA, 6 of 8 for IgM and IgG, and 7 of 8 for rabbit Ig. The persistence of anti-Ig was greatly extended in the monkeys exposed initially to the Formosan strain and then challenged with the Philippine strain. A single monkey exposed once to the Philippine strain developed anti-IgA and anti-rabbit Ig 85 weeks post-infection. No relationship between host reaction to trapped eggs and the development of anti-Ig was discerned. The results suggest that immunization protocols designed for humans be carefully examined for their potential immunopathological side effects.

The first confirmed case of Vibrio parahaemolyticus gastroenteitis in Panamá is reported. This marine organism, causing food poisoning in some countries and isolated only recently from seawater in Panamá, was recovered from the stools of a patient with acute gastroenteritis, as well as from fresh shrimp used in preparing seafood dishes. This person and 39 other individuals became acutely ill a few hours after eating shrimp at the same restaurant.

A group of South Indian subjects was studied for their capacities to acetylate sulfamethazine (SMZ) and dapsone (DDS) and to clear DDS from the circulation. An apparent trimodal distribution of acetylator phenotypes was found in 49 subjects (51% slow, 12% intermediate, and 37% rapid acetylators) from measurements of the percentage acetylation of SMZ in 6-hour plasma samples after administration of 10 mg SMZ/kg. The intermediate phenotype was not discernible from either the percentage acetylation of SMZ in urine (collected concurrently with the plasma after SMZ) or that of DDS in plasma after the ingestion of 50 mg DDS by the same subjects. The latter two measurements yielded a biomdal distribution of 59% slow and 41% rapid acetylators, nearly identical to earlier reported distributions of isoniazid inactivator phenotypes in larger numbers of South Indian tuberculosis patients. In the current group, acetylation of DDS and SMZ was positively correlated. The half-time of disappearance (T½) of DDS, an expression of the rate of clearance from the plasma, ranged from 13 to 40 hours. No correlation was found between the subject's capacity to acetylate DDS and the T½ value for DDS. These results were generally consistent with earlier observations made during similar studies of American and Filipino subjects.

To test whether herpetofauna could be a laboratory model for Mycobacterium ulcerans, 21 anole lizards were inoculated subcutaneously with viable M. ulcerans, 21 with autoclaved organisms, and 14 with an aqueous solution of 0.01% Tween 80. M. ulcerans was recovered in culture from the slowly progressive lesions which developed at the inoculation site in lizerds receiving the viable bacteria. Progressive lesions did not occur in the two control groups. Three patterns of inflammatory response to viable M. ulcerans were observed: 14 lizards developed a diffuse, granulomatous reaction in which acid fast bacilli (AFB) were predominantly intracellular; 1 developed focal, encapsulated granulomas; 5 developed a diffuse, necrotizing granulomatous response in which most AFB were extracellular—similar to the characteristic lesion found in human infections.

Sixty-two volunteers were studied to determine their local cutaneous, serologic, and virologic reactions to smallpox revaccination. Of 55 subjects available for examination, 45 (82%) had major cutaneous reactions. Subjects over 30 years old were more likely to have a major reaction. An increase in complement-fixing antibody titer was found in 74% of revaccinees with a major cutaneous reaction and is felt to be the best serologic indicator of a successful revaccination. Cultures of urine and thoat swab in eight subjects after revaccination did not yield vaccinia virus. Cultures of the vaccination site demonstrated the virus to be present for a mean of 7.8 days (range 0–18 days) which coincided with separation of the vaccination scab from the skin. Presence of virus at the vaccination site did not correlate with antibody response. However, subjects vaccinated more than 3 years previously and subjects with major skin reactions shed vaccinia virus for longer periods than those vaccinated less than 3 years previously or who had equivocal reactions.

Plaque reduction neutralization tests, using five group A arboviruses (chikungunya, Ross River, Getah, Bebaru and Sindbis), were done on sera from human populations in 44 Southeast Asia and Pacific island localities. Specificity of the plaque neutralization test was determined by examining convalescent sera from patients with known alphavirus infections. Chikungunya-specific neutralizing antibodies were demonstrated in sera of persons living in South Vietnam, Northern Malaysia, Indonesia (Kalimantan and Sulawesi), as well as Luzon, Marinduque, Cebu and Mindanao islands in the Philippines. Evidence of Ross River virus infection was found among populations living in West New Guinea and Papua New Guinea mainland, the Bismark Archipelago, Rossel Island and the Solomon Islands. There appeared to be no geographic overlap in the distribution of chikungunya and Ross River viruses, with the separation in their distribution corresponding with Weber's line in the Pacific. Sindbis neutralizing antibodies were found in 7 of 21 populations sampled, but in general the prevalence of infection was low. Four sera, from Vietnam, Malaysia and Mindanao gave monospecific reactions with Getah virus. No evidence of specific Bebaru virus infection was detected. The epidemiology of these five alphaviruses in Southeast Asia and the Pacific islands is discussed.

California encephalitis (CE) virus (snowshoe hare subtype) was isolated from 1 of 38 pools comprising 970 unengorged female Aedes canadensis mosquitoes and from 3 of 152 pools containing 5,676 A. communis mosquitoes which were collected in the Yukon Territory, Canada between latitudes 61 and 66° N during June and July 1974. During four summers 1971 through 1974, this virus was recovered from 26 of 648 pools derived from 30,686 mosquitoes of 4 species. Isolation of CE virus from 1 of 109 pools of Aedes sp. larvae collected during May 1974 suggests maintenance of this virus over winter by transovarial transfer. Infectivity has been maintained in Culiseta inornata mosquitoes which were held continuously at 32° F for 138 days. Neutralizing antibodies to CE virus were detected in 705 of 4,913 (14%) mammals collected during summers 1971 through 1974, including 430 of 1,076 (40%) snowshoe hares (Lepus americanus), 266 of 3,610 (7%) ground squirrels (Citellus undulatus) and 9 of 227 (4%) red squirrels (Tamiasciurus hudsonicus).

The frequency and distribution of La Crosse (LAC) virus overwintering in Aedes triseriatus diapause eggs were studied during 1974 by following 64 tree-hole oviposition sites in four enzootic hardwood forest areas. A direct fluorescent antibody technique, adapted for detection of LAC virus in individual mosquitoes, proved to be a rapid, reliable and economical tool for ascertaining true field infection rates. Virus was found in larvae from each of the four study areas before the seasonal emergence of adults and detected in 10 (0.6%) of 1,698 individually processed adults reared from collected larvae. In one of these study areas, all 12 located tree-holes were enclosed with screen before the seasonal emergence of adults, to ensure that all collected from these sites originated from overwintered eggs. Of 1,280 Aedes triseriatus processed from this area throughout the season, 16 (1.2%) contained virus. Isolates were found in overwintered Aedes triseriatus throughout the summer months, demonstrating the role of these tree-hole sites as foci for both overwintering and continuing summer season source of LAC virus in these forested areas.

Eight patients with acute renal failure following snakebite were studied. Intravascular hemolysis and disseminated intravascular coagulation contributed to the development of acute renal failure in 6 patients. Direct nephrotoxicity causing acute renal failure is postulated in 2 patients, 1 of whom also revealed evidence of mild, disseminated intravascular coagulation. Three patients had histopathological lesions of acute symmetrical cortical necrosis and 3 had acute tubular necrosis. In 1 patient with acute tubular necrosis, in whom direct nephrotoxicity seemed to be responsible for renal failure, the striking histological feature was a uniform debasement and disappearance of tubular epithelium. In 2 patients with a clinical course of acute tubular necrosis, histological lesions could not be documented. All the 5 patients with acute tubular necrosis regained full recovery of renal function, 3 of them with the help of dialysis and 2 with conservative management. None of the 3 patients with acute cortical necrosis survived in spite of intermittent dialysis therapy.

Larvae of a field strain of Culex tarsalis Coq. manifesting a broad spectrum of resistance to organophosphorus (OP) insecticides were selected further by methyl parathion pressure in the laboratory. There was a 6.9× further increase in resistance to methyl parathion in larvae, i.e., from a 13.4× level of resistance in the parental strain to 93.5× level in the F11 generation. With the exception of fenthion and malathion, cross resistance in larvae toward other OP insecticides increased from 1.1- to 8.7-fold over the levels of resistance in the parental strain. The F11 larval population exhibited high levels of cross-resistance to chlorpyrifos (29.6×), fenitrothion (49.4×), parathion (55.6×), fenthion (76.8×), and chlorpyrifos-methyl (253.8×). The high levels and broad spectrum of resistance to diverse OP compounds suggest the involvement of more than one mechanism in resistance. Larval selection also affected the spectrum of OP resistance in adults. The F11 adult population exhibited high levels of resistance to dichlorvos (48×) and chlorpyrifos-methyl (40.1×). Both larvae and adults of the F11 population manifested no resistance to the carbamate insecticides propoxur, Mobam®, Landrin® or carbaryl, or to the chrysanthemate insecticide cismethrin. Resistance to the OP insecticides methyl parathion, parathion, fenitrothion, fenthion and chlorpyrifos-methyl was found to be fairly stable over nine generations in the absence of methyl parathion selection pressure.

Groups of mice were injected with Leishmania donovani strains Et (Burma) or 1S (Sudan) and the courses of infection were followed. Between days 20 and 30 after infection the liver parasite burdens decreased, and the numbers of amastigotes were further reduced by treatment with pentostam. Et- and 1S-recovered mice were challenged by intravenous injection of amastigotes of each strain. Although resistance to superinfection was apparent the L. donovani strains could not be differentiated by this method.

Eight out of 47 Bradypus griseus and 14 out of 18 Choloepus hoffmanni yielded positive cultures for flagellates from blood, skin, liver or spleen. In some cases, more than one species of flagellate was isolated from one animal or site. Although amastigotes were obtained in tissue cultures from several isolates containing different types of promastigotes, only four of these strains (two from each species of host) were infective for hamsters and considered as Leishmania braziliensis. Infection with one of the strains was possible only after it had been passed through tissue culture.

The occurrence of Onchocerca nodules in the Igbos of Nigeria was studied in a biopsy series. There were 90 cases in approximately 5,000 biopsies received in 4.5 years at a central laboratory. The prevalence of infection in males was 1.5 times that of females. The two youngest patients were both aged 3 years; the oldest was approximately 70 years. Of the 79 single-site biopsies, 14 (17.7%) nodules occurred on the head and 65 (82.3%) were done elsewhere. The nodules above the waist line totalled 42 (53.2%) and those below it 37 (46.8%). The favorite location was the forehead cephalically and the hip caudally. Eyelid and breast nodules were also noteworthy.

A 13-year-old Palo Alto boy coughed up an immature Phocanema-type larva about 4 days after having eaten “ceviche” made of raw red snapper marinated in lime juice.

A living, fifth-stage female Angiostrongylus cantonensis 5 mm in length was discovered in the cerebrospinal fluid of a 21-year-old Thai male with eosinophilic meningitis, the second such case to be recorded from Thailand.

Thirteen patients with concomitant chronic salmonellosis and schistosomiasis and with the nephrotic syndrome were studied. Of the seven patients' sera examined, all had markedly low complement C3 and near normal C4 levels. This indirectly suggests an active role of Salmonella endotoxin in the etiology of the nephrosis.

Venezuelan equine encephalitis (VEE) virus strains were recovered from sentinel hamsters exposed in close proximity to homes in rural South Florida. Sentinel hamster surveillance methods over extended periods offer one effective way of uncovering VEE virus activity in relation to human habitation.

Animal Agents and Vectors of Human Disease, by E. C. Faust, P. C. Beaver, and R. C. Jung. ix + 479 pages, illustrated. Lea and Febiger, Philadelphia, Pennsylvania. 1975. $15.00.

Bibliography of Soviet Sources on Medicine and Public Health in the U.S.S.R., A, prepared by L. Perkins. xix + 235 pages. DHEW Publication no. (NIH) 75–773. Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402. 1975. $3.20.

China Medicine As We Saw It, edited by J. R. Quinn. A publication of the John E. Fogarty International Center for Advanced Study in the Health Sciences. xii + 430 pages, illustrated. DHEW Publication No. (NIH) 75–684. 1975. No price.

Diseases Transmitted from Animals to Man, 6th edition, compiled and edited by W. T. Hubbert, W. F. McCulloch, and P. R. Schnurrenberg. xviii + 1,206 pages, illustrated. Charles C Thomas, Springfield, Illinois. 1974. $58.00.

As a physician-researcher with a strong interest in amebiasis, I approached this 179-page monograph with great expectations. In the introduction, the editors explain that the book was created because of new developments in the diagnosis and treatment of amebiasis. They also entice the reader with a list of good “controversial and unsettled questions” which are said to be touched upon in the monograph: “Is Entamoeba histolytica a subtle, insidious, and invasive pathogen from the moment it enters the human body?” “Can amebae live for indeterminate periods of time within the tissues without causing an inflammatory reaction?” “Does a transition from such a tissue phase to a more aggressive form require an association with other pathogenic micro-organisms?” The reader finds, however, that the chapters following contain little or no information even remotely pertinent to these and the other questions raised in the introduction.