The American Journal of Tropical Medicine and Hygiene - Volume 28, Issue 3, May 1979

It has been a singular honor for me to serve our Society as President for the past year. What I envisaged to be an honorary position, requiring little more than preparing a Presidential address and presiding at a council and business meeting, turned out to be an exciting, informative, and engrossing experience. Our Society is dynamic and growing. The membership is interested in expanding the activities of the Society. One of the new programs initiated was the appointment of a Committee on Public Affairs to involve the Society in the health needs of our nation by lobbying for programs in the area of tropical medicine. Being your president has been a privilege, and I wish to express my thanks to the members of the Society for the honor and to the members of the various committees for their untiring efforts in carrying out the business of the Society.

Presidential addresses take many forms: some are philosophical; others cover timely and current research areas.

In the case reported here, a patient with severe Plasmodium falciparum infection with 20% of erythrocytes parasitized was cured by exchange transfusion in conjunction with classical drug therapy.

Trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied alone and in combination to determine their effect in vitro on intracellular Toxoplasma gondii and in vivo against murine toxoplasmosis. In the in vitro experiments, whereas 1 and 2 µg/ml TMP had no demonstrable effect on intracellular T. gondii, 10–20 µg/ml TMP resulted in death of the intracellular organisms; concentrations as high as 100 µg/ml SMZ had no demonstrable effect against the intracellular organisms. When used in combination, a significant synergistic effect was noted with 2 µg/ml TMP-50 µg/ml SMZ. Studies on the kinetics of inhibition and/or killing of Toxoplasma revealed that 18 hours of treatment with 2 µg/ml TMP-50 µg/ml SMZ resulted in irreversible inhibition of the intracellular organisms. When used in vivo against a 50,000 LD100 dose of Toxoplasma, TMP fed by gavage or mixed in the diet had no effect in murine toxoplasmosis at doses as high as 200 mg/kg a day. SMZ administered by gavage had no effect at doses up to 200 mg/kg a day; but at 300 and 400 mg/kg SMZ, protection was 47% and 83%, respectively. Treatment of infected mice was continued for 14 consecutive days, whether the drugs were administered alone or in combination. The combination 200 mg/kg TMP-200 mg/kg SMZ, when administered by gavage, protected 87% of mice. Survival after 14 days of SMZ mixed in the diet was 0% at 100 mg/kg, 47% at 200 mg/kg, and 100% at 300 mg/kg. Survival with the combination was 40% for 200 mg/kg TMP-100 mg/kg SMZ and 100% for 100 mg/kg TMP-200 mg/kg SMZ. The half-life of TMP in serum of Swiss Webster mice was calculated to be 24 min. The results obtained in vivo were inferior to those obtainable with the combination of pyrimethamine plus sulfadiazine. The problems of interpretation of results obtained in the murine model using TMP-SMZ and in their extrapolation to the treatment of the infection in man are discussed.

Two different strains of mice (AKR and NMRI-IVIC) were inoculated intraperitoneally with the virulent Y strain of Trypanosoma cruzi, and then treated with the lysosomotropic ethidium bromide-DNA complex, according to several different treatment schedules. When animals were treated 48 hours after intraperitoneal inoculation with three intraperitoneal doses of EB-DNA no parasitemia was detected, even after 11 weeks, confirming previous results. However, when infection was allowed to become fully established, that is 3–4 weeks after inoculation, and then challenged with several different treatment schedules (with varied doses and timing of administration) we failed to cure established Chagas' disease, suggesting that the claim of effectiveness for this EB-DNA complex is limited to early Chagas' disease.

Age-specific prevalence rates of parasitemia and seroreactivity to Trypanosoma cruzi were determined in a rural area endemic for Chagas' disease in Northeast Brazil. Parasitemia was detected by blood cultures and xenodiagnosis, and serum antibodies to the parasite were measured by the complement fixation (CF) and indirect immunofluorescence (IFA) tests. Of the 116 persons examined, 39 (33.7%) had antibodies and 23 (19.8%) had parasitemia. Ninety-six percent of parasitemic individuals were seropositive and 56% of seropositive individuals were parasitemic. The percentage of seropositive individuals with detectable parasitemia declined with age; all seropositive children in the 1- to 4-year age group and two-thirds of seropositive persons 5–19 years old had parasitemia while only one-third of seropositive adults above 19 years had parasitemia. CF and IFA tests were equally sensitive in detecting persons with parasitemia. Xenodiagnosis was more sensitive than culture for detecting parasitemia, but the two methods together were more sensitive than either method alone. Using the age-dependent relationship of parasitemia to seropositivity determined in this study, the prevalence rate of T. cruzi parasitemia was estimated in a much larger adjacent population in which seropositivity rates and the demographic structure were already known.

A Peace Corps volunteer in Senegal, West Africa contracted cutaneous leishmaniasis which had several noteworthy features. One of the three presenting cutaneous ulcers was associated with subcutaneous nodules and viable organisms were recovered from healing lesions after multiple courses of treatment, including amphotericin B. Yet, the patient was found to exhibit both humoral and cell mediated features of normal immunologic responsiveness. Ultimately, clinical and parasitological cure occurred. The patient's organism was found to produce lesions in the foot pads of mice.

Outbred albino mice infected on the nose and in one foot pad were used as a model for the study of a newly isolated strain of Leishmania tropica from West Africa. The development of local lesions following the inoculation of 107, 105, and 103 amastigotes, respectively, was recorded at weekly intervals through four subsequent animal passages. In addition, the course of infection was followed in four different inbred strains of mice. The specificity and possible spread of infection were checked microscopically by smear preparations and by inoculation of tissue material into NNN medium. Samples for histopathological examination were obtained at different time intervals after the day of infection. The incubation period varied from 2–7 weeks depending upon the size of inoculum. Generally, the mice developed local swelling and, frequently, ulceration at the sites of inoculation. After a few weeks of progress, the lesions assumed a more chronic state, lasting for months without obvious impact on the general health of the mouse. However, the individual response to the infection varied considerably within each group. Histopathologically, parasitized macrophages and polymorphonuclear leucocytes dominated during the first weeks, whereas at later stages of the lesions lymphocytes and plasma cells prevailed. The BALB/c mice differed from the other mouse strains under study by developing a progressive, ultimately fatal infection. Splenomegaly was prominent in the BALB/c mice, whereas clinical signs of generalized infection were missing in the other mouse strains. However, the latter strains also harbored leishmanial parasites in internal organs, as demonstrable by NNN-culture. The study underlines the value of mice for experimental investigations on L. tropica.

The therapeutic effect of sodium stibogluconate, amphotericin B, and metronidazole was studied in an experimental Leishmania tropica infection in outbred white mice inoculated 28, 14, or 0 days previously in the nose and foot pad. The pentavalent antimony and amphotericin were administered subcutaneously for 14 days at doses of 400 mg/kg body weight a day and 12.5 mg/kg a day, respectively, whereas metronidazole was given orally for 14 days at a dose of 50 mg/kg a day. In a separate experiment, inbred BALB/c mice, infected in the foot pad, were treated with pentavalent antimony as before or with an 8-amino-quinoline compound (WR 6026) at a dose of 12 mg/kg a day. The lesions that developed were measured at regular intervals for 7–10 weeks. In outbred mice with established lesions of 4 weeks' duration, no effect of treatment was observed. In mice infected 2 weeks earlier, and especially in animals infected when treatment was started, sodium stibogluconate and amphotericin B prevented or delayed development of lesions during or after the period of treatment. However, soon after termination of treatment most animals showed rapidly growing lesions. Metronidazole had no effect on development of lesions. Results of treatment with sodium stibogluconate in BALB/c mice were similar to those observed with the outbred mice. The 8-amino-quinoline compound (WR 6026) showed only a questionably significant late effect on lesions in BALB/c mice. Viable parasites were cultured from representative mice of all treatment groups many weeks after termination of therapy. This mouse model for certain strains of Leishmania may be useful for experimental therapy studies.

This study is a follow-up of a 1965 investigation of the only known focus of Onchocerca volvulus in Colombia. In the first phase of the current study, 254 persons were examined. Of the 19 individuals found to be infected with O. volvulus, the youngest was a 16-year-old male. Among those included in the 1965 study, 22 were examined again for microfilariae. Two were positive in both studies, 4 were positive in 1965 but negative in 1977 and the remaining 16 were negative on both occasions. The prevalence of infection, based on identification of microfilariae in skin snips, was lower in the current study (7.5%) than the 15.1% recorded 12 years earlier. However, a 50% response to the Mazzotti test (administration of oral diethylcarbamazine) among a limited number of people upstream from the previously identified endemic area suggests that infection with O. volvulus may be quite widespread.

The development of Onchocerca volvulus was compared in Simulium ochraceum and S. metallicum by maintaining infected flies under uniform conditions. Larval development in S. ochraceum was synchronous and orderly so that nearly all larvae reaching the thoracic muscles from a single blood meal matured to third-stage infective larvae within 192 hours. In contrast, development in S. metallicum was asynchronous, slower, and retarded. In this species many first-stage larvae were malformed and stunted after the 5th day of development; and microfilariae and first- and second-stage larvae were still present 8–10 days after a single infecting blood meal when third-stage larvae had developed. The development of O. volvulus in S. ochraceum is more compatible with the intense transmission associated with human disease.

Sixty-three experimental and 58 control cats were infected with Brugia malayi so that the developing and adult worms localized in the regional lymphatics of the hind legs. At 20 days after infection when Brugia were in the 4th larval stage, and at 8 weeks when worms were young adults, cats were divided into groups to test the efficacy of diethylcarbamazine citrate (DEC) at various dosage levels. At 100 mg total DEC/kg no 4th-stage larvae were seen in 5 cats compared with a mean of 20.4 living larvae in each of 5 controls. At this level of DEC, 2 of 5 cats had 1 and 2 adult worms while 4 of 4 controls had a mean of 23.2 living adult worms. At 50 and 25 mg/kg there was a substantial reduction of both 4th stage and adult worms when compared to controls. At 10 mg/kg, 4 of 6 cats had 4th-stage larvae but at a lower level (mean = 7.0) than in 6 controls (mean = 23.2). No reduction of either 4th-stage larvae or adult worms was seen at 1 mg/kg. This study establishes the efficacy of DEC against 4th-stage and adult Brugia malayi in cats, although considerably higher levels of the drug were required than the level previously determined to kill 3rd-stage larvae. It appears that the cat-B. malayi model will be an effective method to compare the efficacy of drugs against adult lymphatic-dwelling filariae.

General evidence of malnutrition such as loss in body weight associated with intestinal parasitism has been attributed to decreased food intake, to intestinal malabsorption, and to changes in host basal metabolism. To establish the relative importance of these factors in this regard, rats with trichinosis were studied. The weights of infected and uninfected animals were followed after being placed on one of three feeding regimens for 1 week—stock diet ad libitum, intraduodenal nutrition, and intravenous nutrition. Infected rats on a stock diet lost weight whereas those on the other two regimens maintained the same weight pattern as uninfected counterparts. The maintenance of body weight occurred despite alterations at the level of the intestinal brush border as indicated by a depression of intestinal disaccharidase activities (sucrase and lactase) and by reduction of monosaccharide absorption (measured as accumulation of β-methyl glucoside) in the proximal, heavily infected region of the small intestine. There was no compensatory increase in enzyme activity nor in the absorptive capacity in the distal gut. Results support the conclusion that inadequate oral food intake rather than changes in basal metabolism or intestinal pathophysiology accounts for weight loss during the intestinal phase of infection.

Compounds which block the formation of the egg shell in female schistosomes are thought to have chemotherapeutic value. One of these compounds, disulfiram, when given chronically in the diet produced a 60% reduction in the mortality of mice carrying a heavy schistosome burden. This reduction in mortality was associated with an 80% decrease in granuloma formation. On the other hand, there was no decrease in the amount of periportal inflammation in drug-treated animals. While the use of this drug results in significant amelioration of schistosomal pathology, its effects are rapidly reversible, thus severely limiting its chemotherapeutic potential.

A program to control schistosomiasis in Puerto Rico was initiated in 1953, using limited chemotherapy and snail control by environmental, biological and chemical means. At the same time, extensive programs of water supply, health education, and free latrine distribution were underway throughout the island. The impact of the program was evaluated initially by examinations of fecal samples from first-grade children until 1966, and subsequently by island-wide surveys using adult worm antigen for skin test on fifth-graders in 1963, 1969, and 1976. There was a decrease in the proportion of children reacting positively to the skin test from 24% in 1963 to 5% in 1976. The decrease in the proportion of positive skin test reactions was one and a half times as great in the area under snail control as in the rest of the endemic area, and most of the decrease outside the snail control program was due to improved water supply. Calibration tests indicated a decrease in prevalence among the entire population, if determined by multiple fecal exams, from 15% in 1963 to less than 4% in 1976. Thus the estimated number of persons passing eggs in Puerto Rico was about 100,000 in 1976, in a population of 3 million. The cost of snail control was minimized by emphasizing environmental and biological methods, showing that the disease can be controlled on a large scale with simple techniques. Eradication of the parasite from Puerto Rico is quite likely in the next few years with the advent of the new drug, oxamniquine, and would be a cheaper strategy than continued snail control.

Schistosomiasis mansoni infection was found in more than 50 tourists who had visited Omo National Park, Ethiopia, and bathed and swum in the Mui River. A survey revealed Schistosoma mansoni infection in 41% of Park residents and in 33% of the neighboring Suri people. Eggs were found in stools and adult worms at autopsy of wild Papio anubis and Cercopithecus aethiops. Trematode larvae were found in 27% of Biomphalaria pfeifferi snails found in the Mui River. The source of the disease and the implications of its spread with the future development of the Omo Valley are discussed.

Seasonal changes in populations of Biomphalaria pfeifferi and Bulinus globosus were observed at 62 locations in Liberia, West Africa. All varieties of water in both urban and rural locations were sampled. A wet season decrease and dry season increase of B. globosus populations in both urban and rural locations, similar to that reported elsewhere in West Africa, was observed. Similar fluctuations of B. pfeifferi populations were noted. The prevalence of schistosome infected vector snails varied markedly between rural and urban locations. At rural sites parasite prevalence followed the appropriate vector snail prevalence. At urban sites a portion of the vector snail population appeared relatively unaffected by seasonal changes. This stable population harbors a reservoir of infected snails that sustain year round transmission. Human infection was sampled in school children in the study area and prevalence of approximately 50% was found for both Schistosoma mansoni and S. haematobium. Added to the malacologic information this suggests less than hyperendemic transmission. The data suggest that urban environments should receive priorities for control programs.

Preparations of eggshells of Schistosoma mansoni and S. japonicum were hydrolyzed and analyzed for amino acid composition. Both species showed great similarities in the proportions of each residue found. The predominant amino acid in shell hydrolysates was found to be glycine, which accounted for 37% of S. mansoni and 45% of S. japonicum amino acids. Four components (glycine, aspartic acid, lysine, and serine) totalled 68–75% of amino acids in the eggshells. Other individual amino acids were present in relatively small proportions ranging from 5.2–0.01%. Less than 1% of the amino acid residues were identified as tyrosine, and bityrosine was detected at a level not exceeding 1 in 1,600 residues. Carbohydrates were estimated to comprise 7.5–10% of the eggshell weight, based on hexose assay, and glucosamine was identified as the principal amino sugar in shell hydrolysates. In vivo labelling of the S. mansoni eggshell was demonstrated following injection of C14-glycine and C14-tyrosine into infected mice and subsequent purification of the shells of eggs recovered from their liver.

Pyoderma was studied among a representative sample of the residents of four remote Amerindian villages, Amazonas State, Brazil, during July-August 1976. The overall prevalence among the 775 inhabitants examined was 11%, with little intervillage variation. When the attack rates for the entire sample population were calculated by 5-year age intervals, the 0- to 4-year-olds had the highest rate, 31%. The highest prevalence, 38%, was found among 3-year-olds. Attack rates were not apparently related to sex. Cultures which were taken from representative pyoderma lesions from people in the four survey villages and from three additional villages were studied by a modified delayed culture technique for recovery of gram-positive pathogens from silica-gel desiccated swabs. Group A and group G B-hemolytic streptococci, coagulase positive Staphylococcus aureus, and Corynebacterium diphtheriae were isolated. Group A S. pyogenes was most commonly found, occasionally as the sole pathogenic species. No nephritogenic M-types were found, although most isolates were not M-typable. The T-types found corresponded to those previously reported as being pyoderma-associated. Most pyoderma-associated C. diphtheriae isolates were non-toxigenic. Biotypes gravis and mitis were equally represented.

The 1,659 non-leprous people in a Micronesian population experiencing an annual leprosy incidence rate of about 7/1,000 were offered 15 acedapsone (DADDS) injections during 1967–1970 for leprosy prevention purposes. Subsequent annual surveillance showed an initial cessation of new cases during the 3-year DADDS campaign, followed by a resumption of cases thereafter at a yearly level of about 2/1,000, with a longer pause and slower rise among those who received the full regimen. A secondary wave of cases that has occurred since 1973 among children born after 1968 shows that post-campaign transmission occurred, probably principally from relapsing multibacillary cases with onset before the campaign. Recommendations are made for a balanced, long-term control program with DADDS preventive treatment limited to contacts of multibacillary cases.

Two cases of abdominal zygomycosis occurring in apparently healthy individuals are presented. They had chronic evolution and histologic aspects similar to those found in subcutaneous zygomycosis. In both cases there was involvement of stomach and transverse colon. In one case the liver, biliary system, pancreas, and duodenum were also involved. Fungal cultures were negative. These cases apparently represent a new form of zygomycosis because, although visceral in localization, the disease presents an evolution and histologic features different from the classical form of visceral zygomycosis. Since this infection can be treated the importance of early diagnosis is stressed.