The American Journal of Tropical Medicine and Hygiene - Volume 27, Issue 3, May 1978

I would certainly be remiss if I did not express my deep appreciation for the honor you have bestowed in giving me the opportunity to serve our Society this year and for the privilege which that provides for this presentation.

Failure of our nation to translate the encouraging expressions of increased interest in international health into effective program activities will reflect a gross lack of both humanitarian concern and enlightened self-interest. The central thesis of this presentation is that to be truly effective such programs must be much more holistic than most of our past efforts and, in particular, that they must give appropriate recognition to the contributions which veterinary medicine and comparative medicine can make in improving human health and welfare. The scope and complexity of this subject permit only a brief and selective summary in this presentation. †

Comment about meaning of words in the title will perhaps assist in establishing the perspective for the discussion.

Two regimens of primaquine in combination with amodiaquine have been compared with amodiaquine alone in known cases of Plasmodium vivax in an endemic area of El Salvador, C.A. A 5-day regimen of primaquine, with dosages based on an adult dose of 15 mg per day, produced a substantial reduction in the numbers of patients experiencing renewed parasite activity and in the number of parasitemias experienced by the group during 9 mo of posttreatment observation, when compared with patients treated only with amodiaquine. A single dose regimen, based on an adult dose of 45 mg, similarly reduced the number of patients with renewed parasite activity and the number of parasitemias in the group. Those patients who experienced malaria attacks subsequent to treatment with either primaquine regimen experienced fewer such attacks than did those receiving amodiaquine alone. It is concluded that such primaquine regimens, which are more practicable for field use than the full 14-day curative regimen, are of value to both the patient and the community through the reduction of parasite episodes and the reduction of the source of mosquito infection for continuation of transmission.

Immunoglobulin M, G, and A concentrations were studied by radial immunodiffusion technique in 16 individuals (two were 16 and 14 yr of age, respectively, while the remaining 14 were 12 yr of age or less) with acute Trypanosoma cruzi infection. Serum samples were obtained from these patients beginning with the onset of symptoms and continuing until several months after treatment with nifurtimox was completed. Soon after infection the concentration of IgM was higher than the average found in healthy children. Some of the samples also had higher values than those found in children with other acute infections. At this time isolated increases in IgG and/or IgA concentrations were also found in T. cruzi-infected patients. Immunoglobulin concentrations had usually returned to normal when treatment with nifurtimox was completed, both in the patients with negative serology and in those who remained positive. However, some of the sera showed isolated higher IgM, IgG, and/or IgA values than those found in healthy controls.

A monospecific rabbit antiserum was prepared against a specific component of Trypanosoma cruzi epimastigote culture forms (designated antigen 5). Rabbits were immunized intradermally in 30–50 sites with the zone of agarose gel in which the component 5:anti-5 complex was visualized after two-dimensional immunoelectrophoresis. With this appropriate antiserum and the total epimastigote soluble extracts, the specific component of T. cruzi was purified by immunoadsorption. Purity and specificity controls of the final product were carried out by prolonged immunization of rabbits, and then by immunoelectrophoretic and two-dimensional electrophoretic analyses.

Trypanosoma (Schizotrypanum) species isolated from bats (Microchiroptera) in Europe and Latin America were examined by determining the buoyant densities of their nuclear and kinetoplastic deoxyribonucleic acid (DNA) and the electrophoretic patterns of six isoenzymes. By these criteria they were separated into three distinct groups—two from Europe (T. dionisii and T. vespertilionis) and one from America. T. dionisii was also separable by its morphology in vitro. Geographical location and DNA buoyant densities suggested that the American stocks were more closely related to T. cruzi than to the European species, though they differed from it marginally in kinetoplastic DNA density and in being non-infective to mice. Similar stocks studied by other workers have been shown to differ from T. cruzi also in reduced infectivity to, and lack of natural association with, Triatominae, and in antigenic composition. It is therefore proposed that trypanosomes of the subgenus Schizotrypanum occurring naturally in Microchiroptera and differing from T. cruzi sensu stricto as outlined above should be treated as a distinct subspecies, T. cruzi marinkellei ssp. nov. T. cruzi sensu stricto thus becomes the nominate subspecies T. cruzi cruzi Chagas 1909.

Four serologic techniques for the diagnosis of visceral larva migrans caused by Toxocara canis, namely indirect hemagglutination (IHA), bentonite flocculation (BF), enzyme-linked immunosorbent assay (ELISA), and double diffusion in agar (Ouchterlony), were evaluated using sera sent to the Center for Disease Control from patients with a presumptive diagnosis of visceral larva migrans (VLM). Patients having 5–6 of the clinical or laboratory criteria for VLM were designated as cases while those with 0–2 criteria served as controls. The sensitivity of the ELISA was 78.3% compared to 18.2%, 25.8%, and 65.2% for the IHA, BF, and Ouchterlony, respectively; the specificity of all four tests was greater than 92%. The predictive value of a positive test was greater than 85% for all tests except the IHA, while the predictive value of a negative test was greater than 85% only for the ELISA. The results of the ELISA were reproducible in different laboratories. Based on these findings, the ELISA using a larval antigen appears to be the serodiagnostic method of choice for VLM.

Despite similarities of topography and climate in the coffee-producing regions of the two countries, human infection with Onchocerca volvulus has rarely been reported in El Salvador, whereas onchocerciasis has long been endemic in the coffee plantations of neighboring Guatemala. The apparent near absence of the infection in El Salvador was investigated in a coffee-growing area in the western part of the country some 50 km from Guatemala's principal onchocerciasis zone. Collections of black flies attracted to humans and, for comparison, to horses were made for 1 yr at elevations from 300–1,330 m, and a skin biopsy survey was conducted among area residents ranging in age from 10 yr to over 60 to estimate the prevalence of microfilarial skin infection. Simulium metallicum and S. callidum accounted for 77 and 21%, respectively, of the flies collected from humans and 87 and 11%, respectively, of those from horses. Both species showed a marked preference for horses as a source of blood. When coming to feed on humans, they chose the legs more often than the shoulders as a feeding site. Other species, which together made up only 2% of the 5,507 flies collected, were S. downsi, S. pulverulentum, S. mexicanum, and S. haematopotum. The highest landing rates recorded for both S. metallicum and S. callidum on humans were at collecting sites from 600–940 m elevation during the October-February period which spans the annual transition from wet to dry seasons. The absence of S. ochraceum from the collections is noteworthy. This anthropophilic black fly frequently attains very high densities in Guatemala, where it is regarded as the principal vector of O. volvulus. No microfilariae were detected in skin biopsies from 941 study area residents, indicating that no significant reservoir of infection exists there and, together with the entomologic data, supporting the assumption that the region is free of endemic human onchocerciasis.

Serum concentrations of IgA, IgG, IgM, IgE, C3, and C4 complement components were estimated in 19 patients with tropical pulmonary eosinophilia (TPE). Thirteen of the patients presented during their first episode of TPE and 6 of them during a relapse of the disease. We found a remarkable elevation of serum IgE level in TPE, which is consistent with earlier reports. In contrast, there was a modest increase in IgM levels and unchanged or even lower levels in IgA and IgG immunoglobulin classes. There seemed to be a direct relationship between IgE level and degree of peripheral blood eosinophilia in TPE. The outstanding finding, however, was a nearly threefold higher mean serum IgE level in patients with relapsing disease as compared to that observed in patients during the primary attack. This is the first reported study of circulating complement components in TPE. A significant rise of serum C3 level was found in these patients; there was no similar elevation of serum C4 component.

A study was undertaken to define the sensitivity and specificity of serological tests in bancroftian and malayan filariasis and correlate the findings with clinical disease. Sera were collected from subjects on three different islands in the Philippines: one endemic for bancroftian filariasis, another endemic for malayan filariasis and the third without endemic filariasis. Antibodies were measured, using Brugia malayi as the source of antigen. Antibodies against adult worms measured by indirect immunofluorescence were found at a titer of 1:8 or greater in all patients with bancroftian or malayan filariasis but not in the control subjects. There was no relationship of antibody titer to clinical status. Antibodies against microfilariae were measured by indirect immunofluorescence and by microfilarial agglutination. A high correlation was observed between the two methods. These antibodies were found in only one quarter, approximately, of patients with filariasis. Microfilarial antibodies were found more commonly in those patients with chronic lymphatic obstruction. It is concluded that measurement of antibodies to adult worms is a useful indicator of infection while microfilarial antibodies are correlated with disease.

The authors have investigated histologic and organ weight changes in the spleens of jirds (Meriones unguiculatus) experimentally infected with subperiodic Brugia malayi and two related species. A total of 214 infected animals were examined between 1 and 700 days post-inoculation: 50 females with B. malayi, 63 males with B. malayi, 51 males with B. pahangi and 50 males with B. patei. The low splenic indices and lack of histologic reactions other than moderate lymphoid hyperplasia during the first 2 mo post-inoculation suggested that, for the most part, splenomegaly was not associated with the decline in whole body worm recoveries which occurs during this interval. At about the end of the prepatent period, spleen weight increased in many jirds. Except among males infected with B. patei, mean splenic indices attained much of their full mean value by the end of the 4th month. B. malayi roughly doubled the normal splenic index, while B. pahangi caused some additional enlargement; B. patei infections yielded erratic but much larger indices. Histologic sections showed expansion of both red and white pulp; maximum follicular activity was observed in the 3rd and 4th months post-inoculation and gradually waned in long-term infections. Plasma cell infiltrates were conspicuous in some long-term infections and amyloidosis developed in a single B. patei spleen. Granulomatous foci associated with microfilariae in tissue were a conspicuous feature of B. pahangi infections. These lesions were also seen in B. patei infections but not among those infected with B. malayi. Although no consistent relationship was established between splenic reaction and level of microfilaremia, the persistence of elevated splenic indices was interpreted as a response to the production of microfilariae and to chronic antigenic stimulation by excretory or secretory materials.

The elimination of adult parasites from the intestines of rats after a first and second infection of Strongyloides ratti was studied. Expulsion after a second infection was anamnestic, indicating that the response is immunologic. Intestinal mast cell responses accompanied damage and expulsion of worms, the secondary mast cell response being more rapid but less intense than the first. Antithymocyte serum suppressed expulsion as well as both the intestinal mast cell and circulating eosinophil responses to primary infection.

Cortisone (5 mg daily subcutaneously) suppressed both primary and secondary immune expulsion of Strongyloides ratti, and reduced the intestinal mast cell response, but did not induce hyperinfection in rats. Cortisone-treated animals expelled primary worm burdens without complication about 2 wk after steroid treatment. A model for gastrointestinal hypersensitivity syndromes is discussed.

A case of anterior spinal artery occlusion associated with acute Schistosoma mansoni infection is reported, and it is suggested that there is a direct relationship. It is postulated that there is initially an arteritis which leads to obstruction of either the anterior spinal artery itself, its branches, or one or more of the tributary anterior radicular arteries.

The intradermal reaction with Schistosoma mansoni adult-worm antigen (35–40 µg/ml nitrogen) was evaluated as an epidemiologic tool in an endemic Puerto Rican community where the prevalence of S. mansoni infection was 36% and the geometric-mean egg count was 17.6 eggs/g. Subcutaneous injections of antigen were made in forearms, and stool specimens were examined for S. mansoni eggs by a formol-ether concentration method. Of 296 persons tested, 43% had positive intradermal reactions (⩾1.0 cm2 and at least twice the area of the control wheal), compared to 48% positive stool examinations. However, sensitivity was low at 36% for children 14 yr old or less, and only 73% to 79% for adults. The test results were very specific for children (96%), but 32% of stool negative adults were positive. Mean wheal area was not directly related to intensity of infection as determined by egg counts in either children or adults, but did increased directly with age. Mean wheal areas were greater for males than females (both children and adults) at all intensities of infection. Because of unsatisfactory sensitivity and specificity the intradermal test may overestimate the prevalence of infection when rates are low, and underestimate prevalence of infection when rates are high. For its proper interpretation, complementary parasitologic data from stool surveys are required.

Four or eight adult Schistosoma mansoni surgically transferred to the mesenteric veins of mice survive well and may play a role in resistance to later cercarial challenge. After receiving transfers of single sex or paired flukes, animals exposed to 50 or 100 cercariae showed decreased numbers of parasites derived from the challenge infection when compared with control animals 30 days later. Although statistical analysis of the data indicated that the presence of transferred S. mansoni probably had an adverse effect on the survival of worms in a subsequent challenge, the results were interpreted as inconclusive.

Protease-containing preacetabular gland secretion can be collected from cercariae of Schistosoma mansoni by stimulation with penetration-inducing skin surface lipid, but the method lacks quantitative control because of variability of the lipid. Two commercially available free fatty acid fractions of skin lipid active in stimulating cercariae to penetrate skin, linolenic and linoleic acids, were substituted for skin surface lipid in a technique which provides an improved method of secretion collection. The pattern of protease activity of secreted enzyme(s) was followed throughout patency of infection of a group of snails with the same date of exposure. Day-to-day variability was a characteristic feature of all parameters studied. Major trends were elevated enzyme activity and cercarial emergence during midpatency.

Human sera from one case of polycystic hydatidosis due to Echinococcus vogeli and from a case of cysticercosis and multiple myeloma were positive to the immunoelectrophoresis (IEP) test for hydatidosis based on the E. granulosus arc 5 positivity criterion. Arc 5 can therefore be elicited in IEP tests of human sera not only by E. granulosus and E. multilocularis but also by E. vogeli antigens. Whether the cross reaction observed in the second serum was due to the multiple myeloma or to the cysticerci remains to be determined. Although arc 5 antigens are known to be present in Taenia hydatigena cyst fluid, this is the first report of an arc 5 due to antigens other than Echinococcus in IEP of human sera.

After two small outbreaks of histoplasmosis in Belize, an epidemiologic survey was carried out. Forty percent of 141 persons in two groups tested demonstrated a positive histoplasmin reaction. In one study group there was a significant association between visiting caves and histoplasmin positivity. Histoplasma capsulatum was not isolated in 20 soil specimens collected from outbreak-associated caves, but was isolated from 1 of 26 bats collected from the same caves. The presence of histoplasmosis in Belize, C.A. is documented, and this disease should be considered in differential diagnosis in patients, both residents and visitors in Belize, with compatible clinical presentations.

A total of 860 Salmonella isolations were made in Peninsular Malaysia from 15 animal species (domestic and wild), eggs, molluscs, flies, and animal feed. The isolations were distributed among 31 serotypes in eight groups. The most common serotype isolated was Salmonella pullorum, followed by S. choleraesuis and S. typhimurium had the widest zoological distribution. The importance of controlling animal salmonellosis is emphasized.

The prevalence of rotavirus infection in hospitalized Venezuelan children with gastroenteritis was studied during the period November 1975 to December 1976. Rotaviruses were the pathogens most frequently associated with gastroenteritis, being found in 121 of 293 (41.3%) patients and in only 3 of 66 (4.5%) controls. Other viruses (adenoviruses, enteroviruses, and small icosahedrical viruses) were detected at a lower frequency both in cases and controls. Rotaviruses were readily detected throughout the year, which may correspond to the absence of seasonal temperature variation in a tropical country such as Venezuela. Children of all age groups examined (0–5 yr) were susceptible to rotavirus infection. The frequency of infection was slightly higher in the age group 13–24 mo, and significantly lower in children younger than 6 mo old. Rotaviruses were readily detected even after 12 days from the onset of illness. These results indicate that rotaviruses may be a major cause of infantile acute gastroenteritis in Venezuela.