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Biomedical subjects

F A Neva

Publications and source records attributed to F A Neva.

At least 55 records · Page 3Linked to original sources

Experimental disseminated strongyloidiasis in Erythrocebus patas. I. Pathology.

Fatal disseminated disease was induced in ten patas monkeys infected with two Southeast Asian strains of Strongyloides stercoralis. While some animals died within 6 weeks after infection, others controlled their infections until placed on high doses of corticosteroids. Larvae were first noted in the stools 11-20 days after transcutaneous exposure to filariform larvae. Daily larval counts tended to increase as the infections progressed, but the number of larvae in the stool was not predictive of whether a monkey would control his infection or succumb to fatal disease. Hyperinfection was confirmed in the six monkeys in which counts were made of the adult female parasites in the duodenum at postmortem, as well as by pathologic findings in all animals. Clinical signs of disease were vague until dyspnea induced by terminal pulmonary hemorrhage occurred. Eosinophilia and/or basophilia were noted intermittently in some infections. Severe necrotizing duodenitis, colitis, and pulmonary hemorrhage were the most conspicuous postmortem findings. Hyperinfection has been predictably induced in a cercopithecoid monkey for the first time; a species which may lend itself to further investigations into the pathogenesis of disseminated strongyloidiasis .

Animals↗

Experimental disseminated strongyloidiasis in Erythrocebus patas. II. Immunology.

Parasite-specific humoral and cellular immune responses were evaluated in seven Erythrocebus patas monkeys experimentally infected with a Southeast Asian strain of Strongyloides stercoralis. Most animals developed high titers of anti-larval surface IgG antibody (as evaluated by the indirect immunofluorescence test), and all animals tested developed specific IgE antibody (as shown by the in vitro histamine release test). Modest lymphoproliferative responses to S. stercoralis antigens were demonstrated in most animals during the early phase of the infection (days 20-40), but disappeared later. Steroid treatment (prednisone, 12.5 mg/kg on alternate days) was given to three animals, but did not appear to significantly affect the immune parameters tested. The degree of the immune responses to S. stercoralis larval antigens did not correlate well with the course of the infection, and several animals died of disseminated disease in spite of demonstrable humoral and cellular responses to these antigens. We suggest therefore that other factors, such as local intestinal immune and nonimmune mechanisms may be of importance in protection against disseminated strongyloidiasis.

Animals↗

Observations on local heat treatment for cutaneous leishmaniasis.

Local heat treatment was tested and found effective in three patients with diffuse cutaneous leishmaniasis (DCL), a form of disease poorly responsive to the usual chemotherapy. A water bath that circulated water through a pad wrapped around the lesion provided a temperature of 39 degrees C to 41 degrees C for a cumulative time of at least 20 hours, over a period of several days. In the DCL patients beneficial effect of heat treatment was documented by pre- and post-treatment biopsies and cultures. Several other patients with ordinary cutaneous leishmaniasis did not respond to the same form of treatment. It was concluded that different strains and/or species of leishmanial parasites vary in their sensitivity to elevated temperature. While local heat treatment may be curative in certain cases of cutaneous leishmaniasis, such therapy is still experimental and should be monitored by quantitative parasitological studies to document its usefulness.

Adolescent↗

Specific and non-specific lymphocyte blastogenic responses in individuals infected with Trypanosoma cruzi.

Lymphocyte blastogenic response to various parasite-specific and non-parasite antigens was measured in 31 Trypanosoma cruzi-infected individuals representing the indeterminate, megadisease and cardiomyopathy forms of Chagas' disease. The non-parasite antigens and mitogens stimulated responses in the peripheral blood mononuclear cell (PBMC) cultures of the infected individuals to levels not different than the stimulation seen in PBMC of the normal control group (n = 10). The cell culture antigen (CC-Ag) derived from trypomastigote-amastigote forms of T. cruzi and the epimastigote antigen (EPI-Ag) elicited a strong response among all infected individuals in contrast to virtually no response among the normal controls. Comparisons among the individuals with T. cruzi infection stimulated with EPI-Ag showed no significant difference between the clinical groups. However, stimulus with CC-Ag showed the megadisease group response to be greater than the response of the indeterminate group, but not different than than of the cardiomyopathy group. The possible biological implications of these findings are discussed.

Adolescent↗

Monocyte suppression of antigen-specific lymphocyte responses in diffuse cutaneous leishmaniasis patients from the Dominican Republic.

Patients from the Dominican Republic with diffuse cutaneous leishmaniasis showed in vivo and in vitro anergy to leishmanial antigen. Relatives of these DCL patients living in the same endemic area frequently showed skin test and lymphocyte reactivity to leishmanial antigens. This further supports the concept of specific anergy in patients with diffuse cutaneous leishmaniasis. Adherent suppressor cells modulate the antigen-specific lymphocyte proliferative response. Suppressor cells could also be isolated by Percoll gradient centrifugation. Co-culturing of lymphocytes and monocytes from HLA-identical leishmanin responders and nonresponders also identified the suppressor cell as a monocyte. In one patient, this suppression disappeared when clinical cure had been accomplished.

Adolescent↗

Leishmaniasis affecting the eyelids.

Leishman-Donovan bodies were recognized in the smear of a biopsy specimen from an eyelid ulcer. The infecting organisms were identified serologically as Leishmania braziliensis panamensis. The ulcer responded to pentavalent antimony. Ultrastructurally, the organisms had double-unit membranes, beneath which lay a palisade of microtubules. At one end of the organism, there was a rudimentary flagellum; at the other, the nucleus. A kinetoplast basal complex separated the two.

Adult↗

Immunologic responses to experimental strongyloidiasis in rats.

Humoral and cellular immune responses were evaluated in Lewis rats infected with high (3000) inocula of Strongyloides ratti larvae (L3). The responses of peripheral and mesenteric node lymphocytes to crude larval antigen (by lymphocyte proliferation assay) sharply rose between days 12 and 16 of the primary infection and days 8 and 12 of the challenge, and decreased promptly to almost preinfection levels. Spleen lymphocytes failed to show any response to the primary infection, but did exhibit a modest response after challenge. The responses of peripheral lymphocytes to the mitogen phytohemagglutinin fell considerably on infection day 8 and then rose sharply to very high levels. Reinfection caused a small decrease in responsiveness, followed by another increase after 10 days. Inoculation of 3000 heat-killed larvae stimulated a response in peripheral lymphocytes similar to that elicited by the inoculation of live larvae. Spleen lymphocytes appeared to be stimulated more by the killed larvae inoculation, whereas only a limited response was found in mesenteric node lymphocytes in animals inoculated with dead larvae. IgG antibody titers against S. ratti antigen were measured by the enzyme-linked immunoabsorbent assay (ELISA). A significant elevation was noted between days 12 and 20 with a return to pre-infection levels between days 80 and 150. Challenge with 3,000 L3 induced a rapid and significant elevation. These data indicate that in rats experimentally inoculated with large numbers of S. ratti larvae a direct relationship exists between the development of cellular and humoral immune responses to larval antigens, the expulsion of the intestinal worms, and the acquisition of resistance to subsequent challenge.

Animals↗

Late metastatic Leishmaniasis in the mouse. A model for mucocutaneous disease.

BALB/c, C57B1/6 and (BALB/c x C57B1/6)F1 mice all proved susceptible to infection by a strain of Leishmania isolated from a Central Brazilian with espundia. The course of disease differed markedly between BALB/c and C57B1/6 mice. BALB/c mice suffered from a rapidly progressive and widely metastatic, but non-ulcerative, disease resembling diffuse cutaneous leishmaniasis. In contrast, C57B1/6 mice initially contained parasite multiplication effectively and appeared clinically cured. However, the parasite could persistently be cultured up to about 1 year post-infection. At that time, the parasite load in the infected footpad increased and a patent disease developed characterized by distinctive ulcerative metastases with destruction of soft-tissue in the nasal region similar to the one observed in espundia. Development of disease in both strains of mice was associated with depression of cell-mediated immunity as monitored by delayed-type hypersensitivity in vivo and lymphocyte transformation in vitro. Thus, our study suggests that diffuse cutaneous leishmaniasis and espundia can be caused by the same strain of parasite, and that the particular clinical expression in the individual mouse is determined by the host response.

Animals↗

Thermosensitivity patterns of Old vs. New World cutaneous strains of Leishmania growing within mouse peritoneal macrophages in vitro.

Infection of mouse peritoneal macrophages in vitro was used to examine the effect of elevated temperature on the intracellular replication of various strains of Leishmania. Of eight cutaneous strains examined, all grew optimally at 35 degrees C. At 37 degrees C the reduction in growth was most pronounced for the New World cutaneous strains, and at 39 degrees C three of four New World cutaneous strains were completely destroyed whereas all of the L. tropica strains survived and exhibited at least 100% growth after 3 days. The results of these in vitro studies correlate closely with the outcome of heat therapy on two patients with cutaneous disease, suggesting that, in general, cutaneous lesions due to L. tropica strains might be less responsive to heat therapy than lesions due to L. mexicana and related strains.

Animals↗

Cellular responses in human strongyloidiasis.

Peripheral lymphocytes from 16 patients with chronic uncomplicated strongyloidiasis and 15 non-infected controls were stimulated in vitro with Strongyloides stercoralis larval antigens, other non-parasite antigens and the T cell mitogen phytohemagglutinin (PHA). In the presence of autologous plasma the patients' responses to Strongyloides antigens were similar to those of controls. When lymphocytes from nine patients were cultured in the presence of normal human serum, responses to parasite antigens were enhanced, while responses to other antigens and to PHA were unaffected. Lymphoproliferative responses to PHA were significantly lower in the patients' group than in the controls. These findings suggest that in chronic strongyloidiasis, in addition to a depression of T cell activity, factors are present in the patients' serum that inhibit parasite-specific cellular responses in vitro.

Cells, Cultured↗

Specific allergic sensitization to Strongyloides antigens in human strongyloidiasis.

Reaginic antibodies to antigens from the human parasite Strongyloides stercoralis were studied by histamine release from basophils in 15 patients with chronic uncomplicated strongyloidiasis and in 12 controls (six North Americans with no evidence of parasitic diseases, two patients with Schistosoma mansoni, two with hookworm, one with Ascaris lumbricoides, and one with Onchocerca volvulus). All of the patients had antibodies to the somatic larval antigens, and 14 of 15 patients also had antibodies to the excretory/secretory products of S. stercoralis larvae. None of the controls had a positive response to any of the antigens tested. These findings indicate that patients with chronic strongyloidiasis have parasite-specific IgE antibodies and that S. stercoralis larval allergens may have a potential role in the immunodiagnosis of strongyloidiasis.

Antigens↗

Specific inhibition of lymphocyte-proliferation responses by adherent suppressor cells in diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis is characterized by multiple nonulcerative skin lesions. Histologically, these lesions are dominated by vacuolated, heavily infected macrophages, with only a few lymphocytes present. A unique focus of diffuse cutaneous leishmaniasis is present in the Dominican Republic. We studied four patients with this disease. None had a delayed reaction to leishmanial antigen on skin tests. The total numbers of lymphocytes and T cells were normal. None of these patients had a lymphocyte-proliferation response to leishmanial antigens, although their responses to other antigens were normal. Adding indomethacin to cultures or decreasing the number of adherent cells by passage of cells over nylon wool reconstituted the lymphocyte responses to leishmanial antigens. Thus, our studies demonstrate that patients with diffuse cutaneous leishmaniasis have a selective anergy to leishmanial antigen, and that an adherent suppressor cell is one mechanism by which this selective immunosuppressive state is modulated.

Adolescent↗

Antibody levels to Trypanosoma cruzi in infected patients with and without evidence of chronic Chagas' disease.

Antibody levels to Trypanosoma cruzi were compared in asymptomatic individuals infected with the parasite as well as those with different forms of chronic Chagas' disease of varying severity. The following three serologic tests were used: complement fixation, direct agglutination with previous treatment of the serum with 2-mercaptoethanol, and the enzyme-linked immunosorbent assay. The clinical groups tested included individuals with (a) a positive serology but no symptoms and without evidence of chronic disease (indeterminate form); (b) mega disease (groups I, II, III, and IV); (c) cardiomyopathy (mild, moderate, and severe); and (d) those with both mega disease and cardiomyopathy (combined form). The mean enzyme-linked immunosorbent assay and complement fixation antibody levels among the various clinical groups showed no statistical differences. With the direct agglutination test patients with mega disease and those with severe cardiomyopathy had slightly higher mean titers than patients in the indeterminate group and those with mild or moderate cardiomyopathy. While there may be possible reasons for these differences, the biological relevance of the findings was concluded to be of dubious significance.

Adult↗

Persistent strongyloidiasis in an immunodeficient patient.

A 56-year-old woman with acquired, common variable immunodeficiency was found to have persistent gastrointestinal as well as pulmonary infection with Strongyloides stercoralis. Repeated courses of treatment with thiabendazole led to marked reduction or loss of Strongyloides stercoralis larvae, but cessation of treatment always led to recurrence of Strongyloides infection. Several small bowel biopsies showed normal villous architecture and little inflammatory response to presence of larvae. Interestingly, no definite symptomatology could be attributed to the Strongyloides infection. It was postulated that the lack of signs and symptoms of strongyloidiasis, as well as poor response to treatment, was related to the immunodeficiency state. With low-dose, long-term interrupted courses of thiabendazole treatment, the Strongyloides infection finally seemed to be cured.

Feces↗

Endemic filariasis on a Pacific island. I. Clinical, epidemiologic, and parasitologic aspects.

The clinical and parasitologic aspects of filariasis were investigated in 459 inhabitants of a South Pacific island endemic for subperiodic Wuchereria bancrofti filariasis. Episodes of filarial fevers, usually with concomitant lymphangitis and/or lymphadenitis, were experienced by 26%. Lymphobstructive lesions, manifest in the later decades of life, were present in 12 with elephantiasis and 24 with hydroceles. Microfilaremia was detectable by membrane filtration of 1 ml of blood in 33% of persons, with a quarter of these having less than 50 microfilariae/ml. Microfilaremia and filarial fevers were more frequent in males than females and in residents of the most inland villages. Neither presence nor magnitude of lymphadenopathy correlated with other manifestations of filariasis except that markedly enlarged inguinal-femoral nodes were more common in those with elephantiasis or hydroceles. A history of filarial fevers did not correlate with presence of microfilaremia. Over 70% of adults had microfilaremia and/or historical or physical manifestations of filariasis. The absence of detectable microfilaremia in many residents with clinical evidence of filariasis and the presence of asymptomatic microfilaremia emphasize the limitations in relying only on microfilaremia rates or clinical findings in the study of the prevalence or manifestations of filarial infection.

Adolescent↗

Non-A, non-B hepatitis after experimental transmission of malaria by inoculation of blood.

In a 1969 prisoner volunteer study of malaria transmission by blood inoculation, six persons were subinoculated sequentially, and acute hepatitis occurred in the last four (sequential study). Subsequently, another 15 volunteers receiving malaria-rich blood from 14 different donors were followed prospectively (prospective study), and hepatitis developed in six. Incubation periods were shorter but serum transaminase levels were higher for the cases of hepatitis occurring in the sequential study than in the prospective study. Although the illnesses were clinically mild, elevations in transaminase levels persisted for more than six months in five and fluctuating transaminase activities were observed in nine of the 10 affected persons. In addition, an 11th prisoner developed sporadic hepatitis. Neither known human hepatitis viruses nor malaria could be implicated in these cases, which were classified as non-A, non-B (NANB) hepatitis. The data suggested that the viremia of short-incubation NANB hepatitis may begin within the first week after inoculation, confirmed that NANB hepatitis may be transmitted either percutaneously or nonpercutaneously, and provided further evidence that there is more than one NANB agent.

Adult↗

Comparison of larval antigens in an enzyme-linked immunosorbent assay for strongyloidiasis in humans.

An enzyme-linked immunosorbent assay for specific antibodies in patients with strongyloidiasis was developed using antigens extracted from the third-stage larvae of Strongyloides stercoralis and Strongyloides ratti. Sera from two groups of patients with strongyloidiasis proven by parasitologic methods, including one group of 29 coded positive sera, and from presumed normal subjects as controls were tested. Sera with optical density values greater than two standard deviations above the mean optical density value for the sera from control subjects were considered to be positive. Using this criterion 82%-84% of 51 positive patients had antibodies to S. stercoralis or S. ratti antigens. Immunosuppression and other factors that might influence antibody responses were associated with some patients who were negative for antibodies to Strongyloides. Antigen from an intestinal nematode of rats, Nippostrongylus brasiliensis, was also evaluated and found to be unsuitable for serodiagnosis of strongyloidiasis because of frequent false-positive as well as false-negative results.

Adult↗

Effect of temperature on multiplication of Leishmania amastigotes within human monocyte-derived macrophages in vitro.

Leishmania tropica, a cause of cutaneous leishmaniasis, multiplied more rapidly within human macrophages in vitro at 35 degrees C than at 37 degree C, and was almost completely eliminated at 39 degrees C. In contrast, Leishmania donovani, the cause of the visceral leishmaniasis, multiplied equally well at 35 degrees C and at 37 degrees C,, and was only 40% eliminated at 39 degrees C. This in vitro study suggests that the localization of the two strains to cooler and warmer regions of the body, respectively, is at least partially explained by the inherent temperature sensitivity of the parasite-macrophage unit. The striking elimination of this strain of L. tropica within macrophages at 39 degrees C may make this model suitable for predicting the clinical response of cutaneous strains to heat therapy.

Humans↗