Showing papers on "Visceral leishmaniasis published in 1987"

An analysis of T cell responsiveness in Indian kala-azar.

Abstract: The inability of most untreated patients with Kala-azar to control their visceral infections with Leishmania donovani has been attributed to a defective cell-mediated immune response to leishmanial antigens. We examined the in vitro response of T cells, including Leu-2+-depleted T cell populations, to determine whether unresponsiveness could be reversed. These studies on patients with visceral leishmaniasis in Bihar, north India, support previous observations regarding T cell unresponsiveness in patients with active disease: it is profound, it is specific, and it is reversible after successful chemotherapy. However, these studies also indicate that the specific unresponsiveness cannot be reversed by depletion of "suppressor" Leu-2+ T lymphocytes, nor by the addition of exogenously supplied human IL 2 to the cultures. One interpretation of these results is that in active cases of Kala-azar, there is an absence of Leishmania-specific T cells in the periphery. The possibility that reactive cells can be found in situ cannot be excluded. The observation that 13 of 25 family members of active cases were able respond to L. donovani in vitro or by skin testing suggests that the frequency of infection within an endemic area in Bihar is very high, and that assays for T cell responsiveness are far better epidemiologic tools for the detection of asymptomatic infection than is ELISA. Identification of such an exposed, Kala-azar-resistant population will be required to study host factors which influence the development of disease in infected individuals.

Malnutrition as a Risk Factor for Severe Visceral Leishmaniasis

Abstract: On a observe une frequence inhabituellement elevee de la malnutrution grave avant l'infection chez les enfants presentant la forme classique. Dans beaucoup de cas la malnutrition joue un role critique dans la progression de la leishmaniose viscerale vers sa forme le plus grave

Evaluation of a newly developed direct agglutination test (DAT) for serodiagnosis and sero-epidemiological studies of visceral leishmaniasis: comparison with IFAT and ELISA

Abstract: A newly developed direct agglutination test (DAT) for visceral leishmaniasis, IFAT and ELISA were applied to sera of patients with visceral leishmaniasis, African and American trypanosomiasis, other parasitic infections and healthy controls. The sensitivities of the 3 tests were comparable (96.3% to 100%); excluding patients with African and American trypanosomiasis, the specificities of DAT and IFAT were 100% and ELISA 87.3%. When trypanosomiasis sera were included, the specificities were 72.6%, 94.3% and 79.4% in DAT, IFAT and ELISA respectively. In 273 sera from a leishmaniasis endemic area (Baringo District, Kenya), the sensitivity was 80% in DAT and IFAT and 60% in ELISA, specificities being 99.6% (DAT), 98.5% (IFAT) and 62.5% (ELISA). As the new DAT is economical and easy to perform, it is recommended for sero-epidemiological field work on visceral leishmaniasis.

Early histopathology of experimental infection with Leishmania donovani in hamsters.

Abstract: The extracellular promastigote stage of Leishmania donovani is inoculated by a phlebotomine sandfly into the skin of a susceptible host, after which visceral dissemination and clinical disease may ensue. Using a hamster model we examined the histopathology of early infection with L. donovani after intradermal inoculation of cultured promastigotes. The initial response was a mixed polymorphonuclear (PMN)-mononuclear phagocyte infiltrate, noted between 1 and 24 hr after inoculation, which became primarily mononuclear by 48 hr. Parasites were initially found intracellularly in both PMN's and mononuclear phagocytes, but by 48 hr they had assumed amastigote-like morphology and were found exclusively in macrophages. The number of parasites per infected macrophage increased during the first week after inoculation, suggesting that intracellular replication of the organism was taking place. This was followed by the formation of granulomas between 4 and 6 wk. By 8 wk intracellular parasites were largely gone. The histologic response was consistent with early destruction of parasites in PMN's, and survival and replication of L. donovani in macrophages. Cutaneous infection with the parasite was eventually controlled locally, coincident with granuloma formation. Despite these local responses, the organism was able to disseminate and eventually produce typical visceral leishmaniasis.

Serodiagnostic assay for visceral leishmaniasis employing monoclonal antibodies.

Abstract: A highly specific and sensitive competitive serodiagnostic assay for visceral leishmaniasis (VL) was developed using species specific Leishmania donovani monoclonal antibodies. This assay, either RIA or ELISA, is based on the specific inhibition of monoclonal antibody binding to a crude parasite homogenate by serum from patients with VL. 15 monoclonal antibodies were examined. The binding of 13 antibodies was significantly inhibited by VL serum and unaffected by normal serum. 3 species-specific monoclonal antibodies, D-2, D-13 and D-14, which recognize different parasite antigens, were chosen for use in the competitive serodiagnostic assay. In 90% of the positive cases, regardless of geographic origin, VL sera inhibited monoclonal antibody binding to the parasite antigen by more than 30%. No false positive was obtained with sera from Chagas disease, lepromatous leprosy, schistosomiasis, malaria, systemic lupus erythematosus, cutaneous or mucocutaneous leishmaniasis, even at serum dilutions (1:100) which cross-react strongly with Leishmania antigen in direct binding assays. Inhibition by negative control sera from areas endemic for VL and from non-endemic areas was negligible. The assay takes less than 24 h, requires minimum amounts of sera or antigen, and is easily standardized allowing interlaboratory comparison of test data. The competitive serodiagnostic assay will be especially useful in areas where Chagas disease is coendemic and the rapid diagnosis of VL by direct binding serodiagnostic assays presents a problem.

Detection of Leishmania donovani soluble antigen and antibody in the urine of visceral leishmaniasis patients.

Abstract: Urine samples from 21 patients with visceral leishmaniasis were examined for the presence of Leishmania donovani soluble antigen and antibody by double counter-current immunoelectrophoresis. 19 samples revealed both antigen and antibody (IgM in 5 and IgG in all samples). 2 urine samples collected 10 and 13 days after Glucantime treatment revealed only antibody (IgG), not soluble antigen.

Histopathological patterns of the liver involvement in visceral leishmaniasis

Abstract: The hepatic changes observed in liver specimen from either biopsy or necropsy of 47 patients with visceral leishmaniasis permited us to define three different histopathological patterns of involvement: typical, nodular, and fibrogenic. These patterns seem to be representative of different evolutive stages of the hepatic involvement in the disease either towards a more benign evolution or to more chronic stage with fibrosis and "cirrhosis". These histopathological evolutive stages are related to the prognosis of the disease.

Immunomodulation of murine visceral leishmaniasis by administration of monoclonal anti-Ia antibodies: differential effects of anti-I-A vs. anti-I-E antibodies.

Abstract: On a B10 genetic background noncure and cure phenotypes for murine visceral leishmaniasis are controlled by H-2. In this report results are presented which show the effects of administering specific anti-I-A and anti-I-E monoclonal antibodies to B10.D2/n (H-2d) noncure mice prior to and during 85 days of infection with Leishmania donovani LV9. The effects of the two anti-Ia antibodies were precisely equivalent in diminishing circulating anti-leishmanial IgG levels throughout infection, possibly as a direct effect of the anti-Ia antibodies in reducing the splenic B cell population. In terms of resolution of liver and spleen parasite loads, which is known to be dependent upon induction of a cell-mediated immune response, dramatically different results were obtained with the two anti-Ia antibodies. Anti-I-A treatment resulted in prolonged exacerbation of disease in liver and spleen. Anti-I-E treatment was associated with enhanced clearance of liver and spleen parasite loads beyond 30 days of infection. The results are consistent with the hypothesis that blocking major histocompatibility complex-restricted antigen presentation by one class II molecule allows T cell responses controlled by the other to predominate. Hence, in H-2d mice, I-E controls suppressor activity while I-A is associated with helper activity for cell-mediated control of infection. The results offer some prospect for the development of haplotype- and class II molecule-specific immunotherapeutic regimens in the host which might prevent the undesirable expansion of T cell populations which exacerbate disease without compromising development of a curative cell-mediated immune response.

Human visceral leishmaniasis: analysis of the specificity of humoral immune response to polypeptides of Leishmania donovani chagasi.

Abstract: . Soluble antigens from Leishmania donovani chagasi were studied in terms of their ability to react with sera from human visceral leishmaniasis. Thirty-six polypeptides, with molecular weights ranging from 14,400 to 123,000 were demonstrated by Western blot analysis. An extensive cross-reactivity with sera from patients with cutaneous leishmaniasis and Chagas' disease also was observed. Two polypeptides (Mr 119,000 and 123,000) reacted with all the sera from visceral leishmaniasis patients. When they were electroeluted from gels and evaluated with respect to specificity to the L. donovani chagasi subspecies, these components were expressed in all strains of Leishmania tested, but not in those of Trypanosoma cruzi. These results indicated that these components are shared by Trypanosomatidae of genus Leishmania. The eluted polypeptides did not react with sera from patients with Chagas' disease, indicating the feasibility of using purified antigens to discriminate between the humoral immune responses in T. cruzi and Leishmania infections.

Antibodies to tubulin in patients with parasitic infections.

Abstract: Sera from a total of 268 patients with protozoan, helminth, bacterial (leprosy and tuberculosis) infections or appropriate controls, were assayed for anti-tubulin antibodies in an indirect enzyme-linked immunosorbent assay (ELISA), using purified tubulin as antigen. Levels of serum anti-tubulin antibody were significantly elevated in 67% of patients with visceral leishmaniasis, in 60% of patients with cutaneous leishmaniasis, in 89% of patients with onchocerciasis, in 100% of patients with schistosomiasis, and in 94% of patients with leprosy. Little or no increase in anti-tubulin antibody levels was seen in sera from patients with malaria (Plasmodium vivax) or tuberculosis.

Activity of purine analogs against Leishmania donovani in vivo.

Abstract: The dose of orally administered 9-deazainosine calculated to suppress 50% of Leishmania donovani amastigotes in hamster livers was 19 mg/kg (body weight) per day; 96 to 99% of Leishmania organisms were eliminated from the liver and spleen of squirrel monkeys by 50 mg/kg per day. Because these activities were greater than that of the experimental clinical agent allopurinol and comparable to that of the classical agent parenteral pentavalent antimony, 9-deazainosine should be considered for clinical development for visceral leishmaniasis.

Visceral leishmaniasis: a case report.

Abstract: Visceral leishmaniasis is diagnosed in a Thai worker returning home from the Middle East. A 39-year-old Thai male who had abdominal swelling, weight loss, hepatosplenomegaly and hyperglobulinemia, was diagnosed by demonstration of organism in liver biopsy and bone marrow aspiration specimen. Amphotericin B was administered in this case.

A direct agglutination test discriminative toward Chagas' disease for the diagnosis of visceral leishmaniasis in Brazil: preliminary results.

Abstract: Summary Two-hundred and sixty-five human sera from Brazil were tested in a direct agglutination assay using trypsinated Leishmania donovani donovani antigen. The assay proved to be of value for the diagnosis of American visceral leishmaniasis in that it was discriminative toward Chagas' disease.

The pathology of experimental visceral leishmaniasis in resistant and susceptible lines of inbred mice.

Abstract: 1. The main pathological features of experimental visceral leishmaniasis were characterized in resistant and susceptible inbred mouse strains. 2. Disseminated granulomas containing parasitized macrophages were found especially in the liver and spleen of two inbred mouse strains, i.e. the resistant DBA/2 and the susceptible C57BL/10 strains, which had been inoculated with Leishmania donovani chagasi amastigotes. 3. The lesions tended to remain granulomatous in nature even during the early acute phase of the more susceptible mouse strain (C57BL/10), and later evolved to a decrease in number of parasites and granulomas and in granuloma diameter. However, no healing occurred up to the end of the observation period of 70 weeks for the C57BL/10 strain. 4. Visceral leishmaniasis in the mouse model does not resemble the classical human Kala-azar, but seems to be more related to oligosymptomatic forms seen in humans living in endemic areas.

Further characterization of Leishmania isolates from children with visceral infection in Alexandria area, Egypt

Abstract: Two visceral Leishmania isolates from children (aged 1 1 2 and 4 years) living in El Agamy area, Alexandria, Egypt, were compared with 5 marker strains, and 2 other human isolates from Sinai and Sudan, identified on clinical and geographical grounds as cutaneous and visceral leishmaniasis respectively. Isoenzyme variations were assessed on the basis of their electrophoretic profiles on cellulose acetate membranes. The enzymes studied were glucose 6-phosphate dehydrogenase E.C.1.1.1.49, phosphoglucomutase E.C.2.7.5.1, 6-phosphogluconate dehydrogenase E.C.1.1.1.44 (6-PGD), glucose phosphate isomerase E.C.5.3.1.9, malate dehydrogenase E.C.1.1.1.37, mannose phosphate isomerase E.C.5.3.1.8 and nucleoside hydrolase E.C.3.2.2.2. The last 4 enzymes could differentiate between cutaneous and visceral strains. The Alexandria strains proved to belong to the L. donovani complex; however, their 6-PGD pattern was identical to that of L. infantum, which was different from that of the L. donovani marker strain.

Subpopulations of T lymphocytes in Kenyan patients with visceral leishmaniasis.

Abstract: Populations of peripheral blood T lymphocytes from patients with Kenyan visceral leishmaniasis were studied using specifically defined antisera (monoclonal antibodies, Ortho-mune OKT3, OKT4, OKT6, and OKT8). The levels of total T lymphocytes and circulating thymocytes were within the same range as those of clinically normal individuals. However, the proportions of the helper/inducer T cells were lower in untreated patients than in the controls (18.9% vs. 39.7%) while the levels of suppressor/cytotoxic T cells were higher than in the controls (40.5% vs. 27.8%). After successful antileishmania treatment these levels showed a gradual return towards normal over a period of one year. It was concluded that immunosuppression observed is due to the levels of peripheral blood helper/inducer and suppressor/cytotoxic T lymphocytes.

Trypsin-treated and coomassie blue-stained epimastigote antigen in a microagglutination test for Chagas' disease.

Abstract: A microagglutination test using trypsin-treated and Coomassie blue-stained Trypanosoma cruzi epimastigote antigen was adapted for the diagnosis of Chagas' disease. When incorporated in the test, 2-mercaptoethanol treatment of chagasic sera had no influence on antibody titer. In contrast, titers in sera from patients with visceral leishmaniasis, African trypanosomiasis, and autoimmune disorders, subjected to similar treatment, showed remarkable decline. Accordingly, a lower cut-off point for Chagas' disease serological negativity could be taken resulting in a higher sensitivity (95.6%); the specificity was 94.7%. Similar specificities were obtained with Leishmania donovani chagasi and L. d. donovani antigens applied to homologous visceral leishmaniasis and heterologous Chagas' sera. Of 316 nonchagasic sera, only 3 with leptospirosis and 1 with leprosy showed seropositive titers prior to and after 2-mercaptoethanol treatment.

Differentiation of Leishmania strains of Indian origin by lectin-mediated agglutination.

Abstract: Characterisation of surface saccharides was carried out in 3 different strains of Indian leishmaniae by 7 lectins. Energy dependent agglutination and role of cytoskeletal disintegrator were also analysed. Wisteria floribunda, peanut agglutinin and soybean agglutinin can be used to differentiate clearly the leishmanial strains causing disease like visceral leishmaniasis, post Kala-azar dermal leishmaniasis and cutaneous leishmaniasis. The remaining lectins have mixed agglutination behaviour towards these strains. The effective concentration of dinitrophenol, sodium azide and colchicine is 10 mM, 25 mM and 1.25 x 10(-2) M, respectively.