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Showing papers on "Visceral leishmaniasis published in 1993"


Journal ArticleDOI
TL;DR: Results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.
Abstract: We have found that an important Th2 cytokine, IL-10, is produced by tissues from patients acutely infected with Leishmania donovani. In all individuals tested, IL-10 mRNA production was increased in lymph nodes taken during acute disease over that observed in postacute samples. In contrast, both pre- and posttreatment lymph nodes had readily detected mRNA for IFN-gamma and IL-2. A down-regulating effect of IL-10 on leishmania-induced proliferative responses was demonstrated when Hu rIL-10 was added to cultures of PBMC from clinically cured individuals. PBMC from individuals with acute visceral leishmaniasis responded to stimulation with leishmania lysate by producing IL-10 mRNA. Simultaneously cultured PBMC collected from the same patients after successful chemotherapy produced no detectable IL-10 mRNA after leishmania antigen stimulation. Neutralizing anti-IL-10 mAb added to PBMC from patients with acute visceral leishmaniasis markedly increased the proliferative response to leishmania lysate. Finally, we observed mRNA for IL-10 and IFN-gamma concurrently in a lesion from a patient with post-kala-azar dermal leishmaniasis (PKDL). These results indicate the production of IL-10 during L. donovani infection, and suggest a role for this cytokine in the regulation of immune responsiveness during visceral leishmaniasis.

454 citations


Journal ArticleDOI
TL;DR: The cloning of a Leishmania chagasi antigen gene and an evaluation of leishmaniasis patient antibody responses to the recombinant protein, rK39, show that rK 39 may replace crude parasite antigens as a basis for serological diagnosis of visceral leish maniasis.
Abstract: We report the cloning of a Leishmania chagasi antigen gene and an evaluation of leishmaniasis patient antibody responses to the recombinant protein, rK39. rK39 contains a 39-amino acid repeat that is part of a 230-kDa protein predominant in L. chagasi tissue amastigotes. Sequence analyses showed this protein, LcKin, to be related to the kinesin superfamily of motor proteins. Southern blot analyses demonstrated LcKin-related sequences in seven species of Leishmania, with conservation of the repeat between L. chagasi and Leishmania donovani. Serological evaluation revealed that 98% (56 of 57) of Brazilian and 100% (52 of 52) of Sudanese visceral leishmaniasis patients have high antibody levels to the rK39 repeat. Detectable anti-K39 antibody was virtually absent in cutaneous and mucosal leishmaniasis patients and in individuals infected with Trypanosoma cruzi. The data show that rK39 may replace crude parasite antigens as a basis for serological diagnosis of visceral leishmaniasis.

419 citations


Journal ArticleDOI
TL;DR: None of the eight soldiers evaluated had classic signs or symptoms of visceral leishmaniasis (kala-azar), but L. tropica can produce visceral infection that can cause unexplained systemic illness in persons returning from areas where this organism is endemic.
Abstract: Background Visceral leishmaniasis, usually caused by Leishmania donovani, has rarely been reported from eastern Saudi Arabia, so it was not expected to affect the soldiers of Operation Desert Storm. Methods We evaluated eight soldiers with visceral leishmanial infection, examining their serum with an immunofluorescent-antibody assay, examining their marrow or biopsy tissue for amastigotes with an indirect immunofluorescent-monoclonal-antibody assay, and culturing the parasites. Cultured promastigotes were isolated and characterized by isoenzyme analysis. Results None of the eight soldiers had classic signs or symptoms of visceral leishmaniasis (kala-azar). Seven soldiers had unexplained fever, chronic fatigue, malaise, cough, intermittent diarrhea, or abdominal pain that began up to seven months after they returned to the United States; one had no symptoms. Five had adenopathy or mild, transient hepatosplenomegaly. None had cutaneous manifestations. Diagnoses were made by bone marrow aspiration (seven pat...

354 citations


Journal ArticleDOI
TL;DR: It is suggested that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host Macrophages that is necessary for the control of leishmanial infection.
Abstract: The immunological mechanisms underlying the susceptibility to disseminated visceral parasitism of mononuclear phagocytes in patients with kala-azar remain undefined. Resistance and susceptibility are correlated with distinct patterns of cytokine production in murine models of disseminated leishmanial disease. To assess lesional cytokine profiles in patients with kala-azar, bone marrow aspirates were analyzed using a quantitative reverse transcriptase PCR technique to amplify specific mRNA sequences of multiple Th1-, Th2-, and/or macrophage-associated cytokines. Transcript levels of IL-10 as well as IFN-gamma were significantly elevated in patients with active visceral leishmaniasis; IL-10 levels decreased markedly with resolution of disease. These findings suggest that IL-10, a potent, pleiotropic suppressor of all known microbicidal effector functions of macrophages, may contribute to the pathogenesis of kala-azar by inhibiting the cytokine-mediated activation of host macrophages that is necessary for the control of leishmanial infection.

346 citations


Book ChapterDOI
TL;DR: The role of the immune response to Leishmania, with particular reference to the cutaneous disease caused by L. major, is discussed, and the concept of suppressor T cells is reviewed.
Abstract: Publisher Summary This chapter discusses the role of the immune response to Leishmania, with particular reference to the cutaneous disease caused by L. major. Leishmaniasis is caused by species of the intracellular protozoan parasite belonging to the genus Leishmania. There are three main categories of leishmaniasis: cutaneous leishmaniasis (oriental sore), mucocutaneous leishmaniasis (espundia), and visceral leishmaniasis (kala-azar). In humans, infection with Leishmania results in a spectrum of disease dependent upon the species involved and the efficiency of the host's immune response to the parasite. Diagnosis of active leishmaniasis is based primarily on the demonstration of the parasite in biopsies. A skin test using a killed whole parasite preparation (leishmanin) is used as a presumptive test. Genetic regulation of leishmaniasis is discussed in reference to mouse and humans, and the concept of suppressor T cells is reviewed. The various cytokines in leishmaniasis, including interferon (IFN) γ and interleukin (IL)-4, IL-10, IL-1, and IL-2 are also discussed.

339 citations


Journal ArticleDOI
TL;DR: An increase in travel, the Indian and Sudanese epidemics of visceral leishmaniasis, parasite resistance to antimony and the emergence of AIDS-related leish maniasis have all increased the urgency for new drugs, and led to reappraisals of the old ones, as discussed here.

215 citations


Journal ArticleDOI
TL;DR: The results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections, where preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma- producing Th1 cells may protect the host from severe disease.
Abstract: Infections in humans by Leishmania donovani parasites can result in a fatal disease, visceral leishmaniasis (VL), or in a self-limiting asymptomatic infection. In murine models of the infection employing Leishmania major, the course of the disease can be directed into a VL-like syndrome by interleukin-4 (IL-4)-producing Th2 cells, or cure may result by Th1 cells secreting gamma interferon (IFN-gamma). The present study examined the potential of human T cells to generate Th1 or Th2 responses to L. donovani. The profiles of IFN-gamma, IL-4, and lymphotoxin secretion after antigen stimulation were analyzed in a panel of L. donovani-reactive CD4+ human T-cell clones generated from individuals who had recovered from VL after antimonial treatment. Two of the T-cell clones produced large amounts of IL-4 without production of IFN-gamma, seven clones produced both IFN-gamma and IL-4, and eight produced only IFN-gamma. This is the first report of a Th1- and Th2-type response in human leishmaniasis. These results suggest that in analogy with murine models, there is a dichotomy in the human T-cell response to L. donovani infections. Preferential activation of IL-4-producing Th2-like cells may be involved in the exacerbation of human VL, whereas activation of IFN-gamma-producing Th1 cells may protect the host from severe disease. Identification of leishmanial antigens activating one or the other type of T cells will be important in the development of vaccines against leishmaniasis.

146 citations


Journal ArticleDOI
TL;DR: In a comparative trial of treatment in southern Sudan, visceral leishmaniasis was diagnosed by the following symptoms: fever for > 1 month, splenomegaly, and antileishmanial direct agglutination test (DAT) titer of > or = 1:25,600.
Abstract: In a comparative trial of treatment in southern Sudan, visceral leishmaniasis was diagnosed by the following symptoms: fever for > 1 month, splenomegaly, and antileishmanial direct agglutination test (DAT) titer of > or = 1:25,600. Patients (200) were randomized to receive sodium stibogluconate (Sbv) at 20 mg/kg/day for 30 days (groups S, n = 99) or Sbv at 20 mg/kg/day plus aminosidine at 15 mg/kg/day for 17 days (group AS, n = 101). Of 192 patients who had spleens or lymph nodes aspirated at entry, 134 (70%) were positive for parasites. During treatment, 7% in group S and 4% in group AS died. All 184 patients who completed treatment were clinically cured. At days 15-17, microscopy of aspirates showed that 57 (95%) of 60 in group AS were negative for parasites compared with 47 (81%) of 58 in group S (P = .018). At day 30, 57 (93.4%) of 61 group S aspirates were negative.

123 citations


Journal ArticleDOI
TL;DR: To construct a DNA probe specific for protozoa that cause visceral leishmaniasis, Pst I fragments of Leishmania infantum genomic DNA were cloned into a Bluescript II SK vector and detected an amount of DNA equivalent to one promastigote of L. infantum.
Abstract: To construct a DNA probe specific for protozoa that cause visceral leishmaniasis, we cloned Pst I fragments of Leishmania infantum genomic DNA into a Bluescript II SK® vector. A clone of 4.3 kb that contained a highly repetitive sequence was isolated and cut with three restriction enzymes: Hae III, Rsa I, and Sau 3A. After a new molecular cloning step, we isolated and sequenced a 140-basepair (bp) fragment. Two oligonucleotides were synthesized to be used as primers for a polymerase chain reaction. Using this probe, we detected an amount of DNA equivalent to one promastigote of L. infantum. This probe showed a high specificity; all protozoa tested that cause visceral leishmaniasis and L. major (one of the causative agents of Old World cutaneous leishmaniasis) showed a 100-bp amplified sequence, whereas other Leishmania strains showed a signal of a different size or else no signal. Moreover, no amplified sequence was obtained with other pathogenic parasites tested (Trypanosoma brucei, T. cruzi, Plasmodium falciparum, Pneumocystis carinii, and Toxoplasma gondii).

98 citations


Journal ArticleDOI
TL;DR: Interferon-γ (IFN-γ) in combination with pentavalent antimony has been used successfully in treating patients refractory to pentavalant antimony and in patients with previously untreated visceral leishmaniasis.
Abstract: Traditionally, the mainstay of visceral and diffuse cutaneous leishmaniasis therapy has been pentavalent antimony, with pentamidine and amphotericin B reserved for refractory cases. Interferon-gamma (IFN-gamma) in combination with pentavalent antimony has been used successfully in treating patients refractory to pentavalent antimony and in patients with previously untreated visceral leishmaniasis (39 total). In addition, 6 patients with diffuse cutaneous leishmaniasis have been treated with combination IFN-gamma and antimony therapy. Preliminary experience with these patients indicates that IFN-gamma is a useful adjunct therapy for severe or refractory cases of visceral leishmaniasis; however, the potential of IFN-gamma in treating diffuse cutaneous leishmaniasis cannot be assessed as current clinical experience is too limited.

97 citations


Journal ArticleDOI
TL;DR: 19 of the 20 patients were without visible parasites in the bone marrow; the mean time to afebrility was 4.2 days; spleen size regressed by a mean of 79% 2 months after therapy; and no patient had clinical or laboratory abnormalities by the end of 6-12 months of follow-up.
Abstract: Amphotericin B is an effective but toxic antileishmanial agent. Lipid-encapsulated amphotericin B should have a high therapeutic index for visceral leishmaniasis because reticuloendothelial cells, the sole site in which Leishmania is found, will phagocytize and concentrate the complex. Amphotericin B cholesterol dispersion (Amphocil; 2 mg/[kg.d] intravenously) was administered to 10 Brazilians with kala-azar for 10 days (cohort 1) and to 10 Brazilians with kala-azar for 7 days (cohort 2). All patients were successfully treated: 19 of the 20 patients were without visible parasites in the bone marrow; the mean time to afebrility was 4.2 days; spleen size regressed by a mean of 79% 2 months after therapy; and no patient had clinical or laboratory abnormalities by the end of 6-12 months of follow-up. Side effects were fever and chills accompanied by respiratory distress, but not nephrotoxicity, in children < 3 years of age.

Journal ArticleDOI
TL;DR: It is concluded that children are indeed more susceptible to visceral leishmaniasis when they are younger and more malnourished, but it remains unclear whether the immunity to VL acquired with age is always acquired as a result of infection.
Abstract: Children are said to be at greater risk of developing visceral leishmaniasis (VL) when they are younger and more malnourished. If malnutrition really is associated with VL, this potentially fatal and visible disease may be a general indicator of community health among the rural and suburban poor. Previous conclusions reached about the roles of malnutrition and age in VL epidemiology are questionable because they may have been confounded by transmission rate, because they have not been able to distinguish between different mechanisms of acquiring immunity, and because empirical observations have not been compared with theoretical expectations. Here we offer a framework with which to investigate these questions quantitatively, and do so with published data from endemic areas of Brazil. We conclude that children are indeed more susceptible to VL when they are younger and more malnourished, but it remains unclear whether the immunity to VL acquired with age is always acquired as a result of infection. The significance for leishmaniasis control, and for the control of other diseases associated with malnutrition, will depend on underlying mechanisms, which are not yet understood.

Journal ArticleDOI
01 Feb 1993-AIDS
TL;DR: Direct visualization of Leishmania amastigotes in leukocytes on peripheral blood smears enabled the diagnosis of kala-azar in a high proportion of HIV-infected patients, and all eight individuals presenting with Leishmaniasis in peripheral blood leukocyte were HIV-positive.
Abstract: The authors sought to compare the clinical and laboratory features of visceral leishmaniasis (kala-azar) in HIV-infected and noninfected subjects and to determine the presence of Leishmania amastigotes in circulating leukocytes using peripheral blood smears. 28 HIV-infected and 6 HIV-negative adult patients diagnoses as having kala-azar and presenting at one institution over a 7-year period were studied by performing a retrospective review of their clinical charts and a reexamination of their peripheral blood smears. There were no significant differences in the clinical presentation and laboratory features of HIV-positive and HIV-negative patients. However Leishmania amastigotes were observed in circulating leukocytes in 8 of 17 available peripheral blood smears (15 from HIV-infected patients). All 8 individuals presenting with Leishmania in peripheral blood leukocytes were HIV-positive. The authors concluded that direct visualization of Leishmania amastigotes in leukocytes on peripheral blood smears enabled the diagnosis of kala-azar in a high proportion (8 of 15; 53%) of the HIV-infected patients. (authors modified)

Journal ArticleDOI
TL;DR: Two cases of visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV) are described and the effectiveness of treatment with liposomal amphotericin B is confirmed, which directly targets infected macrophages and reaches high levels in plasma and tissue.
Abstract: We describe two cases of visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV); both cases were resistant to antimony compounds but were cured with liposomal amphotericin B, with no significant toxicity. A review of the previous reported cases of antimony-resistant visceral leishmaniasis in HIV-infected patients confirmed the effectiveness of treatment with liposomal amphotericin B, which directly targets infected macrophages and reaches high levels in plasma and tissue.

Journal ArticleDOI
TL;DR: Differences in splenic aspirate culture results raise the possibility that combination therapy using IFN-gamma, which was safe and well-tolerated, may accelerate the early parasitologic response in patients with visceral leishmaniasis.
Abstract: Twenty-four Kenyan patients with visceral leishmaniasis were treated for 30 days with either conventional therapy (daily pentavalent antimony, n = 14) or experimental immunochemotherapy (daily antimony plus interferon-gamma [IFN-gamma] every other day, n = 10). All 24 patients responded clinically to treatment, and microscopic splenic aspirate scores rapidly decreased in both groups. As judged by splenic aspirate culture results, IFN-gamma-treated patients responded more quickly (50% versus 22% culture-negative after one week and 75% versus 58% culture-negative after two weeks). While not statistically significant, these differences raise the possibility that combination therapy using IFN-gamma, which was safe and well-tolerated, may accelerate the early parasitologic response in patients with visceral leishmaniasis.

Journal ArticleDOI
TL;DR: The FAST-ELISA system provides a sensitive, specific, and field-adaptable test for canine visceral leishmaniasis, which can be evaluated quickly without the use of a microscope or spectrophotometric results.
Abstract: The Falcon assay screening test-enzyme-linked immunosorbent assay (FAST-ELISA), the latest version of the enzyme-linked immunosorbent assay, uses antigen-coated beads. A 96-well plate can be run in 20 min without electricity or expensive equipment. We compared the FAST-ELISA, a standard ELISA, and an indirect immunofluorescent assay (IFA) for evaluation of canine leishmaniasis under field conditions using samples from 161 dogs from our longitudinal study in the endemic area of Jacobina, Bahia, Brazil. Organisms were isolated by culture (NN medium) or by inoculation of hamsters with samples from 59 of the dogs. When plasma were tested, we found a sensitivity of 88% and a specificity of 90% using the FAST-ELISA with a spectrophotometer. Using the same plasma samples, the IFA had a sensitivity of 75% and a specificity of 93%. The standard ELISA had a sensitivity of 90% and a specificity of 85%. When whole blood was tested with the FAST-ELISA, we found a sensitivity of 85%. There was no significant difference between visual and spectrophotometric results with plasma or whole blood. The FAST-ELISA system provides a sensitive, specific, and field-adaptable test for canine visceral leishmaniasis, which can be evaluated quickly without the use of a microscope or spectrophotometer.

Journal ArticleDOI
TL;DR: Sera from visceral leishmaniasis patients with human immunodeficiency virus (HIV) infection were examined for anti-Leishmania immunoglobulin G (IgG) antibodies and compared with patients without HIV (controls), finding significant titres of specific IgG were found in 81.8% of co-infections.
Abstract: Twenty-two sera from visceral leishmaniasis (VL) patients with human immunodeficiency virus (HIV) infection (50% with the acquired immune deficiency syndrome) were examined for anti-Leishmania immunoglobulin G (IgG) antibodies and compared with 35 sera from VL patients without HIV (controls). Significant titres of specific IgG were found in 81.8% of co-infections. However, while control sera showed a restricted range of anti-Leishmania IgG titres, sera from co-infection cases displayed a considerable degree of variability, both quantitative and qualitative. They were clearly divided into 2 groups: one (18 sera) showing a continuous grading from nil to mid-concentrations of specific antibodies, the other (3 sera) showing titres 30-fold higher than this range. Taking into account the major immunological abnormalities involving humoral response described in HIV patient, the 2 groups may reflect a different sequence of acquisition of the 2 infective agents; the former representing VL acquired after HIV infection, and the latter representing the contrary situation.

Journal ArticleDOI
TL;DR: Results suggest that amphotericin B may be of particular use for T-cell-deficient patients with visceral leishmaniasis, and suggest that the in vivo efficacies of alternative antileishmanial agents also require T cells.
Abstract: In experimental visceral leishmaniasis, euthymic but not athymic (nude) BALB/c mice respond to conventional treatment with pentavalent antimony, indicating that the in vivo efficacy of antimony is T cell dependent. This finding correlates with frequent antimony treatment failures for T-cell-deficient patients with visceral leishmaniasis. To determine whether the in vivo efficacies of alternative antileishmanial agents also require T cells, Leishmania donovani-infected euthymic and nude BALB/c mice were treated with pentamidine or amphotericin B. Pentamidine induced leishmanistatic activity in euthymic mice but had little effect in nude mice. In contrast, amphotericin B exerted potent leishmanicidal activities in both euthymic and nude animals. These results suggest that amphotericin B may be of particular use for T-cell-deficient patients with visceral leishmaniasis.

Journal ArticleDOI
TL;DR: Sera from most acute visceral leishmaniasis patients from Brazil and Sudan had notably high levels of antibody to recombinant (r) gp63, indicating that rgp63 might be a useful constituent of a defined serologic test for visceral leishingmaniasis.
Abstract: A major surface glycoprotein of Leishmania parasites, gp63, is highly conserved among species and is expressed in both infective and intracellular stages. Although much is known about its role in entry and survival in host macrophages, patient antibody responses to this glycoprotein have not been well characterized. The prevalence of anti-gp63 antibody in sera of leishmaniasis patients was evaluated by ELISA. Sera from most acute visceral leishmaniasis patients (84%) from Brazil and Sudan had notably high levels of antibody to recombinant (r) gp63. Sera from other forms of leishmaniasis and from other diseases did not contain significantly elevated levels of anti-gp63 antibody. These results indicate that rgp63 might be a useful constituent of a defined serologic test for visceral leishmaniasis.

Journal ArticleDOI
TL;DR: The granulomatous aspect of the lesions indicates a good immunologic reactivity and suggest that a host-parasite equilibrium does exist in the dog experimental model.
Abstract: Pathological aspects of a subclinical form of experimental canine leishmaniasis is reported here for the first time. Fifteen mongrel dogs were used in the present study. Eight dogs were infected and seven were used as control. Four of the control dogs were inoculated with spleen cells from non-infected hamsters. The eight mongrel dogs inoculated intravenously with amastigotes forms of Leishmania chagasi evolved for periods as long as 25 months without any clinical characteristic sign of classical Visceral Leishmaniasis (VL). Most of the laboratory test results were compatible to those of the seven control animals but culture of bone marrow aspirated material and serologic testing (IIF) demonstrated or provided evidence that the animals were infected. The most important and predominant histopathological lesion in infected animals were epithelioid granulomas presented in the liver, spleen, adrenal gland and lung of some animals. Channels containing erythrocytes in some granulomas of the liver suggest that these granulomas are formed inside sinusoidal capillaries. Despite the animals were proved to be infected and presented characteristic histologic lesions, they did not present external signs of disease. The granulomatous aspect of the lesions indicates a good immunologic reactivity and suggest that a host-parasite equilibrium does exist in the dog experimental model.

Journal ArticleDOI
TL;DR: If stibogluconate is used for treatment of renal transplant recipients, it is advised extreme caution with close observation and combination therapy to be considered instead.
Abstract: A case of a renal transplant recipient who developed pancreatitis during stibogluconate treatment for visceral leishmaniasis and who was successfully treated with a combination of allopurinol and ketoconazole is reported. The features of this case are compared with those of the three previously reported cases of pancreatitis during stibogluconate treatment. Complete cure was achieved during the follow-up period of 15 months. If stibogluconate is used for treatment of renal transplant recipients, we advise extreme caution with close observation and combination therapy to be considered instead.

Journal ArticleDOI
TL;DR: The direct agglutination test (DAT) is a sensitive and specific test to confirm visceral leishmaniasis and is recommended for use under field conditions.
Abstract: The direct agglutination test (DAT) has been assessed as a diagnostic procedure for visceral leishmaniasis. Fifty-six of 58 sera (96·5%) from confirmed cases of visceral leishmaniasis, whose bone marrow aspirates contained Leishmania donovani amastigotes, had agglutinating antibodies above the cut-off titre of 1:800. None of the sera from healthy control subjects from non-endemic or endemic areas had anti-leishmanial antibodies. Similarly, none of the sera obtained from cases of malaria or tuberculosis had agglutinating antibodies above the cut-off titre. A significant decline in agglutinating antibody titre in 3 cases following anti-leishmanial chemotherapy appeared to correlate with regression of clinical symptoms and the absence of amastigotes from bone marrow aspirates. One of 3 cases developed post-kala-azar dermal lesions and sera from this subject had an elevated agglutinating antibody titre. It is concluded that the DAT is a sensitive and specific test to confirm visceral leishmaniasis. As the formalin-fixed promastigotes, stained with Coomassie blue, which are used as antigen could be stored at 4 °C for 6 months without any loss of ability to detect anti-leishmanial antibodies, the DAT is recommended for use under field conditions.

Journal ArticleDOI
TL;DR: This study describes a male patient with human immunodeficiency virus infection, grade IV-C (oropharyngeal moniliasis and Pneumocystis carinii pneumonia), associated with visceral involvement produced by Leishmania braziliensis, identified by deoxyribonucleic acid hybridization after the polymerase chain reaction had been performed.
Abstract: This study describes a male patient with human immunodeficiency virus infection, grade IV-C (oropharyngeal moniliasis and Pneumocystis carinii pneumonia), associated with visceral involvement produced by Leishmania braziliensis which was identified by deoxyribonucleic acid hybridization after the polymerase chain reaction had been performed. The patient was treated with molgramostim in association with meglumine antimonate to enhance macrophage destruction of parasites.

Journal Article
TL;DR: Visceral leishmaniasis was experimentally induced in hamsters by the intracardiac inoculation of 10(7) amastigotes of Leishmania leishmania infantum of canine origin and dogs developed significantly altered hematologic values consisting of mild anemia and moderate leukopenia at PI weeks 8 to 12.
Abstract: Visceral leishmaniasis was experimentally induced in hamsters by the intracardiac inoculation of 10(7) amastigotes of Leishmania leishmania infantum of canine origin. At postinoculation (PI) days 7, 21, 42, and 63, hamsters were euthanatized. Body weights and total parasite numbers of the liver and spleen were determined. Gross and histologic evaluations of tissues were done. Dogs also were inoculated IV with 10(8) amastigotes/kg of body weight. Samples were obtained from dogs prior to infection and at biweekly PI intervals for CBC and serum chemical analysis, for lymphocyte blastogenic assay by use of blood leukocytes, and for ELISA to determine antileishmanial antibody titers. At PI week 12, dogs were necropsied; organ weights, tissue imprints of the liver and spleen, and histologic interpretations of tissues were obtained. Hamsters developed high parasite numbers within 7 days after inoculation, at which time the total parasite numbers in the liver (3.51 x 10(7) amastigotes) was observed to be approximately 11 times that in the spleen (2.93 x 10(6)). The liver had the highest parasite numbers throughout the infection period. Some infected hamsters became either cachectic and emaciated or ascitic. Two of the 10 infected hamsters died at PI days 54 and 58. Moderate to severe hepatosplenomegaly with granulomatous inflammatory reactions characterized by the presence of varied numbers of parasitized macrophages, giant cells, and hepatic Schaumann bodies were observed in infected hamsters. Infected dogs developed significantly altered hematologic values consisting of mild anemia and moderate leukopenia at PI weeks 8 to 12. Hyperproteinemia characterized by hyperglobulinemia (4.5 g/dl) was noticed at PI week 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal Article
TL;DR: Both antigenic and immunogenic gp63 peptide sequences have been defined, some appearing to be conserved among Leishmania species and at least one that appears to be species specific.
Abstract: Both a conserved surface metalloprotease of leishmania, gp63 as well as certain gp63-derived peptides, have been shown to have immunoprophylactic potential in mouse models of leishmaniasis. In addition, PBMC from individuals with cutaneous, mucosal, or cured visceral leishmaniasis respond in vitro to both native and rgp63. In this report, we mapped human T cell epitopes within gp63. T cells from leishmaniasis patients responded in vitro to certain peptides of gp63 by proliferation and IFN-gamma production. One peptide, (PT7), stimulated cells from all individuals tested (n = 7). Anti-PT7 T cell lines derived from PBMC of a mucosal leishmaniasis patient contained a heterogeneous population of cells which responded by proliferation and IFN-gamma production to in vitro stimulation with Leishmania promastigote lysate. Another peptide (PT1) derived from Leishmania chagasi gp63 stimulated PBMC from an L. chagasi patient although the corresponding Leishmania major-derived peptide did not. Both L. major PT7 and L. chagasi PT1 were able to induce anti-Leishmania-specific T cell lines from normal human PBMC. These T cell lines responded to in vitro stimulation with promastigote lysate indicating that both peptides were immunogenic for naive T cells in vitro. In conclusion, both antigenic and immunogenic gp63 peptide sequences have been defined, some appearing to be conserved among Leishmania species and at least one that appears to be species specific.


Journal ArticleDOI
TL;DR: Visceral leishmaniasis was observed in a 50-year-old female liver transplant recipient 1 year following transplantation and the patient remains without signs of active infection 1 year after successful therapy.
Abstract: Visceral leishmaniasis was observed in a 50-year-old female liver transplant recipient 1 year following transplantation. Signs of active infection were low-grade fever, pancytopenia, persistent splenomegaly, positive cultures for leishmania in liver and bone marrow biopsy specimens, and newly positive leishmania serology. Following sequential therapy with pentavalent antimony and amphotericin B, blood values improved massively, bone marrow cultures became negative, and leishmania serology decreased. Secondary prophylaxis with fluconazole was instituted and the patient remains without signs of active infection 1 year after successful therapy.

Journal ArticleDOI
TL;DR: Three consecutive daily doses of AmBisome were sufficient to clear all parasites from the liver of mice, while antimony did so only after 21 doses, and should enable visceral leishmaniasis treatment on an intermittent or outpatient basis, thereby reducing overall treatment costs.
Abstract: Preliminary observations have shown that AmBisome, a liposomal formulation of amphotericin B (Vestar Inc.), is effective and non-toxic in animal and human visceral leishmaniasis. The activity of multiple doses of this drug on Leishmania infantum, in BALB/c mice was investigated, and amphotericin B concentration in liver and spleen was determined. Groups of infected mice were treated intravenously with 3, 5, or 7 doses of AmBisome (3 mg/kg) over 3, 10 and 25 days, respectively. The antileishmanial activity of the drug was compared with that of meglumine antimoniate (28 mg Sbv/kg per day over 21 days). Three consecutive daily doses of AmBisome were sufficient to clear all parasites from the liver of mice, while antimony did so only after 21 doses. Twenty-four-48 h after their last dose all the AmBisome-treated mice showed very high amphotericin B concentrations in liver (61.2-76.2 micrograms/g) and spleen (39.8-72.1 micrograms/g) with no overt signs of toxicity. Mice that received 2 or 4 doses at intervals of 5 to 8 days, maintained drug levels as high as those detected after 3 consecutive doses over 11 and 26 days, respectively. This should enable visceral leishmaniasis treatment on an intermittent or outpatient basis, thereby reducing overall treatment costs.

Journal ArticleDOI
TL;DR: This case reminds us of the possibility of contracting visceral leishmaniasis in Mediterranean countries and illustrates the interesting similarities between these two disorders involving the mononuclear phagocyte system as well as the problems involved in differential diagnosis.
Abstract: A one-year-old Swedish boy developed kala-azar six months after a holiday in Spain. Upon visiting the hospital after one week of illness he demonstrated clinical and laboratory findings of fever, splenomegaly and cytopenia. A fine-needle aspiration biopsy of the spleen revealed hemophagocytosis and he had increased serum levels of the cytokines tumor necrosis factor-alpha and interferon-gamma. Initially, a diagnosis of hemophagocytic lymphohistiocytosis was made. Re-evaluation of the spleen smears and of the bone marrow aspiration revealed Leishmania parasites and subsequent therapy with sodium stibogluconate was successful. This patient illustrates the interesting similarities between these two disorders involving the mononuclear phagocyte system as well as the problems involved in differential diagnosis. This case also reminds us of the possibility of contracting visceral leishmaniasis in Mediterranean countries.

Journal ArticleDOI
TL;DR: The increase in leishmanin positivity with age parallels the age-specific disease profile and indicates an outdoor exposure to infection.
Abstract: A cross-sectional leishmanin skin test was carried out on a sample population of 730 individuals. The overall prevalence of leishmanin positivity was 36·4%; 50·9% of males and 23·2% of females showed positive skin test reaction. The skin-test profile in the study area is typical of an endemic focus of visceral leishmaniasis. The increase in leishmanin positivity with age parallels the age-specific disease profile and indicates an outdoor exposure to infection.