Visceral leishmaniasis

About: Visceral leishmaniasis is a research topic. Over the lifetime, 7486 publications have been published within this topic receiving 184865 citations. The topic is also known as: Kala-Azar & viscus leishmaniasis.

Restoration of IFN-gamma production and lymphocyte proliferation in visceral leishmaniasis.

Abstract: Visceral leishmaniasis is associated with a marked depression of T cell responses, which has been characterized by the absence of IL-2 and IFN-gamma production by lymphocytes on in vitro stimulation with Leishmania Ag. The aim of this study was to evaluate both the mechanism of these immunologic abnormalities and the restoration of in vitro T cell responses to Leishmania Ags. A total of 15 untreated visceral leishmaniasis patients were evaluated. Although IFN-gamma and IL-4 levels in the supernatants of lymphocyte cultures were very low or absent, mRNA for these cytokines and for IL-10 were observed in PBMCs. Addition of IFN-gamma plus IL-2 enhanced lymphocyte proliferation by 158%. Restoration of T cell proliferative responses and IFN-gamma production was also observed by the addition of a neutralizing mAb alpha-IL-10. Neutralizing mAb alpha-IL-4 did not restore T cell responses but alpha-IL-10 and alpha-IL-4 mAbs had a synergistic effect on lymphocyte proliferation. The IFN-gamma levels in supernatants of lymphocyte cultures stimulated with Leishmania chagasi Ag or L. chagasi Ag plus alpha-IL-4, alpha-IL-10, or alpha-IL-4 plus alpha-IL-10 mAbs were 26 +/- 30 pg/ml, 41 +/- 18 pg/ml, 146 +/- 73 pg/ml, and 174 +/- 106 pg/ml, respectively. These data indicate that Th2 cell activation occurs in visceral leishmaniasis and that in vitro production of IFN-gamma and lymphocyte proliferation can be restored by blocking the inhibitory effect of the Th2 cytokines on mononuclear cells.

Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis

Abstract: Visceral leishmaniaisis (kala-azar) is a disseminated protozoal infection transmitted by sandfly bite in which macrophages of the liver spleen and bone marrow are preferentially parasitized and support intracellular replication. Most human infections caused by visceralizing strains of Leishmania are probably subclinical attesting to innate resistance or more likely to T (Th1)-cell-dependent immune responses which induce acquired resistance. While treatment is not given for subclinical infection remote recrudescence still remains a possibility especially if the host becomes T-cell deficient. In contrast if the initial Th1-cell-associated immune response fails to develop or its effector mechanisms are disabled or not properly maintained recently acquired (or reactivated) kala-azar evolves to full expression as a subacute or chronic illness for which treatment is required. (excerpt)

Differential production of Th1- and Th2-derived cytokines does not determine the genetically controlled or vaccine-induced rate of cure in murine visceral leishmaniasis.

Abstract: Recent studies with models of cutaneous leishmaniasis have provoked much interest in the role of CD4+ T cell subsets in determining the outcome of infectious disease In Leishmania major infections, cure vs progressive disease correlates with the expansion of Th1-like or Th2-like CD4+ populations, respectively We have investigated whether similar responses are associated with the differential patterns of infection seen in models of visceral leishmaniasis, caused by L donovani Splenic lymphocytes from infected Lsh congenic C57BL/10 (Lshs;H-2b) and B10L-Lshr (Lshr;H-2b) mice and MHC congenic non-curing B10D2/n (Lshs;H-2d) mice were examined for the production of cytokines representative of these CD4+ populations (IL-2, IL-3, IL-4, IL-5, and IFN-gamma) In all three strains examined, there was no evidence for the production of Th2-restricted cytokines In addition, levels of serum IgE were depressed during the early phase of infection, indicative of in vivo IFN-gamma production In the non-curing B10D2/n strain, late phase of infection was associated with the decreased ability to produce cytokines in response to Ag and not with the production of IL-4 or IL-5 in response to Ag or mitogen Serum IgE levels were also not raised above levels seen in uninfected controls C57BL/10 mice were vaccinated with SDS-PAGE fractionated amastigote Ag bound to nitrocellulose and cytokine levels determined at various times after infection The protocol used for vaccination was able to induce significant modulation of the course of infection in this strain and it was clear that IFN-gamma production in vitro provided an excellent correlate of rate of cure Occasional individuals produced low levels of IL-5 in culture in response to parasite Ag, but this did not correlate with disease progression Together, these data suggest that over-expansion of Th2-type cells and production of their specific cytokines (IL-4 and IL-5) is not a contributing factor to the variable long term course of L donovani infection in these strains of mice

Phase 4 trial of miltefosine for the treatment of indian visceral leishmaniasis

Abstract: Visceral leishmaniasis (VL) is a major public health problem in Bihar accounting for 90% of all cases in India. Development of high levels of resistance to various existing drugs necessitated the search for alternative orally administered drugs. Hospital-based studies have shown that oral miltefosine is a highly effective treatment for VL both in adults and in children. An open single-arm trial was designed to investigate the feasibility of treatment of VL patients with miltefosine in field conditions in 13 centers in Bihar. The phase 4 study was conducted among 1132 adult and pediatric VL patients. Compliance was good with 1084 (95.5%) patients completing the full 28-day treatment course. Nine hundred and seventy-one (85.8%) patients returned for the final cure assessment at 6 months after treatment. The final cure rate was 82% by intention to treat analysis and 95% by per protocol analysis (similar to the 94% cure rate in hospitalized patients). Treatment-related adverse events of common toxicity criteria grade 3 occurred in ~3% of patients including gastrointestinal toxicity and rise in aspertate amino transferase alanine amino transferase or serum creatinine levels similar to previous clinical experience. This study supports the use of miltefosine in an outpatient setting in an area where VL is endemic. (authors)