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.

IL-10 neutralization promotes parasite clearance in splenic aspirate cells from patients with visceral leishmaniasis.

Abstract: The mechanisms underlying the failure to contain the growth of Leishmania parasites in human visceral leishmaniasis (VL) are not understood. L donovani amastigotes were quantified in cultured splenic aspirate cells to assess the function of IL-10 in lesional tissue ex vivo. In 67 patients with active VL, IL-10 neutralization promoted parasite killing in 73% and complete clearance in 30%, while 18% had more parasites and 9% did not change. The splenic cells secreted increased levels of both tumor necrosis factor α (TNFα) and interferon γ (IFNγ) under IL-10-neutralizing conditions. These findings provide direct support for targeting IL-10 as an approach to therapy in human VL.

Treatment of visceral leishmaniasis in Kenya by aminosidine alone or combined with sodium stibogluconate

Abstract: The treatment of leishmaniasis, as currently conducted in Kenya with sodium stibogluconate, is unsatisfactory as it is expensive, resistance and relapses may occur, and major adverse effects have been reported. Recently, aminosidine (paromomycin) sulphate has shown good antileishmanial activity on its own as well as synergism with pentavalent antimony, administered concurrently. The present study was designed to assess the effectiveness of parenteral aminosidine, alone or combined with sodium stibogluconate, in visceral leishmaniasis, compared to treatment by stibogluconate alone. 53 patients were allocated to the 3 therapeutic regimes. The presenting signs and symptoms of leishmaniasis were those commonly seen in the visceral form of the disease, particularly in Kenya. At termination, clinical cures were achieved in all 53 patients with no difference between treatment groups. Spleen aspirates revealed the best parasitological results in patients receiving the combined treatment, with only 13% failures (partial cures+relapses), as opposed to 21% failures with aminosidine alone and 45% with stibogluconate alone. Treatment with aminosidine alone was the cheapest and safest regime.

Loss of virulence in Leishmania donovani deficient in an amastigote-specific protein, A2

Abstract: Leishmania donovani is the etiologic agent of fatal visceral leishmaniasis in man. During their life cycle, Leishmania exist as flagellated promastigotes within the sandfly vector and as nonflagellated amastigotes in the macrophage phagolysosomal compartment of the mammalian host. The transformation from promastigotes to amastigotes is a critical step for the establishment of infection, and the molecular basis for this transformation is poorly understood. To define the molecular basis for amastigote survival in the mammalian host, we previously identified an amastigote stage-specific gene family termed “A2.” In the present study, we have inhibited the expression of A2 mRNA and A2 protein in amastigotes using antisense RNA and show that the resulting A2-deficient amastigotes are severely compromised with respect to virulence in mice. Amastigotes that did survive in the mice had restored A2 protein expression. These data demonstrate that A2 protein is required for L. donovani survival in a mammalian host, and this represents the first identified amastigote-specific virulence factor identified in Leishmania. This study also reveals that it is possible to study gene function in Leishmania through the expression of antisense RNA.

IL-10- and TGF-β-Mediated Susceptibility in Kala-azar and Post-kala-azar Dermal Leishmaniasis: The Significance of Amphotericin B in the Control of Leishmania donovani Infection in India

Abstract: Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-beta in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-gamma and IL-12 production, and elevation of IL-10 and TGF-beta. Cure corresponded with an elevation in IFN-gamma and IL-12 production and down-regulation of IL-10 and TGF-beta. Both CD4(+) and CD8(+) T cells were involved in IFN-gamma and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-beta in some SAG-treated individuals and the elevation of IL-10 and TGF-beta in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-beta levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-beta, IL-10, and Ab production. In addition, the enhancement of CD4(+)CD25(+) T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.