Improved methods to measure end products of nitric oxide in biological fluids: nitrite, nitrate, and S-nitrosothiols.

In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model. Thus, vanadium compounds may be used in combination with Sb(V) in the treatment of Sb(V) resistance cases of kala-azar.

/pdf/use-of-antimony-in-the-treatment-of-leishmaniasis-current-gv1oj9g5ds.pdf

Use of antimony in the treatment of leishmaniasis: current status and future directions.

The role of dogs as the main reservoir of visceral leishmaniasis has led to an increased interest in the immune responses and in Leishmania antigens implicated in protective cellular immunity in canine visceral leishmaniasis. The primary goal is to control the prevalence of human disease. Immune responses in canine visceral leishmaniasis are reviewed. Cellular immune responses toward a Th1 subset mediated by IFN-gamma and TNF-alpha predominate in asymptomatic dogs exhibiting apparent resistance to visceral leishmaniasis. On the other hand, while the role of Th2 cytokines, such as IL-4 and IL-10, in symptomatic animals is still controversial, there is increasing evidence for a correlation of these cytokines with progressive disease. CD8+ cytotoxic T cells seem also likely to be involved in resistance to visceral leishmaniasis. Several Leishmania antigens implicated in protective immune responses are described and some pivotal points for development of an effective vaccine against canine visceral leishmaniasis are discussed.

Immunology of canine leishmaniasis.

Vaccines for leishmaniasis in the fore coming 25 years.

Chemotherapy of canine leishmaniosis.

Following successful chemotherapy in canine visceral leishmaniasis, monocyte-derived macrophages can induce antileishmanial activity via a gamma interferon-dependent mechanism in the presence of autologous lymphocytes. The killing of leishmania correlated with the induction of the NO synthase pathway, because it correlated with the generation of nitrogen derivative production and was abrogated in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of the NO synthase pathway. The level of L-citrulline in serum, which was produced after activation of the NO synthase pathway, was markedly enhanced in dogs receiving successful chemotherapy. Taken together, these data indicate that following successful chemotherapy of visceral leishmaniasis, leishmania parasites are killed by macrophages activated by gamma interferon-producing lymphocytes via an NO-dependent mechanism.

A K Nüssler

Papers

Canine visceral leishmaniasis: successful chemotherapy induces macrophage antileishmanial activity via the L-arginine nitric oxide pathway.