Lymphocyte phenotyping, using cluster-of-differentiation (CD) markers, in young Iraqi children with visceral leishmaniasis.

The lymphocytic phenotypes involved in the pathogenesis of visceral leishmaniasis (VL) in Iraqi children have recently been investigated, in a study based on cluster-of-differentiation (CD) markers. Each case of VL investigated was confirmed parasitologically by the observation of amastigotes in a bone-marrow smear. Compared with the values for the healthy children used as controls, a lymphocyte from an untreated VL case was significantly less likely to be CD3+ or CD4+, significantly more likely to be CD8+, and more (but not significantly more) likely to be CD22+. The untreated cases also had significantly lower CD4+/CD8+ ratios than the controls. Among the untreated cases, gender and age had no apparent effect on any of these variables. After 28 days of treatment with sodium stibogluconate, there was a trend towards normalization in the lymphocytic phenotypes of the VL cases, with significant increases in the CD4+/CD8+ ratios and the percentages of lymphocytes that were CD3+ or CD4+, and a significant decrease in the percentages of lymphocytes that were CD22+.

The mechanism behind the antileishmanial effect of zinc sulphate. II. Effects on the enzymes of the parasites.

When used in vitro, zinc sulphate has a direct antileishmanial effect. To see if this effect involved the inhibition of the parasites' enzymes, extracts of the promastigotes and axenic amastigotes of Leishmania major (MHOM/IQ/93/MRC6) and L. tropica (MHOM/IQ/93/MRC2) were prepared. Zinc sulphate, at various concentrations, was then added to samples of these extracts before the activities, in the samples, of certain key enzymes of the Embden-Meyerhof pathway, hexose-monophosphate shunt and citric-acid cycle, and of two enzymes associated with virulence (protease and acid phosphatase), were determined. The zinc was found to inhibit every enzyme investigated, usually in a dose-dependent manner. Thus the direct antileishmanial effect of zinc may result, partially or entirely, from the inhibition of enzymes that are necessary for the parasites' carbohydrate metabolism and virulence.

The mechanism behind the antileishmanial effect of zinc sulphate. I. An in-vitro study.

In an attempt to determine the possible mechanism(s) behind the antileishmanial activity of zinc sulphate, promastigotes, axenic amastigotes and intracellular amastigotes of both Leishmania major and L. tropica were incubated with different concentrations of the compound. For each of the two Leishmania species, all three forms were found to be inhibited by the zinc sulphate, in a dose-dependent manner, the promastigotes being the most resistant form, followed by the axenic amastigotes. These results indicate that zinc sulphate has a direct antileishmanial effect. Compared with macrophages from starch-treated mice, the macrophages recovered from mice that had been injected intraperitoneally with zinc sulphate (daily for the 4 days prior to the macrophage collection) or BCG (once, 4 days before the cell collection) showed increased phagocytosis and increased killing of L. major and L. tropica. As the effects of the zinc sulphate were not statistically different from those of the known immunomodulating agent BCG, zinc sulphate appears to have an immunomodulating effect, in addition to its direct antileishmanial effect.