Age-influenced population kinetics and immunological responses of Leishmania donovani in hamsters.

Susceptibility of animals to infections depends upon various factors including sex and age of the host, which plays a pivotal role. In this communication, we have investigated the "intake" of Leishmania donovani infection in young (3-4 weeks old) and adult (15-16 weeks old) golden hamsters. The splenic parasite load in young hamsters on day 15 post infection (p.i.) was 54 +/- 4 amastigotes/100 macrophage nuclei and increased to 106.3 +/- 3.5 on day 30 p.i. However, adult group showed 2.2-(P < 0.001) and 1.75-fold (P < 0.001) lesser parasite burden on these days, respectively. But as the disease progresses further, differences in parasite burden become less significant, as revealed by comparable levels of parasite loads at 2 months p.i. Spleen weight measurements correspond to the above observations. In the young group, the levels of antileishmanial antibody rise two and 4.5 times on days 15 and 30 p.i., respectively, as compared to only 1.3 and 2.3 times increase in their respective adult counterparts. However, after 2 months of infection both groups recorded analogous (12-fold) rise in antibody levels. Both mitogenic and antigenic responses in adult hamsters were less suppressed compared to young hamsters on days 15 and 30 p.i. However, both groups exhibited highly suppressed cell-mediated immune (CMI) responses after 2 months of infection. These findings implicate that age of the host may influence the susceptibility and resistance to Leishmania infection.

Leishmania donovani: identification of stimulatory soluble antigenic proteins using cured human and hamster lymphocytes for their prophylactic potential against visceral leishmaniasis.

Most of the studies for the identification of prophylactic antigens that elicit T cell responses were concentrated on membrane proteins of Leishmania donovani. This study was taken up to assess L. donovani soluble promastigote antigens for their ability to stimulate proliferation of peripheral blood mononuclear cells (PBMCs) from cured visceral leishmaniasis (VL) patients, endemic and non-endemic controls and lymphocytes/peritoneal macrophages of cured hamsters. The soluble protein was subjected to sequential precipitation with saturated ammonium sulphate (20%, 40%, 60% and 80%), of which largely 80% fractioned protein showed significant cellular responses in cured patients and hamsters. This fraction was further fractionated into five sub fractions by preparative SDS-PAGE and subjected to re-evaluation for their ability to induce cellular responses. Out of these, only F2 sub fraction belonging to the MW of 97.4-68 kDa stimulated remarkable lymphoproliferative and IFN-gamma responses in cured VL patients and in endemic controls. Similarly, significant lymphoproliferative responses and nitric oxide production were also noticed in cured Leishmania infected animals indicating an element of uniformity in responses between hamster and human. F2 sub fraction, when evaluated for its prophylactic efficacy with BCG against L. donovani challenge in hamster exhibited significant parasite inhibition in spleen (71.1%; p<0.001) and liver (68.2%; p<0.001) as compared to their unvaccinated counterpart. The vaccinated animals showed significant lymphoproliferative response and nitric oxide production but leishmania specific IgG level were suppressed. The results indicate the presence of immunostimulatory and protective molecules in F2 sub fraction which may further be exploited for the development of a vaccine against VL, hitherto an unrealized goal.