EXPERIMENTAL PATHOGENICITY OF VISCEROTROPIC AND DERMOTROPIC ISOLATES OF LEISHMANIA-INFANTUM FROM IMMUNOCOMPROMISED AND IMMUNOCOMPETENT PATIENTS IN A MURINE MODEL

The pathogenicity of 22 strains of Leishmania infantum from 11 HIV-inf ected and 11 immunocompetent patients with visceral (VL, n=16) or cuta neous (CL, n=6) leishmaniasis, belonging to 3 zymodemes (MON-1, n=14; MON-29, n=5; MON-33, n=3), was studied using a murine model. For each strain 16-20 BALB/c mice were infected at day O (dO) by iv. injection of 10(7) stationary-phase promastigotes. Parasite burdens were quantif ied in the spleen and liver of 4-5 mice of each strain at d7, d20, d60 and d90 or d100, using a sensitive culture microtitration technique. A great variability of infection profiles between strains was observed : (i) six strains showed a progressive infection, with a predominance of hepatic parasites at d7 or d20 (10(4)-10(6) g(-1)), then a continuo us rise of splenic parasites reaching 10(5)-10(7) g(-1) at d90 or d100 contrasting with a stagnation or decrease in the liver; (ii) ten stra ins gave a controlled infection with hepatic parasite burden reaching 10(4)-10(5) g(-1) at d7 or d20, followed by a more or less rapid decli ne leading frequently to no detectable parasites; (iii) six strains re sulted in other profiles, i.e., undetectable infection (n=1) or low pa rasite loads (n=4), or late occurrence of parasites in the spleen (n=1 ). No relationship was observed between profile and growth characteris tics in vitro or zymodeme of the strain. Strains originating from CL n ever gave a visceralizing pattern in mice, but belonged more frequentl y to the avirulent type compared to VL strains. Strains from HIV-infec ted patients were not less virulent than those from immunocompetent in dividuals. These results showed that the course of L. infantum infecti on varies markedly with intrinsic parasite factors that display striki ng intraspecific variability.