DermotropicLeishmania donovaniin Sri Lanka: visceralizing potential in clinical and preclinical studies

Abstract

SummaryThe visceralizing potential of apparently dermotropicLeishmania donovaniin Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients andin vivoandin vitroexperimental infection models. CL patients (n= 250) treated effectively with intra-lesional antimony therapy were followed-up six monthly for 4 years. There was no clinical evidence of visceralization of infection (VL) during this period. Infection of BALB/c mice withL. donovani-SL (test) through intra-dermal route led to the development of cutaneous lesions at the site of inoculation with no signs of systemic dissemination, in contrast to the observations made in animals similarly infected with a visceralizing strain ofL. donovani-1S (control). Cytokine (IL-10, IFN-γ) release patterns of splenocytes and lymph node cell cultures derived from mice primed with experimental infections (with either test or control parasites) revealed significantly high IFN-γ response associated with test mice with CL, while prominent IL-10 levels were observed in association with control mice with VL. Furthermore, diminished infection efficiency, intracellular growth and survival ofL. donovani-SL parasites compared withL. donovani-1S were evident throughin vitromacrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature ofL. donovani-SL suggesting natural attenuation of virulence of local parasite strains.