Abstract
The visceralizing potential of apparently dermotropic Leishmania donovani in Sri Lanka (L. donovani-SL) was investigated through long-term follow-up of cutaneous leishmaniasis (CL) patients and in vivo and in vitro experimental 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 with L. 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 of L. 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 of L. donovani-SL parasites compared with L. donovani-1S were evident through in vitro macrophage infection experiments. These studies confirm, for the first time, the essential dermotropic nature of L. donovani-SL suggesting natural attenuation of virulence of local parasite strains.
Highlights
Leishmaniases are a group of vector-borne diseases caused by intracellular protozoa that belong to the genus Leishmania
The sandfly Phlebotomus argentipes var. glaucus was identified as the probable vector for leishmaniasis transmission in Sri Lanka (Gajapathy et al 2013; Senanayake et al 2015)
This paper presents the results of the first study, aimed at delineating the visceralizing potential of L. donovani-SL through long-term follow-up of cutaneous leishmaniasis (CL) patients and the use of both in vivo and in vitro models to study parasite virulence
Summary
In Sri Lanka, leishmaniasis is a recently established disease with over 6500 cases of CL reported so far (Sri Lanka Epidemiology Unit Ministry of Health, 2016), with a few autochthonous (and imported) cases of visceral and mucosal cases (Rajapaksa et al 2005; Abeygunasekara et al 2007). Glaucus was identified as the probable vector for leishmaniasis transmission in Sri Lanka (Gajapathy et al 2013; Senanayake et al 2015). In addition to the genomic variations, several hosts, vectors and other parasite determinants are believed to influence the clinical outcome of leishmaniasis (McCall et al 2013).
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