First Evidence from Sri Lanka for Subphenotypic Diversity within L. donovani-Induced Classical Cutaneous Leishmaniasis

Abstract

Sri Lanka reports a large focus of Leishmania donovani-induced cutaneous leishmaniasis (CL) with CL as the main clinical entity. Two independent, long existed, and clinicoepidemiologically different transmission foci in the northern region (NR) and southern region (SR) were recently reported. Current project is an extension to this previous study. Clinical diversity within a profile of classical cutaneous leishmaniasis (CCL) in a focus of L. donovani-induced CL is described for the first time. Patients with laboratory confirmed CCL ( n = 550 ) from NF and SF were evaluated. Lesions in both foci were found to have all classical developmental stages (small and large nodules, ulcerating nodules, and ulcers) and other identified changes (multiplication, ulceration, and enlargement). Main difference was in the proportions of lesions progressing in to each different stages, proportions of lesion undergoing the main changes, and in timing of these changes during the course of a lesion. Northern focus reported a smaller proportion of lesions showing enlargement and ulceration, and a longer period of time was also required for these changes when compared to same in southern focus. In northern focus, most lesions remained small and nonulcerating and showed a higher tendency to multiply while most lesions reported in southern focus enlarged and ulcerated rapidly and remained single. Current study also evidenced a wider spectrum in the rate and pattern of progression of a skin lesion and high individual variation which could mask these region-based differences. Parasitic, vector-related, or a host etiology is suggested. Slow progressing nonulcerating infections in North may be the result of a well-adopted parasite strain that coevolved with its host for a long period while inducing only a minimal host response. This could be one among many reasons for previously observed silent expansion in northern focus while southern focus remained more confined and stable over time. Small nonprogressive, nondisturbing lesions can play a major role as silent parasite reservoirs in a community. In addition, the laboratory detection rate declined significantly when lesions multiplied and enlarged indicating the need for early laboratory confirmation. Usefulness of identified features in clinical screening and management needs to be considered.

Development of a Highly Sensitive Nested PCR and Its Application for the Diagnosis of Cutaneous Leishmaniasis in Sri Lanka

“…ITS1 is a highly conserved region; however, the associated polymorphisms allow differentiation between species [ 29 ]. The genetic heterogeneity of L. donovani in Sri Lanka is evident through many factors (listed), which can contribute to the differing sensitivity between diagnostic techniques: (i) genomic analysis of L. donovani isolates of global distribution showed that the isolates fell into five large groups based on geographic origin but showed vast genetic variation within these groups (this study included Sri Lankan isolates) [ 30 ]; (ii) sub-phenotypic variation in classical CL caused by L. donovani was evident between the northern and southern foci of disease transmission in Sri Lanka, suggesting strain differences [ 31 ]; (iii) high haplotype diversity, with sub-clusters showing clinically relevant characteristics [ 32 ]; (iv) emergence of treatment failure and non-responsiveness to standard treatment [ 17 , 33 ], which is multifactorial in origin, but genetic variations contribute [ 34 ].…”