Genetic diversity of Leishmania donovani that causes cutaneous leishmaniasis in Sri Lanka: a cross sectional study with regional comparisons

Abstract

Background Leishmania donovani is the etiological agent of visceral leishmaniasis (VL) in the Indian subcontinent. However, it is also known to cause cutaneous leishmaniasis (CL) in Sri Lanka. Sri Lankan L. donovani differs from other L. donovani strains, both at the molecular and biochemical level. To investigate the different species or strain-specific differences of L. donovani in Sri Lanka we evaluated sequence variation of the kinetoplastid DNA (kDNA).MethodsParasites isolated from skin lesions of 34 CL patients and bone marrow aspirates from 4 VL patients were genotyped using the kDNA minicircle PCR analysis. A total of 301 minicircle sequences that included sequences from Sri Lanka, India, Nepal and six reference species of Leishmania were analyzed.ResultsHaplotype diversity of Sri Lankan isolates were high (H d = 0.757) with strong inter-geographical genetic differentiation (F ST > 0.25). In this study, L. donovani isolates clustered according to their geographic origin, while Sri Lankan isolates formed a separate cluster and were clearly distinct from other Leishmania species. Within the Sri Lankan group, there were three distinct sub-clusters formed, from CL patients who responded to standard antimony therapy, CL patients who responded poorly to antimony therapy and from VL patients. There was no specific clustering of sequences based on geographical origin within Sri Lanka.ConclusionThis study reveals high levels of haplotype diversity of L. donovani in Sri Lanka with a distinct genetic association with clinically relevant phenotypic characteristics. The use of genetic tools to identify clinically relevant features of Leishmania parasites has important therapeutic implications for leishmaniasis.Electronic supplementary materialThe online version of this article (10.1186/s12879-017-2883-x) contains supplementary material, which is available to authorized users.

Trends in Recently Emerged Leishmania donovani Induced Cutaneous Leishmaniasis, Sri Lanka, for the First 13 Years

“…Other clinical forms of leishmaniasis still remain a minority, though it may be an underestimation of the true picture [14]. Minimal or absent systemic features in a clear majority of CL cases, negative VL screening assay results in CL, absence of an initial history of CL in reported VL cases [14], and already reported strain difference between CL and VL causing local Leishmania strains [18] indicate that most local skin infections progress without visceralization. However, early evidence of serological response may be indicative of a potential for visceralization on the other hand, though it can also be due to a transient CL associated seroconversion [17].…”

“…Seasonal variation of case distribution with two annual peaks that coincides with the monsoon rain patterns in Sri Lanka was evident since the onset of the epidemic seems to remain unchanged over the time. Presence of an established pattern maintained over a decade period indicates the long-term existence of the local infection, which has been backed up through phylogenetic analyses [8, 18, 31]. This is likely the reflection of seasonal activity of vectors.…”

“…Studies suggested a genetic basis for the different local phenotypes [16]. Meanwhile 34% of active CL infections showed a humoral response though follow-up studies have failed to detect any visceralization of initial CL [17, 18]. The felt local need for disease containment prior to the establishment of more virulent forms was highlighted [19, 20].…”

Leishmaniasis in Northern Syria during Civil War

“…CL caused by L. donovani has also been documented from Cyprus ( 26 ). Moreover, numerous cases of CL caused by L. donovani have been documented from Sri Lanka ( 30 ). In summary, these molecular data demonstrate a surprising diversity of locally endemic Leishmania species causing cutaneous disease.…”

Visceral Leishmaniasis Caused by Leishmania donovani Zymodeme MON-37, Western Ghats, India

“…MT010560). This strain is known to cause CL in the tribal belt of Western Ghats of Kerala ( 6 ) as well as in Sri Lanka ( 7 ). Thus, our investigations evinced that MON-37 zymodeme L. donovani is involved in both CL ( 6 ) and VL manifestations in the foothills of the Western Ghats, whereas MON-2 zymodeme of L. donovani caused VL in other VL-endemic zones across eastern India ( 8 ).…”