Atypical leishmaniasis: A global perspective with emphasis on the Indian subcontinent

Abstract

Background: Among the neglected tropical diseases, leishmaniasis continues to be prevalent in many tropical and subtropical countries despite international, national, and local efforts towards its control and elimination over the last decade. This warrants a critical evaluation of such factors as under-reporting, asymptomatic infections, post kala azar dermal leishmaniasis (PKDL) cases, and drug resistance. In this review, we highlight lesser-understood atypical presentations of the disease involving atypical parasite strains against a background of classical leishmaniasis with a focus on the Indian subcontinent.

Methods and findings: A literature review based on endemic areas, the nature of disease manifestation, and underlying causative parasite was performed with data collected from WHO reports for each country. Searches on PubMed included the term ''leishmaniasis" and "leishmaniasis epidemiology" alone and in combination with each of the endemic countries, Leishmania species, cutaneous, visceral, endemic, non-endemic, typical, classical, atypical, and unusual with no date limit and published in English up to September 2017. Our findings portray a scenario with a wider distribution of the disease in new endemic foci, with new discoveries of parasite-driven atypical disease manifestations in different regions of the world. Unlike the classical picture, some Leishmania species are associated with more than one disease presentation, e.g., the L. donovani complex, generally associated with the visceral form, is now also associated with a cutaneous disease presentation, while L. tropica species complex, known to cause cutaneous disease, can cause viscerotropic disease. This phenomenon points towards the discovery of novel parasite variants as etiologic agents of atypical disease manifestations and represents an excellent opportunity to identify and study genes that control disease virulence and tropism.

Conclusions: The increased recognition of atypical leishmaniasis as an outcome of parasite variants has major implications for leishmaniasis control and elimination. Identifying molecular correlates of parasite isolates from distinct regions associated with different disease phenotypes is required to understand the current epidemiology of leishmaniasis in regions with atypical disease.

Fig 1. Global distribution of classical and atypical leishmaniasis in New and Old World countries.

Solid rectangles indicate region-specific prevalence of classical disease type; CL (green rectangle), VL (pink rectangle), VL and CL (yellow rectangle). Regions with solid circles indicate atypical CL and VL disease form. Different color code of solid circles discriminate the causative parasite species responsible for atypical leishmaniasis; L. tropica VL (blue solid circles), L. amazonensis VL (aquamarine solid circles), L. major VL (black solid circles), L. infantum CL (purple solid circles), L. chagasi CL (gold solid circles), and L. donovani CL (red solid circles). Regions with red stars represent newer disease sites discovered. The map was created using ArcGIS 10.3. Regional distributions of disease were georeferenced with UTM projection taking WGS84 datum. CL, cutaneous leishmaniasis; VL, visceral leishmaniasis.

Fig 2. Geographical distribution of classical and atypical leishmaniasis cases in Indian subcontinent.

Solid circles represent classical CL and VL leishmaniasis, and solid triangles represent atypical CL and VL leishmaniasis with different color codes. Green solid circles and red solid circles represent classical L. tropica CL and L. donovani VL, respectively. Aquamarine solid triangles and black solid triangles represent atypical L. tropica VL and L. donovani CL, respectively. Regions with dotted gold background indicate newer disease sites discovered. Solid colored circles and triangles indicate prevalence of different disease forms and do not represent the number of leishmaniasis cases. The map was created using ArcGIS 10.3. Regional distributions of disease were georeferenced with UTM projection taking WGS84 datum. CL, cutaneous leishmaniasis; VL, visceral leishmaniasis.