Inference of Population Structure of Leishmania donovani Strains Isolated from Different Ethiopian Visceral Leishmaniasis Endemic Areas.

Background: Parasites' evolution in response to parasite-targeted control strategies, such as vaccines and drugs, is known to be influenced by their population genetic structure. The aim of this study was to describe the population structure of Ethiopian strains of Leishmania donovani derived from different areas endemic for visceral leishmaniasis (VL) as a prerequisite for the design of effective control strategies against the disease. Methodology/Principal Findings: Sixty-three strains of L. donovani newly isolated from VL cases in the two main Ethiopian foci, in the north Ethiopia (NE) and south Ethiopia (SE) of the country were investigated by using 14 highly polymorphic microsatellite markers. The microsatellite profiles of 60 previously analysed L. donovani strains from Sudan, Kenya and India were included for comparison. Multilocus microsatellite typing placed strains from SE and Kenya (n = 30) in one population and strains from NE and Sudan (n = 65) in another. These two East African populations corresponded to the areas of distribution of two different sand fly vectors. In NE and Sudan Phlebotomus orientalis has been implicated to transmit the parasites and in SE and Kenya P. martini. The genetic differences between parasites from NE and SE are also congruent with some phenotypic differences. Each of these populations was further divided into two subpopulations. Interestingly, in one of the subpopulations of the population NE we observed predominance of strains isolated from HIV-VL co-infected patients and of strains with putative hybrid genotypes. Furthermore, high inbreeding irreconcilable from strict clonal reproduction was found for strains from SE and Kenya indicating a mixed-mating system. Conclusions/Significance: This study identified a hierarchical population structure of L. donovani in East Africa. The existence of two main, genetically and geographically separated, populations could reflect different parasite-vector associations, different ecologies and varying host backgrounds and should be further investigated. Author Summary: In the Horn of Africa, visceral leishmaniasis, caused by protozoan parasites of the Leishmania donovani complex, continues to pose a major health problem affecting the poorest of the poor. Population genetic studies are crucial for the development of drugs and vaccines against microorganisms. However, our knowledge about the population structure of L. donovani parasites in this region is still very limited. Using a highly discriminatory multilocus microsatellite typing approach, we found a remarkably high genetic diversity among the East African strains of L. donovani studied which grouped into two genetically and geographically distinct populations comprising parasites from SE and Kenya, and those from NE and Sudan. Despite Leishmania being widely regarded as a clonal organism, our results suggest a possible co-existence of clonal and sexually reproducing strains of L. donovani from SE. The information obtained by the present study is helpful for future design of parasite-targeted control measures in East Africa. [ABSTRACT FROM AUTHOR]