Research Article: Genetic Diversity and Population Structure of Trypanosoma brucei in Uganda: Implications for the Epidemiology of Sleeping Sickness and Nagana

Date Published: February 19, 2015

Publisher: Public Library of Science

Author(s): Richard Echodu, Mark Sistrom, Rosemary Bateta, Grace Murilla, Loyce Okedi, Serap Aksoy, Chineme Enyioha, John Enyaru, Elizabeth Opiyo, Wendy Gibson, Adalgisa Caccone, Philippe Büscher.

Abstract: BackgroundWhile Human African Trypanosomiasis (HAT) is in decline on the continent of Africa, the disease still remains a major health problem in Uganda. There are recurrent sporadic outbreaks in the traditionally endemic areas in south-east Uganda, and continued spread to new unaffected areas in central Uganda. We evaluated the evolutionary dynamics underpinning the origin of new foci and the impact of host species on parasite genetic diversity in Uganda. We genotyped 269 Trypanosoma brucei isolates collected from different regions in Uganda and southwestern Kenya at 17 microsatellite loci, and checked for the presence of the SRA gene that confers human infectivity to T. b. rhodesiense.ResultsBoth Bayesian clustering methods and Discriminant Analysis of Principal Components partition Trypanosoma brucei isolates obtained from Uganda and southwestern Kenya into three distinct genetic clusters. Clusters 1 and 3 include isolates from central and southern Uganda, while cluster 2 contains mostly isolates from southwestern Kenya. These three clusters are not sorted by subspecies designation (T. b. brucei vs T. b. rhodesiense), host or date of collection. The analyses also show evidence of genetic admixture among the three genetic clusters and long-range dispersal, suggesting recent and possibly on-going gene flow between them.ConclusionsOur results show that the expansion of the disease to the new foci in central Uganda occurred from the northward spread of T. b. rhodesiense (Tbr). They also confirm the emergence of the human infective strains (Tbr) from non-infective T. b. brucei (Tbb) strains of different genetic backgrounds, and the importance of cattle as Tbr reservoir, as confounders that shape the epidemiology of sleeping sickness in the region.

Partial Text: Trypanosoma brucei is a unicellular protozoan parasite, which causes human and animal trypanosomiasis in tropical Africa, transmitted by tsetse flies (Glossina spp). Trypanosoma brucei consists of three subspecies: T. b. brucei (Tbb), T. b. gambiense (Tbg), and T. b. rhodesiense (Tbr) that are morphologically indistinguishable and classified according to host specificity, type of disease, and geographical distribution [1–3]. Tbr and Tbg cause the acute and chronic forms of Human African Trypanosomiasis (HAT), respectively. Tbr is restricted to certain regions of East Africa, while Tbg is more widespread in West and Central Africa. Both forms of HAT have an overlapping distribution with the non-human infective Tbb, which infects a wide range of wild and domestic animals across the tsetse belt of tropical Africa and is one of the causative organisms of African Animal Trypanosomiasis (AAT) or Nagana. Both Tbr and Tbb can co-occur in the same non-human hosts as well as in the tsetse vector. However, recombination is known to happen only in the salivary glands of the tsetse [4]. Tbr is not a reproductively isolated taxon but regarded as a host-range variant of Tbb [5–7]. A single gene encoding the Serum Resistance Associated (SRA) protein allows Tbr to survive in humans [8]. This gene possesses two main alleles across the Tbr distribution [6–7] The human serum resistance associated gene is ubiquitous and conserved in Tbr throughout East Africa [6]and could potentially be spread naturally by genetic exchange between Tbr and Tbb [9].

The aim of this study was to examine the pattern of genetic differentiation of Tbb and Tbr isolates in Uganda and western Kenya, to understand population structure and the modalities of parasite spread to help support sustainable control strategies for AAT and HAT in this region. Continent wide studies have already shown that Tbr and Tbb strains should not be treated as reproductively isolated taxa, as some Tbb strains are more closely related to Tbr strains than their conspecifics and vice versa [7]. The use of a larger number of highly variable microsatellite loci than in previous studies, coupled with a dense spatial and temporal sampling strategy, enabled us to identify three genetic partitions within the Uganda/Kenya T. brucei isolates that were not revealed by previous studies and the existence of ongoing gene flow between them (Figs. 2 and 3).



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