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

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.

Tsetse Invasion as an Emerging Threat to Socioecological Resilience of Pastoral Communities in Karamoja, Uganda

“…The tsetse provides an ambient environment where the parasites complete their unique breeding life cycle ( Figure 2). The flagellate protozoa infect a wide range of wild and domestic animals as well as humans in sub-Saharan Africa [5]. Infected livestock and humans present diverse clinical manifestations.…”

“…The tsetse phenomenon presents a high disease burden on the human population. This high incidence often leads to decreased agricultural productivity and livestock deaths [5]. Sleeping sickness is an important public health disease in sub-Saharan Africa.…”

“…This identification is particularly important in areas that are experiencing recurrent and sporadic tsetse outbreaks, e.g., in the traditional endemic areas of south-eastern Uganda and the previously unaffected areas in northern Uganda. In these areas, HAT and AAT remain a major health threat to both humans and livestock [5,33].…”

A spatial genetics approach to inform vector control of tsetse flies (Glossina fuscipes fuscipes) in Northern Uganda

“…The human-infective form of sleeping sickness, HAT, is caused by parasites that are closely related to T. b. brucei (Balmer et al, 2010;Sistrom et al, 2014) with two distinct host-evasion types that cause unique disease symptoms known as "chronic" and "acute" sleeping sickness. Although the parasites that cause these two forms of the human disease are currently known in the literature as subspecies T. b. gambiense and T. b. rhodesiense, respectively, the formal taxonomic rank is under revision (Berriman et al, 2005;Echodu et al, 2015;Gibson, Marshall, Marshall, & Godfrey, 1980;Jackson et al, 2010;Sistrom et al, 2016). Regardless of taxonomy, both forms of the disease cause serious human illness and are difficult to treat, and the specific drug treatment course depends on the type and stage of the infection (Fèvre, Picozzi, Jannin, Welburn, & Maudlin, 2006;Fèvre, Wissmann, Welburn, & Lutumba, 2008).…”

Opportunities and challenges for modelling epidemiological and evolutionary dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in West Africa

“…Hybridizations and introgressions represent an additional source of genetic variation that may drive parasite evolution, with the potential for, amongst others, increased host range, altered pathology and resistance to drug therapy (King et al., ). Important examples include the naturally occurring hybridizations between Leishmania infantum and Leishmania major (Ravel et al., ), which have been observed to exhibit enhanced transmission potential and host range (Volf et al., ), and within Trypanosoma brucei subspecies, where introgressions have been shown to be associated with increased virulence and host range (Echodu et al., ; Goodhead et al., ).…”