Investigating trypanosome infection prevalence in three districts of Northern Uganda : a study of trypanosome populations in cattle and humans

The African Trypanosomiases are a suite of diseases affecting humans and animals across sub-Saharan Africa, caused by protozoan trypanosome parasites and transmitted by tsetse flies (Glossina spp.). A number of different trypanosome species cause Animal African Trypanosomiasis (or Nagana) in wildlife and livestock, and have a major impact on animal health, agriculture and the economy. Two subspecies of African trypanosomes infect humans: Trypanosoma brucei gambiense causes a chronic disease in Central and Western Africa and Trypanosoma brucei rhodesiense causes an acute disease in Eastern and Southern Africa. Human African Trypanosomiasis (HAT), or sleeping sickness, is fatal if left untreated. Uganda is the only country to have active but geographically discrete foci of both T. b. gambiense HAT (gHAT) and T. b. rhodesiense HAT (rHAT). Recently, Northwards migration of rHAT has been observed in Uganda, associated with movements of cattle that serve as reservoirs for the zoonotic T. b. rhodesiense parasite. Convergence of the two forms of HAT in districts of Northern Uganda would impact on correct diagnosis and treatment since rHAT and gHAT require different diagnostics and treatment. The work described in this thesis explores the impact of recent cattle-based interventions for the control of zoonotic rHAT, specifically targeted at preventing the Northwards migration of T. b. rhodesiense in cattle in Uganda. Previously, a cross-sectional survey of cattle in 150 villages across 32 rHAT-affected districts of Uganda was undertaken in 2014 using the Polymerase Chain Reaction (PCR); screening determined the prevalence of human-infective T. b. rhodesiense and non-human-infective Trypanosoma brucei brucei parasites. In 2018, cattle from 20 villages in three districts of Northern Uganda were screened to determine change in trypanosome prevalence across these 20 sites. Between 2014 and 2018, overall trypanosome prevalence was observed to have significantly reduced (p < 0.0001) from 59.05% (95% CI 56.02% - 62.02%; 607/1,028) to 15.17% (95% CI 13.07% - 17.54%; 150/989), a trend observed for all individual trypanosome species. The prevalence of Trypanosoma brucei sensu lato decreased from 35.51% (95% CI 32.64% - 38.48%; 365/1,028) to 6.88% (95% CI 5.46% - 8.63%; 68/989), (p < 0.0001), and minimum prevalence of human-infective T. b. rhodesiense reduced from 4.67% (95% CI 3.54% - 6.14%; 48/1,028) to 2.12% (95% CI 1.39% - 3.22%; 21/989), (p = 0.0020). Between 2014 and 2018, the prevalence of Trypanosoma vivax decreased from 15.86% (95% CI 13.75% - 18.22%; 163/1,028) to 4.75% (95% CI 3.59% - 6.26%; 47/989), (p < 0.0001), and the prevalence of Trypanosoma congolense decreased from 31.42% (95% CI 28.66% - 34.32%; 323/1,028) to 5.46% (95% CI 4.21% - 7.06%; 54/989), (p < 0.0001). The scale (and/or direction) of change in prevalence was observed to vary at both district and village level. A human survey for HAT was also undertaken in the same 20 villages in 2018; 5,383 individuals were screened for the presence of Trypanosoma brucei sensu lato DNA using PCR. In total, 10 samples were considered positive for T. brucei sl (0.19%; 95% CI 0.10% - 0.35%) and were examined to determine the sub-species. Association between villages with PCR-positive human samples and the presence of humaninfective T. b. rhodesiense parasites was observed. Human-infective T. b. rhodesiense parasites and non-human-infective T. b. brucei parasites co-exist in the cattle population in Uganda. This thesis explores the dynamics of distribution of human- and non-human-infective T. brucei in cattle before and after treatment; in particular, the impact of interventions on the proportion of T. b. rhodesiense within the T. brucei sl population. On very few occasions does the relative prevalence of T. b. rhodesiense appear to exceed that of T. b. brucei in cattle populations, despite epidemiological theory predicting otherwise. Explanations for these observations are discussed, and progress towards elimination of Human African Trypanosomiasis as a public health problem is considered, taking into account the findings of this thesis.