Livestock and the epidemiology of sleeping sickness: mechanisms and implications
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In recent decades, remarkable progress in the control of Human African trypanosomiasis (HAT)---a bloodborne protozoal parasite transmitted by the tsetse fly (Glossina species)---has led the WHO to set targets for elimination as public health problem (EPHP) by 2020, and elimination of transmission (EOT) by 2030. Global EPHP targets were met in 2018, however most endemic countries are not yet eligible for national EPHP validation, and there are significant challenges to achieving EOT goals. Two forms of HAT, which are geographically- and epidemiologically-distinct, exist: the chronic form, caused by Trypanosoma brucei gambiense (gHAT) and endemic in western and central Africa, and the acute form, caused by T. b. rhodesiense (rHAT) and endemic in eastern and southern Africa. Due to the known importance of animal reservoirs for rHAT EOT targets are set for gHAT alone, resulting in significantly lower investment in rHAT surveillance and control compared with gHAT. Combined with rHAT's acute progression this results in significant underreporting, raising concerns that rHAT will emerge as a major public health problem once gHAT EOT is achieved and donor attention moves away from HAT. With regards to gHAT, uncertainty surrounding animal reservoirs---in particular domestic pigs---as well as latent human reservoirs and undercoverage of high-risk groups by active surveillance activities threaten both the probability of EOT, and re-emergence following EOT. In this dissertation, we used data from the WHO Atlas of HAT, spatial epidemiologic methods, methods drawn from the potential outcomes framework of causal inference, and a stochastic compartmental model to estimate the effect of pig density on HAT risk, to evaluate the feasibility of rHAT EOT with control of domestic animal reservoirs alone, and to decompose the livestock density - HAT effect into three components: (1) the reservoir effect, whereby domestic cattle and pigs infected with trypanosomes serve as a source of human infection, (2) the zooprophylactic effect, whereby tsetse fly preference for livestock protects humans from bites---and therefore trypanosome infection---when livestock are nearby, and (3) the environmental change effect, whereby livestock keeping results in environmental changes that in turn modify tsetse distribution and HAT risk. We conducted this work in four high-burden countries which do not meet WHO criteria for EPHP validation: Uganda (gHAT and rHAT), South Sudan (gHAT), Malawi (rHAT), and Democratic Republic of Congo (DRC, gHAT). Our results suggest pigs may indeed be gHAT reservoirs and, if so, EOT will not be achieved without intervention---trypanocide or, preferably, insecticide treatment---on this reservoir. With regards to rHAT, we found control of the domestic cattle and pig reservoir is critical to control of the disease, in particular in Uganda, but does not lead to EOT. We found evidence of a zooprophlyactic effect in Malawi and South Sudan for both cattle and pigs and in gHAT foci in Uganda for cattle, however we did not detect compelling evidence of an environmental change effect. These results point to the utility of a One Health approach to HAT control, and represent an important contribution to the HAT literature and the efforts of National Sleeping Sickness Control Programs in the study countries. In conjunction with the high-resolution livestock density maps we have produced, our findings will support targeted delivery of expanded and/or enhanced HAT control efforts. Delivering these efforts in a One Health framework, whereby control of animal African trypanosomiasis is coordinated with that of HAT, will increase the likelihood and sustainability of gHAT elimination and ensure rHAT does not subsequently emerge as a major public health problem, reducing the burden of this highly-fatal and poverty-reinforcing disease.
- Epidemiology