Resolving the apparent transmission paradox of African sleeping sickness

Abstract

Human African trypanosomiasis (HAT), or African sleeping sickness, is a fatal disease found throughout sub-Saharan Africa. The disease is close to elimination in many areas, although it was similarly close to elimination once before and subsequently reemerged, despite seemingly low rates of transmission. Determining how these foci persisted and overcame an apparent transmission paradox is key to finally eliminating HAT. By assessing clinical, laboratory, and mathematical data, we propose that asymptomatic infections contribute to transmission through the presence of an overlooked reservoir of skin-dwelling parasites. Our assessment suggests that a combination of asymptomatic and parasitaemic cases is sufficient to maintain transmission at foci without animal reservoirs, and we argue that the current policy not to treat asymptomatic HAT should be reconsidered.

Fig 1. Modelling of the relative contributions of asymptomatic and clinical cases to R₀ in a polymorphic human HAT focus without animal reservoirs.

We estimated the contribution of asymptomatic and clinical infections to R₀ (the basic reproductive number) under equilibrium prevalence by adapting a previously published trypanosomiasis transmission model [11]. Consistent with empirical data showing no domestic or wildlife reservoir, we removed the nonhuman-animal contribution to R₀ and instead allowed for a polymorphic human population in which a fraction (f) of the population develop clinical infections when infected (population I), with the remainder (1–f) developing asymptomatic infections (population II). This leads to $R_0=\sqrt{\frac{1}{(1-i_v^{*})(I_{\mathrm{I}}^{*}+I_{\mathrm{I}\mathrm{I}}^{*})}\left[\frac{I_{\mathrm{I}}^{*}}{1-\frac{I_{\mathrm{I}}^{*}}{fN}}+\frac{I_{\mathrm{I}\mathrm{I}}^{*}}{1-\frac{I_{\mathrm{I}\mathrm{I}}^{*}}{\left(1-f\right)N}}\right]}$, where i*_v is the infected tsetse prevalence, I_I* is the number of clinical infections present at equilibrium, I_II* is the number of asymptomatic infections at equilibrium, and N is the total human population size. We simulated this equation with epidemiologic and demographic surveys from the Forécariah focus in Guinea. Specifically, there were 13 clinical infections and 16 suspected asymptomatic infections identified during the survey. Of the suspected asymptomatic individuals, one-third tested negative on follow-up using the TL test and one-third developed symptoms [10]. Therefore, we set the number of asymptomatic infections as I_II* = 16X (where X~Uniform(1/3,1)) and the number of clinical infections as I_I* = 29–I_II*. The total population size was set as N = 10,837, based on 7,586 surveyed individuals and a survey completeness of 70%. These results suggest that transmission is not sustainable (R₀ < 1) when nearly all infections are either clinical (f > 0.98) or asymptomatic infections (f < 0.02). The shaded areas represent 95% predictive intervals when the number of asymptomatic and clinical infections were sampled 1,000 times. HAT, human African trypanosomiasis; TL, trypanolysis.