Does a One Health approach to human African trypanosomiasis control hasten elimination? A stochastic compartmental modeling approach.

BACKGROUND: . In response to large strides in the control of human African trypanosomiasis (HAT), in the early 2000s the WHO set targets for elimination of both the gambiense (gHAT) and rhodesiense (rHAT) forms as a public health (EPHP) problem by 2020, and elimination of gHAT transmisson (EOT) by 2030. While global EPHP targets have been met, and EOT appears within reach, current control strategies may fail to achieve gHAT EOT in the presence of animal reservoirs, the role of which is currently uncertain. Furthermore, rHAT is not targeted for EOT due to the known importance of animal reservoirs for this form. METHODS: . To evaluate the utility of a One Health approach to gHAT and rHAT EOT, we built and parameterized a compartmental stochastic model, using the Institute for Disease Modeling's Compartmental Modeling Software, to six HAT epidemics: the national rHAT epidemics in Uganda and Malawi, the national gHAT epidemics in Uganda and South Sudan, and two separate gHAT epidemics in Democratic Republic of Congo distinguished by dominant vector species. In rHAT foci the reservoir animal sub-model was stratified on four species groups, while in gHAT foci domestic swine were assumed to be the only competent reservoir. The modeled time horizon was 2005-2045, with calibration performed using HAT surveillance data and Optuna. Interventions included insecticide and trypanocide treatment of domestic animal reservoirs at varying coverage levels. RESULTS: . Validation against HAT surveillance data indicates favorable performance overall, with the possible exception of DRC. EOT was not observed in any modeled scenarios for rHAT, however insecticide treatment consistently performed better than trypanocide treatment in terms of rHAT control. EOT was not observed for gHAT at 0% coverage of domestic reservoirs with trypanocides or insecticides, but was observed by 2030 in all test scenarios; again, insecticides demonstrated superior performance to trypanocides. CONCLUSIONS: EOT likely cannot be achieved for rHAT without control of wildlife reservoirs, however insecticide treatment of domestic animals holds promise for improved control. In the presence of domestic animal reservoirs, gHAT EOT may not be achieved under current control strategies.

Modelling the impact of fexinidazole use on human African trypanosomiasis (HAT) transmission in the Democratic Republic of the Congo.

Gambiense human African trypanosomiasis is a deadly disease that has been declining in incidence since the start of the Century, primarily due to increased screening, diagnosis and treatment of infected people. The main treatment regimen currently in use requires a lumbar puncture as part of the diagnostic process to determine disease stage and hospital admission for drug administration. Fexinidazole is a new oral treatment for stage 1 and non-severe stage 2 human African trypanosomiasis. The World Health Organization has recently incorporated fexinidazole into its treatment guidelines for human African trypanosomiasis. The treatment does not require hospital admission or a lumbar puncture for all patients, which is likely to ease access for patients; however, it does require concomitant food intake, which is likely to reduce adherence. Here, we use a mathematical model calibrated to case and screening data from Mushie territory, in the Democratic Republic of the Congo, to explore the potential negative impact of poor compliance to an oral treatment, and potential gains to be made from increases in the rate at which patients seek treatment. We find that reductions in compliance in treatment of stage 1 cases are projected to result in the largest increase in further transmission of the disease, with failing to cure stage 2 cases also posing a smaller concern. Reductions in compliance may be offset by increases in the rate at which cases are passively detected. Efforts should therefore be made to ensure good adherence for stage 1 patients to treatment with fexinidazole and to improve access to care.