Abstract
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.
Highlights
Human African trypanosomiasis (HAT) is a vector-borne neglected tropical disease mainly affecting people in rural settings in sub-Saharan Africa
While attention should be paid towards treatment adherence regardless of stage in line with World Health Organization (WHO) recommendations [5], this result suggests that compliance in stage 1 patients is especially important for reducing further transmission of the disease
While the median simulated incidence is declining for all scenarios (Fig 2B), there are some potential parameter sets where low compliance leads to an increase in cases (Fig 2A). This is because the observed historic data is compatible with parameters that would lead to an increase in disease incidence if compliance with treatment was low. This result suggests that the situation should be monitored closely after the introduction of fexinidazole, and an increase in cases may indicate that drug compliance is low
Summary
Human African trypanosomiasis (HAT) is a vector-borne neglected tropical disease mainly affecting people in rural settings in sub-Saharan Africa. The gambiense form of the disease (gHAT) accounts for *98% of reported cases, with its greatest burden being in the Democratic Republic of the Congo (DRC) [1]. The burden of disease has reduced significantly since the turn of the Century, with the global number of cases reported to the World Health Organization (WHO) falling from 26,872 in 2001 to 876 in 2019 [2]. While this drop may be due to falling rates of active screening or case reporting, a modelling analysis using Bayesian inference techniques suggested that these declines represent a true reduction in case incidence [3]. Screening at-risk populations for cases has formed the main control measure for gHAT
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