Stop Transmission of Gambiense Human African Trypanosomiasis

Overview

This protocol describes both the epidemiological study which aims at assessing whether over a three-year period a zero prevalence can be achieved when implementing a screen \& treat approach with acoziborole, as well as a nested clinical study aimed at generating further evidence on safety of acoziborole in gambiense human African trypanosomiasis (gHAT) seropositives individuals. The overall coordinator will be ITM. ITM will be fully responsible for the epidemiological study (study Part A), including cost effectiveness and evaluation of diagnostic tests. DNDi will be the legal sponsor of the nested safety clinical study (study Part B) and will ensure compliance with regulatory requirements and good clinical practices (GCP) for this part of the study. We hypothesize that by systematically screening the populations of all endemic villages in a well-defined HAT focus and by expanding gHAT treatment to all seropositives, we will be able to arrive at a zero prevalence over a three-year period. The objectives are to evaluate whether a strategy based on widened treatment for all parasitologically negative seropositive gHAT suspects with acoziborole can lead to interruption of transmission of T.b.gambiense in a mainland focus and to assess the safety of acoziborole in gHAT seropositve individuals and parasitologically negative.

Recently acoziborole, a non-toxic single dose oral drug for gHAT, has passed phase 3 evaluation in adult patients. This drug is envisioned to be used to treat gHAT irrespective of disease stage, thus rendering the lumbar puncture for stage determination redundant. Having available a single dose oral treatment with limited risk of toxicity opens up new perspectives for eliminating the disease. Treating anyone testing positive to a serological screening test, without further need for on the spot parasitological confirmation and stage determination, will greatly simplify procedures in the field, avoid missing many cases, has the potential to increase uptake of screening and may thus even curb transmission of the causative parasite, which is assumed to have only a human reservoir. Although this innovative option for gHAT control is now feasible, its true effectiveness and cost effectiveness for curtailing transmission remain to be determined. The current gHAT control strategy is based on active screening of people living in villages at risk for gHAT by mobile screening teams. All villages from which gHAT cases were reported are screened for three years in a row until no further cases are found. They are then screened once more, two years after the last case was reported. If no further cases are found, transmission is assumed to have been interrupted. This strategy has had a major impact as can be seen from figure 2 above. However, Robays et al. estimated that up to 50% of prevalent cases are not detected or not cured, with major losses occurring during the parasitological confirmation step.\[9\] Other important barriers are the fear of the lumbar puncture required for stage determination and of toxicity of treatment, in particular associated with melarsoprol, no longer in use for gHAT, but still well-known especially by the elder population. Even if up to 50% of prevalent gHAT cases were not treated, the epidemiological data shows that the disease is on the decline. This may however be insufficient to achieve complete elimination of transmission. We hypothesize that by systematically screening the populations of all endemic villages in a well-defined HAT focus and by expanding gHAT treatment to all seropositives, we will be able to arrive at a zero prevalence over a three-year period. Bearing in mind that acoziborole has not yet been registered and that 'screen \& treat' has not yet been adopted as the new policy, we will for the duration of this study continue performing parasitological confirmation on the spot and treat anyone confirmed by parasitology with standard of care. Any serological suspect not confirmed by parasitology on the spot will be offered treatment with acoziborole (study Part B), conditional on a set of inclusion and exclusion criteria If acoziborole allows us to implement a screen \& treat strategy, allowing to detect and treat all g-HAT prevalent cases, and possibly in the future without the limitations of cumbersome diagnostic confirmation on the spot, we expect that elimination of transmission is also possible in a mainland focus. Implementing such a study under relatively well controlled conditions will also allow us to gather further evidence on safety of acoziborole, before a screen \& treat strategy is rolled out on a larger scale. In addition it will provide information on the cost of such a strategy and on some essential parameters of the tests utilized.