Target product profile for a gambiense human African trypanosomiasis individual test to assess infection in low prevalence settings

Overview

Human African trypanosomiasis (HAT) is a life-threatening parasitic infection transmitted by the tsetse fly, that is endemic in Sub-Saharan Africa. Having caused devastating epidemics during the 20th century, its incidence has fallen to historically low levels thanks to sustained and coordinated efforts over the past 20 years. Two trypanosome subspecies cause the disease, with distinct epidemiology: Trypanosoma brucei rhodesiense (Tbr), found in eastern and southern Africa, is harboured by wild and domestic animals which constitute its reservoir, being transmitted occasionally to humans; and Trypanosoma brucei gambiense (Tbg), in western and central Africa, with humans as the main reservoir, accounting for about 93% of the total caseload.

HAT diagnosis relies on laboratory techniques because clinical signs and symptoms are unspecific. Serodiagnostic tests exist only for Tbg and are based on the detection of specific antibodies, thus they are not confirmatory of infection. With the current low disease prevalence, the positive predictive value of serological tests is particularly low. Field-applicable tools include the card agglutination test for trypanosomiasis (CATT) used mainly in active screening by specialized mobile teams, and the rapid diagnostic tests that are more suitable for individual testing at point-of-care. Confirmation of Tbg infection requires microscopic examination of body fluids necessitating specific training. The best performing methods are laborious and reach 85–95% diagnostic sensitivity when performed by skilled personnel.

In gambiense HAT (g-HAT) it has long been observed that repeated rounds of screening followed by treatment of detected cases can bring down the prevalence substantially, and this has been the cornerstone strategy of g-HAT control and elimination. The expected advent of a safer and easy-to-use treatment, would allow for treating seropositive but microscopically unconfirmed individuals (widened treatment), leading to further depletion of the parasite reservoir. But there will be need of monitoring the presence of Tbg infection in the community to keep adapting the control strategy in each setting including its eventual stop. Moreover, in the framework of the HAT elimination targets, this tool would ensure the provision of key data to assess the elimination status in endemic countries.