Target product profile for a gambiense human African trypanosomiasis high-throughput test for verification of elimination

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 now 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 95% 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. Because trypanosomes are identified visually by their characteristic movement, microscopic examination must be done a short time after sampling (< 1 hour).

HAT has been targeted for elimination as a public health problem, defined as a five years’ mean of < 1 case/10 000 inhabitants in all endemic districts in a given country. This status has been reached in several countries which have been or will soon be validated by WHO. The next target is the elimination of transmission of gambiense HAT, defined as zero autochthonous case for at least five consecutive years. Endemic countries reaching either of these goals need to maintain dedicated surveillance because of the persisting risk of re-emergence or re-introduction of HAT.

The progress in HAT elimination is leading to an unintended gradual loss of specialized personnel, while there is clearly need for large-scale testing of populations considered at risk in order to verify the absence of Tbg transmission. This calls for feasible methods using non-specialized personnel, because currently available diagnostic tools are too complex and resource-intensive.