A trypanosome small RNA as a diagnostic for Human and Animal African Trypanosomiasis (360G-Wellcome-204521_Z_16_Z)

(a) Trypanosomiasis is one of the most significant infectious disease threats in sub-Saharan Africa. Two species infect approximately 20 milllion cattle with 3 million deaths per year[1] – at least 55 million cattle are at risk, with an annual cost of $2.5 billion in East Africa alone[2]; 35 million doses of trypanocides are estimated to be used each year across Africa. Trypanosoma brucei historically caused 10,000s of human mortalities per annum – through active case detection this number has been reduced to ~4,000/year (3 million diagnostic tests are used per year)[3]; elimination of human African trypanosomiasis (HAT) by 2030 is a WHO target[4,5](1.7m disability adjusted life years still lost per year). Diagnosis of animal African trypanosomiasis (AAT) is currently largely symptomatic or relies on insensitive microscopy; large quantities of prophylactic drugs are used to prevent disease[6]. A few diagnosis options exist for HAT, but these rely on either antibodies to trypanosome antigens or amplification of DNA. The antibody test cannot differentiate between active infection and exposure, and the DNA target used for the PCR-based approaches often persists after successful treatment[7]. (b) We aim to develop a non-invasive diagnostic based on direct measurement of a trypanosome-derived small RNA (sRNA), which correlates with active infection and can distinguish between trypanosome species. (c) We will validate a candidate sRNA biomarker and optimise sensitivity of sRNA detection in clinically-relevant sample sets (infected cattle for AAT, samples from HAT patients). Using this information we will assess platform utility for AAT and HAT, for development of non-invasive, low-cost, rapid diagnostic tests. (d) Accurate diagnosis will enable targeted treatment of AAT and a significant reduction in the indiscriminate use of prophylactic/therapeutic drugs; for HAT an improved diagnosis would significantly enhance capability to detect and treat cases and therefore improve prospects for elimination. Our aim in this application is to validate the candidate biomarker and potential platform as applicable to both HAT and AAT as it has clear potential for both diseases; given the different needs and potential markets, we envisage that validated marker and identified platform are then developed further independently to tailor application to end-user requirements.