Strategies and Tools to Prevent Trypanocide Failure (STOP-Tryp)

Trypanosomes are single-celled organisms transmitted by tsetse flies that cause serious disease in cattle – African Animal Trypanosomosis (AAT). Found mainly in sub-Saharan Africa, AAT kills 3 million cattle each year, with approximately 60 million cattle at risk, and impacts significantly on food security and livelihoods. The main measure farmers use to combat AAT is drug treatment, but only two drugs are available, both >60 years old. Treatment failures and resistance are widely reported. A new class of therapeutic molecules, the benzoxaborales, has been identified that shows promise as a potential new trypanocide, but to maximise the benefits of any new drug, we need to address current causes of treatment failure, and identify strategies to incorporate the new drug most effectively into existing control methodologies. Our previous research identified that resistance, inappropriate use, and poor drug quality are all linked to treatment failures. We have identified the mechanisms of resistance in the most important trypanosome species, and identified a marker for resistance. We also developed a modelling framework that identified risk factors for resistance. Our model predicts that the frequency of trypanocide use, the amount of tsetse control through applying insecticides to cattle, and whether wildlife hosts are also present, all influence the risk of resistance emergence. Identifying drivers of resistance development is essential in order to identify proactive strategies for managing resistance. In this project, our international, interdisciplinary team will, firstly, identify drivers of resistance across different agro-ecological settings by applying the new marker to samples from cattle, to test how the level of trypanocide use and misuse, insecticide use and presence of wildlife impact levels of resistance. Second, we will test whether drug-resistant parasites are less fit than wild type drug-susceptible parasites; this could compromise transmission and spread of resistance in the field. Third, using the data collected, we will further advance and parameterise our models of AAT control and resistance. The models will enable us to develop integrated strategies for effective and sustainable control that exploit the strengths of current drugs, and assess how to integrate effectively a new drug, across different agro-ecological settings. Lastly, we will collect qualitative and quantitative field data to identify how to address other barriers to effective trypanocide use, including inappropriate use and trypanocide quality, to inform how optimal strategies can actually be achieved. Combining our empirical and theoretical findings will enable us to identify strategies for how to introduce any new drug most effectively, and will directly inform global strategies for improved AAT control. Importantly, we will also develop practical guidance for farmers, veterinary practitioners and policy makers that addresses causes of treatment failure, in order to achieve more effective control of AAT. In turn, impacts on animal health and production can strengthen food security, economic development and poverty alleviation (SDGs 1/2/8). Farmed animal health is a focus area of the BBSRC Research in Agriculture and Food Security Strategic Framework. The Framework specifically highlights that multidisciplinary approaches are needed to address pathogen resistance and develop innovative disease control regimes. This project also tackles the BBSRC strategic challenge of bioscience for sustainable agriculture and food and addresses specific priorities of animal health; combatting antimicrobial resistance; food nutrition and health and sustainably enhancing agricultural production, as well as the cross-council priority of global food security.