Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial

Background Globally, working equines have a continued and growing socioeconomic role in supporting the livelihoods of between 300–600 million people in low income countries which is rarely recognised at a national or international level. Infectious diseases have significant impact on welfare and productivity in this population and equine trypanosomiasis is a priority disease due to its severity and prevalence. Strategies are required to improve the prevention, diagnosis, management and treatment of trypanosomiasis in equines and more data are required on the efficacy and safety of current trypanocidal drugs. Methods A prospective randomised, open-label non-inferiority trial was performed in The Gambia on horses and donkeys that fulfilled 2/5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema). Following randomised trypanocidal treatment (diminazene diaceturate, melarsomine dihydrochloride or isometamidium chloride), animals were observed for immediate adverse drug reactions and follow-up assessment was performed at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma sp. primers. Treatment efficacy was assessed by measuring changes in clinical parameters, clinicopathological results and PCR-status post-treatment after evaluating for bias. Using PCR status as the outcome variable, non-inferiority of isometamidium treatment was determined if the upper bound limit of a 2-sided 95% CI was less than 10%. Results There was a significant beneficial effect upon the Trypanosoma sp. PCR positive population following trypanocidal treatment for all groups. The findings of clinical evaluation and PCR status supported a superior treatment effect for isometamidium. Melarsomine dihydrochloride efficacy was inferior to isometamidium. There were immediate, self-limiting side effects to isometamidium in donkeys (26%). Diminazene had the longest duration of action as judged by PCR status. Conclusions The data support the continued use of isometamidium following careful dose titration in donkeys and diminazene for trypanosomiasis in equines using the doses and routes of administration reported.
Author summary Equine trypanosomiasis is endemic in many areas of the world with high morbidity and mortality in affected populations. Trypanocides form an essential part of current treatment strategies but evidence regarding efficacy in equines is scarce. In order to inform disease management, the efficacy of three trypanocidal drugs was assessed in horses and donkeys that fulfilled 2/5 clinical inclusion criteria for trypanosomiasis in The Gambia. Selected equines received randomised treatment with either isometamidium, diminazene or melarsomine dihydrochloride and were observed for adverse drug reactions. Follow-up was performed at 1 and 2 weeks. Blood collected at each timepoint was analysed for Trypanosoma spp. using a PCR approach. Within the selected population 66% were PCR positive pre-treatment for Trypanosoma spp.. Trypanosome positive individuals responded favourably to each treatment, but clinical evaluation and PCR status post-treatment supported a superior effect for isometamidium. Melarsomine dihydrochloride had inferior efficacy to isometamidium. Immediate adverse side effects were only documented following isometamidium administration in donkeys (26%) and these were self-limiting. Diminazene had the longest duration of action as judged by PCR status. The data support the continued use of isometamidium and diminazene but not melarsomine dihydrochloride for trypanosomiasis in equines at the doses and routes of administration reported.