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

Abstract

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.

Variation in disease phenotype is marked in equine trypanosomiasis

“…DNA extraction and PCR analysis for Trypanosoma sp. was performed as previously outlined ( [31], Additional file 3: Text S1) using highly sensitive and specific primers targeting multicopy satellite DNA target sequences [32]. The pre-treatment blood samples, taken during the initial examination on week 1, were also screened for piroplasmosis using a modified Babesia/Theileria 18S catch-all primer set in a nested PCR assay [33][34][35].…”

Trypanosome infections in naturally infected horses and donkeys of three active sleeping sickness foci in the south of Chad

“…African animal trypanosomiases (AAT) are responsible of major constraints to livestock production in affected countries. Its direct impact is linked to the reduction of livestock productivity while the indirect impacts are associated with a reduced efficiency of draught animals for crop production [6,7]. Although several trypanosome species have been reported in domestic and wild animals residing within HAT foci in west and central Africa [8,9,10,11,12,13], equines have not been addressed thus far (mules, donkeys and horses).…”

“…Viewed their importance, attempts have been refocused to tackle infectious diseases that could compromise the welfare and productivity of these animals [14,15,16,17]. In this light, equine trypanosomiasis was reported as one of the infectious diseases that may have greatest impact upon working equines [7].…”

Trypanosome infections in naturally infected horses and donkeys of three active sleeping sickness foci in the south of Chad

“…African animal trypanosomiases (AAT) are responsible of major constraints to livestock production in affected countries. Its direct impact is linked to the reduction of livestock productivity while the indirect impacts are associated with a reduced efficiency of draught animals for crop production [6,7]. Although several trypanosome species have been reported in domestic and wild animals residing within HAT foci in west and central Africa [8,9,10,11,12,13], equines have not been addressed thus far (mules, donkeys and horses).…”

“…Viewed their importance, attempts have been refocused to tackle infectious diseases that could compromise the welfare and productivity of these animals [14,15,16,17]. In this light, equine trypanosomiasis was reported as one of the infectious diseases that may have greatest impact upon working equines [7].…”