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.

• Authors: Alexandra G Raftery, Saloum Jallow, Jean Rodgers, David G M Sutton
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 13 Issue 3 Pg. e0007175 (03 2019) ISSN: 1935-2735 [Electronic] United States
• PMID: 30901321 (Publication Type: Clinical Trial, Veterinary, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arsenicals
• Phenanthridines
• Triazines
• Trypanocidal Agents
• melarsomine
• isometamidium chloride
• diminazene aceturate
• Diminazene

Topics

• Animals
• Arsenicals (administration & dosage, adverse effects)
• Diminazene (administration & dosage, adverse effects, analogs & derivatives)
• Equidae (parasitology)
• Female
• Gambia (epidemiology)
• Horse Diseases (drug therapy, epidemiology, parasitology)
• Horses
• Male
• Phenanthridines (administration & dosage, adverse effects)
• Prospective Studies
• Random Allocation
• Treatment Outcome
• Triazines (administration & dosage, adverse effects)
• Trypanocidal Agents (administration & dosage, adverse effects)
• Trypanosoma (drug effects)
• Trypanosomiasis (drug therapy, epidemiology, parasitology, veterinary)