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PLoS neglected tropical diseases2019; 13(3); e0007175; doi: 10.1371/journal.pntd.0007175

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: 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. 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%. 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. 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.
Publication Date: 2019-03-22 PubMed ID: 30901321PubMed Central: PMC6447232DOI: 10.1371/journal.pntd.0007175Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study focuses on testing the effectiveness and safety of three drugs to treat trypanosomiasis, a dangerous and prevalent disease in working equines (horses and donkeys), in The Gambia. The results revealed beneficial effects from all treatments, with the drug isometamidium outperforming the others, yet causing temporary side effects in donkeys.

Research Background

  • Equines (horses and donkeys) are essential for the livelihood of individuals in low-income countries. However, their health and productivity are significantly affected by infectious diseases, particularly trypanosomiasis.
  • This study aims to provide valuable data on the efficacy and safety of the currently used drugs i.e., diminazene diaceturate, melarsomine dihydrochloride, or isometamidium chloride for the treatment of trypanosomiasis in equines.

Methodology

  • The study was an open-label non-inferiority trial, which means that it aimed to determine whether a new treatment (isometamidium chloride) is no worse than the already existing treatments (diminazene diaceturate, melarsomine dihydrochloride) in terms of efficacy.
  • Equines that met at least two of the five clinical criteria- anaemia, poor body condition, fever, history of abortion, oedema- were included. These animals were randomly assigned to receive one of the three treatments, and monitored for immediate drug reactions.
  • Post-treatment evaluations were performed after one and two weeks, which included clinical assessments and Polymerase Chain Reaction (PCR) analysis for the presence of Trypanosoma parasites.

Findings

  • All the treatments had a significant positive impact on the Trypanosoma PCR positive population of the equines.
  • The isometamidium chloride treatment was found to be most effective according to the clinical evaluations and PCR status, thus not inferior to the existing treatments.
  • However, isometamidium appeared to cause short-term side effects in 26% of the treated donkeys. Melarsomine dihydrochloride had lesser efficacy compared to isometamidium.
  • Diminazene diaceturate showed the longest duration of action as judged by post-treatment PCR status.

Conclusion

  • The study supports the use of isometamidium for treating trypanosomiasis in working equines, given that the dosage is carefully titrated, especially in donkeys, and the route of administration is reviewed.
  • The longest duration of action was observed with diminazene diaceturate treatment, suggesting that its continued use could also be viable when administered at the reported doses and routes.

Cite This Article

APA
Raftery AG, Jallow S, Rodgers J, Sutton DGM. (2019). Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial. PLoS Negl Trop Dis, 13(3), e0007175. https://doi.org/10.1371/journal.pntd.0007175

Publication

ISSN: 1935-2735
NlmUniqueID: 101291488
Country: United States
Language: English
Volume: 13
Issue: 3
Pages: e0007175
PII: e0007175

Researcher Affiliations

Raftery, Alexandra G
  • The Weipers Centre Equine Hospital, Large Animal Clinical Science and Public Health, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Jallow, Saloum
  • Gambia Horse and Donkey Trust, Sambel Kunda, Central River District, The Gambia.
Rodgers, Jean
  • Institute of Biodiversity, Animal Health & Comparative Medicine, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Sutton, David G M
  • The Weipers Centre Equine Hospital, Large Animal Clinical Science and Public Health, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

MeSH Terms

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

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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