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Christopher A. Cleveland, University of Georgia, 589 D. W. Brooks Drive, Athens, GA 30602. E-mail: ccleve@uga.edu

We thank the team members of Afrique One ASPIRE (http://afriqueoneaspire.org/), Institut de Recherche en Elevage pour le Développement (IRED), for their outstanding contributions in facilitating this work in the field. We also acknowledge Dr. Ajay Sharma (College of Veterinary Medicine, University of Georgia) for his assistance and providing diagnostic imaging techniques on the ferrets.

We also thank R. Bringolf, R. Ratajczak, and the staff at University of Georgia–Athens’s Animal Resources for assistance with this project. The Investigative Histopathology Unit at Michigan State University, East Lansing, is thanked for their expertise in preparing the worm samples for histological examination. A. Majewska would like to acknowledge support from the NIH IRACDA FIRST fellowship program (K12 GM000680/GM/NIGMS NIH HHS/United States).

All procedures involving dogs and ferrets were reviewed and approved by the University of Georgia's institutional animal care and use committee committee (A2019 04-005-Y3-A0 and A2020 05-003-Y1-A0). The findings and conclusions in the article are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention.

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Research Funding:

This work was supported by The Carter Center; a full listing of Carter Center supporters is available at http://www.cartercenter.org/donate/corporate-government-foundation-partners/index.html.

Additional support was provided by the wildlife management agencies of the Southeastern Cooperative Wildlife Disease Study member states through the Federal Aid to Wildlife Restoration Act (50 Stat. 917) and by a U.S. Department of the Interior Cooperative Agreement.

AAM was supported by NIH/NIGMS K12 Postdoctoral Fellowship at Emory University (5K12GM000680-19).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Public, Environmental & Occupational Health
  • Tropical Medicine
  • METRONIDAZOLE
  • THIABENDAZOLE
  • MEBENDAZOLE

Investigating Flubendazole as an Anthelmintic Treatment for Guinea Worm (Dracunculus medinensis): Clinical Trials in Laboratory-Reared Ferrets and Domestic Dogs in Chad

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Journal Title:

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE

Volume:

Volume 106, Number 5

Publisher:

, Pages 1456-1465

Type of Work:

Article | Final Publisher PDF

Abstract:

Dracunculus medinensis (Guinea worm [GW]), a zoonotic nematode targeted for eradication, has been managed using interventions aimed at humans; however, increases in domestic dog GW infections highlight the need for novel approaches. We conducted two clinical trials evaluating the efficacy of subcutaneously injected flubendazole (FBZ) as a treatment of GW infection. The first trial was conducted administering FBZ to experimentally infected ferrets; the second trial involved administering FBZ or a placebo to domestic dogs in the Republic of Tchad (Chad). We found contrasting results between the two trials. When adult gravid female GW were recovered from ferrets treated with FBZ, larvae presented in poor condition, with low to no motility, and an inability to infect copepods. Histopathology results indicated a disruption to morulae development within uteri of worms from treated animals. Results from the trial in Chadian dogs failed to indicate significant treatment of or prevention against GW infection. However, the difference in treatment intervals (1 month for ferrets and 6 months for dogs) or the timing of treatment (ferrets were treated later in the GW life-cycle than dogs) could explain different responses to the subcutaneous FBZ injections. Both trials provided valuable data guiding the use of FBZ in future trials (such as decreasing treatment intervals or increasing the dose of FBZ in dogs to increase exposure), and highlighted important lessons learned during the implementation of a field-based, double-blinded randomized control trial in Chadian dogs.

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© The American Society of Tropical Medicine and Hygiene

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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