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

• Type of Material: Article
• Authors: Christopher A Cleveland, University of Georgia; Kayla B Garrett, University of Georgia; Erin K Box, University of Georgia; Alec T Thompson, University of Georgia; Ellen K Haynes, University of Georgia; Deborah L Elder, University of Georgia; Robert L Richards, University of Georgia; Ania A Majewska, Emory University; Sarah Anne J Guagliardo, The Centers for Disease Control and Prevention, Atlanta; Ryan E Wiegand, The Centers for Disease Control and Prevention, Atlanta; John A Bryan, II, Zachery Consulting LLC; Fernando Torres-Velez, The Carter Center, Atlanta; Karmen Unterwegner, The Carter Center, Atlanta; Mario Romero, The Carter Center, Atlanta; Hubert Zirimwabagabo, The Carter Center, Atlanta; Metinou Sidouin, The Carter Center, Atlanta; Philip Tchindebet Oaukou, Ministry of Health, N’Djamena; Mbang Mahammat Ada, Ministry of Health, N’Djamena; Bongo Nare Richard Ngandolo, Afrique One Aspire; Charles Mackenzie, Emory University; Timothy G Geary, McGill University; Adam J Weiss, The Carter Center, Atlanta; Michael J Yabsley, University of Georgia
• Language: English
• Date: 2022-05-01
• Publisher: AMER SOC TROP MED & HYGIENE
• Publication Version: Final Published Version
• Copyright Statement: © The American Society of Tropical Medicine and Hygiene
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.4269/ajtmh.21-1222
• Title of Journal or Parent Work: AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
• Volume: 106
• Issue: 5
• Start Page: 1456
• End Page: 1465
• Grant/Funding Information: 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).; 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.
• Keywords: METRONIDAZOLE; THIABENDAZOLE; Life Sciences & Biomedicine; Tropical Medicine; MEBENDAZOLE; Public, Environmental & Occupational Health; Science & Technology
• Research Categories: Health Sciences, Public Health; Health Sciences, General

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.