Cleveland Christopher A, Garrett Kayla B, Box Erin K, Thompson Alec T, Haynes Ellen K, Elder Deborah L, Richards Robert L, Majewska Ania A, Guagliardo Sarah Anne J, Wiegand Ryan E, Bryan Ii John A, Torres-Velez Fernando, Unterwegner Karmen, Romero Mario, Zirimwabagabo Hubert, Sidouin Metinou, Oaukou Philip Tchindebet, Ada Mbang Mahammat, Ngandolo Bongo Nare Richard, Mackenzie Charles D, Geary Timothy G, Weiss Adam J, Yabsley Michael J
University of Georgia, Athens, Georgia.
Louisiana State University, Baton Rouge, Louisiana.
Am J Trop Med Hyg. 2022 Feb 28;106(5):1456-65. doi: 10.4269/ajtmh.21-1222.
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.
麦地那龙线虫（几内亚龙线虫[GW]）是一种目标为根除的人畜共患线虫，一直通过针对人类的干预措施进行管控；然而，家犬感染几内亚龙线虫的情况增多凸显了采用新方法的必要性。我们开展了两项临床试验，评估皮下注射氟苯达唑（FBZ）治疗几内亚龙线虫感染的疗效。第一项试验是对经实验感染的雪貂施用FBZ；第二项试验是对乍得共和国（乍得）的家犬施用FBZ或安慰剂。我们在两项试验中发现了截然不同的结果。当从接受FBZ治疗的雪貂体内回收成年妊娠雌虫时，幼虫状况不佳，活力低或无活力，且无法感染桡足类动物。组织病理学结果表明，来自接受治疗动物的虫体子宫内桑葚胚发育受到破坏。在乍得犬身上进行的试验结果未能表明对几内亚龙线虫感染有显著治疗效果或预防作用。然而，治疗间隔的差异（雪貂为1个月，犬为6个月）或治疗时间（雪貂在几内亚龙线虫生命周期中比犬接受治疗的时间晚）可能解释了对皮下注射FBZ的不同反应。两项试验都提供了有价值的数据，为未来试验中使用FBZ提供了指导（例如缩短治疗间隔或增加犬用FBZ剂量以增加接触量），并突出了在乍得犬身上开展基于现场的双盲随机对照试验过程中吸取的重要经验教训。
