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

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.

Surveillance of tick-borne pathogens in domestic dogs from Chad, Africa, in a One Health context

“…A small number of the dogs sampled in this study (n = 13) were positive for B. c. [21,37,38]. The lack of B. c. rossi in our dogs may be due to the low number (n = 14) of dogs infested with Haemaphysalis leachii [11]. Additional studies to determine the distribution and factors related to the presence and intensity of H. leachii are needed to better understand the risk of severe babesiosis to the health of dogs in Chad.…”

“…Currently, there are few data on tick-borne pathogens in domestic dogs in Chad. Previous studies by our group on domestic Chadian dogs revealed high rates of tick infestation [11], a lack of heartworm (Diro laria immitis) infections, and infections with a Brugia sp. that was previously unreported in dogs in Central Africa [12].…”

“…and the molecular detection of E. canis were not surprising, as this pathogen has been reported in dogs from Chad and other African countries. Moreover, most dogs in this study were infested with R. sanguineus [11], the primary vector of E. canis [3,11,[19][20][21][25][26][27][28][29][30][31]. The 86% seroprevalence of Ehrlichia spp.…”

“…Aspects of this study limit the conclusions that can be drawn from the data. Importantly, ticks were opportunistically collected from dogs enrolled in an experimental therapeutic trial for the treatment and prevention of Guinea worms (Dracunculus medinensis) [13]. Therefore, sample size calculations and counts of total tick burden per dog were not performed, which limits the interpretability of the results.…”

Validation of a high‐performance liquid chromatography method for detecting flubendazole and 2‐aminoflubendazole in canine plasma

“…It is routinely used in veterinary medicine for the treatment of selected parasites, primarily gastrointestinal nematodes of poultry and livestock [1]. There is also growing interest in using this drug to treat or prevent filarial infections [1,2]. The mode of action for flubendazole is based on binding to tubulin, with a preferential binding to nematode tubulin compared to mammalian tubulin [3].…”