Randomized Clinical Trial Evaluating a Novel Piperazine-Based Drug as a Treatment for Gastric Cryptosporidiosis in Eastern Indigo Snakes (Drymarchon couperi)

Abstract Gastric cryptosporidiosis caused by Cryptosporidium serpentis has impacted the conservation efforts for the imperiled eastern indigo snake (EIS, Drymarchon couperi ). Multiple treatments, including paromomycin, nitazoxanide-azithromycin-rifabutin, clofazimine, curcumin, and hydrogen peroxide gavage, have been investigated and proved ineffective in eliminating the parasite, necessitating further investigation. A novel piperazine-based compound, MMV665917, has been shown to be more effective than paromomycin, nitazoxanide, and clofazimine in treating cryptosporidiosis in mammals. With these promising results, MMV665917 was selected to investigate as a treatment of gastric cryptosporidiosis in EIS. Twelve EIS naturally infected with C. serpentis were randomly divided into two groups of six: Group A and Group B. Group A received 22 mg/kg MMV665917 daily for 7 days, and Group B received a placebo daily for 7 days. All EIS tolerated the treatment with no adverse effects appreciated. Success was evaluated by C. serpentis –specific probe hybridization qPCR analysis of gastric lavage performed 1, 2, and 3 months following the treatment. Infections persisted following treatment, and there was no statistical difference in qPCR cycle threshold values between the groups or within the groups for the 3 months following treatment ( F = 0.92, P = 0.525). These findings show that MMV665917 dosed at 22 mg/kg daily for 7 days is ineffective in eliminating C. serpentis in EIS and alternative MMV665917 dosing or formulations should be investigated in reptiles.