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Potential Role for Flubendazole in Limiting Filariasis Transmission: Observations of Microfilarial Sensitivity
Flubendazole (FLBZ) is a potent and efficacious macrofilaricide after parenteral administration. Studies in animal models and one trial in patients infected with Onchocerca volvulus revealed that FLBZ elicits minimal effects on microfilariae (mf). Severe complications after ivermectin (IVM) treatment of patients with high Loa loa microfilaraemia are of great concern. We examined the potential of FLBZ to rapidly kill L. loa mf, the phenomenon proposed to underlie the complications. Mf of L. loa were exposed to FLBZ, its reduced metabolite, albendazole, or IVM in vitro. Viability of L. loa mf was unaffected by FLBZ (10 μM, 72 hours); similar results were obtained with mf of Brugia malayi. We also measured the effects of FLBZ on transmission of mf. Aedes aegypti were fed FLBZ-exposed B. malayi mf and dissected 24 hours or 14 days postfeeding to count mf that crossed the midgut and developed to infective L3. FLBZ impaired the ability of mf to cross the midgut, regardless of duration of exposure (≥ 2 hours). FLBZ also prevented the development of mf to L3s, irrespective of duration of exposure or concentration. FLBZ is not microfilaricidal under these conditions; however, it blocks transmission. These results support the possibility that FLBZ may be a useful macrofilaricide in loiasis regions and may limit transmission from treated individuals.
Author Notes
Financial support: This work was supported by awards to Michigan State University and McGill University from the Bill and Melinda Gates Foundation and the Drugs for Neglected Diseases initiative.
Authors’ addresses: Maeghan O’Neill and Timothy G. Geary, McGill University, Institute of Parasitology, Montreal, QC, Canada, E-mails: maeghan.oneill@mail.mcgill.ca and timothy.g.geary@mcgill.ca. Jelil Abdel Njouendou and Samuel Wanji, Department of Microbiology and Parasitology, University of Buea, Buea, Cameroon, E-mails: ajnjouenduo@gmail.com and samwanji@gmail.com. Michael Dzimianski, Erica Burkman, and Andrew Moorhead, Filariasis Research Reagent resource Center, University of Georgia, Athens, GA, E-mails: mdzimianski@uga.edu, eburkman@gmail.com, and amoorhead@uga.edu. Patrick Chouna Ndongmo, Department of Microbiology and Parasitology, University of Buea, Athens, GA, E-mail: ndongmopatrick@yahoo.com. Jonas A. Kengne-Ouafo, Department of Biochemistry and Microbiology, University of Buea, Buea, Cameroon, and Research Foundation for Tropical Diseases and the Environment (REFODTE), Buea, Cameroon, E-mail: arnaudkengne@yahoo.com. Charles D. Mackenzie, Department of Pathobiology and Diagnostoc Investigation, Michigan State University, East Lansing, MI, E-mail: mackenz8@msu.edu.