Albendazole and antibiotics synergize to deliver short-course anti- <i>Wolbachia</i> curative treatments in preclinical models of filariasis

Abstract

Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a 7-day period. Here we have identified a synergy between the anthelmintic albendazole (ABZ) and drugs depleting the filarial endosymbiont <i>Wolbachia</i>, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on <i>Wolbachia</i> but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production. Greater than 99% <i>Wolbachia</i> depletion following 7-day combination of RIF+ABZ also led to accelerated macrofilaricidal activity. Thus, we provide preclinical proof-of-concept of treatment shortening using antibiotic+ABZ combinations to deliver anti-<i>Wolbachia</i> sterilizing and macrofilaricidal effects. Our data are of immediate public health importance as RIF+ABZ are registered drugs and thus immediately implementable to deliver a 1-wk macrofilaricide. They also suggest that novel, more potent anti-<i>Wolbachia</i> drugs under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles.