Albendazole and antibiotics synergize to deliver short-course anti-Wolbachiacurative treatments in preclinical models of filariasis

Turner, Joseph D., Sharma, Raman, Al Jayoussi, Ghaith, Tyrer, Hayley orcid iconORCID: 0000-0002-4447-828X, Gamble, Joanne, Hayward, Laura, Priestley, Richard S., Murphy, Emma A., Davies, Jill et al (2017) Albendazole and antibiotics synergize to deliver short-course anti-Wolbachiacurative treatments in preclinical models of filariasis. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 114 (45). E9712-E9721. ISSN 0027-8424

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Official URL: http://dx.doi.org/10.1073/pnas.1710845114

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 Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to 7 days in preclinical models. ABZ had negligible effects on Wolbachia but synergized with minocycline or rifampicin (RIF) to deplete symbionts, block embryogenesis, and stop microfilariae production. Greater than 99% Wolbachia 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-Wolbachia 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-Wolbachia drugs under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles.


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