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

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Turner, Joseph, Sharma, Raman, Aljayyoussi, Ghaith, Tyrer, Hayley, Gamble, Jo, Hayward, Laura, Priestley, Richard, Murphy, Emma ORCID: https://orcid.org/0000-0001-9421-7777, Davies, Jill, Waterhouse, David, Cook, Darren, Clare, Rachel ORCID: https://orcid.org/0000-0002-3945-0530, Cassidy, Andrew, Steven, Andrew, Johnston, Kelly, Ford, Louise, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and Taylor, Mark (2017) 'Albendazole and antibiotics synergize to deliver short-course anti-Wolbachia curative treatments in preclinical models of filariasis'. Proceedings of the National Academy of Sciences of the United States of America, Vol 114, Issue 45, E9712-E9721.

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Abstract

Elimination of filariasis requires a macrofilaricide treatment that can be delivered within a seven-day period. Here we have identified a novel synergy between the anthelmintic, albendazole (ABZ) and drugs depleting the filarial endosymbiont Wolbachia, a proven macrofilaricide target, which reduces treatment from several weeks to seven 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. >99% Wolbachia depletion following seven-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 is of immediate public health importance as RIF+ABZ are registered drugs and thus immediately implementable to deliver a one-week macrofilaricide. It also suggests novel, more potent anti-wolbachials under development may be capable of delivering further treatment shortening, to days rather than weeks, if combined with benzimidazoles.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 253 Anthelmintics
QV Pharmacology > Anti-Bacterial Agents. Tissue Extracts > QV 350 Anti-bacterial agents (General or not elsewhere classified)
QX Parasitology > QX 20 Research (General)
QX Parasitology > QX 45 Host-parasite relations
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WW Ophthalmology > Diseases. Color Perception > WW 160 Eye infections. Hypersensitivity diseases (General or not elsewhere classified)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.1710845114
Depositing User: Elly Wallis
Date Deposited: 31 Oct 2017 16:18
Last Modified: 06 Jul 2018 15:18
URI: http://archive.lstmed.ac.uk/id/eprint/7746

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