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

Authors :
Mark J. Taylor
Rachel H. Clare
Louise Ford
Andrew Steven
Richard S. Priestley
Emma A Murphy
Joseph D. Turner
Janet Hemingway
Jill Davies
John McCall
David Waterhouse
Stephen A. Ward
Andrew Cassidy
Hayley E. Tyrer
Kelly L. Johnston
Raman Sharma
Darren A. N. Cook
Laura Hayward
Joanne Gamble
Ghaith Al Jayoussi
Source :
Proceedings of the National Academy of Sciences. 114
Publication Year :
2017
Publisher :
Proceedings of the National Academy of Sciences, 2017.

Abstract

Significance Filarial nematode infections, caused by Wuchereria bancrofti , Brugia malayi (elephantiasis), and Onchocerca volvulus (river blindness) infect 150 million of the world’s poorest populations and cause profound disability. Standard treatments require repetitive, long-term, mass drug administrations and have failed to interrupted transmission in certain sub-Saharan African regions. A drug cure using doxycycline, which targets the essential filarial endosymbiont Wolbachia , is clinically effective but programmatically challenging to implement due to long treatment durations and contraindications. Here we provide proof-of-concept of a radical improvement of targeting Wolbachia via identification of drug synergy between the anthelmintic albendazole and antibiotics. This synergy enables the shortening of treatment duration of macrofilaricidal anti- Wolbachia based treatments from 4 wk to 7 d with registered drugs ready for clinical testing.

Details

ISSN :
10916490 and 00278424
Volume :
114
Database :
OpenAIRE
Journal :
Proceedings of the National Academy of Sciences
Accession number :
edsair.doi.dedup.....3f6d7a218a281b4cf44f8ee599d17385