Turner, Joseph D, Sharma, Raman, Al Jayoussi, Ghaith, Tyrer, Hayley E, Gamble, Joanne 
ORCID: 0000-0001-7302-3412, Hayward, Laura, Priestley, Richard S, Murphy, Emma A, Davies, Jill, Waterhouse, David et al (show 10 more authors)
(2017)
Albendazole and antibiotics synergize to deliver short-course anti-<i>Wolbachia</i> curative treatments in preclinical models of filariasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 114 (45).
E9712-E9721.
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | filariasis, Wolbachia, macrofilaricide, albendazole, combination therapy |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 23 Jan 2019 11:32 |
| Last Modified: | 11 Oct 2023 00:25 |
| DOI: | 10.1073/pnas.1710845114 |
| Open Access URL: | https://www.pnas.org/content/pnas/114/45/E9712.ful... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3031674 |
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