Novel anti-Wolbachia drugs, a new approach in the treatment and prevention of veterinary filariasis?

Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476, Marriott, Amy, Hong, David, O’ Neill, Paul, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 (2020) 'Novel anti-Wolbachia drugs, a new approach in the treatment and prevention of veterinary filariasis?'. Veterinary Parasitology, Vol 279, p. 109057.

Text Turner anti-Wolbachia drugs review AHS Turner et al_revised_.docx - Accepted Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (7MB)

Abstract

Filarial nematodes are tissue-dwelling parasitic worms that can cause a range of disfiguring pathologies in humans and potentially lethal infections of companion animals. The bacterial endosymbiont, Wolbachia, is present within most human and veterinary filarial pathogens, including the causative agent of heartworm disease, Dirofilaria immitis. Doxycycline-mediated drug targeting of Wolbachia leads to sterility, clearance of microfilariae and gradual death of adult filariae. This mode of action is attractive in the treatment of filariasis because it avoids severe host inflammatory adverse reactions invoked by rapid-killing anthelmintic agents. However, doxycycline needs to be taken for four weeks to exert curative activity. In this review, we discuss the evidence that Wolbachia drug targeting is efficacious in blocking filarial larval development as well as in the treatment of chronic filarial disease. We present the current portfolio of next-generation anti-Wolbachia candidates discovered through phenotypic screening of chemical libraries and validated in a range of in vitro and in vivo filarial infection models. Several novel chemotypes have been identified with selected narrow-spectrum anti-Wolbachia specificity and superior time-to-kill kinetics compared with doxycycline. We discuss the opportunities of developing these novel anti-Wolbachia agents as either cures, adjunct therapies or new preventatives for the treatment of veterinary filariasis.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Bacteria > QW 150 Proteobacteria. Rickettsiaceae, Wolbachia WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases WC Communicable Diseases > Tropical and Parasitic Diseases > WC 765 Prevention and control WC Communicable Diseases > Tropical and Parasitic Diseases > WC 850 Nematode infections (General) WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
Faculty: Department:	Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI):	https://doi.org/10.1016/j.vetpar.2020.109057
Depositing User:	Cathy Waldron
Date Deposited:	03 Mar 2020 14:25
Last Modified:	15 Feb 2021 02:02
URI:	https://archive.lstmed.ac.uk/id/eprint/13878

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