title: Anti-Wolbachia drug discovery and development: safe macrofilaricides for onchocerciasis and lymphatic filariasis.
abstract: Anti-Wolbachia therapy delivers safe macrofilaricidal activity with superior therapeutic outcomes compared to all standard anti-filarial treatments, with the added benefit of substantial improvements in clinical pathology. These outcomes can be achieved, in principle, with existing registered drugs, e.g. doxycycline, that are affordable, available to endemic communities and have well known, albeit population-limiting, safety profiles. The key barriers to using doxycycline as an mass drug administration (MDA) strategy for widespread community-based control are the logistics of a relatively lengthy course of treatment (4-6 weeks) and contraindications in children under eight years and pregnancy. Therefore, the primary goal of the anti-Wolbachia (A·WOL) consortium is to find drugs and regimens that reduce the period of treatment from weeks to days (7 days or less), and to find drugs which would be safe in excluded target populations (pregnancy and children). A secondary goal is to refine regimens of existing antibiotics suitable for a more restricted use, prior to the availability of a regimen that is compatible with MDA usage. For example, for use in the event of the emergence of drug-resistance, in individuals with high loiasis co-infection and at risk of severe adverse events (SAE) to ivermectin, or in post-MDA 'endgame scenarios', where test and treat strategies become more cost effective and deliverable.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Taylor
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.affiliation: Tropical Parasitic Diseases Unit, Northwick Park Institute for Medical Research, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Townson
authors.affiliation: New England Biolabs, Inc., 240 County Road, Ipswich, MA 01938, USA.
authors.forename: Barton E
authors.initials: BE
authors.lastname: Slatko
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017178:Brugia malayi / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D002648:Child; D004318:Doxycycline / Q000494:pharmacology; D055808:Drug Discovery; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D005369:Filaricides / Q000494:pharmacology*; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology; D008118:Loiasis / Q000188:drug therapy* / Q000469:parasitology; D017181:Onchocerca volvulus / Q000187:drug effects / Q000382:microbiology / Q000502:physiology; D009855:Onchocerciasis / Q000188:drug therapy* / Q000469:parasitology; D011247:Pregnancy; D013559:Symbiosis / Q000187:drug effects; D020577:Wolbachia / Q000187:drug effects* / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D005369:Filaricides; D007559:Ivermectin; D004318:Doxycycline