title: Antibiotic chemotherapy of onchocerciasis: in a bovine model, killing of adult parasites requires a sustained depletion of endosymbiotic bacteria (Wolbachia species).
abstract: Development of a drug lethal to adult Onchocerca volvulus (i.e., macrofilaricide) is a research priority for the control of human onchocerciasis. Using bovine O. ochengi infections, we investigated the effects of oxytetracycline administered in a short intensive regimen (SIR; 10 mg/kg daily for 14 days), compared with a prolonged intermittent regimen (PIR; 20 mg/kg monthly for 6 months) or a combination of both (COM), on the viability of adult worms and their endosymbiotic bacteria (Wolbachia species). The long-term treatments eliminated >80% (COM) or >60% (PIR) of adult female worms (P<.001), and the COM regimen effected a sustained depletion of Wolbachia organisms. Conversely, SIR was not macrofilaricidal and only transiently depleted Wolbachia densities, which repopulated worm tissues by 24 weeks after treatment. These results unequivocally demonstrate the macrofilaricidal potential of tetracyclines against Onchocerca infection and suggest that intermittent, protracted administration will be more effective than continuous shorter term treatment.
authors.affiliation: Liverpool School of Tropical Medicine and Faculty of Veterinary Science, University of Liverpool, United Kingdom.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gilbert
authors.forename: Charles K
authors.initials: CK
authors.lastname: Nfon
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Makepeace
authors.forename: Leo M
authors.initials: LM
authors.lastname: Njongmeta
authors.forename: Ian M
authors.initials: IM
authors.lastname: Hastings
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Pfarr
authors.forename: Alfons
authors.initials: A
authors.lastname: Renz
authors.forename: Vincent N
authors.initials: VN
authors.lastname: Tanya
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Trees
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology*; D004195:Disease Models, Animal; D009854:Onchocerca / Q000382:microbiology*; D009855:Onchocerciasis / Q000188:drug therapy* / Q000662:veterinary*; D013559:Symbiosis / Q000187:drug effects*; D013754:Tetracyclines / Q000494:pharmacology* / Q000627:therapeutic use; D020577:Wolbachia / Q000187:drug effects* / Q000502:physiology
chemical_list: D013754:Tetracyclines