• Alexander Yaw Debrah, Sabine Specht, Ute Klarmann-Schulz, Linda Batsa, Sabine Mand, Yeboah Marfo-Debrekyei, Rolf Fimmers, Bettina Dubben, Alexander Kwarteng, Mike Osei-Atweneboana, Daniel Boakye, Arcangelo Ricchiuto, Marcelle Büttner, Ohene Adjei, Charles D Mackenzie, and Achim Hoerauf.
• Faculty of Allied Health Sciences, Kwame Nkrumah University of Science and Technology Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana.
• Clin. Infect. Dis. 2015 Aug 15; 61 (4): 517-26.

BackgroundIvermectin (IVM) has been the drug of choice for the treatment of onchocerciasis. However, there have been reports of persistent microfilaridermia in individuals from an endemic area in Ghana after many rounds of IVM, raising concerns of suboptimal response or even the emergence of drug resistance. Because it is considered risky to continue relying only on IVM to combat this phenomenon, we assessed the effect of targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline for these individuals with suboptimal response.MethodsOne hundred sixty-seven patients, most of them with multiple rounds of IVM, were recruited in areas with IVM suboptimal response and treated with 100 mg/day doxycycline for 6 weeks. Three and 12 months after doxycycline treatment, patients took part in standard IVM treatment.ResultsAt 20 months after treatment, 80% of living female worms from the placebo group were Wolbachia positive, whereas only 5.1% in the doxycycline-treated group contained bacteria. Consistent with interruption of embryogenesis, none of the nodules removed from doxycycline-treated patients contained microfilariae, and 97% of those patients were without microfilaridermia, in contrast to placebo patients who remained at pretreatment levels (P < .001). Moreover, a significantly enhanced number of dead worms were observed after doxycycline.ConclusionsTargeting the Wolbachia in O. volvulus is effective in clearing microfilariae in the skin of onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment. Strategies can now be developed that include doxycycline to control onchocerciasis in areas where infections persist despite the frequent use of IVM.Clinical Trials RegistrationISRCTN 66649839.© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

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