Doxycycline as a novel strategy against bancroftian filariasis—depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production
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Chemotherapy of onchocerciasis by doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals (n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) doxycycline 200 mg/day for 6 weeks; (2) doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria.
KeywordsLymphatic filariasis Wuchereria bancroft Wolbachia Doxycycline Ivermectin
We would like to thank the individuals of the district health management in East Nzema, Western Region, Ghana, for their cooperation. We would like to thank Mr. John Larbi, Dr. Matthias Grade, and Dr. Yeetey Enuameh for excellent support. Dr. Hoerauf acknowledges financial support by the German Research Foundation (DFG-grant Ho 2009/1-3); the European Commission (grant ICA4-CT-2002-10051), and Caritas Charity.
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