The Efficacy of Doxycycline Treatment on Mansonella perstans Infection: An Open-Label, Randomized Trial in Ghana

Abstract

Treating <i>Mansonella perstans</i> is challenged by the low efficacy of registered antihelminthics. <i>Wolbachia</i> endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with <i>Wuchereria bancrofti</i> and <i>Onchocerca volvulus</i> infections. This open-label, randomized study sought to confirm that i) <i>Wolbachia</i> are present in <i>M. perstans</i> in Ghana and ii) doxycycline treatment will deplete <i>Wolbachia</i> and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with <i>M. perstans</i> infection were randomized into early (immediate) and delayed (6 months deferred) treatment groups, given doxycycline 200 mg/day for 6 weeks, and monitored for MF and <i>Wolbachia</i> levels at baseline, 4, 12, and 24 months after the study onset (= time of randomization and start of treatment for the early group). Per protocol analysis revealed that the median MF/mL in the early group declined from 138 at baseline to 64 at month 4 and further to 0 at month 12. In the delayed group, MF load did not change from a baseline median of 97 to 102 at month 4 but declined to 42 at month 12, that is, 6 months after receiving treatment, trailing the early group as expected. By month 24, both treatment groups had reached a median MF level of 0. After treatment, <i>Wolbachia</i> were depleted from MF by ≥ 1-log drop compared with baseline levels. We conclude that <i>M. perstans</i> in Ghana harbor <i>Wolbachia</i> that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.