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

Abstract

Treating Mansonella perstans is challenged by the low efficacy of registered antihelminthics. Wolbachia endobacteria provide an alternative treatment target because depletion results in amicrofilaremia in filarial infections with Wuchereria bancrofti and Onchocerca volvulus infections. This open-label, randomized study sought to confirm that i) Wolbachia are present in M. perstans in Ghana and ii) doxycycline treatment will deplete Wolbachia and cause a slow, sustained decline in microfilariae (MF). Two hundred and two Ghanaians with M. perstans 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 Wolbachia 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, Wolbachia were depleted from MF by ≥ 1-log drop compared with baseline levels. We conclude that M. perstans in Ghana harbor Wolbachia that are effectively depleted by doxycycline with subsequent reduction in MF loads, most likely because of interruption of fertility of adult worms.

Figure 1.

Recruitment and treatment profile of study participants.

Figure 2.

Changes in MF loads after doxycycline treatment—primary end point. Microfilariae were filtered onto 3 µM Whatman Nucleopore filters, Giemsa-stained, and counted as MF/mL of blood. Data were transformed by adding one to all values before plotting logarithmically. Comparison of MF/mL was performed within the treatment group at baseline and the 4-, 12-, and 24-month follow-up visits. The red horizontal line represents the median values in each group at each time point. Early and delayed refer to the staggered treatment of the two randomized groups. Early = the group that received treatment immediately after randomization. Delayed = the group that received treatment 6 months after randomization and acted as control to the Early group at the 4- and 12-month follow-up points. The graph was generated with GraphPad Prism 5.0 for Windows (La Jolla, CA). MF = microfilariae.