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

Linda Batsa Debrah,Yusif Mubarik,Richard O Phillips,Norman Nausch,Achim Hoerauf,Ute Klarmann-Schulz,Christine Lämmer,Marc Jacobsen,Alexander Yaw Debrah,Kenneth Pfarr,Anna-Lena Sander,Laura E Layland,Wellington Owusu,Vera Serwaa Opoku,Manuel Ritter

doi:10.4269/ajtmh.18-0491

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.

Highlights

Mansonella perstans infection, a vector-borne disease transmitted by female midges of the genus Culicoides, is an infection that, not officially listed by the WHO, is to be considered a neglected tropical disease
We have shown that M. perstans–microfilaremic individuals are characterized by increased TH2 and regulatory cell populations concomitant with reduced systemic cytokine/chemokine and increased filaria-specific IgG4 levels,[11] which might lead to increased susceptibility and worsened disease course of HIV, tuberculosis (TB), and malaria,[12,13,14] and the lower efficacy of bacillus Calmette–Guerin vaccination against TB.[15]
In contrast to other filarial diseases such as onchocerciasis caused by O. volvulus treated with ivermectin and lymphatic filariasis caused by W. bancrofti treated with ivermectin and/or DEC plus albendazole, M. perstans infection is not treated effectively with these drugs.[1,5]

Summary

Introduction

Mansonella perstans infection, a vector-borne disease transmitted by female midges of the genus Culicoides, is an infection that, not officially listed by the WHO, is to be considered a neglected tropical disease. It affects more than 100 million people mainly in rural areas of Central Africa, the Caribbean, and South America.[1,2] Recent reports suggest high prevalence in Ghana.[3,4] In the middle belt of Ghana, the overall prevalence was 32%, but some communities had prevalences of up to 75%. The severity of these clinical manifestations is, in most cases, not very obvious because M. perstans is often coendemic with other filarial parasites in the hosts, making it difficult to assign clinical symptoms to M. perstans.[3,8]

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