Abstract

BackgroundFor two decades, onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). In some Ghanaian communities, the long-term use of IVM was associated with a more rapid than expected skin repopulation by mf after treatment. Here, we assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients.MethodologyOnchocercal nodules were surgically removed just before (D0) and 80 days (D80) after a standard dose of IVM in two cohorts with different treatment histories: a group who had received repeated doses of IVM over 13 years, and a control group with no history of large-scale treatments. Excised nodules were digested with collagenase to isolate adult worms. Embryograms were prepared with females for the evaluation of their reproductive capacities.Principal FindingsOocyte production was not affected by IVM. The mean number of intermediate embryos (morulae and coiled mf) decreased similarly in the two groups between D0 and D80. In contrast, an accumulation of stretched mf, either viable or degenerating, was observed at D80. However, it was observed that the increase in number of degenerating mf between D0 and D80 was much lower in the frequently treated group than in the control one (Incidence Rate Ratio: 0.25; 95% CI: 0.10–0.63; p = 0.003), which may indicate a reduced sequestration of mf in the worms from the frequently treated group.Conclusion/SignificanceIVM still had an embryostatic effect on O. volvulus, but the effect was reduced in the frequently treated cohort compared with the control population.

Highlights

  • The macrocyclic lactone drug ivermectin (IVM) has a broad spectrum of applications against arthropods and nematodes

  • In Brugia malayi, a filarial nematode closely related to O. volvulus, it has been postulated that IVM may paralyze the muscle associated with the excretory vesicle, leading to a reduction in the release of immunomodulators from the parasite that enable evasion of the host immune system [6]

  • Embryogenesis of O. volvulus was not affected by ivermectin

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Summary

Introduction

The macrocyclic lactone drug ivermectin (IVM) has a broad spectrum of applications against arthropods and nematodes. In Brugia malayi, a filarial nematode closely related to O. volvulus, it has been postulated that IVM may paralyze the muscle associated with the excretory vesicle, leading to a reduction in the release of immunomodulators from the parasite that enable evasion of the host immune system [6]. Following a standard therapeutic dose (150 mg/kg of bodyweight), this so-called microfilaricidal effect of IVM leads to a 98% clearance of the skin mf within 2–3 weeks [7]. Onchocerciasis control has been based on mass treatment with ivermectin (IVM), repeated annually or six-monthly. This drug kills Onchocerca volvulus microfilariae (mf) present in the skin and the eyes (microfilaricidal effect) and prevents for 3–4 months the release of new mf by adult female worms (embryostatic effect). We assessed whether the embryostatic effect of IVM on O. volvulus has been altered following frequent treatment in Cameroonian patients

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