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Rates of microfilarial production by Onchocerca volvulus are not cumulatively reduced by multiple ivermectin treatments

Published online by Cambridge University Press:  03 October 2008

CHRISTIAN BOTTOMLEY ,
VALERIE ISHAM ,
RICHARD C. COLLINS  and
MARIA-GLORIA BASÁÑEZ
CHRISTIAN BOTTOMLEY
Affiliation:
Department of Primary Care & Population Sciences, Royal Free Hospital, Rowland Hill Street, London NW3 2PF
VALERIE ISHAM
Affiliation:
Department of Statistical Science, University College London, Gower Street, London WC1E 6BT
RICHARD C. COLLINS
Affiliation:
P.O. Box 715, Sonoita, AZ 85637, USA
MARIA-GLORIA BASÁÑEZ*
Affiliation:
Department of Infectious Disease Epidemiology, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG
*
*Corresponding Author: Department of Infectious Disease Epidemiology, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG. Tel: +44 (0)20 7594 3295. E-mail: m.basanez@imperial.ac.uk
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Summary

Regular distribution of ivermectin reduces onchocerciasis transmission and morbidity by killing, within humans, the microfilarial stage of the parasite (microfilaricidal effect). In addition, ivermectin exerts a so-called embryostatic effect by which microfilarial production by the adult female worm becomes suppressed during a number of weeks after treatment. To assess the overall effect of ivermectin on onchocerciasis transmission and evaluate the likelihood of local elimination of the infection it is important to estimate the magnitude of the anti-fertility effect over the course of a treatment programme. Estimates of the effect of repeated drug treatments on the production of microfilariae by adult Onchocerca volvulus were obtained by developing a model that was fitted to data collected from three hyperendemic communities in Guatemala, where eligible residents received ivermectin twice per year for two and a half years. The data consist of microfilarial load measurements in the skin, collected just before each six-monthly treatment during the programme. The model that is developed describes the dynamics of an individual host's expected microfilarial load over the 30-month study period. We adopt a Bayesian approach and use Markov chain Monte Carlo (McMC) techniques to fit the model to the data. Combining estimates from the three villages, average microfilarial production in the first six months post-treatment was reduced by ~64% of its pre-treatment level, regardless of values chosen for the pre-ivermectin fertility rate within plausible ranges. Increased adult worm death rate after treatment (to mimic removal of macrofilariae via nodulectomy during the programme) resulted in a smaller estimated magnitude of the embryostatic effect (rate of microfilarial production was reduced by ~58% of pre-ivermectin value). After subsequent treatments, the rate of microfilarial production appeared to be similarly decreased. The data and analyses therefore do not support the hypothesis of a cumulative effect of multiple ivermectin treatments on microfilarial production by female worms.

Keywords

Onchocerca volvulusmicrofilariaemultiple ivermectin treatmentsBayesian hierarchical modelGuatemala
Type
Research Article
Information
Parasitology , Volume 135 , Special Issue 13: Mathematical modelling of parasitic infections: from data and parameter estimation to evolutionary implications , November 2008 , pp. 1571 - 1581
Copyright
Copyright © 2008 Cambridge University Press

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