Parasitology

Research Article

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

CHRISTIAN BOTTOMLEYa1 p1, VALERIE ISHAMa2, RICHARD C. COLLINSa3 and MARIA-GLORIA BASÁÑEZa4 c1

a1 Department of Primary Care & Population Sciences, Royal Free Hospital, Rowland Hill Street, London NW3 2PF

a2 Department of Statistical Science, University College London, Gower Street, London WC1E 6BT

a3 P.O. Box 715, Sonoita, AZ 85637, USA

a4 Department of Infectious Disease Epidemiology, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG

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.

(Received May 30 2008)

(Revised August 13 2008)

(Accepted August 13 2008)

(Online publication October 03 2008)

Correspondence:

c1 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

p1 Current address: Infectious Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT

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