Skip to main content
    • Aa
    • Aa

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


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.

Corresponding author
*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:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

E. S. Alley , A. P. Plaisier , B. A. Boatin , K. Y. Dadzie , J. Remme , G. Zerbo and E. M. Samba (1994). The impact of five years of annual ivermectin treatment on skin microfilarial loads in the onchocerciasis focus of Asubende, Ghana. Transactions of the Royal Society of Tropical Medicine and Hygiene 88, 581584.

M.-G. Basáñez and M. Boussinesq (1999). Population biology of human onchocerciasis. Philosophical Transactions of the Royal Society of London B 354, 809826.

M.-G. Basáñez , S. D. S. Pion , E. Boakes , J. A. N. Filipe , T. S. Churcher and M. Boussinesq (2008). Effect of single-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis. Lancet Infectious Diseases 8, 310322.

M.-G. Basáñez , S. D. S. Pion , T. S. Churcher , L. P. Breitling , M. P. Little and M. Boussinesq (2006). River blindness: a success story under threat? PLoS Medicine 3, e371.

M.-G. Basáñez , K. Razali , A. Renz and D. Kelly (2007). Density-dependent host choice by disease vectors: epidemiological implications of the ideal free distribution. Transactions of the Royal Society of Tropical Medicine and Hygiene 101, 256269.

C. Bourguinat , B. F. Ardelli , S. D. S. Pion , J. Kamgno , J. Gardon , B. O. L. Duke , M. Boussinesq and R. K. Prichard (2008). P-glycoprotein-like protein, a possible genetic marker for ivermectin resistance selection in Onchocerca volvulus. Molecular and Biochemical Parasitology 158, 101111.

C. Bourguinat , S. D. S. Pion , J. Kamgno , J. Gardon , B. O. L. Duke , M. Boussinesq and R. K. Prichard (2007). Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment. PLoS Neglected Tropical Diseases 1, e72.

S. Diallo , M. A. Aziz , M. Larivière , J. S. Diallo , I. Diop-Mar , O. N'Dir , S. Badiane , D. Py , H. Schulz-Key and P. Gaxotte (1986). A double-blind comparison of the efficacy and safety of ivermectin and diethylcarbamazine in a placebo controlled study of Senegalese patients with onchocerciasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 80, 927934.

H. P. Duerr , K. Dietz and M. Eichner (2005). Determinants of the eradicability of filarial infections: a conceptual approach. Trends in Parasitology 21, 8896.

H. P. Duerr , K. Dietz , H. Schulz-Key , D. W. Büttner and M. Eichner (2003). Density-dependent parasite establishment suggests infection-associated immunosuppression as an important mechanism for parasite density regulation in onchocerciasis. Transactions of the Royal Society of Tropical Medicine and Hygiene 97, 242250.

F. Engelbrecht and H. Schulz-Key (1984). Observations on adult Onchocerca volvulus maintained in vitro. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 212215.

J. Gardon , M. Boussinesq , J. Kamgno , N. Gardon-Wendel , Demanga-Ngangue and B. O. L. Duke (2002). Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet 360, 203210.

W. R. Gilks , N. G. Best and K. K. C. Tan (1995). Adaptive rejection Metropolis sampling within Gibbs sampling. Applied Statistics 44, 455472.

J. W. Haefner (1996). Modeling Biological Systems. Principles and Applications. Chapman and Hall, New York.

W. E. Kershaw , B. O. L. Duke and F. H. Budden (1954). Distribution of microfilariae of O. volvulus in the skin; its relation to the skin changes and to eye lesions and blindness. British Medical Journal 2, 724729.

M. P. Little , L. P. Breitling , M.-G. Basáñez , E. S. Alley and B. A. Boatin (2004). Association between microfilarial load and excess mortality in onchocerciasis: an epidemiological study. Lancet 363, 15141521.

S. E. O. Meredith and H. B. Dull (1998). Onchocerciasis: the first decade of Mectizantrade mark treatment. Parasitology Today 14, 472474.

N. Metropolis , A. W. Rosenbluth , M. N. Rosenbluth , A. H. Teller and E. Teller (1953). Equations of state calculations by fast computing machines. Journal of Chemical Physics 21, 10871092.

D. H. Molyneux and J. B. Davies (1997). Onchocerciasis control: moving towards the millennium. Parasitology Today 13, 418425.

M. Y. Osei-Atweneboana , J. K. Eng , D. A. Boakye , J. O. Gyapong and R. K. Prichard (2007). Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study. Lancet 369, 20212029.

A. P. Plaisier , E. S. Alley , B. A. Boatin , G. J. Van Oortmarssen , H. Remme , S. J. De Vlas , L. Bonneux and J. D. Habbema (1995). Irreversible effects of ivermectin on adult parasites in onchocerciasis patients in the Onchocerciasis Control Programme in West Africa. Journal of Infectious Diseases 172, 204210.

A. P. Plaisier , G. J. van Oortmarssen , J. Remme and J. D. Habbema (1991). The reproductive lifespan of Onchocerca volvulus in West African savanna. Acta Tropica 48, 271284.

F. O. Richards , B. Boatin , M. Sauerbrey and A. Sékétéli (2001). Control of onchocerciasis today: status and challenges. Trends in Parasitology 17, 558563.

H. Schulz-Key and M. Karam (1986). Periodic reproduction of Onchocerca volvulus. Parasitology Today 2, 284286.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 1
Total number of PDF views: 2 *
Loading metrics...

Abstract views

Total abstract views: 89 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 27th May 2017. This data will be updated every 24 hours.