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Evidence for macrofilaricidal activity of ivermectin against female Onchocerca volvulus: further analysis of a clinical trial in the Republic of Cameroon indicating two distinct killing mechanisms

  • B. O. L. DUKE (a1)
Abstract

During a 3-year trial of the effects of ivermectin (MectizanR) on adult worms and microfilariae of Onchocerca volvulus in the Republic of Cameroon, comparison was made between the percentages of calcified and uncalcified moribund (M) and dead (D) adult female worms dying following (a) the standard dose (150 μg/kg) given annually; (b) high doses (400, then 800 μg/kg) given annually; and (c and d) these same doses given at 3-monthly intervals. In the killing of adult female O. volvulus worms, the relative rôles of (a) natural causes; (b) a presumed, direct, anthelminthic, macrofilaricidal action of ivermectin; and (c) a potentially fatal pleomorphic ovarian neoplasm (PN), of which the incidence is increased by ivermectin treatment, are herein further investigated and discussed. It is concluded that ivermectin per se has a considerable direct macrofilaricidal action against female worms and that this lethal effect is supplemented by the drug's ability in some worms to increase the incidence, and the spread throughout the body of the worm, of the potentially fatal PN ovarian tumour. In moribund and dead ivermectin-treated female worms that were heavily invaded by PN, it is probable that the neoplasm was chiefly responsible for their death, but the additional direct anthelminthic action of the drug, which by itself has been responsible for the death of many other female worms, cannot be excluded as having played a supplementary lethal rôle. Similar problems as to the exact means by which adult female worms are killed may arise now that ivermectin is used in Africa for the mass treatment of lymphatic filariasis; or if and when the macrofilaricidal actions on O. volvulus of other drugs, which are closely related to ivermectin, come to be investigated.

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Tel/Fax: 0044 1 524 66187. E-mail: bold10@hotmail.com
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AWADZI, K., OPOKU, N. O., ATTAH, S. K., ADDY, E. T., DUKE, B. O. L., NYAME, P. K. & KSHIRSAGAR, N. A. ( 1997). The safety and efficacy of amocarzine in African onchocerciasis and the influence of ivermectin on the clinical and parasitological response to treatment. Annals of Tropical Medicine and Parasitology91, 281296.

DUKE, B. O. L., MARTY, A. M., PEET, D. L., GARDON, J., PION, S. D. S., KAMGNO, J. & BOUSSINESQ, M. ( 2002). Neoplastic change in Onchocerca volvulus and its relation to ivermectin treatment. Parasitology125, 431444.

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GARDON, J., BOUSSINESQ, M., KAMGNO, J., GARDON-WENDEL, N., DEMANGA-NGANGUE & DUKE, B. O. L. ( 2002). Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet360, 203210.

KAMGNO, J., GARDON, J., GARDON-WENDEL, N., DEMANGA-NGANGUE, DUKE, B. O. L. & BOUSSINESQ, M. ( 2004). Adverse systemic reactions to treatment of onchocerciasis with ivermectin at normal and high doses given annually or three-monthly. Transactions of the Royal Society of Tropical Medicine and Hygiene98, 496504.

SCHULZ-KEY, H. & KARAM, M. ( 1984). Quantitative assessment of microfilariae and adults of Onchocerca volvulus in ethanol-fixed biopsies and nodules. Transactions of the Royal Society of Tropical Medicine and Hygiene78, 157159.

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Parasitology
  • ISSN: 0031-1820
  • EISSN: 1469-8161
  • URL: /core/journals/parasitology
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