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Genetic polymorphism of the β-tubulin gene of Onchocerca volvulus in ivermectin naïve patients from Cameroon, and its relationship with fertility of the worms

Published online by Cambridge University Press:  03 October 2005

C. BOURGUINAT
Affiliation:
Institute of Parasitology, McGill University, Sainte Anne-de-Bellevue, Quebec, Canada H9X3V9
S. D. S. PION
Affiliation:
Department of Infectious Disease Epidemiology, Imperial College, Norfolk Place, London W2 1PG, UK
J. KAMGNO
Affiliation:
Laboratoire d'Epidémiologie et de Santé publique, Centre Pasteur du Cameroun, BP 1274, Yaoundé, Cameroon
J. GARDON
Affiliation:
Laboratoire d'Epidémiologie et de Santé publique, Centre Pasteur du Cameroun, BP 1274, Yaoundé, Cameroon Institut de Recherche pour le Développement, UR 24 Epidémiologie et Prévention, CP 9214 Obrajes, La Paz, Bolivia
N. GARDON-WENDEL
Affiliation:
Laboratoire d'Epidémiologie et de Santé publique, Centre Pasteur du Cameroun, BP 1274, Yaoundé, Cameroon
B. O. L. DUKE
Affiliation:
River Blindness Foundation, 2 Hillside, Lancaster LA1 1YH, UK
R. K. PRICHARD
Affiliation:
Institute of Parasitology, McGill University, Sainte Anne-de-Bellevue, Quebec, Canada H9X3V9
M. BOUSSINESQ
Affiliation:
Laboratoire d'Epidémiologie et de Santé publique, Centre Pasteur du Cameroun, BP 1274, Yaoundé, Cameroon Département Sociétés et Santé, Institut de Recherche pour le Développement, 213 rue La Fayette, 75480 Paris Cedex 10, France

Abstract

Observations of low response of patients infected with Onchocerca volvulus to ivermectin suggest that the parasite may be under a selection process toward potential resistance. To limit the extension of this phenomenon, it is crucial to characterize the genes of O. volvulus that are involved. For this, O. volvulus adult worms collected before the introduction of ivermectin in an onchocerciasis endemic area of central Cameroon were genotyped for β-tubulin. To derive a baseline to investigate the selective pressure of ivermectin, we analysed (1) the frequency distribution of the β-tubulin alleles, and (2) the relationship between the different β-tubulin related genotypes and the fertility status of the female worms. The frequency of allele b of the β-tubulin gene was very low, as it was observed in West Africa. We observed a deficit of heterozygous female worms leading to Hardy Weinberg disequilibrium, which might be explained by a shorter life-span of these worms compared to the homozygous worms. Unexpectedly, our results also show that the heterozygous female worms were much less fertile than the homozygotes: more than two thirds of the homozygotes were fertile, whereas only 37% of the heterozygotes were fertile. These results will be further considered when analysing post-treatment data.

Type
Research Article
Copyright
2005 Cambridge University Press

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