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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 ,
S. D. S. PION ,
J. KAMGNO ,
J. GARDON ,
N. GARDON-WENDEL ,
B. O. L. DUKE ,
R. K. PRICHARD  and
M. BOUSSINESQ
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
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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.

Keywords

Onchocerca volvulusβ-tubulingenetic polymorphismfertilityCameroon
Type
Research Article
Information
Parasitology , Volume 132 , Issue 2 , February 2006 , pp. 255 - 262
Copyright
2005 Cambridge University Press

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References

REFERENCES

Ali, M. M., Mukhtar, M. M., Baraka, O. Z., Homeida, M. M., Kheir, M. M. and Mackenzie, C. D. ( 2002). Immunocompetence may be important in the effectiveness of Mectizan (ivermectin) in the treatment of human onchocerciasis. Acta Tropica 84, 49–53.CrossRefGoogle Scholar
Ardelli, B. F. and Prichard, R. K. ( 2004). Identification of variant ABC-transporter genes among Onchocerca volvulus collected from ivermectin-treated and untreated patients in Ghana, West Africa. Annals of Tropical Medicine and Parasitology 98, 371–384.CrossRefGoogle Scholar
Ardelli, B. F. and Prichard, R. K. ( 2005). Reduced genetic variation of an Onchocerca volvulus ABC transporter gene following treatment with ivermectin. Transactions of the Royal Society of Tropical Medicine and Hygiene (in the Press).Google Scholar
Awadzi, K., Attah, S. K., Addy, E. T., Opoku, N. O., Quartey, B. T., Lazdins-Helds, J. K., Ahmed, K., Boatin, B. A., Boakye, D. A. and Edwards, G. ( 2004 a). Thirty-month follow-up of sub-optimal responders to multiple treatments with ivermectin, in two onchocerciasis-endemic foci in Ghana. Annals of Tropical Medicine and Parasitology 98, 359–370.Google Scholar
Awadzi, K., Boakye, D. A., Edwards, G., Opoku, N. O., Attah, S. K., Osei-Atweneboana, M. Y., Lazdins-Helds, J. K., Ardrey, A. E., Addy, E. T., Quartey, B. T., Ahmed, K., Boatin, B. A. and Soumbey-Alley, E. W. ( 2004 b). An investigation of persistent microfilaridermia despite multiple treatments with ivermectin in two onchocerciasis endemic foci in Ghana. Annals of Tropical Medicine and Parasitology 98, 231–249.Google Scholar
Blackhall, W. J. ( 1999) Genetic variation and multiple mechanisms of anthelmintic resistance in Haemonchus contortus. Ph.D. thesis, McGill University.
Boussinesq, M. and Gardon, J. ( 1999). La résistance de Onchocerca volvulus à l'ivermectine: une éventualité à considérer. Annales de l'Institut Pasteur/Actualités 10, 81–91.CrossRefGoogle Scholar
Boussinesq, M., Gardon, J., Kamgno, J., Demanga-Ngangue, Pion, S. D. S. and Duke, B. O. L. ( 2001). Studies on the macrofilarial population of Onchocerca volvulus in hyper-endemic villages of the Central province of Cameroon. Annals of Tropical Medicine and Parasitology 95, 379–388.CrossRefGoogle Scholar
Eng, K. L. J. and Prichard, R. K. ( 2005). A comparison of genetic polymorphism in populations of Onchocerca volvulus from untreated- and ivermectin-treated patients. Molecular and Biochemical Parasitology 142, 193–202.CrossRefGoogle Scholar
Freeman, A. S., Nghiem, C., Li, J., Ashton, F. T., Guerrero, J., Shoop, W. L. and Schad, G. A. ( 2003). Amphidial structure of ivermectin-resistant and susceptible laboratory and field strains of Haemonchus contortus. Veterinary Parasitology 110, 217–226.CrossRefGoogle Scholar
Gardon, J., Boussinesq, M., Kamgno, J., Gardon-Wendel, N., Demanga-Ngangue and Duke, B. O. L. ( 2002). Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial. Lancet 360, 203–210.CrossRefGoogle Scholar
Grant, W. ( 2000). What is the real target for ivermectin resistance selection in Onchocerca volvulus? Parasitology today 16, 501–502.Google Scholar
Kläger, S. ( 1988). Investigations of enzymatically isolated male Onchocerca volvulus: qualitative and quantitative aspects of spermatogenesis. Tropical Medicine and Parasitology, 39, 441–445.Google Scholar
Remme, J., Ba, O., Dadzie, K. Y. and Karam, M. ( 1986). A force-of-infection model for onchocerciasis and its applications in the epidemiological evaluation of the Onchocerciasis Control Programme in the Volta River basin area. Bulletin of the World Health Organization 64, 667–681.Google Scholar
Schulz-Key, H. ( 1988). The collagenase technique: how to isolate and examine adult Onchocerca volvulus for the evaluation of drug effects. Tropenmedizin und Parasitologie 39, 423–440.Google Scholar
Schulz-Key, H., Albiez, E. J. and Büttner, D. W. ( 1977). Isolation of living adult Onchocerca volvulus from nodules. Tropenmedizin und Parasitologie 28, 428–430.Google Scholar
Schulz-Key, H. and Karam, M. ( 1984). Quantitative assessment of microfilariae and adults of Onchocerca volvulus in ethanol-fixes biopsies and nodules. Transactions of the Royal Society of Tropical Medicine and Hygiene 78, 157–159.CrossRefGoogle Scholar
Vamosi, S. M. and Schluter, D. ( 1999). Sexual selection against hybrids between sympatric stickleback species: evidence from a field experiment. Evolution 53, 874–879.CrossRefGoogle Scholar
Via, S., Bouck, A. and Skillman, S. ( 2000). Reproductive isolation between divergent races of pea aphids on two hosts. II. Selection against migrants and hybrids in the parental environments. Evolution 54, 1626–1637.Google Scholar