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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Genetic selection of low fertile Onchocerca volvulus by ivermectin treatment
PLoS Neglected Tropical Diseases, Volume 1, No. 1, Article e72, Year 2007
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Description
Background: Onchocerca volvulus is the causative agent of onchocerciasis, or "river blindness". Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug. Should ivermectin resistance be developing, it would have a genetic basis. We monitored genetic changes in parasites obtained from the same patients before use of ivermectin and following different levels of ivermectin exposure. Methods and Findings: O. volvulus adult worms were obtained from 73 patients before exposure to ivermectin and in the same patients following three years of annual or three-monthly treatment at 150 μg/ kg or 800 μg/kg. Genotype frequencies were determined in β-tubulin, a gene previously found to be linked to ivermectin selection and resistance in parasitic nematodes. Such frequencies were also determined in two other genes, heat shock protein 60 and acidic ribosomal protein, not known to be linked to ivermectin effects. In addition, we investigated the relationship between β-tubulin genotype and female parasite fertility. We found a significant selection for β-tubulin heterozygotes in female worms. There was no significant selection for the two other genes. Quarterly ivermectin treatment over three years reduced the frequency of the β-tubulin "aa" homozygotes from 68.6% to 25.6%, while the "ab" heterozygotes increased from 20.9% to 69.2% in the female parasites. The female worms that were homozygous at the β-tubulin locus were more fertile than the heterozygous female worms before treatment (67% versus 37%; p=0.003) and twelve months after the last dose of ivermectin in the groups treated annually (60% versus 17%; p<0.001). Differences in fertility between heterozygous and homozygous worms were less apparent three months after the last treatment in the groups treated three-monthly. Conclusions: The results indicate that ivermectin is causing genetic selection on O. volvulus. This genetic selection is associated with a lower reproductive rate in the female parasites. We hypothesize that this genetic selection indicates that a population of O. volvulus, which is more tolerant to ivermectin, is being selected. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. © 2007 Bourguinat et al.
Authors & Co-Authors
Bourguinat, Catherine
Canada, Sainte-anne-de-bellevue
Mcgill University, Macdonald Campus
Pion, Sébastien David Serge
France, Limoges
Institut D’epidémiologie Neurologique et de Neurologie Tropicale
Kamgno, Joseph
Cameroon, Yaounde
National Onchocerciasis Task Force Cameroon
Gardon, Jacques
France, Marseille
Ird Institut de Recherche Pour le Developpement
Duke, Brian O.L.P.J.
United Kingdom, Lancaster
River Blindness Foundation
Boussinesq, Michel
France, Marseille
Ird Institut de Recherche Pour le Developpement
Prichard, Roger K.
Canada, Sainte-anne-de-bellevue
Mcgill University, Macdonald Campus
Statistics
Citations: 109
Authors: 7
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pntd.0000072
Research Areas
Genetics And Genomics
Infectious Diseases
Sexual And Reproductive Health
Study Design
Cross Sectional Study
Participants Gender
Female