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Onchocerciasis parasite shows signs of resistance

Published on January 31, 2008 at 6:37 PM · No Comments

Onchocerciasis is an infection caused by Onchocerca volvulus, a parasite nematode worm transmitted to humans by a species of black fly of the Simulium genus whose larvae develop in fast-flowing rivers.

Infected subjects suffer not only from severe skin lesions but also eye damage that can lead to irreversible loss of sight, hence the name 'river blindness'. A huge majority (99%) of the 37 million people infected by the parasite live in SubSaharan Africa.

Ivermectin, a medicine capable of killing the parasite embryos (the microfilariae) circulating in the organism of patients and temporarily interrupting the nematode's reproduction, is the only treatment used for onchocerciasis control. Since 1995, the African Programme for Onchocerciasis Control (APOC) has been covering 19 of the continent's 28 countries hit by the disease. Access to this treatment is possible for 70 million people and has significantly diminished the onchocerciasis-induced morbidity. However, the doubling of cases of infection in certain communities of Ghana between 2000 and 2005, in spite of annual treatments, created fear of the emergence of ivermectin-resistant strains. Such apprehension appears particularly justified in that a high degree of therapeutic cover is achieved during mass distribution campaigns and hence only a tiny part of the parasite population targeted remains unexposed to drug treatment pressure.

Since 1994, a team of IRD researchers, working jointly with Cameroon researchers and others from McGill University of Montreal, has been monitoring a cohort of Cameroon patients benefiting from repeated treatments with ivermectin. Regular parasite sampling from these subjects was performed over a 13-year period in order to determine the changes in the genetic structure of Onchocerca volvulus populations. Each occasion involved measurement of the genotype frequency of heterozygotes and homozygotes for the gene coding ß-tubulin, a protein involved in the organization of the parasite's cells. The team focused on this particular gene because it acts as a marker of resistance to ivermectin in other nematode species parasitic on cattle. As a control, they monitored the changes in genotype frequency of two other genes, known for their high evolutionary stability over time. The proportion of homozygotes and heterozygotes for these two genes remained stable throughout the investigation, but the situation was completely different for the ß-tubulin gene.

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