Abstrato

Analysis of Onchocerca volvulus β-tubulin gene polymorphism in the Mbonge sub-division of Cameroon: Evidence of gene selection by ivermectin.

Shintouo C Mounchili, Mingo A Ghogomu, Stephen M Ghogomu, Ferdinand N Njume, Robert A Shey, Jacob Souopgui

Ivermectin (IVM) still remains the only safe drug for the mass control of onchocerciasis, and the continued success of control programmes depends on its efficacy. However, the reliance on a single drug for decades might become problematic due to possible development of IVM resistance as has occurred in nematode parasites of livestock and the filarial heartworm of dogs. Drug resistance is a genetic phenomenon resulting from changes in the genetic profile of the parasite population that would be seen as a selection for particular alleles of genes. One gene shown to be linked to IVM selection in Onchocerca volvulus and also known to be associated with IVM resistance in veterinary nematodes is the beta (β) tubulin gene. Assessment of parasitological response profile of O. volvulus to IVM and genetic analysis of β-tubulin gene could reveal the association between O. volvulus worm genotype and IVM selection. Onchocercal nodules were surgically removed from onchocerciasis patients in two cohorts with different treatment histories: a group that had received repeated doses of IVM at least for the previous 3 years, and a control group with no history of IVM treatment. Reverse transcription (RT) PCR of β-tubulin transcripts revealed comparable expression levels in both IVM exposed and naïve worms. Restriction fragment length polymorphism of the β-tubulin gene revealed a selection of the G allele in IVM-exposed worms as against the T allele in the IVM naïve population. This evidence of IVM selection suggests that IVM resistance may be emerging in the Mbonge Sub-Division and thus requires monitoring.