Project Summary
Onchocerciasis control and elimination programmes worldwide are largely dependent on the sustained efficacy of ivermectin (IVM). However, recent reports on sub-optimal responses to IVM treatment and evidence of genetic selection in Onchocerca volvulus, has raised concerns about the possible emergence of IVM resistance. We have carried out a fifteen months epidemiological study involving the assessment of parasitological response profile of O. volvulus to IVM treatment in Ghana, a parallel vector study and conducted genetic analysis to select single nucleotide polymorphism (SNPs) for development of genetic marker.
Our results showed average mf prevalence of 18.4% in 22 communities, with three semi-annual communities showing persistent microfilaria and skin mf repopulation three months after IVM treatment. Transmission has been found to be on-going in over 80% of the communities, Earlier than expected skin mf repopulation was observed in four communities and embryogramme analysis showed about 50% of the communities habouring 1-6% of adult female worms showing sub-optimal response to IVM. Genetic analyses carried out on well-characterized O. volvulus samples have identified four SNPs in β-tubulin genes that are associated with poor IVM response phenotypes. The genotype configuration, GG/CC/TT/GG occurring at four SNP sites, 1183 T/G, 1188 T/C, 1308 C/T and 1545 A/G was found to be strongly associated (p<0.01) with poor IVM response phenotype worms. Also three other SNPs occurring at consecutive nucleotides positions at 1268 T/A, 1269 A/T, 1270 T/A showed much stronger association with poor IVM response phenotype worms. Currently 70% of full length DNA sequence of gamma amino butyric acid (GABA) receptor HG1 has been cloned for genotyping and potential SNP markers selection. These SNPs have been selected as potential genetic marker for validation and marker development