Parasitological Responses of Onchocerca Volvulus to Ivermectin Treatment And Genetic Analysis of Beta Tubulin Gene

ABSTRACT           

Ivermectin (IVM) still remains the only safe drug for the mass control of onchocerciasis, and the continued success of the control programmes depends on its efficacy. However, recent reports show that there are populations of adult Onchocerca volvulus responding suboptimally to IVM. This requires assessment of parasitological response profile of O. volvulus to IVM and genetic analysis of Beta-tubulin gene known to be associated with IVM selection, to determine the association between worm phenotypes and genotypes. A fifteen month longitudinal study involving skin snipping, three rounds of bi-annual IVM treatment and nodulectomies was carried out in seven selected endemic communities. A total of 584 subjects were assessed for microfilaria (mf) load at the beginning of the study and then treated with IVM. Out of these, 87 subjects who were mf positive at pre-treatment assessment were then followed-up on days 180, 270 and 360 after the first IVM treatment study and nodulectomies conducted at day 452 (90 days after the third IVM treatment). Nodules were digested, adult worms removed and embryogram analysis performed. A total of 59 worms were selected from Jagbengbendo and Takumdo communities for genetic analysis on a 684 bp DNA fragment of Beta-tubulin gene. Out of the 584 subjects assessed, we observed an overall nodule and mf prevalence and community microfilarial load (CMFL) of 20.9%, 14.9% and 3.1 mf/s respectively. The majority of subjects responded well to IVM treatment, except 3.3% from Chabon, 5.3% from Kojobone and 8.3% from Agblekeme II who responded poorly or sub-optimally to IVM. Genetic analysis showed four Single Nucleotide Polymorphisms (SNPs) at genomic positions 1183 (T/G), 1188 (T/C), 1308 (C/T) and 1545 (A/G), with the homozygote genotypes of the latter three SNPs showing significant association (p