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 sub-
optimally 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<0.05) to the poor response phenotype worms. A 364bp DNA sequence of beta-
tubulin gene, encompassing the four SNPs, has been proposed for developing a molecular
marker to detect IVM resistance. This study shows that IVM resistance is emerging in some
endemic communities and requires monitoring.
