A comparison of genetic polymorphism in populations of Onchocerca volvulus from untreated- and ivermectin-treated patients.
An analysis of the polymorphism of 16 genes from Onchocerca volvulus was undertaken, in two populations of worms from either ivermectin-naïve patients or patients who had been repeatedly treated with ivermectin, in Ghana. Six genes were selected for analysis because studies in other nematodes had suggested a possible association with ivermectin resistance. The other 10 genes were included as control genes and have not been associated with ivermectin resistance. Twelve of the 16 genes were polymorphic, including five of the candidate genes and seven of the control genes. In all of the control genes and four of the candidate genes, there were no differences in genetic polymorphism between the untreated and ivermectin treatment worms. However, there were statically significant differences (chi2=0.05) in allelic frequencies between the untreated and treatment derived worms for P-glycoprotein and beta-tubulin genes; both genes which have been previously associated with ivermectin resistance in other nematodes. These genes were in Hardy-Weinberg equilibrium in the untreated population. However, the P-glycoprotein alleles, in the worms from the patients under treatment were not in Hardy-Weinberg equilibrium, and analysis of the allele frequencies of beta-tubulin suggested that this gene may have also been under selection in the worms from the ivermectin-treated patients. This data provides evidence of genetic selection by ivermectin on O. volvulus and indicates that investigations should be made to determine whether ivermectin resistance is developing. The beta-tubulin and P-glycoprotein genes may prove useful for monitoring for possible development of ivermectin resistance.
Eng
J K L
JK
Institute of Parasitology, McGill University, 21,111 Lakeshore Road, Sainte Anne-de-Bellevue, Que., Canada H9X 3V9.
Prichard
R K
RK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001483:Base Sequence; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005369:Filaricides / Q000627:therapeutic use*; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017181:Onchocerca volvulus / Q000187:drug effects* / Q000235:genetics*; D009855:Onchocerciasis / Q000188:drug therapy* / Q000469:parasitology; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D014404:Tubulin / Q000737:chemistry / Q000235:genetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005369:Filaricides; D014404:Tubulin; D007559:Ivermectin