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Ivermectin (IVM) has been in operational use for the control of onchocerciasis for two decades and remains the only drug of choice. To investigate the parasitological responses and genetic profile of Onchocerca volvulus, we carried out a 21 month epidemiological study to determine the response of the parasite to IVM in 10 Ghanaian endemic communities. Onchocerca nodules were surgically removed from patients in three IVM response categories (good, intermediate and poor) and one IVM naïve community. DNA from adult worms was analyzed to determine any association between genotype and IVM response phenotypic. Embryogramme analysis showed significantly higher reproductive activity in worms from poor response communities, which had up to 41% of females with live stretched microfilaria (mf) in utero, despite IVM treatment, compared with good response communities, which had no intra-uterine stretched mf. β-tubulin isotype 1 gene has been shown to be linked to IVM selection in O. volvulus and also known to be associated with IVM resistance in veterinary nematodes. We have genotyped the full length genomic DNA sequence of the β-tubulin gene from 127 adult worms obtained from the four community categories. We found SNPs at 24 sites over the entire 3696 bp. Eight of the SNPs occurred at significantly higher (p < 0.05) frequencies in the poor response communities compared with the good response communities and the IVM naïve community. Phenotypic and genotypic analyses show that IVM resistance has been selected and the genotype (1183GG/1188CC/1308TT/1545GG) was strongly associated with the resistance phenotype. Since the region in the β-tubulin gene where these four SNPs occur is within 362 bp, it is feasible to develop a genetic marker for the early detection of IVM resistance.

A sensitive and selective reversed-phase high-performance liquid chromatographic method for the determination of albendazole and its active metabolite albendazole sulphoxide in plasma has been developed. It involves single-step extraction of plasma with dichloromethane, evaporation of the solvent and chromatography on a muBondapak phenyl column with a mobile phase of water containing 1% (v/v) triethylamine-methanol-acetonitrile (70:10:20, v/v) at pH 3.1. Run time is 12 min. The assay satisfies all of the criteria required for use in clinical pharmacokinetic studies and possesses important advantages, notably speed and expense, over current methods.

Onchocerciasis is a major cause of blindness, and much of the blindness due to onchocerciasis is caused by chorioretinitis. Little is known about the progression of lesions in the posterior segment in either untreated or treated disease. The authors studied the progression of onchocercal chorioretinitis in 57 patients from 1 to 3 years. Changes were documented from detailed ocular examinations, fundus photographs, and fluorescein angiograms, and included live intraretinal microfilariae, intraretinal hemorrhages, cotton-wool opacities, intraretinal pigment, white and shiny intraretinal deposits, retinal pigment epithelial window defects, and atrophy. Depigmentation at the edge of chorioretinal scarring progressed at a rate of up to 200 microns per year. Ivermectin or mebendazole treatment did not appear to alter the progress of depigmentation at the edge of chorioretinal scars. These observations suggest that onchocercal chorioretinitis is associated with early changes in the retina and retinal pigment epithelium, and that disease in the posterior segment may progress rapidly.

Ocular fluids and sera from 12 onchocerciasis patients and nine age-matched controls living in Tamale, Ghana, were examined for the presence of anti-retinal autoantibodies by the indirect immunoperoxidase technique. Antibodies directed against autoantigens of the inner retina (nerve fiber, ganglion cell, and Müller cell) were found in the sera of 10 of 12 patients, but in only three of nine controls (P less than 0.003). Autoimmune antibodies against the outer segment of the photoreceptor were noted in 7 of 12 patients, in contrast to only one of nine controls (P less than 0.02). Findings with the ocular fluids generally mirrored those with the sera. These autoantibodies could not be absorbed by conventional techniques using either retinal S-antigen (S-Ag) or the interphotoreceptor retinoid binding protein, an observation suggesting that other ocular antigens are involved. Such anti-retinal antibodies, especially those directed against the inner retina, may play a significant role in the pathogenesis of the retinal degeneration and optic atrophy that occur as a consequence of onchocerciasis.