Viability of adult Onchocerca volvulus after six 2-weekly doses of ivermectin.

Clinical and community-based trials in Liberia and elsewhere have shown ivermectin to be a safe, single-dose microfilaricide effective against Onchocerca volvulus [1, 2]. The drug also prevents the escape of intra0uterine microfilariae from the female worm and leads to their degeneration in utero [3]. However, when given in a single oral dose of 100-200 [microgram]/kg body weight, ivermectin has shown no evidence of any macrofilaricidal action against O. volvulus. The objective of the present trial was to find out whether a short, intense course of six doses of ivermectin at 100 [microgram]/kg each (i.e., at the minimum effective single-dose microfilaricidal level), given at 2-week intervals, might kill the adult worms of O. volvulus. Materials and methods Site of the trial, selection of patients and treatment The trial was carried out on the Liberian Agricultural Company's (LAC) rubber plantation at Buchanan, in Grand Bassa County, Liberia, in the forest zone of West Africa. Sixty male plantation workers, aged 21-55 years and weighing 51-72 kg, volunteered to take part after having been made aware of the nature and purpose of the study. All had at least one palpable nodule, and usually several, but were otherwise in good health. Ethical clearance for the trial was obtained from the Liberian Ministry of Health, the World Health Organization, the Case Western Reserve University School of Medicine, and Merck Sharp and Dohme. The 60 patients were divided at random into two groups of 30. The ivermectin group received six oral doses of ivermectin (scored Mectizan tablets (Merck), containing 6 mg of ivermectin), which were given at 2-week intervals over 10 weeks between 1 August and 10 October 1988. Those weighing 51-69 kg received a 6-mg dose and those of 70 kg and over received 7.5 mg, i.e., all treatments were in the range of 87-118 [microgram]/kg. Chlorpheniramine, a potent antihistamine with sedative properties, which is believed to have no effect on O. volvulus, was selected as a placebo. Patients in the control group received chlorpheniramine tablets, similar in appearance to the Mectizan tablets. A careful watch was kept for serious adverse reactions during and after treatment but none was encountered. History of previous treatment; removal of nodules All palpable nodules located before treatment and found again at the time of nodulectomy were removed surgically (under local anaesthesia with 2% lignocaine) four months after the last treatment, i.e., 5-20 February 1989. Six patients (five of whom were in the control group) did not report for nodulectomy. A few of the "nodules" removed (including the only one in one patient from the ivermectin group) turned out to be small lymph nodes or lipomata. Two, totally calcified "tombstone" nodules were also excluded from the analysis. In all, 184 O. volvulus nodules were examined from 53 patients. In the ivermectin group, 28 patients (mean age 33 years; mean weight 59 kg) provided a total of 82 nodules (mean number per patient 2.9; range 1-13). In the control group, 25 patients (mean age 34 years; mean weight 60 kg) provided a total of 102 nodules (mean number per patient 4.1; range 1-12). As shown in Table 1, and as part of the community-based trial then being carried out on the LAC plantation [2], 19 patients in the ivermectin group and 21 of the controls had received single-dose treatment with ivermectin at 150 [microgram]/kg in October 1987 (i.e., nine months before the time of nodulectomy) and/or in October 1988. [TABULAR DATA OMITTED] Fixation and examination of nodules Of the 184 O. volvulus nodules removed, 81 were fixed whole in cold 10% buffered formalin (using 20 times the volume of the nodules) for 24 hours. The formalin was then changed and each nodule was bisected to allow better penetration of the fixative. …