Onchocerca volvulus nodules were removed from 77 fully compliant patients in a longitudinal study of ivermectin treatment in Sierra Leone. The patients had participated in a randomized controlled trial and received either 4 annual doses o f ivermectin or I o 6-monthly doses over 6 years. Worms were examined 9 months after the last treatment for evidence of changes in morphology, viability and reproductivity. The findings were compared with results for the 2 groups obtained a t earlier surveys of the same study population. Repeated treatment at 6 and 12-month intervals has resulted in a marked ageing of the male worm population profile and a significant reduction in the proportion o f live female worms found in the nodules. In addition, there has been a reduction in reproductivity of 9 0 % o r more. However, most of the worms found were still alive and potentially fertile, underlining the need for the continuation of regular ivermectin treatment to maintain the benefits achieved.
A double-blind placebo-controlled trial of ivermectin was started in 1987 in 6 villages in southern Sierra Leone. 1625 villagers, 93% of the total population, were surveyed before treatment and allocated at random to the trial. Onchocerciasis was hyperendemic and of moderate intensity in the area. Typical onchocerciasis skin lesions were seen in most cases; the blindness rate was 1.5% and a further 4.3% had visual impairment. Six months after treatment 988 subjects (80%) were reassessed and microfilarial loads in the ivermectin group were found to be 10% of control levels. Additionally, blood eosinophil concentrations were reduced by one-quarter. The severity, but not the prevalence, of skin lesions was significantly reduced in the ivermectin group, with a particularly marked effect on papular eruptions. There had been no reduction in the prevalence of itching, nor had markers of general health shown improvement after ivermectin. Ivermectin is an effective microfilaricidal agent and may improve Onchocerca-related skin lesions after a single dose. However, the lack of obvious benefit to a target population after the first dose of ivermectin may reduce compliance with subsequent doses. This has implications for planned mass treatment initiatives in onchocerciasis endemic regions.
Degrees of itching were estimated before and for 6 months after a fourth dose of ivermectin or placebo was given to 97 subjects in Sierra Leone. There was no reduction in itching attributable to ivermectin at any stage, but there were non-significant increases in the prevalence, severity and localization of itching within the first 2 months after ivermectin compared to placebo. We also found that cell-mediated immune responses to Onchocerca volvulus were significantly increased 4 weeks after a single dose of ivermectin compared to before treatment. A temporary reversal of the state of immunosuppression in people with onchocerciasis may counterbalance the reduction in skin microfilarial loads following ivermectin, with no consequent reduction in itching. The lack of effect of ivermectin on itching, a major symptom of onchocerciasis, while disappointing, need not detract from the success of mass distribution programmes.
We have studied the adverse reactions reported after ivermectin in 1745 villagers in southern Sierra Leone, allocated at random to receive ivermectin or placebo and treated 'double-blind' with 4 doses at six-monthly intervals. Six months after the fourth dose all eligible villagers received ivermectin regardless of their previous treatment. At the first treatment round more adverse reactions were reported by villagers treated with ivermectin than by those who received placebo. Reactions occurred most often on the second day after treatment. There were significant correlations between an individual's skin microfilarial load and the risk of developing adverse reactions. On re-treatment there was no significant excess of reported adverse reactions in the ivermectin group compared to the placebo group. Unlike other adverse reactions, the risk of cutaneous reactions after the first dose of ivermectin was not correlated with skin microfilarial load. In addition, after re-treatment with ivermectin, cutaneous reactions were reported significantly more often than with placebo. We confirm that ivermectin is safe for mass distribution, but adverse reactions should be monitored and treated after the first dose. Throughout this study ivermectin was well tolerated, with significantly more villagers returning for re-treatment after ivermectin than placebo, and all adverse reactions were self-limiting or successfully managed with symptomatic treatment. We question whether strict clinical monitoring should be routine at re-treatment, when only cutaneous reactions were consistently reported. If clinical monitoring could be used more selectively, distribution campaigns might be easier to manage and more cost-effective.
There are plans to use mass treatment with ivermectin to clear all Africa of the worst ocular and cutaneous effects of onchocerciasis. However, there remains uncertainty about the most suitable treatment regimen and the likely effects of ivermectin on onchocercal skin disease. We have followed 948 subjects for over 6 years in a double-blind, randomized, controlled study of ivermectin for onchocerciasis in a hyperendemic focus in Sierra Leone. Using an intention-to-treat analysis we found a microfilarial prevalence of 16% 6 months after up to 4 annual doses of ivermectin, and 13% prevalence in the group receiving up to 10 doses of ivermectin at 6-monthly intervals. Microfilarial loads were well suppressed in both groups, but repopulation data suggest that adult female worms are still alive and fecund, strongly underlining the need to continue treatment. A clear effect of ivermectin was demonstrated on itching, with about one-third of cases being alleviated. Significant reductions in the prevalence of serious hyperkeratosis, and possibly dyspigmentation (leopard skin), were noted, but not for any other onchocercal skin lesion. Six-monthly and annual treatment regimens with ivermectin were equally effective in terms of dermatological and parasitological impact.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.