River blindness (onchocerciasis) is caused by the filarial nematode Onchocerca volvulus, a parasite transmitted by Similium blackflies. Around 37 million people worldwide are suspected to be infected. Ivermectin, in the form of an annual dose, is the drug that has been widely used for river blindness (onchocerciasis) since 1987, and due to this long-term use a study into resistance to its effects is timely. Although invermectin does not kill substantial numbers of adult O. volvulus at standard doses, it prevents them releasing microfilariae and keeps skin counts of microfilariae low.
Professor Roger Prichard, Institute of Parasitology, McGill University, Montreal, Quebec, Canada, and colleagues studied 2,501 people in 20 communities in Ghana, West Africa. Of these, 19 had been receiving between 6-18 annual doses of ivermectin, while one community had never been given ivermectin.
In the first phase of the study, all the participants were tested for levels of microfilarial load by taking 2mm skinsnips (skin samples) prior to their 2004 annual ivermectin dose, and 30 days after treatment to determine the effect of the ivermectin. For the second phase, skin snips were taken from 342 individuals from ten communities, who had tested positive at pre-treatment assessment, at 90 and 180 days after treatment.
The researchers found that microfilaria prevalence ranged from 2.2% to 51.8%, and community microfilarial load in treated communities ranged from 0.06-2.85 microfilariae per snip. Despite treatment, prevalence rate doubled in two communities between 2000 and 2005.
Although ivermectin clears 100% of microfilariae in 99% of those treated, 90 days later four of 10 communities had significant microfiliarae repopulation, ranging from 7-21% of pre-treatment counts. This rose to nearly 54% by day 180. In the other six communities studied, microfilariae repopulation was controlled as expected.
The authors conclude: “Ivermectin remains a potent microfilaricide. However, our results suggest that resistant adult parasite populations, which are not responding as expected to ivermectin, are emerging. A high rate of repopulation of skin with microfilariae will allow parasite transmission, possibly with ivermectin-resistant O. volvulus which could eventually lead to recrudescence of the disease.”
In an accompanying Comment, Dr Peter Hotez, President, Sabin Vaccine Institute and Department of Microbiology, Immunology, & Tropical Medicine, George Washington University, Washington, DC, USA, says there is a moral imperative to continue ivermectin treatment to control river blindness.
He says: “We need to anticipate the possibility of further ivermectin resistance and greatly increase our current level of effort and support to develop and test a new generation of control tools for onchocerciasis.”
He concludes: “Now is the time for global health leaders to build on the strengths of community-directed treatment with ivermectin, and advocate and support the development, testing, and distribution of a new generation of onchocerciasis-control tools.”
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