24 genome contains 9 million base pairs, the largest bacterial genome sequenced so far (3, 5). S. avermectinius turned out to be a marvel of bacterial engineering. Seventeen genes encode the necessary enzymes to produce avermectin in an elaborate 53-step synthesis (3, 5). Despite decades of searching worldwide, no other naturally occurring organism has been discovered with the ability to manufacture avermectin, and the only place where S. avermectinius has been found is at the golf course in Japan. Some parasites of ruminants, including cattle, have become resistant, but despite 35 years of constant worldwide use, ivermectin remains an important veterinary drug. And after more than 25 years of constant monotherapy in humans, no convincing evidence of Onchocerca volvulus resistance to ivermectin has emerged (12). But, it looms as a possibility. Investigators have seen a few cases of poor responsiveness, and residual micro-larvae have sometimes been observed after ivermectin treatment (5). Also, because ivermectin kills only immature larvae, it must be administered repeatedly as long as the adult worms are producing new larvae. For these reasons, the search continues for alternative drugs, especially those that target adult worms.
Skin Snip Assay The skin snip assay is a common diagnostic test for onchocerciasis. It involves removing some skin from an inflamed area and placing the snipped skin in saline to encourage micro-larvae to leave the skin. Microscopic examination determines the larval load.
In the meantime, the parasite responsible for river blindness is disappearing, thanks to the communitybased programs. Recent studies have shown that in some areas, where ivermectin treatment has been ongoing for 15-17 years, the parasite has been eliminated. In these areas, researchers stopped treatment with ivermectin for up to 5 years and saw no re-emergence of micro-larvae in skin snip samples. The investigators thus established proof of principle that eradication of river blindness with ivermectin is possible and feasible (17). This has prompted WHO to change its strategy from control of onchocerciasis to onchocerciasis elimination (15, 17).
Ivermectin is a splendid gift from the earth
Reprinted with permission from Nobel Media AB 2105, Photo: Alexander Mahmoud
In 2015, Satoshi Ōmura and William Campbell received the Nobel Prize in Physiology or Medicine for their discovery of the avermectins and development of ivermectin. In his Nobel lecture, Ōmura, noting the soil origins of avermectin, said , “Ivermectin is a splendid gift from the earth” (7).
References 1. Steyer R (July 13, 1986) What’s new in animal health care: a bovine drug that helps people see. New York Times; available from: http://www.nytimes.com/1986/07/13/business/what-snew-in-animal-health-care-a-bovine-drug-that-helps-peoplesee.html. 2. Crump A and Otoguro K (2005) Satoshi Ōmura: in pursuit of nature’s bounty. Trends in Parasitology 21(3):126-132. 3. Ōmura S and Crump A (2004) The life and times of ivermectin—a success story. Nature Rev Microbiol 2:984-989. 4. Collins K (2004) Profitable gifts: A history of the Merck Mectizan® donation program and its implications for international health. Perspect Biol Med 47(1):100-109. Dr. William C. Campbell beside his wife, Mrs. Mary Campbell
The Pharmacologist • March 2016