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Typical Antiparasitic


Onchocerciasis, also known as river blindness, has been a scourge to humanity for thousands of years. This disease, which is transmitted through the bite of an infected black fly, has caused suffering and disability among many of the world's poorest people--the vast majority of them in Africa. Merck's discovery, development, and 1987 decision to donate ivermectin to those who need it, in perpetuity, has freed millions of people from this parasitic disease that causes itching, skin nodules, disfigurement, and blindness.

8325ivermectin_eyes.tifcxd WHO/APOC/TDR/ANDY CRUMP

KANUNGU DISTRICT An elderly Ugandan woman, almost blind as a result of long-term onchocerciasis.

Onchocerca volvulus, which causes river blindness, is a species of filarial nematode. O. volvulus-infected Simulium black flies, which live near rapidly moving bodies of water, release infective-stage larvae when they bite people and feed on their blood. In the human host, the larvae mature into adult worms. Maturation takes place in a nodule or lump under the skin. Within a year of infection, females spawn microfilariae. Females can produce around 2,000 microfilarae per day for their 14-year life span.

The microfilariae have a particular affinity for eye tissue and can cluster there. Although most microfilariae die before reproducing, they cause severe inflammation, which is manifested as severe itching and swelling. Inflammation in the eyes leads to blindness.

Over the years, millions of acres of fertile agricultural lands in Africa had been abandoned by people fleeing river blindness; this flight resulted in hunger and poverty in addition to the obvious physical suffering of infected individuals. Starting in 1974, rivers were sprayed for larvae under the auspices of the World Bank's Onchocerciasis Control Program. But at that time, the limited treatments for infected people were frequently more dangerous than the infestations.

William Campbell, now retired, was a veterinary researcher in Merck's animal health division. His specialty was parasitology, and he had a strong interest in human parasitic diseases. In 1975, Merck was analyzing thousands of soil samples for potential active compounds for animal drugs. One sample, collected from a golf course in Japan, proved powerful against parasites.

Working with this sample, Campbell led an interdisciplinary group that discovered the avermectins--highly effective antiparasitic agents. Ivermectin is a semisynthetic derivative of one of these avermectins.

Ivermectin proved to be effective against certain worms in horses. In 1982, Merck and the World Health Organization (WHO) began studying ivermectin's effects on parasites in humans. These studies had extraordinary results.

With one annual dose, ivermectin paralyzes microscopic and mature worms. The worms stop moving around in the skin and other tissues, the itching stops, and blindness and disfigurement can be prevented. The worms' paralysis lasts a year, during which there is no spawning. Each year, another dose is given. After 15 years, the life cycle of the worm is broken.

In arthropods and nematodes, the -aminobutyric acid (GABA) receptor is found primarily in the peripheral nervous system (neuromuscular junction). According to literature from the American Society of Health-System Pharmacists, ivermectin binds to neuronal membranes, increasing the release of GABA, which then binds to the GABA receptor-chloride channel complex of postsynaptic neuronal membranes. This causes an influx of chloride ions, which hyperpolarize the neuronal membranes decreasing nerve transmission. This results in a flaccid paralysis.

In October 1987, P. Roy Vagelos, then Merck's chairman and chief executive officer, announced that the company would donate Mectizan (Merck's ivermectin) for the treatment of river blindness to all who need it for as long as needed. This donation brought about one of the most successful public-private partnerships in history.

Merck worked with WHO to distribute Mectizan to millions of people in remote locations. In 1988, the company formed the Mectizan Expert Committee to review and approve applications from nongovernmental development organizations, ministries of health, and local health agencies for free supplies of the medicine. Also in 1988, the Carter Center, in Atlanta, and Merck established the Merck Mectizan Donation Program.

As a result of these and other partnerships, Merck has provided ivermectin to treat more than 200 million people in 33 countries since 1987. According to a 2003 report, the program has helped reopen nearly 25 million hectares of arable land for settlement and cultivation--enough land to feed 17 million people each year.

Other pharma donation programs have followed; for example, GlaxoSmithKline has donated an antifilariasis drug; Pfizer has donated an antitrachoma drug; and Novartis has donated a multidrug regimen for Hansen's disease (leprosy).

Sir John Kerr, former ambassador to the U.S. for the U.K. and Northern Ireland, addressed this point in 1997: "The elimination of river blindness as a public health problem can be followed with other diseases, and the application of the principles that have been established so successfully can be applied in other sectors of development."—LINDA RABER


The Top Pharmaceuticals
That Changed The World
Vol. 83, Issue 25 (6/20/05)
Table Of Contents


Ivermectin structure


  • Mixture containing
    >=80% (10E,14E,16E,
    -12-yl 2,6-dideoxy- 4-O-(2,6-dideoxy-3

Other Names

  • Mectizan

CAS Registry

  • 70288-86-7