October 01, 2004
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Control of onchocerciasis in Africa and elimination in Latin America seem within reach

The introduction of Mectizan improved vector-control efforts, freeing many areas of Africa from the effects of the disease.

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When microfilaria invade the eye, a person’s eyesight is diminished and ultimately blindness results. Ivermectin can kill the microfilaria, thus preventing eye damage and the blindness caused by onchocerciasis.

Close-up picture of an eye damaged as a result of infection with Onchocerca volvulus, the parasite that causes onchocerciasis.


Images: World Health Organization/Training in Tropical Diseases

After more than 50 years of efforts, control or elimination of onchocerciasis on two continents seems possible by the end of the decade, according to an expert on the disease.

Sustained community-directed control of onchocerciasis could happen by 2010 in endemic areas of Africa, and there is potential for its elimination from endemic Latin American areas by 2007, according to Bjorn Thylefors, MD, an ophthalmologist and director of the Mectizan Donation Program.

Key to the success of control efforts was the introduction of the drug Mectizan (ivermectin, Merck) and the subsequent creation of the Mectizan Donation Program in 1987 by the maker of the drug, Dr. Thylefors said.

Before the Mectizan program, efforts to control onchocerciasis mainly focused on endemic areas in Africa and were carried out by the Onchocerciasis Control Program (OCP), an effort funded by the World Health Organization and the World Bank. The OCP focused on controlling Simulium black fly populations, which transmit the Onchocerca volvulus filarial worm that causes onchocerciasis.

This vector-control approach was somewhat effective, Dr. Thylefors said, but chemotherapy with Mectizan complemented these efforts by the OCP. Mectizan is more effective and safer than previous onchocerciasis drugs such as diethylcarbamazine, which is associated with severe itching and skin reactions, headaches and fever for several days, he said.

Mectizan is administered only once a year, but it can be taken up to four times a year at up to 20 times the normal dose without risking toxicity or other adverse reactions, he said.

“We have never had any problems with intoxication or pregnancy or anything. Although it is recommended not to give it during pregnancy, we know there have been inadvertent dosings, but there has never been a link between any pregnancy-related illness or fetal development issues or anything of that kind,” he said.

Merck’s Mectizan Donation Program distributes ivermectin free of charge to onchocerciasis-endemic countries in Africa and Latin America. More than 50 million treatments have been administered annually over the past 17 years.

Initial vector control

According to Dr. Thylefors, the first successful attempt at controlling onchocerciasis was in 1949 in Kenya, where the insecticide DDT was used to eradicate black fly populations. In 1969, vector-control efforts were expanded to cover a much larger area, giving rise to the OCP, he said.

The OCP began in 1972 and used aircraft to spray insecticide on breeding sites used by black flies.

The OCP was terminated in 2002. Dr. Thylefors said it had a successful start but ran into difficulty because the black flies began developing resistance to the insecticides.

While the OCP was focusing on vector control, Merck was researching the anthelmintic treatment invermectin, particularly for use with livestock and dogs, he said.

Merck researchers realized that because the drug had such a strong antiparasite effect on worms similar to the Onchocerca volvulus, it was possible it could be effective in humans. Merck, together with the WHO, then carried out 7 years of clinical trials and eventually gained approval for use of the drug in humans.

“They realized that if they administered this medication once a year in a low dose, in fact you could keep the disease down. … You could stop the progression of the disease,” Dr. Thylefors said.

“But you had to give it every year to keep that going because it does not kill the onchocerciasis adult worm, it just kills the small worms, the microfilaria, and gradually reduces the fertility of the adult worm,” he said.

Mectizan Donation Program

According to Dr. Thylefors, Merck realized it could never sell the drug in Africa and instead established an expert committee that created the Mectizan Donation Program.

“They decided they would just give it away for as long as necessary and as much as necessary to control onchocerciasis as a public health problem in the 35 countries where the disease is endemic — six countries in Latin America and 29 countries in Africa,” Dr. Thylefors said.

“It was a gift; it is a donation program. That principle has been followed since and is still followed today. The authorities allow for the import of this drug and the use of it for public health purposes and do not charge taxes on this donation,” he said.

He noted treatment with Mectizan complemented vector-control efforts, and the two strategies together proved to be effective at controlling the disease.

“Most of the areas that are today free from onchocerciasis are so as a result of the combined effect of vector control and Mectizan distribution,” he said.

Potential for elimination

According to Dr. Thylefors, Latin America has much lower rates of onchocerciasis than Africa, with less than 500,000 persons at risk in Latin American compared with more than 90 million at risk in Africa.

Also, the breeding habits of the vector flies in Latin America are different from those of black flies in Africa. It was discovered that regular use of ivermectin alone could reduce the number of microfilaria in the skin to interrupt transmission of the disease.

So in 1992, the Pan-American Health Organization created the Onchocerciasis Elimination Program for the Americas with the goal of eliminating onchocerciasis in the six endemic Latin American countries — Brazil, Colombia, Ecuador, Guatemala, Mexico and Venezuela.

“In the Americas, there is truly the opportunity to eliminate the disease once and for all, and that is hoped to happen by the year 2007,” Dr. Thylefors said.

The prevalence of onchocerciasis in Africa is much higher than in Latin America. But because of the effectiveness of the Mectizan Donation Program, the African Program for Onchocerciasis Control (APOC) was created in 1995 by the World Bank, the WHO, the United Nations Development Program and the Food and Agriculture Organization of the United Nations.

The APOC seeks to establish sustainable, community-directed treatment programs in all endemic areas of Africa by 2010. Local distributors are trained to provide the treatment, report any side effects and refer patients for treatment, if necessary.

Dr. Thylefors noted the APOC involves only the distribution of Mectizan but covers 19 endemic countries in Africa that were not included in the original ivermectin programs.

“That has been extremely successful in terms of high compliance rates, and it seems to be working out well in all these countries,” he said.

New onchocerciasis drug

Joining the fight against onchocerciasis, Wyeth Pharmaceuticals announced in May that after 3 years of informal cooperation, it is collaborating with the WHO in a clinical trial of a new onchocerciasis treatment, moxidectin.

According to the company, moxidectin has shown an effect against the adult Onchocerca volvulus worms in animal models. Wyeth is collaborating with the WHO and the WHO Special Program for Research and Training in Tropical Diseases to determine whether the drug can be added to existing disease control efforts.

The study, a phase 2 proof-of-concept clinical trial, will be undertaken at the WHO’s Onchocerciasis Chemotherapy Research Center in Hohoe, Ghana. Wyeth is providing clinical supplies and resources for data management and analysis.

According to Doug Petkis, a press contact for Wyeth Pharmaceuticals, results of the trial will not be available until approximately 2 years after it begins. He told Ocular Surgery News that preclinical models have shown that moxidectin acts similarly to ivermectin, leading to paralysis and death of the parasite.

He said it is thought moxidectin may be more effective than ivermectin because it is eliminated from the body more slowly.

Mr. Petkis could not comment about Wyeth’s plans for marketing or distribution of the drug, should it receive regulatory approval.

“After completion of clinical trials necessary to register moxidectin, additional community effectiveness trials are necessary to best determine how a product would work and the best way to distribute the product, given the clinical characteristics that have been determined,” he said.

For Your Information:
  • Bjorn Thylefors, MD, can be reached at the Mectizan Donation Program, 750 Commerce Drive, Suite 400, Decatur, GA 30030; 404-371-1460; e-mail: bthylefors@taskforce.org.
  • Merck & Co., maker of Mectizan (ivermectin), can be reached at 351 North Sumneytown Pike, North Wales, PA 19454; 267-305-7896; fax: 267-305-4283; Web site: www.merck.com.
  • Wyeth Pharmaceuticals, maker of moxidectin, can be reached at 5 Giralda Farms, Madison, NJ 07940, United States; Web site: www.wyeth.com.
  • OSN Staff Writer Michael Piechocki covers the ophthalmology in Europe and the Asia-Pacific region. He also specializes in oculoplastics.