Global program to eliminate elephantiasis has early success in Egypt

Organizers of a 20-year global effort to eliminate a parasitic infection that is a leading cause of disability have an early victory to savor: a five-year Egyptian elimination campaign has mostly succeeded, according to a new report in the March 25 issue of The Lancet. Infection with the parasites, threadlike filarial worms, can lead to the dramatic, disfiguring swelling known as elephantiasis.

Researchers from Washington University School of Medicine in St. Louis and Ain Shams University in Egypt found that after five years of annual mass treatments with two drugs, rates of filarial infection sharply declined in Egypt.

"The parasite's transmission efficiency is low, so the thinking is that once we get human infection rates below a critical level, remaining infections will die out without further intervention," says senior author Gary Weil, M.D., professor of medicine and of molecular microbiology at Washington University. "Our assessments suggest that the Egyptian campaign to eliminate these infections, which was implemented by the Egyptian Ministry of Population and Health, has achieved its goals in most areas of the country."

Filarial worms are nematodes closely related to the heartworm parasites that infect dogs and cats. Infections with the worms, which are spread by mosquitoes, can lead to lymphatic filariasis, a condition where the worms lodge in lymphatic vessels. This triggers inflammation that blocks the drainage normally provided by the lymphatic system and leads to massive swelling of the legs, known as elephantiasis, and genital deformities, which are called hydroceles.

"In addition to causing disability, the disfigurement created by elephantiasis is often a source of great social stigmatization," Weil notes.

Epidemiologists estimate 120 million people are infected with filarial worms in 83 tropical countries. Of those infected, approximately 40 million have clinical symptoms. As many as 1.2 billion people are at risk of infection with the parasites, which can live and reproduce for several years inside the human body. According to the World Health Organization (WHO), lymphatic filariasis is a leading cause of chronic disability in the world.

Policymakers at World Health Assembly meetings in 1997 endorsed filariasis as a candidate disease for global elimination for several reasons: the worms that cause the disease are inefficiently transmitted, they are not known to infect any species other than humans and mosquitoes, and they are vulnerable to three drugs, albendazole, ivermectin and DEC (diethylcarbamazine).

"The manufacturers of the first two drugs later generously decided to donate the medicines to the global program," Weil says. "The third medicine is not free but is very inexpensive."

The assembly passed a resolution calling for the elimination of filariasis by 2020. The strategy the WHO chose for eliminating the parasite is called mass drug administration (MDA).

"In regions where the parasite is known to be present, you annually give two medications that kill the worms," Weil explains. "With the exception of pregnant women and children under two years of age, these drugs are given to everyone in the region without testing each person for the infection."

Planners estimated that five annual repetitions of the MDA program would be needed to drive parasite infection rates down to levels where the few remaining infections would die off on their own. Egypt became one of the first countries to start a five-year MDA program in 2000, working to reach 2.5 million people in 181 Egyptian localities affected by lymphatic filariasis.

"The drugs are free or inexpensive, but distribution on this scale in rural villages and poor areas is a big, expensive job," Weil says. "Donations from foundations and wealthy countries helped fund the distribution in Egypt, and more of that same support is needed for campaigns in other countries."

Working in collaboration with colleagues at Washington University including William D. Shannon, Ph.D., associate professor of biostatistics and researchers at Ain Shams in Egypt, Weil developed a plan for assessing the degree to which the Egyptian MDA program was successful. Using several different tests, some of which were developed in Weil's lab, Egyptian scientists annually assessed infection rates during the MDA program in two villages north of Cairo and two villages south of Cairo. Each village has a population of 3,000 to 5,000.

The tests revealed sharply declining infection rates over the course of the MDA program. For example, tests of first graders for an antibody that reveals prior exposure to the parasite declined from 18.2 percent positive prior to MDA to 0.2 percent positive after the fifth round of MDA. A test for infection in mosquitoes also showed infection rates plummeted after MDA.

Two of the four villages studied did not quite achieve elimination targets after 5 years of MDA; they will receive a sixth round of treatments in 2006 to ensure that the parasite is eliminated.

Assessment of the Egyptian campaign's results was funded as a part of the International Collaborations in Infectious Diseases Research (ICIDR) program at the National Institutes of Health. Weil recently received a new ICIDR grant for an added $5 million over five years for a larger program to assess and follow-up filariasis elimination in Egypt.

"With new collaborators from Erasmus University in Holland and Smith College in Massachusetts, we will work with the Ain Shams University group to monitor 44 Egyptian villages, checking to see if remaining infections die out as expected or if the parasite shows any signs of resurgence," he says. "We'll also be looking at the goals WHO has set for these programs in terms of how far we need to drive infection rates down: are the current targets too stringent? Would it be helpful to have phased goals?"

Weil notes that the filariasis elimination program, which is now coordinating MDA treatments in 35 nations, has to confront a diverse array of economic, cultural and logistical obstacles.

He praises the Egyptian health ministry's efforts to increase acceptance of the need to participate in the MDA program, noting that it used approaches such as educational comic books and television advertisements featuring Egyptian celebrities to promote public awareness.

"The world faces many challenges in bringing this kind of MDA campaign to the 83 nations where the parasite is present, but this first assessment of a completed five-year MDA program is very encouraging," Weil says.

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Ramzy RMR, El Setouhy M, Helmy H, Ahmed ES, Abd Elaziz KM, Farid HA, Shannon WD, and Weil GJ. Effect of yearly mass drug administration with diethylcarbamazine and albendazole on bancroftian filariasis in Egypt: a comprehensive assessment. The Lancet, March 25, 2006.

Funding from the National Institutes of Health supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


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