Researchers reach milestone in fight against lymphatic filariasis

Four annual mass treatments of single doses of safe and inexpensive drugs found effective

Researchers report in the December 5 issue of the New England Journal of Medicine reaching an important milestone in learning how to halt a major mosquito-borne disease affecting 120 million people around the world. The disease, called lymphatic filariasis and commonly known as elephantiasis, is a leading cause of physical disfigurement, social ostracism, and economic loss throughout Africa, Asia, South America, and islands of the Pacific Ocean. The disease can lead to dramatically swollen and disfigured legs, arms, breasts, and genitals.

Treating 2500 residents in a remote area of Papua New Guinea in the South Pacific, the researchers from Case Western Reserve University School of Medicine, University Hospitals of Cleveland, and Papua New Guinea Institute of Medical Research found dramatic results with four annual mass treatments of single doses of safe and inexpensive anti-filarial (anti-worm) drugs. There was a greater than 95 percent decrease in mosquito transmission, nearly complete prevention of new infections in children, reduction of infection rates in the communities to less than one percent, and remarkably, cure of severe disease manifestations such as extremely enlarged arms and legs, and genital disfigurement. Combined with conclusions drawn from mathematical analysis of the interrelationships between the potentials of mosquito transmission and human infection, the report clearly sets the precedent that annual mass treatment with safe and inexpensive medications can go a long way toward eliminating this devastating disease.

James W. Kazura, M.D., the paper’s senior author, notes that this work represents an important milestone in the world-wide effort to combat filariasis. “Until this study, it was not clear that eradication and significant decreases in mosquito-borne transmission and disease severity could be realized even on a small scale.” Kazura is a professor of medicine at CWRU and UHC.

Lymphatic filariasis is caused by microscopic juvenile parasitic worms that are transmitted to humans by mosquitoes containing these infective parasites. The juvenile parasites migrate from the site of the mosquito bite and ultimately develop into adult worms in the lymphatic system of the human host, where they cause the hallmark inflammation of filariasis. In many rural areas of Papua New Guinea, Africa, and India, nearly 10 percent of persons suffer from elephantiasis by adulthood, and large numbers of men develop such swelling of the scrotum that it can reach the size of a grapefruit. Transmission is continued in nature when the microscopic offspring of adult worms, called microfilariae, circulate in the bloodstream and are subsequently ingested by blood-feeding mosquitoes. After further development in the mosquito, the parasites are capable of infecting humans when the insect takes its next blood meal.

Building on more than 20 years of research and clinical investigations on filariasis, the project was conducted in Papua New Guinea, where transmission of filariasis and other serious infectious diseases such as malaria reach the highest levels seen anywhere in the world.

“Performance of a study in this setting to determine whether inexpensive and safe medications could decrease transmission of filariasis and control its clinical outcomes represents an extraordinarily tough test or ’proof of principle’ of the Global Plan to Eradicate Lymphatic Filariasis,” says Kazura. “This plan, officially launched by the World Health Assembly in Geneva in 1997, states that filariasis is one of six diseases that is potentially eradicable. The target date to achieve this goal at a global level has been set at 2020. With support from the Bill and Melinda Gates Foundation and other non-governmental philanthropic organizations, administration by the Global Alliance through the Carter Center in Atlanta and World Health Organization, and donation of anti-filarial drugs by GlaxoSmithKline and Merck Pharmaceuticals, the infrastructure to implement the control plan in Africa, Latin America, Asia, and Pacific island nations has been growing over the past several years.

“This study provides essential guidelines to control this infectious disease and points the way to the ultimate eradication of filariasis on a global level,” says Kazura.

“The work also poses interesting and challenging new research questions that should enable the testing of new hypotheses on how genetics and immunity determine infection susceptibility in humans and contribute to the development and ultimately prevention of lymphatic disease,” he says.

An accompanying editorial written by Eric A. Ottesen, M.D., of Emory University, says this study has yielded important conclusions. “It should serve as a touchstone for future evaluations of other programs, both inside and outside the research community,” it states.