October 1, 2007

Parasitic Worm Genome Gives Insight into Elephantiasis

Photograph of legs, with left leg extremely swollen Elephantiasis of the leg.Dr. F.W. O'Connor, courtesy of Wellcome Library, London.

Scientists have sequenced the genome of a tiny threadlike worm that can live for a decade in the human body and cause the debilitating disease elephantiasis, a painful and extreme enlargement of limbs and other body parts. The genome reveals dozens of potential new targets for drugs or vaccines to fight elephantiasis and similar parasitic diseases.

The worm, Brugia malayi, is one of several related parasites known as filarial nematodes, which infect more than 150 million people worldwide. These parasites thrive in tropical regions, including parts of Africa, Asia and Latin America. Filarial nematodes cause several chronic human diseases, including elephantiasis and river blindness.

B. malayi is one of two filarial parasites that cause elephantiasis. It spreads from person to person via mosquito bites, which deposit worm larvae into the skin. The parasites wend their way to the body's lymph nodes and vessels, which normally drain fluid from the body's tissues and help to fight infection. As the parasites grow into adult worms, they tend to cluster together in the lymph vessels, effectively blocking the drainage of fluids. Surrounding tissues swell, leading to a condition known as lymphatic filariasis. If the swollen tissues and skin become thick and hard, the disease may eventually develop into elephantiasis. According to the World Health Organization, elephantiasis seriously disfigures and incapacitates about 40 million people around the globe.

An international team of scientists reported on their completion of the B. malayi draft genome sequence in the September 21, 2007, issue of Science. Their work was funded by NIH's National Institute of Allergy and Infectious Diseases (NIAID). The researchers found that B. malayi has about 2,000 fewer protein-coding genes in its genome than the non-parasitic nematode Caenorhabditis elegans. By comparing the genomes of the 2 worms, the scientists uncovered genetic adaptations that may help B. malayi survive in the body. They also identified several proteins that seem unique to the parasite.

The scientists say that the newly uncovered genome may help to overcome some of the shortcomings of today's treatments for B. malayi infection. Current drugs mostly target the larvae and do not completely kill adult worms. Because the adult worms are so long-lived, infected patients often need to take their medications for years. In addition, the worms can cause massive immune reactions when they die.

"Filarial diseases are treatable, but the current treatments were discovered decades ago," says NIAID Director Dr. Anthony Fauci. "There is an urgent need for new discoveries in this area because of the limitations of the current drugs, including toxicities and the development of resistance."

Now, with the genome in hand, the researchers have already identified several potential drug targets for disrupting different phases of the nematode's life cycle.

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