The Elephantiasis “Genetic Code” Puzzle Solved!

“Filarial diseases are treatable, but the current treatments were discovered decades ago,” says NIAID Director Anthony S. Fauci, M.D. “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.” The B. malayi genome reveals dozens of potential new targets for drugs or vaccines and should provide new opportunities for understanding, treating and preventing elephantiasis and similar diseases.

“Having a complete genetic blueprint gives us a better understanding of what genes are important for different processes so you can target them more specifically,” says Elodie Ghedin, Ph.D., who led the sequencing project while at the Institute for Genomic Research, now part of the J. Craig Venter Institute, a not-for-profit research organization based in Rockville, Maryland. Dr. Ghedin is now a professor at the University of Pittsburgh School of Medicine.

When a mosquito bites someone infected with B. malayi, it ingests microscopic worms that develop into infectious larvae. These larvae are then deposited onto the skin of the next person bitten. Once the parasites penetrate the skin, they wend their way to the body’s lymphatic system—a network of fine vessels and organs that drains fluid from the body’s tissues and plays a key role in coordinating the immune response by concentrating immune cells in the lymph nodes. Male and female worms cluster, intertwining in the draining vessels just below the lymph nodes, and mate. A fertile female may produce 1,000 or more larvae a day and grow to be three or four inches long.

This filarial union can cause severe disease. Because they most often position themselves in front of vessels draining liquid from the lymph nodes, the worms can effectively obstruct the drainage. This causes the surrounding tissues to fill with fluid and swell to elephantine proportions.

As the disease progresses, tissues in the swelling arms, legs or scrotum can die or become infected, turning black and oozing puss. To make matters worse, the fluid accumulation can lead to permanent disfigurement over time as the swollen limbs become solid masses with connective tissue, blood vessels and nerve endings. Reducing the bulbous tissue may require major surgery.

Female B. malayi worms can live up to eight years in the human body. This longevity complicates elephantiasis treatment because existing drugs for treating the disease target the larvae only and do not completely kill the adult worms. The drugs often must be taken for years, and the worms can cause massive immune reactions when they die, releasing foreign molecules in the body.

The worm’s longevity is curious because it lives for years in the shadow of the lymph node, where immune cells meant to clear the body of infections congregate. One way the worm survives is by releasing chemicals that dampen the human immune response. B. malayi is so good at this that most people who are infected have no symptoms: The worms can live in their bodies for years without their even knowing it.

Understanding how this particular parasite has adapted to humans may yield medical benefits far beyond those places where elephantiasis is common, according to collaborator Alan L. Scott, Ph.D., of the Bloomberg School of Public Health at Johns Hopkins University. Worms can be viewed as foreign tissue transplanted into the human body. But unlike baboon hearts or pig kidneys, which the immune system quickly rejects, worms can survive for years in the body. Discovering how they do so may someday benefit transplant surgery, according to Dr. Scott.

Source: Eurekalert
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