Dangerous Waters

If you want to study life, study parasites. That advice comes from Patrick J. Skelly, a Tufts researcher who is known as the Worm Guy among his colleagues. “There are far more parasitic creatures than nonparasitic creatures,” Skelly says. “The more you learn about them, the more you are aghast. They are just unbelievable.”

Take the schistosome worm. A freshwater parasite of the class known as helminths, it slips through the skin and into the body. Once inside, it travels through the bloodstream to the vessels of the liver, where it matures and finds a mate. A few weeks later, the pair migrate to their final destination, the blood vessels around either the gut or the bladder, where the female lays her eggs—several hundred in a single day. The eggs bore through the blood vessel walls and wind up in the colon or bladder, from which they exit the body as waste. While living and breeding inside the body, the invaders may remain undetected for a decade or more. But eventually they cause a debilitating and sometimes life-threatening illness known as schistosomiasis. Its symptoms range from gut pain, chronic diarrhea, and anemia in mild cases to kidney failure, bladder cancer, or enlarged organs.

Some 780 million people worldwide—over a tenth of the planet’s inhabitants—are at risk. According to the World Health Organization, schistosomiasis afflicts about 200 million people, mostly in Africa but also in Asia, Latin America, and the Caribbean. Schistosomiasis is a disease of poverty, second only to malaria in its toll on human health. The lack of clean drinking water and adequate sanitation creates ideal conditions for the parasite, which is carried by freshwater snails, to infect the body when the skin comes into contact with infested water. More than 200,000 people die from schistosomiasis each year, prompting the U.S. Centers for Disease Control and Prevention to call the infection the world’s most deadly neglected tropical disease.

Only a handful of research teams worldwide are working to find vaccines and treatments, and Skelly’s lab at Cummings School of Veterinary Medicine is one of them. The Molecular Helminthology Laboratory, which Skelly runs with Charles B. Shoemaker, is tackling one of the schistosome’s biggest mysteries. Skelly removes a small vial from his desk drawer and holds it up to the light. Perhaps a dozen whitish worms are clearly visible, the size and shape of this capital letter G. “They’re quite big, these worms,” Skelly says. “Yet we don’t see the host’s immune system attacking them.”

Normally, when immune cells encounter suspicious foreign cells, the body mounts a full-blown immune response. But with schistosomiasis, the body ignores the worm and responds only to its eggs, which are what touch off the disease symptoms. Somehow adult schistosome worms manage to slip by the body’s defense system without raising an alarm. “How come there are no blood clots or immune cells around them?” Skelly asks. “What are they doing to turn these things off?”

Skelly and his team think the place to look for answers is on the worms’ skin. “That’s what’s touching the blood, of course,” Skelly says. Lacking a true mouth and digestive system, schistosomes absorb glucose from human blood through their skin, using special glucose-transporting molecules as their eating utensils. It’s such a crucial function that Skelly and Shoemaker figured the glucose transporters, which act like tiny revolving doors, must be among the worms’ least stealthy skin proteins. “If you want to get the sugar, you have to stick those things out there,” Skelly says. If the scientists can isolate the glucose transporter or another schistosome surface molecule, and generate enough of it, they may have the basis for developing a vaccine.

A vaccine could be a longer-term solution than the current treatment, a drug called praziquantel that kills the adult worms in a person’s bloodstream. Praziquantel is a fine remedy if you’re an American who got infected during a trip to Africa. But if you live there, you’re likely to become reinfected often. Karen C. Kosinski, E11, an assistant professor of public health and community medicine at Tufts School of Medicine and a Tisch College faculty fellow, has been studying schistosomiasis in Ghana, where it’s estimated that nearly two-thirds of people are infected. “It would be great if everybody had access to drugs, but they don’t,” Kosinski says, noting that many Ghanaians can’t afford even a sixty-seven-cent dose of praziquantel.

Skelly and a research assistant professor in the lab, Akram Da’darah, are looking for other chinks in the schistosomes’ armor as well: skin proteins that might make vulnerable targets for new drugs. In 2003, the pair pioneered a technique called RNA interference that enabled them to switch off the parasite’s genes. Recently, they discovered a gene containing the blueprint for a particular skin enzyme. When the scientists used the RNA interference technique to alter production of the enzyme, the worm could no longer infect the host. The enzyme’s presence had been suspected for years, Da’darah says, but no one had identified it. “We were able to isolate it.”

Now the search is on for a way to disable that enzyme. Da’darah has screened nearly two thousand chemicals to see whether one might be the magic bullet. So far, he has twelve promising candidates. If any of them can interfere with the enzyme enough to compromise the worm’s ability to infect its host, it could lead to a new remedy for a plague that has been around literally for ages: scientists have found evidence of schistosome worms in Egyptian mummies.

JACQUELINE MITCHELL is a senior health sciences writer at Tufts. A version of this article first appeared in Cummings Veterinary Medicine.