No Fluke: New weapon against tropical parasite

An experimental drug shows potential against schistosomiasis, a scourge that infects millions of people throughout the tropics. Tests in mice suggest that the drug might complement the sole effective treatment currently used to fight this disease.

Schistosomes are blood flukes, or flatworms, that infect people through the skin during the parasite’s waterborne larval stage. The larvae penetrate the circulatory system and ultimately settle in the liver, where they feed on blood and develop into adult worms. Females then lay eggs, some of which the infected person excretes in feces, potentially spreading the parasite. Other eggs lodge in the liver and other tissues, eliciting immune responses and causing the abdominal pain, fever, and malaise that mark schistosomiasis.

Scientists at the University of California, San Francisco several years ago found that a drug called K11777 kills the protozoan that causes Chagas’ disease, which is common in South America. That observation led them to test the drug against schistosomiasis.

K11777 deactivates enzymes called cysteine proteases, which a schistosome needs to digest proteins drawn from human blood. Disabling these enzymes “seems to starve the animal,” says study coauthor Conor R. Caffrey, a parasitologist.

In the January PLoS Medicine, Caffrey and his colleagues report the drug’s potent effect on the schistosomiasis parasite.

In one test, the researchers infected 10 mice with larval Schistosoma mansoni and, starting a week later, injected each animal daily for 5 weeks with either K11777 or an inert solution. By the end of that period, the drug-treated mice had less than one-tenth as many parasite eggs in their livers and only one-fifth as many surviving flatworms as the untreated mice did. When researchers infected seven other mice and gave each animal K11777 starting the next day, five were cured of the parasite after 2 weeks.

Flatworms taken from mice treated with the drug showed reduced activity of the cysteine protease called cathepsin B, suggesting that this enzyme is a prime target of K11777.

“Certain facets of this organism are clearly highly dependent on cysteine proteases,” says parasitologist Edward J. Pearce of the University of Pennsylvania in Philadelphia. The report “goes from hypothesis to initial findings—and now to something with clinical promise,” he says.

At present, only a drug called praziquantel can cure schistosomiasis, and it works differently than K11777 does. Praziquantel can cure a patient in 3 days, Caffrey says, but schistosomes evade it during the first month of infection. By contrast, K11777 appears most potent against early-stage infections and might therefore complement praziquantel.

Caffrey adds that it’s risky to rely on a single drug against a parasite that infects more than 200 million people. The pathogen might develop resistance to praziquantel.

The malaria drug artesunate (SN: 2/7/04, p. 94: Available to subscribers at Malaria drug boosts recovery rates) also kills schistosomes in lab studies. But using that medication against schistosomiasis in the many areas endemic to both diseases might contribute to malarial resistance to artesunate, Pearce cautions.

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