A research team supported by the National Institutes of Health (NIH) Roadmap and the National Institute of Allergy and Infectious Diseases (NIAID) has identified chemical compounds that hold promise as potential therapies for schistosomiasis, a parasitic disease that afflicts more than 200 million people worldwide.
The findings were reported today in the advance online publication of the journal Nature Medicine.
In their paper, researchers from Illinois State University (ISU) in Normal, Ill., and NIH's Chemical Genomics Center (NCGC) report that chemical compounds known as oxadiazoles can inhibit an enzyme vital to survival of Schistosoma, a group of parasitic flatworms that cause schistosomiasis. The NCGC, established in 2004 by the NIH Roadmap for Medical Research, includes a set of strategic initiatives drawing collectively from the agency-wide research resources of NIH.
“New therapeutic agents are sorely needed if we hope to ease the burden of schistosomiasis on the world's health,” said NIH Director Elias A. Zerhouni, M.D. “These findings exemplify what academic researchers can accomplish with access to translational infrastructure and technologies that have previously been beyond their reach.”
Schistosomiasis, also known as bilharzia or snail fever, affects an estimated 207 million people, most of whom live in developing nations in tropical areas. About 20 million of those people are seriously disabled due to severe anemia, diarrhea, internal bleeding and/or organ damage. In addition, another 280,000 die of the disease each year.
People become infected with Schistosoma when they wade, swim or bathe in fresh water inhabited by snails, which serve as the worms' intermediate hosts. The microscopic worms enter the human body by boring through the skin and migrate into the blood vessels that supply the intestinal and urinary systems. After the worms mature and reproduce, their eggs are eliminated in human urine and feces. If human waste contaminated by worm eggs finds its way into fresh water, the cycle begins again.
Currently, people living in more than 70 tropical nations require annual or semi-annual drug treatment to rid their bodies of the parasite. Since the 1980s, praziquantel has effectively been the sole drug used for this purpose. Public health experts are concerned that the Schistosoma parasites will become resistant to praziquantel and the drug will lose its effectiveness, as has been the case for agents used to combat many other infectious diseases such as malaria and tuberculosis.
“The search for new drugs for schistosomiasis is imperative if we are to control this devastating disease that exacts an enormous toll, both in terms of human suffering and economic development,” said NIAID Director Anthony S. Fauci, M.D.
The new research, which was conducted with Schistosoma maintained in laboratory conditions, shows that an oxadiazole compound was effective in inhibiting a crucial worm enzyme, called thioredoxin glutathione reductase (TGR). Furthermore, in tests of laboratory mice infected with Schistosoma, this compound killed the parasite in all of its stages, from larva to adult. The results exceeded all benchmarks set by the World Health Organization for potential new compounds to treat schistosomiasis. Importantly, the researchers also showed that the compound was active against all three major species of Schistosoma worms that infect humans.