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Progress In The Fight Against A Parasite That Causes Diarrheal Disease

Scientists are reporting progress in the fight against a parasite that's a major cause of diarrheal disease in the developing world.

To make progress against any microbial disease, scientists usually try to find ways to tinker with the microbe's genes, looking for weak spots that could be exploited with drugs.

But tinkering with the genes of Cryptosporidium parvum has been difficult, if not completely impossible. No one has been able to figure out how to apply the standard tools of molecular biology to this parasite, because it's particularly difficult to work with in the lab. Now that's changing, thanks to work done by Boris Striepen and his colleagues at the University of Georgia in Athens.

Cryptosporidium is a protozoan parasite, a cousin of the malaria parasite, Plasmodium. It infects the gut and causes severe diarrhea. You get it by drinking contaminated water. In the United States, disease outbreaks are frequently associated with swimming pools. In 1993, an outbreak in Milwaukee sickened approximately 400,000.

For the most part, no one in this country dies from Cryptosporidium infection. "It's very unpleasant for a week or two, but then it's over," says Striepen.

It's a different story in the developing world. "Small children, especially small malnourished children, are very susceptible," he says. "They can develop chronic [diarrhea] and die from the disease."

A 2014 study found Cryptosporidium was the second leading cause of diarrheal disease in sub-Saharan Africa and South Asian.

Striepen says there's only one effective drug, Nitazoxanide, for treating Cryptosporidium infection, and it doesn't work well for patients at highest risk. There's also no vaccine.

But finding new cures and a vaccine for Cryptosporidium infection has been hampered by two factors.

"The biggest challenge is we cannot grow it really in the laboratory," he says. Scientists like to be able to grow organisms in the lab because they're far easier to study and manipulate.

The other factor has been the lack of genetic tools. "There's no technology to study the genetics of the organism." And because there was no way to grow Cryptosporidium in the lab, there was no good way to create that technology.

Despite the hurdles, Striepen decided he had to try to develop these tools.

He and his students tried for 10 years, "but we failed every time, quite miserably."

Then, along came something called CRISPR. It's a new technology that makes it far easier to modify the genes of organisms, even organisms you can't easily grow in the lab.

Using CRISPR, Striepen and his colleagues were able to develop a system for altering genes in Cryptosporidium. They still can't grow the parasite in the lab, "but we can infect animals, and so that way using laboratory animals we can propagate the infection, and therefore we can also propagate these organisms that we have changed," he says.

And they can also use the infected animals to test drug or vaccine candidates.

When he started out working on Cryptosporidium, he knew developing this genetic tool kit was a high risk project, but it was also high reward. These days, everyone seems to agree that it's crucial for researchers to try risky projects if they are to make important advances.

"But while you're doing that it's quite an uncomfortable position to be in," says Striepen. "I woke up some nights and I thought, these poor kids who work with me in the lab, I bring them out onto this hail Mary project and I risk their careers. So it's really very gratifying to see that it worked and that we can make some real progress and make a real contribution."

The new work appears in the journal, Nature.

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