By Eric Sorensen, WSU News
PULLMAN, Wash.— Jenni Zambriski is an expert on fulminant diarrhea. It’s as gross as it sounds, but her research has the upside of potentially saving millions of young lives.
Zambriski and an international group of colleagues announce in the latest the journal Nature that they have found a drug for treating cryptosporidiosis, a diarrheal disease that is a major cause of child mortality in the developing world. Zambriski, a clinical assistant professor in Washington State University’s Paul G. Allen School for Global Animal Health, is one of three lead authors of the Nature paper, having developed a way to use calves as an animal model for testing the drug.
Selected from more than 6,000 candidates, the drug had an almost immediate effect on infected calves, Zambriski said.
“When you give them this drug, 24 hours later you walk in their stall and they’re ready to play,” she said.
There is currently no effective treatment for cryptosporidiosis, particularly among the malnourished and HIV-positive infants that it kills in large numbers. Diarrheal disease kills some 800,000 people a year, mostly in sub-Saharan Africa and south Asia. A 2013 study in The Lancet reported that Cryptosporidium was the second most common pathogen causing diarrhea in children under 12 months.
The pathogen, a type of amoeba, attaches itself to cells that line the small intestine. Pulling the cell wall over itself like a shroud, it sucks nutrients, breeds and erupts, killing the cell and releasing progeny to repeat the process. The dead cells turn the intestine into a “slip and slide,” said Zambriski.
The ensuing diarrhea purges the body of electrolytes, ions that conduct the electricity of nerve signals, including the firing of muscles. Eventually, the heart can’t pump, leading to the perverse scenario in which a child of less than a year old can die of a heart attack.
The pathogen is common on dairy farms and can cause substantial economic losses for farmers. Water treatment systems for the most part keep it under control in the developed world, with notable exceptions. A 1993 outbreak in Milwaukee sickened more than 1 million people and killed more than 100. Zambriski herself has been infected twice. The second time, she had to be hospitalized after a calf knocked off a protective mask.
“Sure enough, seven days later, I have explosive diarrhea,” she said.
The threat of illness has led to a certain vigilance among colleagues and student researchers in Zambriski’s lab.
“My students so much as break wind and I get a text message,” she said.
For her recent research, Zambriski tried to recreate in calves the circumstances in which a child might get sick. After giving the calves the pathogen, the researchers waited for them to get severe diarrhea, then waited for the parasite to show up in the stool, as would happen after a child was taken to a clinic and was diagnosed by a doctor.
Every 12 hours, the researchers documented the calves’ appetite, alertness, hydration and fecal consistency, which ranged from normal (“feces retain form”) to moderate diarrhea (“a puddle, not a patty”) to severe diarrhea (“easily flow down a surface leaving little to no adherent material”).
The research also involved capturing poop directly from the source, blending it and baking it.
“This is how you know you have dedicated students,” Zambriski said.
Zambriski’s colleagues, including scientists at the Novartis Institute for Tropical Diseases and the University of Georgia’s Center for Tropical and Emerging Global Diseases, winnowed 6,220 drug candidates to one: a compound called KDU731 that inhibits crypto’s ability to produce energy. Calves showed improvement after two treatments with the compound. Within 72 hours, most of the calves no longer had severe diarrhea.
Zambriski and her colleagues now hope to test the safety of their candidate drug more extensively. Zambriski would also like to investigate using it in agricultural settings, particularly dairy farms.
A previous WSU News story about Zambriski can be found HERE
Media contact: Jenni Zambriski, clinical assistant professor, Paul G. Allen School for Global Animal Health, 509-335-4514, j.zambriski@wsu.edu