UGA researchers report milestone in global fight against a major cause of diarrheal disease
Athens, Ga. – Infectious disease scientists from research institutions including the University of Georgia have reported the discovery and early validation of a drug that shows promise for treating cryptosporidiosis, a diarrheal disease that is a major cause of child mortality and for which there is no vaccine or effective treatment.
“Cryptosporidiosis is largely a disease of poverty,” said Boris Striepen, Distinguished Research Professor of Cellular Biology in UGA’s Franklin College of Arts and Sciences and a member of the Center for Tropical and Emerging Global Diseases. “Globally, it primarily affects infants in developing countries, but there are patients in the U.S.-those with weakened immune systems, such as HIV/AIDS or transplant patients-that would benefit greatly from new therapeutics.”
Striepen began studying crypto, as researchers often call the parasite that causes cryptosporidiosis, more than a decade ago. Now he and Sumiti Vinayak, assistant research scientist at UGA’s Center for Tropical and Emerging Global Diseases, along with scientists at Novartis and Washington State University, have reported the discovery of KDU731, a potent inhibitor of cryptosporidium, in the journal Nature.
Identifying KDU731 as a potential drug for the treatment of cryptosporidiosis began with the screening of a selection of 6,200 compounds that showed strong activity against the related malaria parasite. The Novartis team led by Ujjini H. Manjunatha and Thierry T. Diagana identified compounds with activity against crypto and found KDU731 particularly promising based on preclinical data.
Using a new mouse model, UGA’s Striepen and Vinayak showed that oral treatment with the drug dramatically reduced intestinal infection of immunocompromised mice. Additional research, led by Jennifer A. Zambriski at Washington State University, showed that treatment with KDU731 also leads to rapid resolution of diarrhea and dehydration in neonatal calves, a clinical model of cryptosporidiosis that closely resembles human infection.
Crypto is most commonly spread through tainted drinking or recreational water. When a person drinks contaminated water, parasites emerge from spores and invade the cells that line the small intestine, causing severe diarrhea that can last for up to three weeks.
In 1993, more than 400,000 people living in the Milwaukee, Wisconsin, area were infected and became ill when one of the city’s water treatment systems malfunctioned. More than 100 people, mostly AIDS patients, died during the outbreak.
Outbreaks have also been linked to swimming pools and water parks. Crypto is the most common cause of diarrheal illness and outbreaks linked to recreational water because it is not easily killed by chlorine and can survive up to 10 days in properly treated water.
The Centers for Disease Control and Prevention reported at least 32 outbreaks in U.S. facilities during 2016-twice as many as in 2014, according to preliminary data in the agency’s May 18 Morbidity and Mortality Weekly Report.
Recent global studies have shown crypto to be one of the most important causes of life-threatening diarrhea in infants and toddlers, especially in areas that lack access to clean water. There is no vaccine and only one drug, nitazoxanide, approved by the U.S. Food and Drug Administration, but it provides no benefit for those in gravest danger-malnourished infants and immunocompromised patients.
Crypto is notoriously difficult to work with in a laboratory setting, but Striepen has developed new genetic techniques that make it easier to detect and follow the parasite. One technique involves manipulating crypto so that it emits light and is easier to detect and measure. For this study, Striepen’s team engineered a new “reporter” parasite that is amenable to whole-animal imaging, allowing the researchers to non-invasively track and record dissipation of the infection during treatment.
Striepen’s genetically modified organisms have been made available to researchers across the world in the hope that more scientists will be drawn to studying crypto.
“This is an important problem,” he said. “No one institution can solve it alone. It needs significant investment, and it needs a lot of people with good ideas.”
“The discovery of this compound represents an important step toward urgently needed treatment for gravely ill children around the world,” said Thierry Diagana, head of the Novartis Institutes for Tropical Diseases.
An online version of the study is available at http://dx.doi.org/10.1038/nature22337.
Writer: Allyson Mann
Contact:Boris Striepen Sumiti Vinayak
‘Prestigious recognition’: UGA entomologist elected to National Academy of Sciences
First appeared in ColumnsUniversity of Georgia Regents’ Professor Michael R. Strand has received one of the highest honors a scientist can receive—election to the National Academy of Sciences.
Strand, who holds an appointment in the entomology department of the College of Agricultural and Environmental Sciences and an affiliated appointment in the genetics department of the Franklin College of Arts and Sciences, is UGA’s eighth member of the National Academies, which include the National Academy of Sciences, National Academy of Engineering and National Academy of Medicine.
“The University of Georgia commends Dr. Strand on this most prestigious recognition,” said President Jere W. Morehead. “Dr. Strand’s influential research is representative of the high caliber of faculty at UGA and the strength of our growing research enterprise.
It is an honor to have him represent this university in an organization of such tremendous national importance.”
Strand’s primary research interests are in the study of the interactions among insects, parasites and microorganisms. Applications of his work focus on insects that are important to agriculture and that transmit human diseases such as malaria and Zika virus. His work has garnered nearly $28 million in external funding from agencies such as the National Institutes of Health, U.S. Department of Agriculture and National Science Foundation. He has published more than 220 research papers, and his findings have been cited at a level that places him in the top 1 percent of entomologists and among the top 5 percent in the fields of biology and biochemistry.
“Dr. Strand’s work underscores the profound impacts that basic science can have on agriculture and human health,” said Senior Vice President for Academic Affairs and Provost Pamela Whitten. “He exemplifies the kind of world-changing research and instruction that make the University of Georgia one of the nation’s leading public universities.”
Strand’s expertise is sought around the globe. He has delivered invited seminars and symposia in nearly every department of entomology in the U.S. and at universities and conferences in Europe, Asia, South America, Africa and Australia. In Athens, he has taught undergraduate survey courses in entomology and has mentored more than 50 doctoral students and postdoctoral fellows who have gone on to careers in government, industry and academia.
Strand has earned several honors over the course of his career, including being named a Fellow of the American Association for the Advancement of Science and of the Entomological Society of America. In 2013, he was named Regents’ Professor, an honor bestowed by the Board of Regents of the University System of Georgia to distinguished faculty whose scholarship or creative activity is recognized both nationally and internationally as innovative and pace setting.
He joined the UGA faculty in 2001 and is a member of the university’s Center for Tropical and Emerging Global Diseases and its Faculty of Infectious Diseases. He earned his bachelor’s degree and doctorate from Texas A&M University and was a postdoctoral researcher at Imperial College London.
The National Academy of Sciences is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and—with the National Academy of Engineering and the National Academy of Medicine—provides science, engineering and health policy advice to the federal government and other organizations.
UGA entomologist Michael Strand elected to National Academy of Sciences
Athens, Ga. – University of Georgia Regents’ Professor Michael R. Strand has received one of the highest honors a scientist can receive-election to the National Academy of Sciences.
Strand, who holds an appointment in the entomology department of the College of Agricultural and Environmental Sciences and an affiliated appointment in the genetics department of the Franklin College of Arts and Sciences, is UGA’s eighth member of the National Academies, which include the National Academy of Sciences, National Academy of Engineering and National Academy of Medicine.
“The University of Georgia commends Dr. Strand on this most prestigious recognition,” said President Jere W. Morehead. “Dr. Strand’s influential research is representative of the high caliber of faculty at UGA and the strength of our growing research enterprise. It is an honor to have him represent this university in an organization of such tremendous national importance.”
Strand’s primary research interests are in the study of the interactions among insects, parasites and microorganisms. Applications of his work focus on insects that are important to agriculture and that transmit human diseases such as malaria and Zika virus. His work has garnered nearly $28 million in external funding from agencies such as the National Institutes of Health, U.S. Department of Agriculture and National Science Foundation. He has published more than 220 research papers, and his findings have been cited at a level that places him in the top 1 percent of entomologists and among the top 5 percent in the fields of biology and biochemistry.
“Dr. Strand’s work underscores the profound impacts that basic science can have on agriculture and human health,” said Senior Vice President for Academic Affairs and Provost Pamela Whitten. “He exemplifies the kind of world-changing research and instruction that make the University of Georgia one of the nation’s leading public universities.”
Strand’s expertise is sought around the globe. He has delivered invited seminars and symposia in nearly every department of entomology in the United States and at universities and conferences in Europe, Asia, South America, Africa, and Australia. In Athens, he has taught undergraduate survey courses in entomology and has mentored more than 50 doctoral students and postdoctoral fellows who have gone on to careers in government, industry and academia.
Strand has earned several honors over the course of his career, including being named a Fellow of the American Association for the Advancement of Science and of the Entomological Society of America. In 2013, he was named Regents’ Professor, an honor bestowed by the Board of Regents of the University System of Georgia to distinguished faculty whose scholarship or creative activity is recognized both nationally and internationally as innovative and pace setting.
He joined the UGA faculty in 2001 and is a member of the university’s Center for Tropical and Emerging Global Diseases and its Faculty of Infectious Diseases. He earned his bachelor’s degree and Ph.D. from Texas A&M University and was a postdoctoral researcher at Imperial College London.
The National Academy of Sciences is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and-with the National Academy of Engineering and the National Academy of Medicine-provides science, engineering and health policy advice to the federal government and other organizations.
Writer: Sam Fahmy