Major study evaluates use of antibiotics against diarrhea
Scientists at the University of Washington and Kenya Medical Research Institute are working to discern whether antibiotics could help prevent thousands of child deaths from diarrheal disease.
A four-year, $2.5 million grant from the World Health Organization is supporting UW's role in the largest clinical trial to date examining diarrhea-management. It aims to determine potential benefits of antibiotics as well as potential harms, such as antibiotic resistance.
Diarrhea remains a leading cause of death in children, mostly affecting children under 2 years in sub-Saharan Africa and Asia. More than a half-million children under 5 died from diarrheal disease in 2013, according the UW Institute for Health Metrics and Evaluation.
“That children continue to die from diarrhea is unacceptable,” said Patty Pavlinac, UW acting assistant professor of global health and one of the lead researchers. Although interventions have greatly reduced diarrhea deaths attributed to dehydration, "young children with bacterial causes of diarrhea experience other severe consequences, including malnutrition, gastrointestinal dysfunction, and death, which are unaddressed with existing interventions," she said.
The researchers hope to build on earlier findings that three of the four leading infectious causes of diarrhea may be treatable with antimicrobial agents. Specifically, a double-blind, placebo-controlled clinical trial will determine the ability of two antibiotics to reduce risk of death in children under 2 with diarrhea and dehydration or malnutrition.
Some 15,000 children will be enrolled at study sites in Kenya, Mali, Malawi, Tanzania, Bangladesh, India, and Pakistan. Each child will be randomly assigned to a three-day course of azithromycin, ciprofloxacin or a placebo. Patients will be followed for 90 days to assess risk of death or chronic malnutrition.
A subset of children will be followed for an additional three months, along with another child in their household, to monitor for development of antimicrobial resistance and to evaluate potential impact on their intestinal health.
The study's ambitious scope is designed to provide clear evidence for or against using antibiotics to treat diarrhea, in order to inform an update of WHO guidelines created more than 20 years ago. The current guidelines do not recommend antibiotics unless blood is present in the stool, an indicator for bacterial infection that misses a large number of treatable diarrhea cases.
Many experts have questioned why the guidelines do not recommend antibiotics as a common practice for treating high-risk children with diarrhea, especially when they are readily prescribed to healthy American travelers who have little to no risk of death from diarrhea.
Investigators from the University of Washington Center for Women, Children and Adolescent Health and Kenya Medical Research Institute will lead the Kenya field site of this multicountry trial under leadership of the WHO Maternal, Newborn, Child, & Adolescent Health Research and Development Team. Researchers also include Judd Walson, Benson Singa and Christine McGrath.