Drug Development Global Program

Why is malnutrition so hard to treat?

By William A. Petri, Jr., Chief, Division of Infectious Diseases & International Health, University of Virginia

Photo: William A. Petri, Jr.

Photo: William A. Petri, Jr.

For a number of years, I have worked with my colleague Rashidul Haque in Dhaka, Bangladesh, studying the health of infants in urban slums. There, we have studied the problems of infections, vaccine failures, and impaired growth and development. In this setting, a typical child is infected with four different enteric pathogens by the age of one month and sickened with three to four episodes of diarrhea. In the first year of life, a child will experience an equal number of acute respiratory infections.

One of the striking things to me has been the development of malnutrition in the children that we study. While only one in ten is born malnourished, nearly half are stunted (i.e., two standard deviations short for age, a measure of long-term malnutrition) by two years of age. A few years ago, one of my fellows, Cynthia Snider, suggested we intervene and treat this malnutrition, rather than observing from the sidelines. I agreed, and together with Rashidul, we instituted a program of supplemental feeding and nutritional counseling. Mothers and their malnourished children came into our clinic each morning where they were taught about nutrition and responsive feeding. In addition, the mothers gave their children complementary feedings with a rice and soy-based food containing vitamins and micronutrients. To our surprise, this approach resulted in almost zero impact. As I learned later, it was not that we were doing anything wrong; failure to respond is the rule and not the exception.

After spending a significant amount of time in the community and finding a poor response to nutritional interventions, we came to believe that damage to the intestine might be one explanation for the difficulty of stopping malnutrition and reversing its effects. The leaky, chronically inflamed, and poorly functioning gut of a child exposed to unsanitary living conditions and repeated bouts of infection, including diarrheal disease, has been called “environmental enteropathy,” or EE. First described in the Gambia more than 50 years ago, the small intestine in EE becomes inflamed due to a dysregulated inflammatory response to enteric infections, and develops blunted villi, making it difficult to absorb nutrients as they pass through the intestine.

“The image on the left (a) shows a healthy, normally functioning small intestine. In the image on the right (b), the small intestine has become inflamed, resulting in blunted villi and impaired nutrient absorption, a syndrome known as environmental enteropathy. Photos: Samuel Garcia.**”

The image on the left (a) shows a healthy, normally functioning small intestine. In the image on the right (b), the small intestine has become inflamed, resulting in blunted villi and impaired nutrient absorption, a syndrome known as environmental enteropathy. Photos: Samuel Garcia.1

EE is associated with malnutrition, failure of the polio and rotavirus vaccines, and poor language and cognitive development.2 My team and others have generated evidence showing that EE may be caused by gut infections, one of which is cryptosporidiosis. This suggests that cryptosporidia is important not only for the severe diarrhea that it causes, but also for potentially explaining why nutritional treatment has failed in the children in Dhaka. Understanding the problem is the first step to a solution, and we are greatly encouraged to see the scientific community coalescing behind efforts to develop new, effective treatment for this infection.

More information

 


1. Garcia S. Malabsorption and malnutrition in Mexico. The American Journal of Clinical Nutrition. 1968;21(9):1066–1076.
2. Naylor C, Lu M, Haque R, et al. Environmental enteropathy, oral vaccine failure and growth faltering in infants in Bangladesh. EBioMedicine. 2015;2(11):1759–1766.

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