Having defined the magnitude, major new etiologies, key novel mechanisms and short-term impact of persistent diarrheal illnesses and even certain "asymptomatic" enteric infections in a model collaboration and cohort of children born into active prospective surveillance in an urban shantytown in Northeast Brazil, we are now have a unique opportunity to define for the first time the long-term DALY (disability adjusted life years) impact of early childhood enteric infections on nutritional status defined by anthropometry, physical activity and fitness, and cognitive function over extended periods (even years later). We postulate, based on our short-term impact data, that the greatest long-term impact will occur in children with persistent diarrheal illnesses and in those with low height-for-age Z (HAZ) scores.
Having also shown the potential short-term benefits of a new glutamine-based oral rehydration and nutrition therapy (ORNT) and of vitamin A (with studies of zinc pending) on speeding the repair of damaged intestinal barrier function, we can now determine the potential long-term benefits of glutamine-based ORNT, with vitamin A and zinc therapy (targeting children with persistent diarrhea or reduced HAZ, as noted above). We shall also examine the intermediate (ie 1- 6 months) and long-term (greater than 6 months) effects of specific emerging enteric infections we have found to be important, enteroaggregative E. coli, and Cryptosporidium parvum. Coupled with our new developments of stable glutamine derivatives, the above data on full long-term DALY impact of persistent diarrhea, enteric infections and malnutrition, and the data on benefits of glutamine-based ORNT with vitamin A and zinc will ultimately allow us to calculate a much more meaningful cost-effectiveness (in "dollars per DALY averted) of selected treatment of high risk children (ie any with a persistent diarrheal illness that extends greater than 14 days, or a height for age Z score of less than 0.5). This model, longstanding collaboration and prospective field cohort surveillance will also enable the use of molecular tools currently being developed to define the epidemiology and microbiology of such newly recognized major agents as enteroaggregative E. coli as well as opening new opportunities to train both US and international scientists in highly relevant bench and field investigation. This pioneering work builds on our unique opportunity to define for the first time the potentially huge (developmental and economic) burden of early childhood enteric infections, as well as holding promise for demonstrating a key intervention targeted at the most vulnerable subset of the population in greatest need.