The Intestinal Pathobiome: Its Reality and Consequences Among Infants and Young Children in Resource-Limited Settings

The work by Taniuchi and colleagues at the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh and the University of Virginia, Charlottesville, presented in this issue of The Journal [1], is both significant and thought provoking. It complements the work of the Global Enterics Multi-Center Study (GEMS), an international consortium of sites using cutting-edge and traditional molecular and microbiological techniques to asses the burden and causative agents of intestinal infections among impoverished children in a number of locations around the world. Both the GEMS andTaniuchi et al have found a stark reality: it is “normal” to be able to detect a range of enteropathogens in the intestines of infants and young children in resource-limited settings, including those under surveillance with no evident diarrhea. This has advanced the concept of “enteropathogen excess” to ascribe etiology to specific episodes of diarrhea in these children. The work by Taniuchi et al advances this concept. Their team used a molecular diagnostic, quantitative polymerase chain reaction, multiplex approach targeting 32 potential enteropathogen gene targets. They performed this analysis at a community level, in an informal settlement area of Dhaka, Bangladesh, enrolling 147 infants in a birth cohort and following them up through 1 year of life, collecting surveillance as well as diarrhea-related stool samples. The results were striking. On average, these infants had approximately 4.7 episodes of diarrhea in their first year of life, or an episode of clinically apparent diarrhea approximately every 2.5 months. The mean duration of the episodes was 5.5 days, indicating that these infants had diarrhea for approximately 1 of their first 12 months of life. Detecting multiple pathogens in diarrheal stool samples was the norm, with a mean of 5.6 pathogens identified in each diarrheal sample. But perhaps the most striking finding, one that matches that seen by GEMS, was the detection of a mean of 4.3 enteropathogens in the surveillance stool samples collected from asymptomatic infants without diarrhea. Taniuchi et al found that this enteropathogenic burden was present and detectable within the first month of life and persisted throughout the year of observation of the birth cohort, necessitating the use of a “pathogen excess approach” to attempt to ascribe causative agents to a specific episode of diarrhea. They not only incorporated a concept of pathogen excess, but they also determined whether the pathogen was detected in the recent surveillance stool samples from the infant in question. Using this approach, they were able to whittle down the list of potential causative agents from >5 to approximately 3 for specific episodes of diarrhea. Looking at all diarrheal episodes, enteroaggregative Escherichia coli, Campylobacter, enteropathogenic E. coli, rotavirus, and Entamoeba histolytica were the most commonly identified probable contributors to diarrhea. When the authors considered only episodes of diarrhea that were moderate to severe, rotavirus, E. histolytica, and Cryptosporidium spp. rose to the top of the list. The team also performed a sobering comparison, performing a similar analysis on stool samples from of well infants in a Virginia daycare center, as well as in infants with diarrhea in Virginia. The norm in the United States was to be able to identify <1 enteropathogen in stool samples, including during diarrheal episodes. These results suggest that we need to revise how we conceptualize the enteropathogenic burden of infants in resourcelimited areas of the world. Depressingly, it seems “normal” to be able to detect many pathogens in the intestines of Received and accepted 11 June 2013; electronically published 16 September 2013. Correspondence: Edward T. Ryan, Massachusetts General Hospital, Division of Infectious Diseases, 55 Fruit St, Jackson 504, Boston, MA 02114 (etryan@partners.org). The Journal of Infectious Diseases 2013;208:1732–3 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/infdis/jit509