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In developing countries where diarrheal disease is a leading cause of morbidity and mortality in children under 5 years of age, enteric coinfection is common. There is little understanding, however, of the biologic interaction between coinfecting pathogens. The authors investigated the potential for synergistic interaction between coinfecting pathogens on diarrhea pathogenesis using an epidemiologic framework. They conducted community-based, case-control studies in 22 communities in northwestern Ecuador between 2003 and 2008. Risk ratios of diarrhea associated with single infections and coinfections were estimated. Interaction between coinfecting pathogens was assessed through departure from risk ratio additivity and multiplicativity after adjustment for age. On the additive scale, the authors found departure from the null value of 0 for rotavirus-Giardia coinfections (interaction contrast ratio = 8.0, 95% confidence interval: 3.1, 18.9) and for rotavirus-Escherichia coli coinfections (interaction contrast ratio = 9.9, 95% confidence interval: 2.6, 28.4). On the multiplicative scale, they found departure from the value of 1 for rotavirus-Giardia coinfections (multiplicative interaction = 3.6, 95% confidence interval: 1.3, 8.7). This research provides epidemiologic evidence for synergism between rotavirus and other enteric pathogens. During coinfection, the pathogenic potential of each organism appears to be enhanced. The potential for pathogenesis to be more severe in the presence of a rotavirus coinfection amplifies the need for rotavirus vaccination.

Synergistic Effects Between Rotavirus and Coinfecting Pathogens on Diarrheal Disease: Evidence from a Community-based Study in Northwestern Ecuador