Explaining unexplained diarrhea and associating risks and infections.

Gastrointestinal illnesses are common afflictions. However, knowledge of their etiology is often lacking. Moreover, most cases of infections with reportable enteric pathogens (Campylobacter jejuni, Escherichia coli O157:H7, Salmonella, Shigella, Yersinia, Cryptosporidia and Giardia) have sporadic modes of acquisition, yet control measures are often biased towards mitigation of risks discerned by outbreak analysis. To determine the etiology of unexplained diarrhea it is important to study populations that can be matched to appropriate controls and to couple thorough classic microbiologic evaluation on receipt of specimens with archiving and outgrowth capabilities. Research evaluations should address the potential roles of a broad panel of candidate bacterial pathogens including diarrheagenic E. coli, Listeria monocytogenes, Helicobacters and jejuni Campylobacters, and also apply novel massively parallel sequencing and nucleic acid detection technologies that allow the detection of viral pathogens. To fill voids in our knowledge regarding sources of known enteric pathogens it will be critical to extend case-control studies to assess risk factors and exposures to patients with non-epidemic illnesses and to appropriate controls. By filling these gaps in our knowledge it should be possible to formulate rational prevention mechanisms for human gastrointestinal illnesses.