Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal illness in children and travelers in low- and middle-income countries. When volunteers are infected with ETEC strains, as part of experimental infection studies, some do not develop diarrhea. To improve our understanding of how these volunteers are protected, we investigated the association between stool ETEC DNA concentration, as determined by quantitative PCR, and the development and severity of disease in 21 volunteers who had been experimentally infected with ETEC strain TW10722. We found a strong association between maximum stool ETEC DNA concentration and the development of diarrhea: all of the 11 volunteers who did not develop diarrhea had <0.99% TW10722-specific DNA in their stools throughout the follow-up period of up to 9 days, while all of the 10 volunteers who did develop diarrhea had maximum DNA concentrations of ≥0.99%. Most likely, these maximum stool TW10722 DNA concentrations reflect the level of intestinal colonization and the risk of experiencing diarrhea, thereby, seems to be directly dependent on the level of colonization. Thus, the development and availability of vaccines and other prophylactic measures, even if they only partially reduce colonization, could be important in the effort to reduce the burden of ETEC diarrhea.
Keywords: controlled human infection model; diarrhea; enterotoxigenic Escherichia coli; experimental infection in humans; feces; heat-stable enterotoxin; quantitative PCR; small intestine; vaccine.