Validation of Quantitative Microbial Risk Assessment Using Epidemiological Data from Outbreaks of Waterborne Gastrointestinal Disease.

The assumptions underlying quantitative microbial risk assessment (QMRA) are simple and biologically plausible, but QMRA predictions have never been validated for many pathogens. The objective of this study was to validate QMRA predictions against epidemiological measurements from outbreaks of waterborne gastrointestinal disease. I screened 2,000 papers and identified 12 outbreaks with the necessary data: disease rates measured using epidemiological methods and pathogen concentrations measured in the source water. Eight of the 12 outbreaks were caused by Cryptosporidium, three by Giardia, and one by norovirus. Disease rates varied from 5.5 × 10 to 1.1 × 10 cases/person-day, and reported pathogen concentrations varied from 1.2 × 10 to 8.6 × 10 per liter. I used these concentrations with single-hit dose-response models for all three pathogens to conduct QMRA, producing both point and interval predictions of disease rates for each outbreak. Comparison of QMRA predictions to epidemiological measurements showed good agreement; interval predictions contained measured disease rates for 9 of 12 outbreaks, with point predictions off by factors of 1.0-120 (median = 4.8). Furthermore, 11 outbreaks occurred at mean doses of less than 1 pathogen per exposure. Measured disease rates for these outbreaks were clearly consistent with a single-hit model, and not with a "two-hit" threshold model. These results demonstrate the validity of QMRA for predicting disease rates due to Cryptosporidium and Giardia.