Development of an Interspecies Nested Dose-Response Model for Mycobacterium avium subspecies paratuberculosis

Mycobacterium avium subspecies paratuberculosis (MAP) causes chronic inflammation of the intestines in humans, ruminants, and other species. It is the causative agent of Johne's disease in cattle, and has been implicated as the causative agent of Crohn's disease in humans. To date, no quantitative microbial risk assessment (QMRA) for MAP utilizing a dose-response function exists. The objective of this study is to develop a nested dose-response model for infection from oral exposure to MAP utilizing data from the peer-reviewed literature. Four studies amenable to dose-response modeling were identified in the literature search and optimized to the one-parameter exponential or two-parameter beta-Poisson dose-response models. A nesting analysis was performed on all permutations of the candidate data sets to determine the acceptability of pooling data sets across host species. Three of four data sets exhibited goodness of fit to at least one model. All three data sets exhibited good fit to the beta-Poisson model, and one data set exhibited goodness of fit, and best fit, to the exponential model. Two data sets were successfully nested using the beta-Poisson model with parameters = 0.0978 and N-50 = 2.70 x 10(2) CFU. These data sets were derived from sheep and red deer host species, indicating successful interspecies nesting, and demonstrate the highly infective nature of MAP. The nested dose-response model described should be used for future QMRA research regarding oral exposure to MAP.