A meta-analysis of the effect of dose and age at exposure on shedding of Mycobacterium avium subspecies paratuberculosis (MAP) in experimentally infected calves and cows

A meta-analysis was performed using all published and one unpublished long-term infection-challenge experiments to quantify the age- and dose-dependence of early and late shedding of Mycobacterium avium subsp. paratuberculosis (MAP) in cattle. There were 194 animals from 17 studies that fulfilled the inclusion criteria, of which 173 received a known dose of MAP and 21 were exposed naturally. Results from parametric time-to-event models indicated that challenging older calves or using multiple-exposure experimental systems resulted in a smaller proportion and shorter duration of early shedding as well as slower transition to late shedding from latent compartments. Calves exposed naturally showed variable infection progression rates, not dissimilar to other infection routes. The log-normal distribution was most appropriate for modelling infection-progression events. The infection pattern revealed by the modelling allowed better understanding of low-grade endemicity of MAP in cattle, and the parameter estimates are the basis for future transmission dynamics modelling.