Proceedings of the 10th International Colloquium on Paratuberculosis

#149 A meta-analysis <strong>of</strong> <strong>the</strong> effect <strong>of</strong> dose and age-at-exposure on shedding <strong>of</strong> Mycobacterium
avium subspecies paratuberculosis (MAP) in experimentally infected calves and cows
Rebecca Mans Mitchell, Graham F Medley, Michael T Collins, Ynte H Schukken
College <strong>of</strong> Veterinary Medicine,Cornell University, USA; Department <strong>of</strong> Biological Sciences, University <strong>of</strong> Warwick,
United Kingdom; Department <strong>of</strong> Pathobiological Sciences, School <strong>of</strong> Veterinary Medicine, University <strong>of</strong> Wisconsin, USA
Calves artificially challenged with high doses <strong>of</strong> MAP bacteria have been reported to become infectious more
quickly relative to low-dose challenge infections. However, <strong>the</strong> relationship between dose <strong>of</strong> challenge and
speed <strong>of</strong> this progression has never been fully quantified. In ordinary differential equation (ODE)-based ma<strong>the</strong>matical
models <strong>of</strong> infectious dynamics within herds, it is common to assume a constant rate <strong>of</strong> exit from each
stage (compartment) <strong>of</strong> <strong>the</strong> infection process. Studies <strong>of</strong> properties <strong>of</strong> exit rate distributions indicated that <strong>the</strong>
nature and heterogeneity <strong>of</strong> infection progression are highly influential on infection dynamics and may impact
<strong>the</strong> efficacy <strong>of</strong> intervention strategies being evaluated.
In this research, a meta-analysis was performed using all published and one unpublished long-term
infection-challenge experiments to quantify <strong>the</strong> age- and dose-dependence <strong>of</strong> early and late shedding <strong>of</strong>
Mycobacterium avium subsp. paratuberculosis (MAP). Studies were included if sufficient experimental details
and sampling frequency were reported, resulting in 197 animals from 17 studies <strong>of</strong> which 176 were infected
with a known dose and 21 were exposed naturally. Parametric time-to-event models indicated that challenging
calves at a younger age and with a higher challenge dose resulted in faster transitions into shedding periods
and longer durations <strong>of</strong> shedding. Experimentally infected calves shed during two distinct phases, with an
Early Shedding stage within 12 months <strong>of</strong> infection, a Carrier period in which no bacteria can be cultured and
a subsequent Late Shedding stage. In <strong>the</strong> current analysis, <strong>the</strong> possibility that animals do not experience
Early Shedding but enter an Incubation period before Late Shedding is considered. The log-normal distribution
was <strong>the</strong> most appropriate underlying distribution for infection-progression events. Calves that were exposed
naturally showed variable progression rates, but not dissimilar to o<strong>the</strong>r infection routes.
We propose that <strong>the</strong> observed infection patterns allow better understanding <strong>of</strong> low-grade endemicity <strong>of</strong>
MAP in cattle. This work resulted in transition parameter estimates for future transmission dynamic modelling.
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