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Transmission and dose–response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens

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  • A.J.K. Conlan
  • J.E. Line
  • K. Hiett
  • C. Coward
  • P.M. Van Diemen
  • M.P. Stevens
  • M.A. Jones
  • J.R. Gog
  • D.J. Maskell

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    Rights statement: Copyright 2011 The Royal Society

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http://rsif.royalsocietypublishing.org/content/8/65/1720.abstract
Original languageUndefined/Unknown
Pages (from-to)1720-1735
Number of pages16
JournalJournal of the Royal Society, Interface
Volume8
Issue number65
Publication statusPublished - 2011

Abstract

Dose–response experiments characterize the relationship between infectious agents and their hosts. These experiments are routinely used to estimate the minimum effective infectious dose for an infectious agent, which is most commonly characterized by the dose at which 50 per cent of challenged hosts become infected—the ID50. In turn, the ID50 is often used to compare between different agents and quantify the effect of treatment regimes. The statistical analysis of dose–response data typically makes the assumption that hosts within a given dose group are independent. For social animals, in particular avian species, hosts are routinely housed together in groups during experimental studies. For experiments with non-infectious agents, this poses no practical or theoretical problems. However, transmission of infectious agents between co-housed animals will modify the observed dose–response relationship with implications for the estimation of the ID50 and the comparison between different agents and treatments. We derive a simple correction to the likelihood for standard dose–response models that allows us to estimate dose–response and transmission parameters simultaneously. We use this model to show that: transmission between co-housed animals reduces the apparent value of the ID50 and increases the variability between replicates leading to a distinctive all-or-nothing response; in terms of the total number of animals used, individual housing is always the most efficient experimental design for ascertaining dose–response relationships; estimates of transmission from previously published experimental data for Campylobacter spp. in chickens suggest that considerable transmission occurred, greatly increasing the uncertainty in the estimates of dose–response parameters reported in the literature. Furthermore, we demonstrate that accounting for transmission in the analysis of dose–response data for Campylobacter spp. challenges our current understanding of the differing response of chickens with respect to host-age and in vivo passage of bacteria. Our findings suggest that the age-dependence of transmissibility between hosts—rather than their susceptibility to colonization—is the mechanism behind the ‘lag-phase’ reported in commercial flocks, which are typically found to be Campylobacter free for the first 14–21 days of life.

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