|Line, John - Eric|
|Van Diemen, Pauline|
Submitted to: Journal of the Royal Society Interface
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/21/2011
Publication Date: 5/18/2010
Citation: Hiett, K.L., Line, J.E., Conlan, A.J., Coward, C., Van Diemen, P.M., Stevens, M.P., Jones, M.A. 2010. Transmission and dose–response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens. Journal of the Royal Society Interface. DOI: 10.1098/rsif.2011.0125. Interpretive Summary: Campylobacter spp. are one of the leading causes of human bacterial food-borne illness worldwide and are commensally associated with normal poultry gastrointestinal flora. In the US, retail chickens have contamination rates up to 60% - 80% with high bacterial counts for fresh chickens and even frozen chickens. The pathways involved in the colonization of poultry flocks remain unclear and these are hosts for the bacteria that are routinely housed together in groups. Dose-response studies are an essential method for the risk assessment of infectious agents and for characterizing the relative infectiousness of di'erent pathogens. For social animals, such as poultry, health and welfare regulations recommend that animals are housed in groups for experimental studies wherever possible. Group housing is considerably more practical and cheaper than individual housing, however it introduces the possibility that transmission can occur between co-housed hosts such as commercial poultry. Experiments were completed to determine if co-housed hosts such as chickens would reduce the amount of infectious bacteria that can commensally colonize chicken gastrointestinal systems and therefore increase contamination of poultry. It was demonstrated that transmission between co-housed birds reduces the apparent value of the infectious bacterial dose. Also, the age-dependence of transmissibility between birds, rather than their susceptibility to colonization, is the key mechanism driving the “lag-phase” reported in commercial 'ocks, which are typically found to be Campylobacter free for the 'rst 14-21 days of life.
Technical Abstract: Dose-response experiments characterize the relationship between infectious agents and their hosts. They are used to estimate the minimum e'ective infectious dose (ID50), compare between di'erent agents and quantify the e'ect 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 di'erent agents and treatments. We derive a simple correction to the likelihood for standard dose-response models which allows us to estimate dose-response and transmission parameters simultaneously, which we use 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 e'cient 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 from 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 di'ering response of chickens with respect to host-age and in vivo passage of bacteria. Our 'ndings suggest that the age-dependence of transmissibility between hosts, rather than their susceptibility to colonization, is the key mechanism driving the “lag-phase” reported in commercial 'ocks, which are typically found to be Campylobacter free for the 'rst 14-21 days of life.