title: Transmission and dose-response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens.
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 ID(50). In turn, the ID(50) 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 ID(50) 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 ID(50) 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.
authors: Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, UK. a.j.k.conlan@damtp.cam.ac.uk
authors: Andrew J K
authors: AJ
authors: Conlan
authors: John E
authors: JE
authors: Line
authors: Kelli
authors: K
authors: Hiett
authors: Chris
authors: C
authors: Coward
authors: Pauline M
authors: PM
authors: Van Diemen
authors: Mark P
authors: MP
authors: Stevens
authors: Michael A
authors: MA
authors: Jones
authors: Julia R
authors: JR
authors: Gog
authors: Duncan J
authors: DJ
authors: Maskell
references: J R Soc Interface. 2007 Oct 22;4(16):819-29
references: 17472905
references: Nature. 2000 Feb 10;403(6770):665-8
references: 10688204
references: Risk Anal. 2006 Dec;26(6):1613-21
references: 17184401
references: J Gen Microbiol. 1957 Feb;16(1):38-58
references: 13406218
references: Appl Environ Microbiol. 2001 May;67(5):2388-92
references: 11319130
references: Bacteriol Rev. 1965 Mar;29:102-41
references: 14295982
references: Epidemiol Infect. 2002 Aug;129(1):147-53
references: 12211582
references: Vet Microbiol. 2003 Apr 2;92(3):225-35
references: 12523984
references: Infect Immun. 2004 Jul;72(7):3769-76
references: 15213117
references: Proc Biol Sci. 2009 Jun 22;276(1665):2233-42
references: 19324752
references: Epidemiol Infect. 2002 Apr;128(2):325-32
references: 12002551
references: J Hyg (Lond). 1958 Sep;56(3):323-46
references: 13587983
references: Appl Environ Microbiol. 2009 Feb;75(3):625-8
references: 19047389
references: Appl Environ Microbiol. 2003 Sep;69(9):5372-9
references: 12957925
references: Avian Dis. 1994 Apr-Jun;38(2):341-9
references: 7526839
references: J Vet Diagn Invest. 2009 Jul;21(4):437-45
references: 19564491
references: Avian Dis. 1999 Oct-Dec;43(4):763-7
references: 10611992
references: Appl Environ Microbiol. 2000 Jun;66(6):2536-40
references: 10831435
references: J Wildl Dis. 2007 Oct;43(4):660-7
references: 17984261
references: Avian Dis. 1990 Jul-Sep;34(3):595-601
references: 2241686
references: Risk Anal. 1999 Dec;19(6):1251-60
references: 10765461
references: Virology. 1962 Nov;18:477-85
references: 13960255
references: FEMS Immunol Med Microbiol. 2007 Feb;49(1):155-8
references: 17156078
references: Poult Sci. 2001 Feb;80(2):156-60
references: 11233003
references: J Hyg (Lond). 1954 Jun;52(2):189-93
references: 13174799
references: Risk Anal. 2000 Aug;20(4):513-20
references: 11051074
references: Appl Environ Microbiol. 2005 Oct;71(10):5765-70
references: 16204486
references: J Gen Microbiol. 1993 Jun;139 Pt 6:1171-5
references: 8360610
references: J Food Prot. 2008 Feb;71(2):264-70
references: 18326174
references: Nature. 1952 Aug 16;170(4320):288
references: 12993144
references: Appl Environ Microbiol. 2003 Aug;69(8):4343-51
references: 12902214
references: Am J Epidemiol. 1983 Oct;118(4):573-82
references: 6637984
references: Vet Microbiol. 2010 Jul 14;143(2-4):314-8
references: 20022713
references: Poult Sci. 2008 Sep;87(9):1700-6
references: 18753435
references: Poult Sci. 2006 Jul;85(7):1145-50
references: 16830853
references: Avian Dis. 1988 Apr-Jun;32(2):330-4
references: 3401176
references: Epidemiol Infect. 1996 Aug;117(1):213-5
references: 8760971
references: Appl Environ Microbiol. 2008 Sep;74(17):5408-13
references: 18641155
references: Rev Infect Dis. 1987 May-Jun;9(3):488-93
references: 3299635
references: Avian Dis. 1985 Apr-Jun;29(2):392-9
references: 4026733
references: Anim Health Res Rev. 2002 Dec;3(2):95-105
references: 12665109