Transmission and dose-response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens.
Transmission and dose-response experiments for social animals: a reappraisal of the colonization biology of Campylobacter jejuni in chickens.
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DOI：
10.1098/rsif.2011.0125
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发表时间：
2011-12-07
期刊：
影响因子：
--
通讯作者：
Maskell DJ
中科院分区：
文献类型：
--
作者：
Conlan AJ;Line JE;Hiett K;Coward C;Van Diemen PM;Stevens MP;Jones MA;Gog JR;Maskell DJ
剂量反应实验描述了传染因子与其宿主之间的关系。这些实验通常用于估计感染因子的最低有效感染剂量，其最常见的特征是50%的攻击宿主感染的剂量，即ID50。反过来，ID50常被用来比较不同的药物和量化治疗方案的效果。剂量-反应数据的统计分析通常假设给定剂量组内的宿主是独立的。对于群居动物，特别是鸟类，在实验研究中，宿主通常是成群居住在一起的。对于非传染性病原体的实验，这不会造成实际或理论上的问题。然而，合住动物之间传染因子的传播将改变所观察到的剂量-反应关系，这将影响ID50的估计以及不同因子和治疗之间的比较。我们对标准剂量-反应模型的似然进行了简单的修正，使我们能够同时估计剂量-反应和传输参数。我们使用这个模型来表明：同住动物之间的传播降低了ID50的表观值，并增加了重复之间的可变性，导致独特的全有或全无反应；就所使用的动物总数而言，个体住房始终是确定剂量-反应关系的最有效的实验设计；根据先前发表的实验数据对鸡体内弯曲杆菌传播的估计表明，发生了相当大的传播，这大大增加了文献中报告的剂量-反应参数估计的不确定性。此外，我们证明，在弯曲杆菌的剂量-反应数据分析中考虑传播挑战了我们目前对鸡对宿主年龄和细菌在体内传代的不同反应的理解。我们的研究结果表明，宿主之间传播的年龄依赖性——而不是它们对定植的易感性——是商业鸡群中“滞后期”背后的机制，这些鸡群通常在出生后的14-21天内没有弯曲杆菌。
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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