Advanced survival models for risk-factor analysis in scrapie

Advanced survival models for risk-factor analysis in scrapie
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DOI:
10.1099/vir.0.81981-0
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发表时间:
2007-02-01
影响因子:
3.8
通讯作者:
Joly, Pierre
Joly, Pierre
中科院分区:
医学3区
文献类型:
--
作者:
Corbiere, Fabien;Barillet, Francis;Joly, Pierre

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由于长潜伏期和羊群管理的混杂效应,羊瘙痒病暴发的准确流行病学研究很难进行。在这项研究中,641 Manech红脸羊从6个羊瘙痒症影响的领域羊群在比利牛斯山脉,法国,监测临床羊瘙痒症超过6-9年的时间。在此期间,记录了170例羊瘙痒症临床病例,一半被淘汰的动物被提交进行死后传染性海绵状脑病诊断,以评估其感染状态。收集的数据进行了分析,使用“混合治愈模型”的方法,允许区分影响的PrP基因型和羊群起源的发病率和潜伏期。进行模拟以评估这种统计模型对所收集数据的适用性。正如预期的那样,ARR杂合子绵羊感染的风险低于ARQ/ARQ个体,并且临床发病年龄较大。相反,与ARQ/ARQ相比,VRQ单倍型与感染风险增加有关,但潜伏期不短。考虑到鸡群效应,我们观察到高发病率与较短的潜伏期无关,潜伏期在具有类似感染风险的鸡群中可能存在显著差异。这些结果有力地支持了这样的结论,即其他参数,如代理或羊群管理的性质,可能会干扰羊瘙痒病感染的羊群的流行病学动态。
Because of the confounding effects of long incubation duration and flock management, accurate epidemiological studies of scrapie outbreaks are difficult to carry out. In this study, 641 Manech red-faced sheep from six scrapie-affected field flocks in Pyrenees Atlantiques, France, were monitored for clinical scrapie over a 6-9 year period. Over this period, 170 scrapie clinical cases were recorded and half of the culled animals were submitted for post-mortem transmissible spongiform encephalopathy diagnosis to assess their infectious status. Collected data were analysed using a 'mixture cure model' approach, which allowed for the discriminating effect of PrP genotype and flock origin on incidence and incubation period. Simulations were performed to evaluate the applicability of such a statistical model to the collected data. As expected, ARR heterozygote sheep were less at risk of becoming infected than ARQ/ARQ individuals and had a greater age at clinical onset. Conversely, when compared with ARQ/ARQ, the VRQ haplotype was associated with an increased infection risk, but not a shorter incubation period. Considering the flock effect, we observed that a high incidence rate was not associated with shorter incubation periods and that the incubation period could be significantly different in flocks harbouring similar infection risks. These results strongly support the conclusion that other parameters, such as the nature of the agent or flock management, could interfere with epidemiological dynamics of the infection in scrapie-affected flocks.