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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Repeated challenge with prion disease: The risk of infection and impact on incubation period
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Repeated challenge with prion disease: The risk of infection and impact on incubation period

机译：病毒疾病的反复挑战：感染的风险和潜伏期的影响

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Natural exposure to prion disease is likely to occur throughout successive challenges, yet most experiments focus on single large doses of infectious material. We analyze the results from an experiment in which rodents were exposed to multiple doses of feed contaminated with the scrapie agent. We formally define hypotheses for how the doses combine in terms of statistical models. The competing hypotheses are that only the total dose of infectivity is important (cumulative model), doses act independently, or a general alternative that interaction between successive doses occurs (to raise or lower the risk of infection). We provide sample size calculations to distinguish these hypotheses. In the experiment, a fixed total dose has a significantly reduced probability of causing infection if the material is presented as multiple challenges, and as the time between challenges lengthens. Incubation periods are shorter and less variable if all material is consumed on one occasion. We show that the probability of infection is inconsistent with the hypothesis that each dose acts as a cumulative or independent challenge. The incubation periods are inconsistent with the independence hypothesis. Thus, although a trend exists for the risk of infection with prion disease to increase with repeated doses, it does so to a lesser degree than is expected if challenges combine independently or in a cumulative manner. [References: 11]
机译：successive病毒的自然暴露很可能会在连续的挑战中发生，但是大多数实验都集中在单个大剂量的感染性物质上。我们分析了一个实验的结果，在该实验中，啮齿动物暴露于多剂量的被痒病菌污染的饲料中。我们根据统计学模型正式定义剂量组合的假设。相互竞争的假设是，只有总的传染性剂量才是重要的（累积模型），剂量是独立起作用的，或者是连续剂量之间发生相互作用（提高或降低感染风险）的一般选择。我们提供样本量计算以区分这些假设。在实验中，如果材料以多重挑战的形式出现，并且两次挑战之间的时间延长，那么固定的总剂量会大大降低引起感染的可能性。如果一次消耗掉所有物料，则孵化期较短且变化较小。我们表明感染的可能性与每个剂量充当累积或独立挑战的假设不一致。潜伏期与独立性假设不一致。因此，尽管存在随着重复剂量感染risk病毒疾病的风险增加的趋势，但是这种趋势的程度小于如果挑战独立地或以累积方式组合时所预期的程度。 [参考：11]

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