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Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures

机译：一次或多次暴露后兔吸入性炭疽的剂量反应模型

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摘要

There is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous-Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose-response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively.
机译：有必要提高我们的能力，以表征低剂量暴露后吸入性炭疽的风险。最常考虑的暴露场景是攻击过程中发生的一次暴露。但是，长期每日低剂量暴露也代表了现实的暴露情况，例如，居住区域较长的人们可能遇到的情况。鉴于此，当前工作的目的是为两个兔子吸入性炭疽剂量反应数据集建模。一个数据集来自对气雾化的炭疽芽孢杆菌埃姆斯孢子的单次暴露。第二个数据集使兔子反复暴露于炭疽杆菌埃姆斯孢子的气溶胶中。对于多次暴露数据，将累积剂量（即各个日剂量的总和）用于模型。致命是双方的回应。使用Benchmark Dose软件评估了六个模型：对数概率，对数逻辑，Weibull，指数，γ和二分希尔。所有模型都针对任一数据集产生了可接受的拟合。指数模型被确定为这两个数据集的最佳拟合模型。统计测试表明，单次暴露指数模型结果与多次暴露指数模型结果之间没有显着差异，这表明两个数据集之间的疾病风险相似。对于单次暴露和多次暴露指数剂量反应模型，预期引起10％致死率的剂量分别为15600吸入孢子和18200吸入孢子，而95％较低的置信区间分别为9800吸入孢子和9200吸入孢子。

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  • 来源
    《Risk analysis》 |2016年第11期|2031-2038|共8页
  • 作者

    Gutting Bradford W.; Rukhin Andrey; Marchette David; Mackie Ryan S.; Thran Brandolyn;

  • 作者单位

    Naval Surface Warfare Ctr, CBR Concepts & Experimentat Branch B21, Dahlgren Div, Dahlgren, VA USA;

    Naval Surface Warfare Ctr, Sensor Fus Branch A43, Dahlgren Div, Dahlgren, VA USA;

    Naval Surface Warfare Ctr, Sensor Fus Branch A43, Dahlgren Div, Dahlgren, VA USA;

    Naval Surface Warfare Ctr, CBR Concepts & Experimentat Branch B21, Dahlgren Div, Dahlgren, VA USA;

    Army Publ Hlth Ctr Provis, Aberdeen Proving Ground, MD 21010 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    BMDS; dose response; inhalation anthrax; rabbit; risk assessment;

    机译：BMDS;剂量反应;吸入炭疽病;兔子;风险评估;

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