Go Natacha, Belloc Catherine, Bidot Caroline, Touzeau Suzanne
BIOEPAR, INRA, Oniris, LUNAM Université, Nantes, France.
MaIAGE, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
Math Med Biol. 2019 Jun 13;36(2):179-206. doi: 10.1093/imammb/dqy005.
Understanding the impact of pathogen exposure on the within-host dynamics and its outcome in terms of infectiousness is a key issue to better understand and control the infection spread. Most experimental and modelling studies tackling this issue looked at the impact of the exposure dose on the infection probability and pathogen load, very few on the within-host immune response. Our aim was to explore the impact on the within-host response not only of the exposure dose, but also of its duration and peak, for contrasted virulence levels. We used an integrative modelling approach of the within-host dynamics at the between-cell level. We focused on the porcine reproductive and respiratory syndrome virus, a major concern for the swine industry. We quantified the impact of exposure and virulence on the viral dynamics and immune response by global sensitivity analyses and descriptive statistics. We found that the area under the viral curve, an indicator of the infection severity, was fully determined by the exposure intensity. The infection duration increased with the strain virulence and, for a given strain, exhibited a positive linear correlation with the exposure intensity logarithm and the exposure duration. Taking into account the exposure intensity is hence necessary. Besides, representing the exposure due to contacts by a single punctual dose would tend to underestimate the infection duration. As the infection severity and duration both contribute to the pig infectiousness, a prolonged exposure of the adequate intensity would be recommended in an immuno-epidemiological context.
了解病原体暴露对宿主内动态变化及其传染性结果的影响，是更好地理解和控制感染传播的关键问题。大多数解决这一问题的实验和建模研究关注的是暴露剂量对感染概率和病原体载量的影响，而很少关注宿主内免疫反应。我们的目的是探讨不同毒力水平下，暴露剂量、暴露持续时间及其峰值对宿主内反应的影响。我们采用了细胞间水平的宿主内动态变化综合建模方法。我们聚焦于猪繁殖与呼吸综合征病毒，这是养猪业主要关注的问题。我们通过全局敏感性分析和描述性统计，量化了暴露和毒力对病毒动态变化和免疫反应的影响。我们发现，病毒曲线下面积作为感染严重程度的一个指标，完全由暴露强度决定。感染持续时间随毒株毒力增加，并且对于给定毒株，与暴露强度对数和暴露持续时间呈正线性相关。因此，考虑暴露强度是必要的。此外，用单次点状剂量表示接触引起的暴露往往会低估感染持续时间。由于感染严重程度和持续时间都影响猪的传染性，在免疫流行病学背景下，建议进行足够强度的长时间暴露。
