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Mechanistic modeling of salmonellosis

机译：沙门氏菌病的机理建模

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The serious limitation of the available human data contributes to the need for making simplifying assumptions for dose-response modeling which has led to frequent use of a single function, the beta-Poisson function, as a default dose-response modelform. This function is a concave, low-dose linear function. Sub-linear or convex curves may be more appropriate for some host-pathogen interactions due to the series of highly regulated innate and acquired defense systems of the healthy human body that protect against most microbial challenges. A systematic investigation of the steps of non-typhoid salmonellosis in humans leads to biological motivations for sub-linear, or non-concave, dose-response curves in microbial risk assessment. Three phenomena were identified that might contribute to sub-linear, or non-concave, dose-response curves: (1) clumping of bacterial cells in microcolonies in a food matrix; (2) quorum sensing, or density-dependency in expression of virulence genes or other metabolic actions; and (3) need, at least in some circumstances, for multiple lesions for progression to symptomatic illness. This investigation suggests that microbial risk assessors should routinely employ a variety of model forms in addition to the commonly used beta-Poisson model to depict more fully the uncertainty of the "true" dose-response model.
机译：现有人类数据的严重局限性导致需要简化剂量反应模型的假设，从而导致频繁使用单一功能β-泊松功能作为默认的剂量反应模型形式。此函数是凹的低剂量线性函数。亚线性或凸曲线可能更适合某些宿主-病原体的相互作用，这是由于一系列健康人体健康的先天和后天防御系统可以抵御大多数微生物的挑战。对人类非伤寒沙门氏菌病步骤的系统研究导致了微生物风险评估中亚线性或非凹形剂量反应曲线的生物学动机。确定了可能导致亚线性或非凹形剂量反应曲线的三种现象：（1）食物基质中微菌落中的细菌细胞团块; （2）群体感应或毒力基因表达或其他代谢作用的密度依赖性; （3）至少在某些情况下，需要多个病变发展为有症状的疾病。这项研究表明，微生物风险评估人员除应使用常用的β-泊松模型外，还应常规采用多种模型形式，以更全面地描述“真实”剂量反应模型的不确定性。

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