A mechanistic underpinning for sigmoid dose-dependent infection

Theoretical models of environmentally transmitted diseases often assume that transmission is a constant process, which scales linearly with pathogen dose. Here we question the applicability of such an assumption and propose a sigmoidal form for the pathogens infectivity response. In our formulation, this response arises under two assumptions: 1) multiple invasion events are required for a successful pathogen infection and 2) the host invasion state is reversible. The first assumption reduces pathogen infection rates at low pathogen doses, while the second assumption, due to host immune function, leads to a saturating infection rate at high doses. The derived pathogen dose:infection rate -relationship was tested against an experimental data on host mortality rates across different pathogen doses. Compared to two simpler alternatives, the sigmoidal function gave a better fit to patterns in host mortality rate (process), as well as host mortality (endpoint). Combining these alternative app...

环境传播疾病的理论模型通常假设传播过程为恒定过程，且与病原体剂量呈线性比例关系。本文对该假设的适用性提出质疑，并提出病原体感染性响应的S形曲线形式。在我们的建模框架中，该响应基于两项假设推导得出：1）成功的病原体感染需要多次入侵事件；2）宿主的入侵状态是可逆的。第一项假设会降低低病原体剂量下的感染速率，而第二项假设源于宿主免疫功能，会在高剂量下使感染速率趋于饱和。我们针对不同病原体剂量下的宿主死亡率实验数据，对推导得到的病原体剂量与感染速率的关系进行了验证。相较于两种更简化的备选模型，该S形函数能够更好地拟合宿主死亡率（过程层面）以及宿主死亡率（观测终点）的分布规律。结合这些备选的……