Fan Ruili, Geritz Stefan A H
Department of Mathematics and Statistics, University of Helsinki, FIN-00014, Finland.
Department of Mathematics and Statistics, University of Helsinki, FIN-00014, Finland.
J Theor Biol. 2023 Sep 7;572:111575. doi: 10.1016/j.jtbi.2023.111575. Epub 2023 Jul 7.
Cross-immunity, as an evolutionary driver, can contribute to pathogen evolution, particularly pathogen diversity. Healthcare interventions aimed at reducing disease severity or transmission are commonly used to control diseases and can also induce pathogen evolution. Understanding pathogen evolution in the context of cross-immunity and healthcare interventions is crucial for infection control. This study starts by modelling cross-immunity, the extent of which is determined by strain traits and host characteristics. Given that all hosts have the same characteristics, full cross-immunity between residents and mutants occurs when mutation step sizes are small enough. Cross-immunity can be partial when the step size is large. The presence of partial cross-immunity reduces pathogen load and shortens the infectious period inside hosts, reducing transmission between hosts and improving host population survival and recovery. This study focuses on how pathogens evolve through small and large mutational steps and how healthcare interventions affect pathogen evolution. Using the theory of adaptive dynamics, we found that when mutational steps are small (only full cross-immunity is present), pathogen diversity cannot occur because it maximises the basic reproduction number. This results in intermediate values for both pathogen growth and clearance rates. However, when large mutational steps are allowed (with full and partial cross-immunity present), pathogens can evolve into multiple strains and induce pathogen diversity. The study also shows that different healthcare interventions can have varying effects on pathogen evolution. Generally, low levels of intervention are more likely to induce strain diversity, while high levels are more likely to result in strain reduction.
交叉免疫作为一种进化驱动力，可推动病原体进化，尤其是病原体多样性。旨在降低疾病严重程度或传播的医疗干预措施通常用于控制疾病，也可诱导病原体进化。在交叉免疫和医疗干预的背景下理解病原体进化对于感染控制至关重要。本研究首先对交叉免疫进行建模，其程度由菌株特征和宿主特性决定。假设所有宿主具有相同特征，当突变步长足够小时，宿主机体与突变体之间会出现完全交叉免疫。当步长较大时，交叉免疫可能是部分性的。部分交叉免疫的存在会降低病原体载量，缩短宿主体内的感染期，减少宿主间的传播，并提高宿主种群的存活率和恢复能力。本研究聚焦于病原体如何通过小的和大的突变步长进化，以及医疗干预如何影响病原体进化。利用适应性动力学理论，我们发现当突变步长较小时（仅存在完全交叉免疫），病原体多样性不会出现，因为这会使基本繁殖数最大化。这导致病原体生长率和清除率均处于中间值。然而，当允许较大的突变步长时（同时存在完全和部分交叉免疫），病原体可进化为多种菌株并诱导病原体多样性。该研究还表明，不同的医疗干预措施对病原体进化可能有不同影响。一般来说，低水平干预更有可能诱导菌株多样性，而高水平干预更有可能导致菌株减少。
