Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast relapsing strains in tropical areas, and slow relapsing strains in temperate areas with seasonal transmission. We hypothesise that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimise transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year round transmission, transmission potential is optimised at intermediate relapse frequencies of 2-3 months: slower relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be 6-9 months, coinciding with the duration between seasonal transmission peaks. We predict there is a threshold degree of seasonality, below which fast relapsing tropical strains are selected for, and above which slow relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.

间日疟原虫疟疾（Plasmodium vivax malaria）的复发频率存在显著差异：热带地区分布有速复发株，而存在季节性传播的温带地区则存在缓复发株。我们提出假说：间日疟原虫复发过程中的多数表型多样性，源于为优化特定环境下的传播潜力而进行的复发频率选择，这一过程与毒力权衡假说相似。我们构建了间日疟原虫传播的数学模型，并计算了基本再生数R₀，以此探究传播潜力如何随复发频率与季节性变化。在全年均存在传播的热带区域，传播潜力在2~3个月的中等复发频率下达到最优：缓复发株虽能提升向蚊媒进行后续传播的概率，却也会增加被速复发株竞争排除的风险。对于温带株而言，季节性是影响其复发频率的重要驱动因素，首次复发的预测时长为6~9个月，这与季节性传播高峰之间的间隔时长一致。我们预测存在一个季节性阈值：当季节性程度低于该阈值时，会倾向于选择速复发的热带株；当季节性程度高于该阈值时，缓复发的温带株将占据主导地位，这为已观测到的复发表型全球分布格局提供了解释。