Antigenic Diversity, Transmission Mechanisms, and the Evolution of Pathogens

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Abstract
Pathogens have evolved diverse strategies to maximize their transmission fitness. Here we investigate these strategies for directly transmitted pathogens using mathematical models of disease pathogenesis and transmission, modeling fitness as a function of within- and between-host pathogen dynamics. The within-host model includes realistic constraints on pathogen replication via resource depletion and cross-immunity between pathogen strains. We find three distinct types of infection emerge as maxima in the fitness landscape, each characterized by particular within-host dynamics, host population contact network structure, and transmission mode. These three infection types are associated with distinct non-overlapping ranges of levels of antigenic diversity, and well-defined patterns of within-host dynamics and between-host transmissibility. Fitness, quantified by the basic reproduction number, also falls within distinct ranges for each infection type. Every type is optimal for certain contact structures over a range of contact rates. Sexually transmitted infections and childhood diseases are identified as exemplar types for low and high contact rates, respectively. This work generates a plausible mechanistic hypothesis for the observed tradeoff between pathogen transmissibility and antigenic diversity, and shows how different classes of pathogens arise evolutionarily as fitness optima for different contact network structures and host contact rates. Infectious diseases vary widely in how they affect those who get infected and how they are transmitted. As an example, the duration of a single infection can range from days to years, while transmission can occur via the respiratory route, water or sexual contact. Measles and HIV are contrasting examples—both are caused by RNA viruses, but one is a genetically diverse, lethal sexually transmitted infection (STI) while the other is a relatively mild respiratory childhood disease with low antigenic diversity. We investigate why the most transmissible respiratory diseases such as measles and rubella are antigenically static, meaning immunity is lifelong, while other diseases—such as influenza, or the sexually transmitted diseases—seem to trade transmissibility for the ability to generate multiple diverse strains so as to evade host immunity. We use mathematical models of disease progression and evolution within the infected host coupled with models of transmission between hosts to explore how transmission modes, host contact rates and network structure determine antigenic diversity, infectiousness and duration of infection. In doing so, we classify infections into three types—measles-like (high transmissibility, but antigenically static), flu-like (lower transmissibility, but more antigenically diverse), and STI-like (very antigenically diverse, long lived infection, but low overall transmissibility).