Antigenic Diversity, Transmission Mechanisms, and the Evolution of Pathogens

Alexander Lange,Neil M Ferguson,Rustom Antia

doi:10.1371/journal.pcbi.1000536

Alexander Lange, Neil M Ferguson + Show 1 more

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https://doi.org/10.1371/journal.pcbi.1000536

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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.

Highlights

There are two major principles by which pathogens avoid their elimination: escaping the host immune response via antigenic variation or immune evasion, or transmission to a new immunologically naive host
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

Summary

Introduction

There are two major principles by which pathogens avoid their elimination: escaping the host immune response via antigenic variation or immune evasion, or transmission to a new immunologically naive host. Transmitted pathogens which cause chronic diseases, such as many sexually transmitted infections (STIs), tend to rely more on the former, while many acute infections, for instance measles, rely more on high transmissibility. Pathogens such as measles show very little antigenic diversity, with immune responses being strongly cross-reactive between strains. There are those pathogens which have intermediate levels of both immune escape and transmissibility — such as influenza, rhinovirus and RSV (here referred to as FLIs — flu-like infections). The relationship between so-called infection and transmission modes with respect to substitution rates of RNA viruses has been investigated in [5]

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