Abstract
Dose response in micro-parasite infections is usually shallower than predicted by the independent action model, which assumes that each infectious unit has a probability of infection that is independent of the presence of other infectious units. Moreover, the prevalence of mixed-genotype infections was greater than predicted by this model. No probabilistic infection model has been proposed to account for the higher prevalence of mixed-genotype infections. We use model selection within a set of four alternative models to explain high prevalence of mixed-genotype infections in combination with a shallow dose response. These models contrast dependent versus independent action of micro-parasite infectious units, and homogeneous versus heterogeneous host susceptibility. We specifically consider a situation in which genome differences between genotypes are minimal, and highly unlikely to result in genotype-genotype interactions. Data on dose response and mixed-genotype infection prevalence were collected by challenging fifth instar Spodoptera exigua larvae with two genotypes of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV), differing only in a 100 bp PCR marker sequence. We show that an independent action model that includes heterogeneity in host susceptibility can explain both the shallow dose response and the high prevalence of mixed-genotype infections. Theoretical results indicate that variation in host susceptibility is inextricably linked to increased prevalence of mixed-genotype infections. We have shown, to our knowledge for the first time, how heterogeneity in host susceptibility affects mixed-genotype infection prevalence. No evidence was found that virions operate dependently. While it has been recognized that heterogeneity in host susceptibility must be included in models of micro-parasite transmission and epidemiology to account for dose response, here we show that heterogeneity in susceptibility is also a fundamental principle explaining patterns of pathogen genetic diversity among hosts in a population. This principle has potentially wide implications for the monitoring, modeling and management of infectious diseases.
Highlights
Models of micro-parasitic infection and transmission have been instrumental to the study of infectious disease dynamics [1,2]
Previous reports suggested that dose response in L5 larvae of this insect was shallow [13,42,43]. Confirming these previous reports, we found a dose response that was much shallower than predicted by a model based on independent action hypothesis (IAH) and fixed probability of infection among hosts
IAH was not supported in four out of six pathosystems tested, raising an intriguing question: how are a shallow dose response and a high frequency of mixed-genotype infection to be simultaneously explained in a single model? Here we examined the infection process of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) in S. exigua L5 in detail, and considered a number of models that could potentially describe the infection process when IAH fails
Summary
Models of micro-parasitic infection and transmission have been instrumental to the study of infectious disease dynamics [1,2]. A comparatively well tested aspect is how the rate of host infection is influenced by the density of infectious hosts [5,6], or the concentration of micro-parasite infectious units [7]. If it is known how the rate of host infection changes, it is possible to predict dynamic behavior with simple epidemiological models [1]. What is clear is that the data generally do not support simple model predictions for dose-response relationships [7,9,10,11,12,13]. It is not entirely clear what mechanisms are responsible for deviations from model predictions, but heterogeneity in host susceptibility to infection is often implicated as an explanatory factor
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