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Published on: April 6, 2015
Heterogeneous host susceptibility enhances prevalence of mixed-genotype micro-parasite infections
Wopke van der Werf1, Lia Hemerik, Just M Vlak
1Centre for Crop Systems Analysis, Wageningen University, Wageningen, The Netherlands.
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.
Insights
Host susceptibility variation explains shallow dose response and high mixed-genotype infections in micro-parasite studies. This finding impacts infectious disease modeling and management strategies.
Area of Science:
- * Ecology and Evolutionary Biology
- * Infectious Disease Epidemiology
- * Virology
Background:
- * Standard micro-parasite infection models often fail to predict observed shallow dose-response curves and higher-than-expected prevalence of mixed-genotype infections.
- * Existing models assume independent action of infectious units and homogeneous host susceptibility, which do not fully capture real-world infection dynamics.
- * A gap exists in probabilistic models explaining the simultaneous occurrence of shallow dose response and increased mixed-genotype infection prevalence.
Purpose of the Study:
- * To identify a probabilistic model that accurately explains both shallow dose response and high prevalence of mixed-genotype infections.
- * To investigate the roles of dependent versus independent action of infectious units and homogeneous versus heterogeneous host susceptibility.
- * To elucidate the impact of host susceptibility heterogeneity on mixed-genotype infection prevalence.
Main Methods:
- * Model selection was employed, comparing four alternative probabilistic models of micro-parasite infection.
- * Experimental data were generated by challenging Spodoptera exigua larvae with two genotypes of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV).
- * Infection dose-response and mixed-genotype prevalence were analyzed using the selected models.
Main Results:
- * An independent action model incorporating host susceptibility heterogeneity successfully explained both the shallow dose response and the high prevalence of mixed-genotype infections.
- * Theoretical analysis confirmed a strong link between host susceptibility variation and increased mixed-genotype infection prevalence.
- * No evidence supported dependent action of infectious units; virions appeared to act independently.
Conclusions:
- * Heterogeneity in host susceptibility is a critical factor driving both dose-response patterns and the prevalence of mixed-genotype infections.
- * This study demonstrates, for the first time, the specific influence of host susceptibility heterogeneity on mixed-genotype infection dynamics.
- * The findings underscore the importance of considering host heterogeneity in micro-parasite transmission models and have broad implications for infectious disease management.
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