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Updated: Jan 19, 2026

Author Spotlight: Advanced Enteroid Model for Studying Host-Pathogen Interactions
Published on: April 5, 2024
Inferring Pathogen Type Interactions Using Cross-sectional Prevalence Data: Opportunities and Pitfalls for Predicting
Irene Man1,2, Jacco Wallinga1,2, Johannes A Bogaards1,3
1From the Center for Infectious Diseases Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Background:
Many multivalent vaccines target only a subset of all pathogenic types. If vaccine and nonvaccine types compete, vaccination may lead to type replacement. The plausibility of type replacement has been assessed using the odds ratio (OR) of co-infections in cross-sectional prevalence data, with OR > 1 being interpreted as low risk of type replacement. The usefulness of the OR as a predictor for type replacement is debated, as it lacks a theoretical justification, and there is no framework explaining under which assumptions the OR predicts type replacement.
Methods:
We investigate the values that the OR can take based on deterministic S usceptible- I infected- S usceptible and S usceptible- Infected- Recovered- S usceptible multitype transmission models. We consider different mechanisms of type interactions and explore parameter values ranging from synergistic to competitive interactions.
Results:
We find that OR > 1 might mask competition because of confounding due to unobserved common risk factors and cross-immunity, as indicated by earlier studies. We prove mathematically that unobserved common risk factors lead to an elevation of the OR, and present an intuitive explanation why cross-immunity increases the OR. We find that OR < 1 is predictive for type replacement in the absence of immunity. With immunity, OR < 1 remains predictive under biologically reasonable assumptions of unidirectional interactions during infection, and an absence of immunity-induced synergism.
Conclusions:
Using the OR in cross-sectional data to predict type replacement is justified, but is only unambiguous under strict assumptions. An accurate prediction of type replacement requires pathogen-specific knowledge on common risk factors and cross-immunity.
Insights
The odds ratio (OR) can predict pathogen type replacement, but only under specific conditions. Factors like common risk factors and cross-immunity can complicate OR interpretation, necessitating pathogen-specific data for accurate predictions.
Area of Science:
- Epidemiology
- Mathematical Biology
- Infectious Disease Dynamics
Background:
- Multivalent vaccines may not cover all pathogenic types, potentially leading to type replacement if vaccine and non-vaccine types compete.
- The odds ratio (OR) is commonly used to assess type replacement risk from co-infection data, with OR > 1 suggesting low risk.
- The reliability of OR as a type replacement predictor is debated due to a lack of theoretical justification and clear assumptions.
Purpose of the Study:
- To investigate the behavior of the odds ratio (OR) in predicting pathogen type replacement.
- To determine the conditions under which the OR accurately reflects the risk of type replacement.
- To explore the influence of common risk factors and cross-immunity on OR values.
Main Methods:
- Utilized deterministic Susceptible-Infected-Susceptible (SIS) and Susceptible-Infected-Recovered-Susceptible (SIRS) multitype transmission models.
- Modeled various interaction mechanisms between pathogen types, from synergistic to competitive.
- Analyzed parameter ranges to understand OR behavior under different interaction scenarios.
Main Results:
- OR > 1 can mask competition due to confounding from unobserved common risk factors and cross-immunity.
- Mathematical proofs demonstrate that common risk factors elevate the OR, and cross-immunity intuitively increases it.
- OR < 1 predicts type replacement in the absence of immunity and remains predictive with immunity under specific biological assumptions.
Conclusions:
- Using the OR to predict type replacement from cross-sectional data is justified but requires strict assumptions.
- Accurate prediction of type replacement necessitates pathogen-specific knowledge regarding common risk factors and cross-immunity.
- The interpretation of OR values for type replacement risk is context-dependent and requires careful consideration of underlying epidemiological factors.
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