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Published on: February 23, 2014
Variation in pneumococcal invasiveness metrics is driven by serotype carriage duration and initial risk of disease
Benjamin J Metcalf1, Kristofer Wollein Waldetoft2, Bernard W Beall3
1School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia; Center for Microbial Dynamics and Infection, Georgia Institute of Technology, Atlanta, Georgia; Centers for Disease Control and Prevention, Atlanta, Georgia.
Abstract:
Streptococcus pneumoniae is an opportunistic pathogen that, while usually carried asymptomatically, can cause severe invasive diseases like meningitis and bacteremic pneumonia. A central goal in S. pneumoniae public health management is to identify which serotypes (immunologically distinct strains) pose the most risk of invasive disease. The most common invasiveness metrics use cross-sectional data (i.e., invasive odds ratios (IOR)), or longitudinal data (i.e., attack rates (AR)). To assess the reliability of these metrics we developed an epidemiological model of carriage and invasive disease. Our mathematical analyses illustrate qualitative failures with the IOR metric (e.g., IOR can decline with increasing invasiveness parameters). Fitting the model to both longitudinal and cross-sectional data, our analysis supports previous work indicating that invasion risk is maximal at or near time of colonization. This pattern of early invasive disease risk leads to substantial (up to 5-fold) biases when estimating underlying differences in invasiveness from IOR metrics, due to the impact of carriage duration on IOR. Together, these results raise serious concerns with the IOR metric as a basis for public health decision-making and lend support for multiple alternate metrics including AR.
Insights
This study reveals flaws in using invasive odds ratios (IOR) to measure Streptococcus pneumoniae invasiveness. Attack rates (AR) may be more reliable for public health decisions regarding disease risk from different serotypes.
Area of Science:
- Epidemiology
- Infectious Disease Modeling
- Public Health Microbiology
Background:
- Streptococcus pneumoniae causes invasive diseases like meningitis and pneumonia.
- Identifying high-risk serotypes is crucial for public health management.
- Current invasiveness metrics include invasive odds ratios (IOR) and attack rates (AR).
Purpose of the Study:
- To assess the reliability of IOR and AR metrics for estimating Streptococcus pneumoniae invasiveness.
- To develop an epidemiological model of carriage and invasive disease to evaluate metric performance.
- To identify potential biases in invasiveness estimations using IOR.
Main Methods:
- Developed a mathematical epidemiological model for S. pneumoniae carriage and invasive disease.
- Analyzed model behavior to identify metric failures, particularly with IOR.
- Fitted the model to both longitudinal and cross-sectional data.
Main Results:
- Mathematical analyses showed qualitative failures with the IOR metric, including declining values with increasing invasiveness.
- Invasive disease risk is highest around the time of colonization.
- IOR metrics can introduce substantial (up to 5-fold) biases in invasiveness estimation due to carriage duration.
Conclusions:
- The IOR metric has significant limitations and raises concerns for public health decision-making.
- Alternate metrics, such as attack rates (AR), are supported by the findings.
- Accurate assessment of serotype invasiveness is critical for effective public health strategies against S. pneumoniae.
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