Available online 22 November 2023, 100731

Reliable metrics of pneumococcal serotype invasiveness are essential for research.

Invasive disease risk is maximal at or near time of colonization.

The invasive odds ratio (IOR) metric is confounded by serotype carriage duration.

The attack rate (AR) is robust to variation in carriage duration.

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.

Streptococcus pneumoniae

Invasive Disease

Virulence

Compartmental model

Carriage Duration

Published by Elsevier B.V.