Date of Award

January 2026

Document Type

Open Access Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Inci Yildirim

Second Advisor

Daniel Weinberger

Abstract

AbstractBackground: Invasive pneumococcal disease (IPD) remains a significant cause of morbidity and mortality among children globally, despite the widespread use of protein conjugate vaccines (PCVs). While the introduction and implementation of these vaccines have drastically reduced the incidence of vaccine-type invasive disease, shifts in circulating serotypes raise concerns of serotype replacement. Methods: This study is a retrospective observational study of pediatric IPD cases in Massachusetts from 2002 – 2025. Over the course of these 23 years, the Massachusetts Department of Public Health has operated an enhanced population-based, statewide surveillance system for IPD. Isolates of Streptococcus pneumoniae from normally sterile sites were collected from incident cases. These samples were then serotyped and tested for antimicrobial susceptibility. The Massachusetts Department of Public Health then conducted interviews with caregivers and primary care providers of children with IPD to collect demographic and clinical data. Cases were stratified by vaccine eras (PCV7, PCV7 to PCV13 transition, PCV13, and PCV20). Analyses included incidence rates, serotype distribution, and clinical outcomes. Logistic regression models were used to assess associations between risk factors and outcomes, including hospitalization and mortality. PPSV23 vaccine effectiveness was estimated against non-PCV7, non-PCV13, and non-PCV20 serotypes using the indirect-cohort method for unadjusted estimates and logistic regression models for adjusted estimates. Comorbidities were defined as diseases that increase the risk for invasive pneumococcal disease (IPD) by U.S. Centers for Disease Control and Prevention (CDC) definitions.1 Results: Our analysis included a total of 1,491 instances of IPD across 23 years of observation. The overall incidence of IPD has decreased over time. An average incidence rate of 7.1 per 100,000 was estimated for the PCV7 era, which decreasing to 2.1 per 100,000 in the current PCV20 era. Shifts in serotype distribution were observed over time, with non-vaccine serotypes accounting for 10.8% of IPD cases during the PCV7 era and 33.3% during the PCV20 era. Children with comorbidities were found to have 50% greater odds with an odds ratio (OR) of 1.50 and a 95% confidence interval (95% CI) of 0.70 – 2.95 for mortality during IPD events compared to those without comorbidities. There was no difference in the odds of hospitalization between the two groups in our study (OR 1.00, 95% CI 0.76 – 1.33). PPSV23 demonstrated mixed effectiveness against non-PCV serotypes. Its effectiveness against non-PCV7 and non-PCV13 was limited, but against non-PCV20 a statistically significant VE of 79.0% was observed. There was no statistically significant difference between the VE of PPSV23 between children with and without comorbidities. Conclusions: In this analysis, a substantial shift was observed in serotype distributions among children with IPD in Massachusetts across the past 23 years. Non-vaccine serotypes now make up the majority of IPD cases in the present era. Despite the threat that serotype replacement poses, overall incidence rates of IPD have decreased substantially. In the present vaccine era (PCV20) children in Massachusetts face an average incidence rate of 2.1 per 100,000. Our results support the need for ongoing surveillance and evaluation of vaccine formulations to further reduce the burden of invasive pneumococcal disease.

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This is an Open Access Thesis.

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