Comparative effectiveness of pneumococcal vaccination strategies to prevent invasive pneumococcal disease: a population-based cohort study at the veterans health administration in the United States

Shinya Hasegawa; Michael P Jones; Satoshi Kakiuchi; Eli N Perencevich; Michihiko Goto

doi:10.1016/j.cmi.2024.09.006

Comparative effectiveness of pneumococcal vaccination strategies to prevent invasive pneumococcal disease: a population-based cohort study at the veterans health administration in the United States

Clin Microbiol Infect. 2024 Sep 17:S1198-743X(24)00437-3. doi: 10.1016/j.cmi.2024.09.006. Online ahead of print.

Authors

Shinya Hasegawa¹, Michael P Jones², Satoshi Kakiuchi³, Eli N Perencevich⁴, Michihiko Goto⁵

Affiliations

¹ Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
² Center for Access and Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA; Department of Statistics and Actuarial Science, University of Iowa College of Liberal Arts and Science, Iowa City, IA, USA.
³ Infection Control and Education Center, Department of Internal Medicine, Nagasaki University Hospital, Nagasaki City, Nagasaki, Japan.
⁴ Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; Center for Access and Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA.
⁵ Department of Internal Medicine, University of Iowa, Iowa City, IA, USA; Center for Access and Delivery Research and Evaluation, Iowa City Veterans Affairs Health Care System, Iowa City, IA, USA. Electronic address: michihiko-goto@uiowa.edu.

PMID: 39299558
DOI: 10.1016/j.cmi.2024.09.006

Abstract

Objectives: Comparative effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent polysaccharide vaccine (PPSV23), and their combinations for adults in preventing invasive pneumococcal disease (IPD) has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing IPD, using population-based data from the Veterans Health Administration (VHA) in the United States.

Methods: We included all patients who were between 65 and 74 years, had established primary care within VHA between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrolment to the onset of IPD, considering death a competing risk event, and used Cox regression models to estimate cause-specific hazards. PCV13 only, PPSV23 only, PCV13 after PPSV23, and PPSV23 after PCV13 were incorporated into models as time-dependent covariates. Patient demographics and comorbidities were also included in the model.

Results: A total of 3 044 067 patients were enrolled in the cohort, with 863 958 deaths (28.4%) and 1731 cases of IPD (0.06%) during the study period. The overall incidence rate of IPD in this population was 5.36 per 100 000 patient-years. A total of 921 070 patients (30.3%) received at least one dose of effective pneumococcal vaccine. In multivariate analysis adjusted for comorbidities, PCV13 alone was not associated with the reduced risk of IPD, whereas PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.59-0.83). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR, 0.54; [0.36-0.83]) compared with PPSV23 followed by PCV13 (aHR, 0.73; [0.58-0.91]).

Discussion: In this large cohort study at the VHA, the combination of PCV13 and PPSV23, particularly PCV13 followed by PPSV23, was associated with a lower risk of IPD, indicating additional benefits in combined vaccinations with potential importance in vaccination order. Further studies are needed to evaluate the effect of newer pneumococcal vaccines.

Keywords: Cohort study; Comparative effectiveness; Invasive pneumococcal disease; Pneumococcal vaccine; Time-dependent cox.