Non-invasive pneumococcal pneumonia due to vaccine serotypes: A systematic review and meta-analysis

Louise Lansbury; Benjamin Lim; Tricia M McKeever; Hannah Lawrence; Wei Shen Lim

doi:10.1016/j.eclinm.2022.101271

Non-invasive pneumococcal pneumonia due to vaccine serotypes: A systematic review and meta-analysis

EClinicalMedicine. 2022 Jan 24:44:101271. doi: 10.1016/j.eclinm.2022.101271. eCollection 2022 Feb.

Authors

Louise Lansbury^{1

2}, Benjamin Lim³, Tricia M McKeever^{1

2}, Hannah Lawrence^{1

2

4}, Wei Shen Lim^{2

4}

Affiliations

¹ Division of Epidemiology and Public Health, University of Nottingham, Nottingham, UK.
² National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, UK.
³ Faculty of Biology (School of Medicine), University of Cambridge, Cambridge, UK.
⁴ Department of Respiratory Medicine, Nottingham University Hospitals NHS Trust, Nottingham, UK.

Abstract

Background: Non-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform vaccination policies and the updating of pneumococcal vaccines.

Methods: We conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by pneumococcal vaccine serotypes. We searched MEDLINE, EMBASE and PubMed from 1 January 1990 to 30 March 2021. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRD42020192002).

Findings: Twenty-eight studies were included (34,216 patients). In the period 1-5 years after introduction of childhood PCV10/13 immunisation, 18% of CAP cases (95% CI 13-24%) were attributable to pneumococcus, with 49% (43-54%) of pneumococcal CAP due to PCV13 serotypes. The estimated proportion of pneumococcal CAP was highest in one study that used 24-valent serotype-specific urinary-antigen detection (ss-UAD)(30% [28-31%]), followed by studies based on diagnostic serology (28% [24-33%]), PCR (26% [15-37%]), ss-UAD14 (17% [13-22%]), and culture alone (14% [10-19%]). A higher estimate was observed in Europe (26% [21-30%] than North America (11% [9-12%](p<0·001). PCV13-serotype estimates were also influenced by serotyping methods.

Interpretation: Non-invasive pneumococcal CAP and vaccine-type pneumococcal CAP remains a burden in older adults despite widespread introduction of pneumococcal infant immunisation. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking.

Keywords: Older adults; Pneumococcal vaccines; Pneumonia; Serotype; Streptococcus pneumoniae.