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

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%](<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.