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

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.

Figure 1

PRISMA flow diagram for study selection.

Figure 2

Forest plot of the pooled estimated proportion of CAP due to Streptococcus pneumoniae, stratified by the method of pneumococcal serotyping employed by included studies. Key: UAD24: 24-valent serotype-specific urinary antigen detection, UAD14: 14-valent serotype-specific urinary antigen detection, PCR: polymerase chain reaction (S. pneumoniae isolated by PCR with sequential multiplex PCR using 29 serotype specific primer pairs). Sensitivity analysis excluding 1 study (di Pasquale) considered to be at risk of some selection bias: UAD24: 30% (28–31), UAD14: 17% (13–22), Serology: 28% (24–33), PCR: 26% (15–37), Isolates: 13% (11–15), Overall I²=98.75%.

Figure 3

Estimated proportion CAP due to S. pneumoniae stratified by continent.

Figure 4

Estimated proportion of pneumococcal CAP due to PCV13 vaccine serotypes in the period after introduction of PCV10/13 immunisation programmes, stratified by the method of pneumococcal serotyping employed by included studies. Legend: Sensitivity analysis excluding 4 studies (Benfield, Horacio, Kim, Sando) considered to be at risk of some selection bias: UAD24: 37% (33–40), UAD14: 56% (49–63), PCR: 66% (53–77), Isolates: 54% (47–60), Overall I²=92.14%.