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. MethodsWe 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.

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States

“…Nevertheless, the burden of non-IPD, particularly CAP, is substantial. A recent international meta-analysis estimated that in the period 1–5 years after introduction of PCV10/PCV13 vaccines, ∼18% of CAP continued to be due to pneumococcal disease; about half of the cases (49%) were associated with PCV13 serotypes [ 38 ]. In the United States, an estimated 569 260 cases of nonbacteremic CAP occur annually in adults ≥50 years of age, resulting in estimated medical and indirect costs of >$4 billion in 2013 US dollars [ 39 ].…”

Changes in serotype prevalence of Streptococcus pneumoniae in Southampton, UK between 2006 and 2018

“…In the UK serotype 3 still causes 9.4% of all age IPD, with 19A causing 5.6% and 7F causing 1.6%. The persistence of serotype 3 as a major cause of disease has been noted in many other countries as well 22 , 23 . Previous work has determined that both limited direct (immunological) protection from childhood immunisations with knock-on effects for herd immunity are the main causes 24 , 25 .…”

The Association Between Antihypertensive Drug Use and Hospitalization for Pneumonia in the General Population: A Case-Crossover Study Using the National Health Insurance Database of Korea

“… 32 33 Pathogens of community-acquired pneumonia, such as Streptococcus pneumoniae or Haemophilus influenza , are highly affected by vaccination and herd immunity. 34 Therefore, a lowered risk of pneumonia in the general population may result from an immunity preventive effect on a main pathogen rather than the impact of a specific antihypertensive drug. 35 …”