Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against vaccine serotype pneumococcal pneumonia in adults: A case-control test-negative design study.

BACKGROUND: Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is available in the United Kingdom to adults aged 65 years or older and those in defined clinical risk groups. We evaluated the vaccine effectiveness (VE) of PPV23 against vaccine-type pneumococcal pneumonia in a cohort of adults hospitalised with community-acquired pneumonia (CAP). METHODS AND FINDINGS: Using a case-control test-negative design, a secondary analysis of data was conducted from a prospective cohort study of adults (aged ≥16 years) with CAP hospitalised at 2 university teaching hospitals in Nottingham, England, from September 2013 to August 2018. The exposure of interest was PPV23 vaccination at any time point prior to the index admission. A case was defined as PPV23 serotype-specific pneumococcal pneumonia and a control as non-PPV23 serotype pneumococcal pneumonia or nonpneumococcal pneumonia. Pneumococcal serotypes were identified from urine samples using a multiplex immunoassay or from positive blood cultures. Multivariable logistic regression was used to derive adjusted odds of case status between vaccinated and unvaccinated individuals; VE estimates were calculated as (1 - odds ratio) × 100%. Of 2,357 patients, there were 717 PPV23 cases (48% vaccinated) and 1,640 controls (54.5% vaccinated). The adjusted VE (aVE) estimate against PPV23 serotype disease was 24% (95% CI 5%-40%, p = 0.02). Estimates were similar in analyses restricted to vaccine-eligible patients (n = 1,768, aVE 23%, 95% CI 1%-40%) and patients aged ≥65 years (n = 1,407, aVE 20%, 95% CI -5% to 40%), but not in patients aged ≥75 years (n = 905, aVE 5%, 95% CI -37% to 35%). The aVE estimate in relation to PPV23/non-13-valent pneumococcal conjugate vaccine (PCV13) serotype pneumonia (n = 417 cases, 43.7% vaccinated) was 29% (95% CI 6%-46%). Key limitations of this study are that, due to high vaccination rates, there was a lack of power to reject the null hypothesis of no vaccine effect, and that the study was not large enough to allow robust subgroup analysis in the older age groups. CONCLUSIONS: In the setting of an established national childhood PCV13 vaccination programme, PPV23 vaccination of clinical at-risk patient groups and adults aged ≥65 years provided moderate long-term protection against hospitalisation with PPV23 serotype pneumonia. These findings suggest that PPV23 vaccination may continue to have an important role in adult pneumococcal vaccine policy, including the possibility of revaccination of older adults.

Pneumococcal serotype trends, surveillance and risk factors in UK adult pneumonia, 2013-18.

BACKGROUND: Changes over the last 5 years (2013-18) in the serotypes implicated in adult pneumococcal pneumonia and the patient groups associated with vaccine-type disease are largely unknown. METHODS: We conducted a population-based prospective cohort study of adults admitted to two large university hospitals with community-acquired pneumonia (CAP) between September 2013 and August 2018. Pneumococcal serotypes were identified using a novel 24-valent urinary monoclonal antibody assay and from blood cultures. Trends in incidence rates were compared against national invasive pneumococcal disease (IPD) data. Persons at risk of vaccine-type pneumonia (pneumococcal conjugate vaccine (PCV)13 and pneumococcal polysaccharide vaccine (PPV)23) were determined from multivariate analyses. FINDINGS: Of 2934 adults hospitalised with CAP, 1075 (36.6%) had pneumococcal pneumonia. The annual incidence of pneumococcal pneumonia increased from 32.2 to 48.2 per 100 000 population (2013-18), predominantly due to increases in PCV13non7-serotype and non-vaccine type (NVT)-serotype pneumonia (annual incidence rate ratio 1.12, 95% CI 1.04 to 1.21 and 1.19, 95% CI 1.10 to 1.28, respectively). Incidence trends were broadly similar to IPD data. PCV13non7 (56.9% serotype 3) and PPV23non13 (44.1% serotype 8) serotypes were identified in 349 (32.5%) and 431 (40.1%) patients with pneumococcal pneumonia, respectively. PCV13-serotype pneumonia (dominated by serotype 3) was more likely in patients in the UK pneumococcal vaccination clinical risk group (adjusted OR (aOR) 1.73, 95% CI 1.31 to 2.28) while PPV23-serotype pneumonia was more likely in patients outside the clinical risk group (aOR 1.54, 95% CI 1.13 to 2.10). INTERPRETATION: The incidence of pneumococcal CAP is increasing, predominantly due to NVT serotypes and serotype 3. PPV23-serotype pneumonia is more likely in adults outside currently identified clinical risk groups.

Patient-reported outcome measures in the recovery of adults hospitalised with community-acquired pneumonia: a systematic review.

Symptomatic and functional recovery are important patient-reported outcome measures (PROMs) in community-acquired pneumonia (CAP) that are increasingly used as trial end-points. This systematic review summarises the literature on PROMs in CAP.Comprehensive searches in accordance with the PRISMA statement were conducted to March 2017. Eligible studies included adults discharged from hospital following confirmed CAP and reporting PROMs.15 studies (n=5644 patients) were included; most were of moderate quality. Studies used a wide range of PROMs and assessment tools. At 4-6 weeks post-discharge, the commonest symptom reported was fatigue (45.0-72.6% of patients, three studies), followed by cough (35.3-69.7%) and dyspnoea (34.2-67.1%); corresponding values from studies restricted by age <65 years (two studies) were lower: fatigue 12.1-25.7%, cough 19.9-31.9% and dyspnoea 16.8-27.5%. Functional impairment 4 weeks post-discharge was reported in 18-51% of patients (two studies), while median time to return to normal activities was between 15 and 28 days (three studies).Substantial morbidity is reported by patients up to 6 weeks post-discharge. There is weak methodological consistency across existing studies. A core set of PROMs for use in future studies is suggested.

Carriage of Streptococcus pneumoniae in adults hospitalised with community-acquired pneumonia.

OBJECTIVES: We aimed to determine the prevalence of and risk factors for nasopharyngeal and oral pneumococcal carriage in adults with community-acquired pneumonia (CAP), and the relationship between carried and disease-causing serotypes. METHODS: Between 2016 and 2018, nasopharyngeal swabs, oral-fluid, and urine were collected from hospitalised adults recruited into a prospective cohort study of CAP. Pneumococcal carriage was detected by semi-quantitative real-time PCR of direct and culture-enriched nasopharyngeal swabs and culture-enriched oral-fluid. LytA and piaB positive/indeterminate samples underwent semi-quantitative serotype/serogroup-specific real-time-PCR. Serotypes in urine were identified using a 24-valent serotype-specific urinary-antigen assay. RESULTS: We included 465 CAP patients. Nasopharyngeal carriage was detected in 34/103 (33.0%) swabbed pneumococcal pneumonia patients and oral carriage in 18/155 (12%) of sampled pneumococcal pneumonia patients. Concordance between nasopharyngeal/urine serotypes and oral/urine serotypes was 70.6% and 50% respectively. Serotypes 3 (26%, 22.2%), 8 (19.7%, 19.4%), non-typeable (11.6%, 13.9%) and 19A/F (7.5%, 8.3%) were most prevalent in urine and nasopharyngeal swabs respectively, with non-typeable (35%) and 15A/F (17%) most prevalent in oral-fluid. Pneumococcal carriage was significantly associated with pneumococcal pneumonia (nasopharyngeal adjusted odds ratio [aOR] 8.1, 95% confidence interval [CI] 3.8-17.2; oral aOR 5.5, 95% CI 2.1-13.3). All-cause CAP patients ≥65 years had lower odds of nasopharyngeal carriage (aOR 0.47, 95% CI 0.24-0.91) and current smokers had higher odds of oral carriage (aOR 2.69, 95% CI 1.10-6.60). CONCLUSIONS: The association between nasopharyngeal carriage and pneumococcal CAP was strong. Adult carriage and disease from serotypes 8 and 19A may support direct protection of adults with PCV vaccines.

Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018-20; a multicentre UK cohort study.

Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. Findings: Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients. Interpretation: Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. Funding: Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

The feasibility and tolerability of using inspiratory muscle training with adults discharged from the hospital with community-acquired pneumonia.

INTRODUCTION: Patients experience substantial morbidity following discharge from hospital and during recovery from communi-ty-acquired pneumonia (CAP). Inspiratory muscle training (IMT) has demonstrated improved functional capacity and reduced patient-reported symptoms. To date the safety and tolerability of these methods have not been determined in CAP patients recovering following hospitalization. Accordingly, this study aimed to assess the safety and tolerability of IMT in adults discharged from hospital with CAP. MATERIAL AND METHODS: Participants received an IMT device (POWERbreathe KHP2) and completed 9-weeks IMT training with weekly follow-up. Frequency (twice daily) and load (50% PImax) were fixed throughout, but training volume increased incrementally (2-week habituation phase, 7-week training phase). Primary outcomes of interest included IMT safety and tolerability. RESULTS: Twenty-two participants were recruited; 16 were male, mean age 55.2 years (range 27.9-77.3). From 1183 possible training days, side effects were reported on 15 occasions by 10 individual participants. All reported side-effects were assessed as grade 1 and did not prevent further training. Participant-reported IMT acceptability was 99.4%. CONCLUSION: Inspiratory muscle training is safe and tolerable in patients following hospitalisation for CAP. Patient satisfaction with IMT is high and it is viewed by patients as being helpful in their recovery. Distinguishing CAP-related symptoms and device-related side effects is challenging. Symptom prevalence declined during follow-up with concurrent improvements in spirometry observed. Further research is required to determine the efficacy of IMT interventions following CAP and other acute respiratory infections.