The burden of PCV13 serotypes in hospitalized pneumococcal pneumonia in Spain using a novel urinary antigen detection test. CAPA study
Introduction
Pneumococcal disease in adults, including community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD), is a global health problem, mainly affecting individuals with chronic diseases such as COPD, diabetes mellitus and heart disease. The increased risk for pneumococcal pneumonia is present all year around [1] and the total disease burden comes mainly from non-invasive episodes, because IPD represents only a fraction [2].
There are more than 90 different pneumococcal serotypes showing diverse clinical expression, invasiveness and outcome. The distribution of circulating pneumococcal serotypes depends on several factors including the presence of underlying diseases, contact with children, and vaccination status, and changes over time making continuous monitoring necessary. Vaccinating children with the 7-valent pneumococcal conjugate vaccine (PCV7) achieved a reduction in adult invasive pneumococcal disease caused by serotypes included in the vaccine and a drift in others [3]. The impact that the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 for healthy children has had on the burden of pneumococcal pneumonia in adults due to PCV13 serotypes, particularly CAP without bacteraemia and CAP in high risk groups, is not well known [4]. Moreover, its indirect effect on pneumococcal pneumonia in adults is uncertain, although some impact has been found in the UK, where infant PCV coverage is around 95% [5]. In adults aged 65 and older, PCV13 has demonstrated efficacy in the prevention of pneumococcal pneumonia and invasive pneumococcal disease [6].
We hypothesized that the distribution of pneumococcal serotypes in adults, in both invasive and non-invasive pneumonia, might have changed after the introduction of PCV13 for children [7] and that this distribution may vary depending on the patients’ comorbidity and/or risk factors [8]. Given the fact that hospitalization for pneumonia is not decreasing [9] and that S. pneumoniae is the main causative microorganism, updated information will be a key factor for implementing effective strategies to decrease the incidence of CAP.
The aim of our study was to evaluate the burden of pneumococcal pneumonia in adults with regard to the distribution of PCV13 serotypes using the new UAD test in urine according to comorbidities and/or risk habits in immunocompetent patients after the introduction of PCV13 in children.
Section snippets
Patients and methods
A prospective multicentre epidemiological study was performed in three tertiary-care teaching hospitals from the National Spanish Health System, covering a population around 900.000 inhabitants (Hospital La Fe 285.000, Hospital Clinic 300.000, Hospital Galdakao 310.000) in immunocompetent adults aged ≥18 years, hospitalized during November 2011 to November 2014. Patients were considered to have CAP when they presented a new radiologic infiltrate accompanied by acute signs and symptoms suggestive
Results
A total of 1258 patients were recruited from November 2011 to November 2014 (Table 1). Microbiological aetiology was found in 573 patients (45.5%): 368 (29.3%) S. pneumoniae, 24 (1.9%) L. pneumophila, 19 (1.5%) Staphylococcus aureus, 21 (1.7%) Influenza virus, 12 (1.0%) other virus, and 129 (10.3%) others microorganisms (Fig. 1). Pneumococcal CAP was diagnosed in 368 patients. No significant changes were observed in the percentage of all-cause CAP due to S. pneumoniae during the three years of
Discussion
The most outstanding findings of our study are 1. More than 60% of pneumococcal CAP cases in immunocompetent adults were caused by PCV13 serotypes (74.6% in invasive episodes and 57.4% in non-invasive episodes) showing no significant changes from 2011 to 2014. 2. The most frequent serotypes in pneumococcal CAP were 3, 1, 7F and 19A. 3. The percentage of CAP caused by PCV13 serotypes varied slightly according to the presence of underlying conditions (from 49.2% in previous CAP to 64.9% in
Acknowledgements
Members of the CAPA study team are: A. Torres, C. Cilloniz, A. San José, F. Marco, E. Polverino, R. Amaro, (H. Clinic, Barcelona, Spain); R. Menéndez, R. Méndez, I. Amara, J.L. López Hontangas, B. Montull, A. Gimeno, A. Gil (H. Universitario y Politécnico La Fe, Valencia, Spain); PP. España, A. Uranga, A.P. Martínez de la Fuente, (H. Galdakao-Usansolo, Galdácano, Spain); E. Pérez-Trallero, J.M. Marimón, M. Ercibengoa (H. Universitario Donostia, San Sebastián, Spain); A. Fernández-Villar, M.I.
Funding
This study was sponsored by Pfizer.
Disclaimer
The views expressed in this publication are those of the author(s) and not necessarily those of the sponsor.
Competing interests
R.M., A. T., P.P. E. and E. P-T report grants to their Institutions from Pfizer S.L.U., Madrid, Spain, for this study, and support from Pfizer S.L.U. for travelling to meetings for the study or other purposes during the conduction of the study.
C.M., I.C., C.B., A.G., J.S. and M.L. S. are employees of Pfizer S.L.U., Madrid, Spain.
Ethics approval
The ethics committee of each hospital approved the study. Patients provided written informed consent to participate in the study.
References (35)
- et al.
Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study
Lancet Infect Dis
(2015) - et al.
Community acquired pneumonia. New guidelines of the Spanish Society of Chest Diseases and Thoracic Surgery (SEPAR)
Arch Bronconeumol
(2010) - et al.
Redefining risk categories for pneumococcal disease in adults: critical analysis of the evidence
Int J Infect Dis
(2015) - et al.
Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance
Lancet Infect Dis
(2015) - et al.
Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England
Vaccine
(2014) - et al.
Indirect effects of childhood pneumococcal conjugate vaccination on invasive pneumococcal disease: a systematic review and meta-analysis
Lancet Glob Heal
(2017) - et al.
Pulmonary complications of pneumococcal community-acquired pneumonia: incidence, predictors, and outcomes
Clin Microbiol Infect
(2012) - et al.
Which individuals are at increased risk of pneumococcal disease and why? Impact of COPD, asthma, smoking, diabetes, and/or chronic heart disease on community-acquired pneumonia and invasive pneumococcal disease
Thorax
(2015) - et al.
The role of Streptococcus pneumoniae in community-acquired pneumonia
Semin Respir Crit Care Med
(2016) - et al.
A systematic review of the burden of vaccine preventable pneumococcal disease in UK adults
BMC Pulm Med
(2016)
Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia
Eur Respir J
Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults
N Engl J Med
Pneumococci can persistently colonize adult patients with chronic respiratory disease
J Clin Microbiol
Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine
Clin Vaccine Immunol
Single-step multiplex PCR assay for determining 92 pneumococcal serotypes
J Clin Microbiol
Cited by (23)
Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay
2022, VaccineCitation Excerpt :Infections by Streptococcus pneumoniae (or pneumococcus) range from asymptomatic colonization [1] to potentially life-threatening diseases like invasive pneumococcal diseases (IPD) and pneumococcal community acquired pneumonia (pCAP) [2–24]. Both IPD and pCAP, whether bacteremic or non-bacteremic, are associated with high morbidity and mortality and have significant impacts on public health and healthcare resources worldwide [3–29]. Risk factors for serious outcomes in pCAP or IPD include individuals with underlying medical conditions and age (e.g. children<5 years or adults 65 + years) [9–24].
Non-invasive pneumococcal pneumonia due to vaccine serotypes: A systematic review and meta-analysis
2022, eClinicalMedicineCitation Excerpt :In the one study which utilised a 24-valent ss-UAD, the proportion of pneumococcal CAP due to PCV-13 serotypes was 37% (95% CI 33–40%).41 By continent, the highest proportion of pneumococcal CAP caused by PCV13 serotypes was noted when studies from North America were pooled, all of which employed ss-UAD14 (59%, 95% CI 47–71%, 4 studies, I2=95%),22,31,37,39 followed by Europe (48%, 95% CI 40–56%, 8 studies, I2=94·3%) for which serotyping methods varied between the included studies.15,24,28,30,33,38,41,43 The pooled estimate was lowest in studies from Asia, all of which were based on serotyping of pneumococcal isolates (41%, 95% CI 34–49%, 4 studies, I2=70·1%).26,27,29,35(Supplementary Figure 5)
Epidemiology of community-acquired pneumonia in the era of extended serotype-covering multivalent pneumococcal conjugate vaccines
2020, VaccineCitation Excerpt :Among PCV13 serotypes, serotypes 3 and 19A primarily contributed to the significant burden of pneumococcal CAP in Korean adults. Serotypes 3 and 19A remain as the prevalent serotypes of pneumococcal CAP worldwide, even after the introduction of PCV13 into childhood immunization programs [12,30-33]. Similar to South Korea, the US, UK, and Japan reported that serotypes 3 and 19A were the major pneumococcal pneumonia serotypes, even though PCV13 coverage has reached more than 90% in children [16].
Smoking Cessation/Vaccinations
2020, Clinics in Chest MedicineCommunity-Acquired Pneumonia. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) Guidelines. 2020 Update
2020, Archivos de BronconeumologiaPneumococcal conjugate serotype distribution and predominating role of serotype 3 in German adults with community-acquired pneumonia
2020, VaccineCitation Excerpt :When comparing the data of our previous analysis of the years 2002 to 2011 [10], the proportion of PCV13 coverage in patients with pneumococcal CAP identified by routine microbiological tests halved from 62.7% during the pre-PCV13 period 2002 to 2009 to 31.6% PCV13 coverage in the current study. This decrease is stronger compared to the Spanish CAPA study, where PCV13 serotypes still accounted for 60% of pneumococcal CAP between 2011 and 2014 [38]. However in our study, after 2014 we neither observed a further decrease of PCV13 serotypes (OR trend per year for 2013–2016: 0.84, 95% CI 0.64–1.11) nor of PCV13 serotypes without serotype 3 (OR trend per year for 2013–2016: 0.76, 95% CI 0.49–1.18).