Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

BackgroundFew studies have measured the burden of community-acquired pneumonia (CAP) and pneumococcal vaccine-type CAP in Japan after the introduction of the 23-valent pneumococcal polysaccharide vaccine into the adult national immunization program (NIP) for individuals ≥ 65 years of age in 2014. In this study, we estimated the incidences of CAP and Streptococcus pneumoniae CAP among Japanese adults between 2015 and 2020.Research QuestionWhat are the incidences of CAP and S pneumoniae CAP among Japanese adults? What are the common pneumococcal serotypes detected in patients with S pneumoniae CAP?Study Design and MethodsThis prospective, population-based, multicenter, active surveillance study enrolled adults ≥ 18 years of age with clinically and radiologically confirmed CAP in Goto City, Japan. S pneumoniae was detected using standard-of-care blood and sputum cultures, BinaxNOW, and serotype-specific urinary antigen detection assays.ResultsA total of 2,103 patients with CAP were enrolled; 84% were ≥ 65 years of age and 6.7% died during the study. The annual CAP, S pneumoniae CAP, 13-valent pneumococcal conjugate vaccine (PCV13) serotype CAP, and 20-valent pneumococcal conjugate vaccine (PCV20) serotype CAP incidences per 100,000 population were 1,280, 227, 63, and 110, respectively. S pneumoniae was detected in 17.8% of all patients with CAP by any detection method, with 4.9%, 5.5%, and 8.6% of cases of CAP resulting from PCV13, 15-valent pneumococcal conjugate vaccine, and PCV20 serotypes, respectively. Applying Goto’s incidence and case fatality rate to the Japanese population, assuming PCV20 has the same vaccine efficacy and duration of protection as PCV13 and if licensed in Japan for the prevention of CAP, the inclusion of PCV20 in the NIP for adults ≥ 65 years of age could prevent 29,036 cases of CAP and 2,275 CAP-related deaths per year.InterpretationGiven the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Few studies have measured the burden of community-acquired pneumonia (CAP) and pneumococcal vaccine-type CAP in Japan after the introduction of the 23-valent pneumococcal polysaccharide vaccine into the adult national immunization program (NIP) for individuals ≥ 65 years of age in 2014. In this study, we estimated the incidences of CAP and Streptococcus pneumoniae CAP among Japanese adults between 2015 and 2020. What are the incidences of CAP and S pneumoniae CAP among Japanese adults? What are the common pneumococcal serotypes detected in patients with S pneumoniae CAP? This prospective, population-based, multicenter, active surveillance study enrolled adults ≥ 18 years of age with clinically and radiologically confirmed CAP in Goto City, Japan. S pneumoniae was detected using standard-of-care blood and sputum cultures, BinaxNOW, and serotype-specific urinary antigen detection assays. A total of 2,103 patients with CAP were enrolled; 84% were ≥ 65 years of age and 6.7% died during the study. The annual CAP, S pneumoniae CAP, 13-valent pneumococcal conjugate vaccine (PCV13) serotype CAP, and 20-valent pneumococcal conjugate vaccine (PCV20) serotype CAP incidences per 100,000 population were 1,280, 227, 63, and 110, respectively. S pneumoniae was detected in 17.8% of all patients with CAP by any detection method, with 4.9%, 5.5%, and 8.6% of cases of CAP resulting from PCV13, 15-valent pneumococcal conjugate vaccine, and PCV20 serotypes, respectively. Applying Goto’s incidence and case fatality rate to the Japanese population, assuming PCV20 has the same vaccine efficacy and duration of protection as PCV13 and if licensed in Japan for the prevention of CAP, the inclusion of PCV20 in the NIP for adults ≥ 65 years of age could prevent 29,036 cases of CAP and 2,275 CAP-related deaths per year. Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Take-home PointsStudy Question: What are the incidences of community-acquired pneumonia (CAP) and Streptococcus pneumoniae CAP among Japanese adults?Results: The annual incidences of CAP and S pneumoniae CAP were high in Goto City (1,280 and 227 cases per 100,000 population, respectively) and increased with age.Interpretation: Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Study Question: What are the incidences of community-acquired pneumonia (CAP) and Streptococcus pneumoniae CAP among Japanese adults? Results: The annual incidences of CAP and S pneumoniae CAP were high in Goto City (1,280 and 227 cases per 100,000 population, respectively) and increased with age. Interpretation: Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit. Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality. Age of 65 years of older and certain medical conditions are risk factors for CAP,1Torres A. Peetermans W.E. Viegi G. Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review.Thorax. 2013; 68: 1057-1065Crossref PubMed Scopus (406) Google Scholar and the incidence and mortality of CAP are highest among the elderly.2Ramirez J.A. Wiemken T.L. Peyrani P. et al.Adults hospitalized with pneumonia in the United States: incidence, epidemiology, and mortality.Clin Infect Dis. 2017; 65: 1806-1812Crossref PubMed Scopus (280) Google Scholar,3Theilacker C. Sprenger R. Leverkus F. et al.Population-based incidence and mortality of community-acquired pneumonia in Germany.PLoS One. 2021; 16e0253118Crossref Scopus (15) Google Scholar With 28.7% of the Japanese population being 65 years of age or older, pneumonia was ranked the fifth leading cause of death in 2019 (77.2 deaths per 100,000 population).4Dunne E.M. Cilloniz C. von Mollendorf C. et al.Pneumococcal vaccination in adults: what can we learn from observational studies that evaluated PCV13 and PPV23 effectiveness in the same population?.Archivos de Bronconeumología. 2023; Crossref Scopus (0) Google Scholar Because Japan has become the first super-aged society in the world,5D’Ambrogio E. Japan’s aging society. European Parliament website.https://www.europarl.europa.eu/RegData/etudes/BRIE/2020/659419/EPRS_BRI(2020)659419_EN.pdfDate accessed: September 16, 2022Google Scholar the burden of pneumonia is expected only to increase. Streptococcus pneumoniae is a leading cause of bacterial CAP. However, the use of pneumococcal conjugate vaccine (PCV) has reduced the proportion of disease attributed to S pneumoniae in children and adults.6Moore M.R. Link-Gelles R. Schaffner W. 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; 15: 301-309Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar,7Sherwin R.L. Gray S. Alexander R. et al.Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae serotypes in US adults aged ≥50 years with community-acquired pneumonia.J Infect Dis. 2013; 208: 1813-1820Crossref PubMed Scopus (0) Google Scholar In June 2010, a 7-valent PCV was introduced into the national immunization program (NIP) for children in Japan, replaced by a 13-valent PCV (PCV13) in 2013.8Yanagihara K. Kosai K. Mikamo H. et al.Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan.Int J Infect Dis. 2021; 102: 260-268Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar PCV13 coverage in Japanese children is high (> 95%), and a substantial decline (45%) in the CAP hospitalization rate has been observed among children younger than 5 years.9Takeuchi N. Naito S. Ohkusu M. et al.Epidemiology of hospitalised paediatric community-acquired pneumonia and bacterial pneumonia following the introduction of 13-valent pneumococcal conjugate vaccine in the national immunisation programme in Japan.Epidemiol Infect. 2020; 148: e91Crossref PubMed Scopus (16) Google Scholar Currently, two pneumococcal vaccines are available in Japan for adults. The 23-valent pneumococcal polysaccharide vaccine (PPSV23) was introduced into the adult NIP in October 2014 for adults ≥ 65 years of age and for adults 60 to 64 years of age with certain medical conditions.8Yanagihara K. Kosai K. Mikamo H. et al.Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae associated with invasive pneumococcal disease among adults in Japan.Int J Infect Dis. 2021; 102: 260-268Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar The cumulative vaccination rate of PPSV23 among adults ≥ 65 years of age was 74% at the end of 2018.10Naito T. Suzuki M. Fujibayashi K. et al.The estimated impact of the 5-year national vaccination program on the trend of 23-valent pneumococcal polysaccharide vaccine vaccination rates in the elderly in Japan, 2009-2018.J Infect Chemother. 2020; 26: 407-410Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar In 2014, PCV13 was approved in adults ≥ 65 years of age in Japan, and in 2020, this approval was extended to include individuals 6 to 64 years of age with underlying medical conditions. However, PCV13 is not included in the adult NIP in Japan.11Fukusumi M. Chang B. Tanabe Y. et al.Invasive pneumococcal disease among adults in Japan, April 2013 to March 2015: disease characteristics and serotype distribution.BMC Infect Dis. 2017; 17: 2Crossref PubMed Scopus (37) Google Scholar Recently, higher-valent PCVs—15-valent PCV (including PCV13 serotypes plus serotypes 22F and 33F; Merck & Co., Inc.) and 20-valent PCV (PCV20; including PCV13 serotypes and seven additional serotypes: 8, 10A, 11A, 12F, 15B, 22F, and 33F; Pfizer, Inc.)—have been licensed by the US Food and Drug Administration and European Medicines Agency for use in adults ≥ 18 years of age12Committee for Medicinal Products for Human Use, European Medicines AgencySummary of opinion (initial authorisation): Apexxnar. European Medicines Agency website.https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-apexxnar_en.pdfDate accessed: September 16, 2022Google Scholar, 13Committee for Medicinal Products for Human Use, European Medicines AgencySummary of opinion (initial authorisation): Vaxneuvance. European Medicines Agency website.https://www.ema.europa.eu/en/documents/smop-initial/chmp-summary-positive-opinion-vaxneuvance_en.pdfDate accessed: September 16, 2022Google Scholar, 14Kobayashi M. Farrar J.L. Gierke R. et al.Use of 15-valent pneumococcal conjugate vaccine and 20-valent pneumococcal conjugate vaccine among U.S. adults: updated recommendations of the Advisory Committee on Immunization Practices - United States, 2022.MMWR Morb Mortal Wkly Rep. 2022; 71: 109-117Crossref PubMed Scopus (87) Google Scholar and are undergoing clinical evaluations in Japan. In an aging society like Japan, it is important to understand the burden of CAP in adults and the degree to which CAP may be prevented with the current and next-generation pneumococcal vaccines. However, while studies have been conducted measuring the burden of CAP and vaccine-type (VT) CAP in Japan, the most comprehensive data were obtained between 2011 and 2013,15Morimoto K. Suzuki M. Ishifuji T. et al.The burden and etiology of community-onset pneumonia in the aging Japanese population: a multicenter prospective study.PLoS One. 2015; 10e0122247Crossref Scopus (128) Google Scholar which was before PPSV23 introduction into the NIP for older adults in 2014. Herein, we present the results from a population-based CAP incidence study among adults in Goto City, Japan, between 2015 and 2020. Although the population aging rate (≥ 65 years) in Goto City (36.8% in 2015) was higher than that in Japan as a whole (29.1% in 2021),16Statistics Bureau of JapanPopulation estimates. Statistics Bureau of Japan website.https://www.stat.go.jp/english/index.htmlDate accessed: January 18, 2023Google Scholar Goto City is epidemiologically similar to Japan as whole. Therefore, the findings in this study are generalizable to Japan. This was a prospective, multicenter, active-surveillance, population-based incidence study. Residents ≥ 18 years of age in Goto City, Japan, with suspected CAP were screened at all hospitals and outpatient clinics. Goto City is located in the southwest part of Japan, encompassing 11 inhabited islands. Of the 39,808 inhabitants, 85% are ≥ 18 years of age.17Glick H.A. Miyazaki T. Hirano K. et al.One-year quality of life post-pneumonia diagnosis in Japanese adults.Clin Infect Dis. 2021; 73: 283-290Crossref Scopus (11) Google Scholar Study participants were recruited between December 2015 and November 2020. All health-care facilities in Goto City, including four hospitals and 25 outpatient clinics, were include in the study. The study was approved by the ethics review committees and was registered in the University Hospital Medical Information Network (registration ID: [removed]). Patients signed the written informed consent before enrollment. All patients who sought treatment at the participating health-care facilities and demonstrated signs, symptoms, and radiographic evidence of pneumonia were screened for inclusion. To be included, patients: (1) had to be ≥ 18 years of age; (2) had to be a resident of Goto City; (3) had to have a diagnosis of pneumonia based on the presence of two or more of the signs and symptoms of cough; purulent sputum; fever (axillary temperature ≥ 37° C); dyspnea, tachypnea, or both; WBC count of > 10,000/mm3 or > 15% bands or WBC count of < 4,500/mm3; elevated C-reactive protein (CRP) level; hypoxemia; or abnormal auscultatory findings suggestive of pneumonia; (4) had to show a pneumonia pattern (eg, alveolar infiltrative shadow associated with air bronchogram) on chest radiography or chest CT scan imaging; and (5) had to be willing and able to provide a urine sample. Patients were excluded if: (1) they were transferred to a participating health-care facility after having been hospitalized for ≥ 48 h at another hospital. (2) they had hospital-acquired pneumonia (ie, pneumonia developed ≥ 48 h after hospitalization), (3) they had received PPSV23 or PCV13 within the past 30 days (because vaccine receipt may cause false-positive urinary antigen detection [UAD] results), or (4) they had been enrolled previously in the study within the past 30 days. For patients who were eligible for the study, demographics, medical history, pneumococcal vaccination history within the last 5 years, pneumonia severity on admission, and clinical outcomes were collected. Patients were followed for up to 30 days after enrollment. The pneumococcal vaccination history was confined to 5 years because PPSV23 was introduced into the adult NIP in 2014 and the study participants were recruited between 2015 and 2020. Further, only a small proportion of participants had received PCV13. Therefore, confining pneumococcal vaccination history to the previous 5 years should have provided a reasonable coverage estimate. The risk status of participants (high risk, at risk, and low risk) was determined based on the presence of certain medical conditions (based on Shea et al18Shea K.M. Edelsberg J. Weycker D. Farkouh R.A. Strutton D.R. Pelton S.I. Rates of pneumococcal disease in adults with chronic medical conditions.Open Forum Infect Dis. 2014; 1: ofu024Crossref PubMed Google Scholar and on the US Advisory Committee on Immunization Practices guidelines) (e-Table 1). Sputum and specimens from normally sterile sites were collected as part of standard-of-care practice and underwent culture at Goto Central Hospital Laboratory. S pneumoniae isolates then were sent to the German National Reference Center for Streptococci for confirmatory testing and serotyping using the Quellung reaction. Urine samples were collected as a study-related procedure for BinaxNOW S pneumoniae antigen card, and UAD assays were performed at Pfizer’s Vaccines Research and Development Laboratory. The UAD assays are multiplex immunoassays based on the Luminex technology. By capturing serotype-specific S pneumoniae polysaccharides secreted in human urine, the UAD assays simultaneously can detect multiple S pneumoniae serotypes.19Kalina W.V. Souza V. Wu K. et al.Qualification and clinical validation of an immunodiagnostic assay for detecting 11 additional Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Infect Dis. 2020; 71: e430-e438Google Scholar,20Pride M.W. Huijts S.M. Wu K. et al.Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Vaccine Immunol. 2012; 19: 1131-1141Crossref PubMed Scopus (87) Google Scholar The UAD 1 assay detects all 13 serotypes contained in PCV13 (1, 3, 4, 5, 6A/C, 6B, 7F/A, 9V/A, 14, 18C/A/B/F, 19A, 19F, and 23F), and the UAD 2 assay detects 11 additional serotypes (2, 8, 9N, 10A/39, 11A/D/F, 12F, 15B/C, 17F/A, 20A/B, 22F/A, and 33F/A). The UAD 1 and 2 assays and corresponding positivity cutoff values were validated clinically, demonstrating high sensitivity and specificity against urine specimens obtained from patients with radiography-confirmed bacteremic CAP.19Kalina W.V. Souza V. Wu K. et al.Qualification and clinical validation of an immunodiagnostic assay for detecting 11 additional Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Infect Dis. 2020; 71: e430-e438Google Scholar,20Pride M.W. Huijts S.M. Wu K. et al.Validation of an immunodiagnostic assay for detection of 13 Streptococcus pneumoniae serotype-specific polysaccharides in human urine.Clin Vaccine Immunol. 2012; 19: 1131-1141Crossref PubMed Scopus (87) Google Scholar However, the sensitivity and specificity for nonbacteremic CAP have not been determined because of a lack of a reference standard for this outcome. A patient was defined as having CAP if the patient met all the eligibility criteria described previously, was defined as having pneumococcal CAP if the patient had CAP and showed positive culture results for S pneumoniae (including sputum) or BinaxNOW or UAD assay test positive results and was defined as having PCV13 VT CAP or PCV20 VT CAP if the patient had pneumococcal CAP with one of the PCV13 serotypes or PCV20 serotypes detected by culture (including sputum) or the UAD assays. Descriptive statistical analysis was performed. Continuous variables were summarized as mean ± SD, medians, and minimum and maximum values, and a difference in two means and its CI were evaluated by the two-sample t test. Categorical variables were described as frequencies and percentages, and a difference in two proportions and its CI were evaluated by z test based on the binomial theory. Incidences of CAP, pneumococcal CAP, PCV13 VT CAP, and PCV20 VT CAP were calculated with the numerators based on the number of cases and denominators using age-specific population data of Goto City.21McLaughlin J.M. Jiang Q. Gessner B.D. et al.Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: a systematic review and pooled analysis.Vaccine. 2019; 37: 6310-6316Crossref Scopus (31) Google Scholar Incidence per 100,000 population was shown by age group (18-64 years, 65-79 years, and ≥ 80 years) and by study year (2015 through 2020). For estimating the effect of introducing PCV20 into the adult NIP in Japan, we assumed PCV20 vaccine efficacy (VE) to be the same as that of PCV13 VE, which is 45.56% for the prevention of first episodes of vaccine-type CAP in adults ≥ 65 years of age, as demonstrated in the CAPiTA study.22Bonten M.J. Huijts S.M. Bolkenbaas M. et al.Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.N Engl J Med. 2015; 372: 1114-1125Crossref PubMed Scopus (836) Google Scholar This assumption was made because PCV20 is built on the manufacturing platform successfully established by PCV13 and the immune responses to PCV20 in adults have been noninferior to PCV13.23Essink B. Sabharwal C. Cannon K. et al.Pivotal phase 3 randomized clinical trial of the safety, tolerability, and immunogenicity of 20-valent pneumococcal conjugate vaccine in adults aged ≥18 years.Clin Infect Dis. 2022; 75: 390-398Crossref PubMed Scopus (0) Google Scholar To calculate CAP cases preventable by PCV20, the PCV20 VT CAP annual incidence rate from Goto City was multiplied by Japan’s population to obtain annual PCV20 VT CAP cases among adults ≥ 65 years of age. Then the annual PCV20 VT CAP cases were multiplied by PCV20 VE of 45.56% to arrive at the number of cases per year preventable by PCV20. To calculate CAP-related deaths preventable by PCV20, the annual all-cause CAP death rate from Goto City was multiplied by Japan’s population to obtain annual all-cause CAP deaths among adults ≥ 65 years of age. Then, the annual all-cause CAP deaths were multiplied by the proportion of CAP cases caused by PCV20 serotypes and PCV20 VE of 45.56% to arrive at CAP-related deaths per year preventable by PCV20. In Japan, the use of PCV13 in adults ≥ 65 years of age is extremely low, and recent evidence supports limited protection against nonbacteremic pneumonia (which makes up by far most cases of pneumococcal pneumonia) in adults vaccinated with PPSV23.4Dunne E.M. Cilloniz C. von Mollendorf C. et al.Pneumococcal vaccination in adults: what can we learn from observational studies that evaluated PCV13 and PPV23 effectiveness in the same population?.Archivos de Bronconeumología. 2023; Crossref Scopus (0) Google Scholar,10Naito T. Suzuki M. Fujibayashi K. et al.The estimated impact of the 5-year national vaccination program on the trend of 23-valent pneumococcal polysaccharide vaccine vaccination rates in the elderly in Japan, 2009-2018.J Infect Chemother. 2020; 26: 407-410Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar Therefore, we expect prior vaccination with either PCV13 or PPSV23 to have little or no effect on the calculations of the potential benefit of PCV20 against pneumonia. Of 2,105 patients screened, 2,103 patients were eligible and included in the analysis population (Table 1). Two screened patients were not included in the analysis because the radiographic findings were not compatible with CAP. The mean age at consent was 77.6 years, 1,765 patients (83.9%) were ≥ 65 years of age, and 53.9% were female. The mean pneumonia severity index (PSI) score on admission was 108.9, with 39.0% and 28.6% of patients having class IV or V PSI scores, respectively. The mean CURB-65 score was 1.7 and 20.7% of patients had a CURB-65 score of 3 to 5. Pneumococcal vaccination within the previous 5 years was reported for 414 of 2,103 patients (19.7%), with 6.8% in adults 18 to 64 years of age and 22.2% in adults ≥ 65 years of age. In total, 70.7% of all patients were hospitalized; the mean hospital stay duration was 14.1 days. Mortality during the study was 6.7% (141/2,103), and in-hospital mortality was 6.2% (130/2,103). Among patients who died, 94.3% (133/141) were ≥ 65 years of age and 5.7% (8/141) were 18 to 64 years of age. Among patients ≥ 18 years of age, 18 to 64 years of age, and ≥ 65 years of age, 69.5%, 64.5%, and 70.4% were at risk or high risk, respectively (Table 2).Table 1Demographics and Clinical Characteristics of Patients With CAPVariableAge Group, y18-64 (n = 338)≥ 65 (n = 1,765)≥ 18 (n = 2,103)Age at consent, y No.3381,7652,103 Mean ± SD51.1 ± 12.182.6 ± 8.677.6 ± 14.8 Median56.084.082.0 Interquartile range19-6465-10319-103Sex Female186 (55.0)948 (53.7)1,134 (53.9) Male152 (45.0)817 (46.3)969 (46.1)Pneumonia severity index No.3381,7642,102 Mean ± SD64.6 ± 32.3117.4 ± 34.0108.9 ± 38.9 Median57.0115.0109.0 Interquartile range13-19455-27513-275 GradeI139 (41.1)102 (5.8)241 (11.5)II82 (24.3)46 (2.6)128 (6.1)III43 (12.7)267 (15.1)310 (14.7)IV59 (17.5)762 (43.2)821 (39.0)V14 (4.1)587 (33.3)601 (28.6)Missing1 (0.3)1 (0.1)2 (0.1)CURB-65 score No.3381,7652,103 Mean ± SD0.3 ± 0.61.9 ± 0.91.7 ± 1.0 Median0.02.02.0 Interquartile range0-41-50-5 0254 (75.1)0 (0.0)254 (12.1) 160 (17.8)708 (40.1)768 (36.5) 222 (6.5)624 (35.4)646 (30.7) 31 (0.3)328 (18.6)329 (15.6) 41 (0.3)102 (5.8)103 (4.9) 50 (0.0)3 (0.2)3 (0.1)Prior vaccine Pneumococcal vaccine within 5 y23 (6.8)391 (22.2)414 (19.7) Prior PPSV23 use9 (2.7)376 (21.3)385 (18.3) Prior PCV13 use15 (4.4)14 (0.8)29 (1.4)Hospitalized Yes145 (42.9)1,342 (76.0)1,487 (70.7) No193 (57.1)423 (24.0)616 (29.3)Hospitalization durationaOnly participants with hospital admission date and discharge date were included in the analysis. No.1239871,110 Mean ± SD13.2 ± 7.714.2 ± 6.914.1 ± 7.0 Median12.013.013.0 Interquartile range1-401-351-40Hospitalization duration ≥ 30 dbPatients with ongoing hospitalization status and with study end date 30 d after hospital admission date were included, in addition to patients with actual stays of ≥ 30 d.27 (8.0)373 (21.1)400 (19.0)Death8 (2.4)133 (7.5)141 (6.7) Death caused by pneumonia5 (1.5)100 (5.7)105 (5.0)Time from hospitalization to death No.8130138 Mean ± SD12.5 ± 9.012.4 ± 8.612.4 ± 8.6 Median11.010.510.5 Interquartile range3-281-311-31Death in hospital7 (2.1)123 (7.0)130 (6.2)Death after hospital discharge1 (0.3)7 (0.4)8 (0.4)Data are presented as No. (%), unless otherwise indicated. CAP = community-acquired pneumonia; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine.a Only participants with hospital admission date and discharge date were included in the analysis.b Patients with ongoing hospitalization status and with study end date 30 d after hospital admission date were included, in addition to patients with actual stays of ≥ 30 d. Open table in a new tab Table 2Baseline Medical Characteristics of Patients With CAPVariableAge Group, y18-64 (n = 338)≥ 65 (n = 1,765)≥ 18 (n = 2,103)Risk level High86 (25.4)593 (33.6)679 (32.3) At risk132 (39.1)650 (36.8)782 (37.2) Low120 (35.5)522 (29.6)642 (30.5)High risk Chronic renal failure19 (5.6)189 (10.7)208 (9.9) Immunosuppressive therapy41 (12.1)205 (11.6)246 (11.7) Immunodeficiency0 (0.0)0 (0.0)0 (0.0) AIDS0 (0.0)0 (0.0)0 (0.0) HIV infection0 (0.0)0 (0.0)0 (0.0) Hematologic cancer3 (0.9)41 (2.3)44 (2.1) Cancer (solid tumor)43 (12.7)276 (15.6)319 (15.2) Organ transplantation1 (0.3)0 (0.0)1 (0.0) Biologic agent2 (0.6)8 (0.5)10 (0.5) Splenectomy2 (0.6)9 (0.5)11 (0.5) No. of high-risk conditions162 (18.3)473 (26.8)535 (25.4)223 (6.8)106 (6.0)129 (6.1)31 (0.3)13 (0.7)14 (0.7)≥ 40 (0.0)1 (0.1)1 (0.0)1 with ≥ 1 at-risk condition38 (11.2)313 (17.7)351 (16.7)≥ 2 with ≥ 1 at-risk condition10 (3.0)84 (4.8)94 (4.5)At risk COPD20 (5.9)331 (18.8)351 (16.7) Asthma44 (13.0)167 (9.5)211 (10.0) Congestive heart failure10 (3.0)339 (19.2)349 (16.6) Diabetes mellitus38 (11.2)404 (22.9)442 (21.0) Liver disease38 (11.2)220 (12.5)258 (12.3) Smoke100 (29.6)93 (5.3)193 (9.2) No. of at-risk conditions197 (28.7)435 (24.6)532 (25.3)228 (8.3)173 (9.8)201 (9.6)36 (1.8)34 (1.9)40 (1.9)≥ 41 (0.3)8 (0.5)9 (0.4)Other risk factors Used antibiotics in the past 90 d72 (21.3)545 (30.9)617 (29.3) Living with children88 (26.0)19 (1.1)107 (5.1)Data are presented as No. (%). CAP = community-acquired pneumonia. Open table in a new tab Data are presented as No. (%), unless otherwise indicated. CAP = community-acquired pneumonia; PCV13 = 13-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine. Data are presented as No. (%). CAP = community-acquired pneumonia. Among all patients, the annual incidence of CAP was 1,280 cases per 100,000 population. CAP incidence increased with age, and the incidence among adults ≥ 80 years of age was 11.8 times the incidence among adults 18 to 64 years of age (4,288 per 100,000 population vs 362 per 100,000 population) and 3.2 times the incidence among those 65 to 79 years of age (4,288 per 100,000 population vs 1,352 per 100,000 population) (Fig 1). A similar relationship between incidence and age was observed for pneumococcal CAP, PCV13 VT CAP, and PCV20 VT CAP. In all adults 18 to 64 years of age, those 65 to 79 years of age, and those ≥ 80 years of age, annual incidences per 100,000 population were 227, 89, 260, and 645, respectively, for pneumococcal CAP; 63, 23, 80, and 171, respectively, for PCV13 VT CAP; and 110, 47, 159, and 244, respectively, for PCV20 VT CAP. Extrapolating the CAP incidence and the case fatality rate to Japan’s population and assuming PCV20 has the same VE and duration of protection as PCV13,22Bonten M.J. Huijts S.M. Bolkenbaas M. et al.Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults.N Engl J Med. 2015; 372: 1114-1125Crossref PubMed Scopus (836) Google Scholar if licensed, PCV20 immunization in Japanese adults ≥ 65 years of age could prevent 29,036 CAP cases and 2,275 CAP-related deaths per year. Between 2015 and 2020, CAP incidence and pneumococcal CAP incidence generally remained stable, except for year 5 (December 2019-November 2020) during which the incidences were lower compared with other study years (Fig 2). Urine samples were not collected in 68 of 2,103 patients (3.2%); however, S pneumoniae was detected by culture in 5 of 68 patients (7.3%) from whom a urine sample was not collected. Among 2,099 patients who had diagnostic results available, S pneumoniae was detected in 373 patients (17.8%) by UAD assays, BinaxNOW, or culture (Table 3). S pneumoniae was detected by UAD alone in 78 of 2,099 patients (3.7%; 78/373 patients [20.9%] with pneumococcal CAP), by BinaxNOW alone in 125 of 2,099 patien