A retrospective cohort study evaluating the incidence of herpes zoster and postherpetic neuralgia after a live attenuated Oka-strain herpes zoster vaccine in a real-world setting in Japan.

BACKGROUND: In Japan, freeze-dried live attenuated Oka-strain varicella-zoster virus vaccine, VVL (BIKEN), is available for adults aged ≥50 years to prevent herpes zoster (HZ). Although an increase in the antibody titer and cellular immune response has been demonstrated following vaccination with VVL (BIKEN), to date, no clinical studies have shown that the vaccine decreases the incidence of HZ and postherpetic neuralgia (PHN). This study investigated the incidence of HZ and PHN among adults aged ≥50 years who received a single dose of VVL (BIKEN) to prevent HZ. METHODS: This retrospective cohort study investigated the incidence of HZ and PHN among adults aged ≥50 years who received a single dose of VVL (BIKEN) at a large hospital and affiliated clinics in Japan. A dispensing database and electronic medical records were used to identify vaccine recipients and cases of HZ and PHN. The end date of the follow-up period and the reason to end the follow-up were defined to avoid underestimating the incidence. The analysis was stratified according to age, sex, immunocompromising conditions, and use of immunosuppressant therapy. Vaccine effectiveness was estimated using published estimates of the incidence of HZ and PHN in the unvaccinated population in Japan. RESULTS: A total of 1175 patients were enrolled in the study. During a median follow-up period of 3.36 years, HZ was diagnosed in 27 participants (15 men [2.8%] and 12 women [1.9%]). The incidence of HZ among VVL (BIKEN) recipients was 7.67/1000 person-years. The incidence of PHN was 0.82/1000 person-years. The vaccine effectiveness was estimated as 27.8% [95% confidence interval (CI), -29.8 to 63.9%] and 73.8% [95% CI, 38.6-100%] against HZ and PHN, respectively. CONCLUSIONS: The VVL (BIKEN) had limited effectiveness at preventing HZ, but relatively good effectiveness at preventing PHN. VVL (BIKEN) might have a role as an affordable alternative.

Long-term impact of pneumococcal conjugate vaccines for children on adult pneumococcal pneumonia in Japan: Two multicenter observational studies from 2011 to 2020.

BACKGROUND: Pediatric pneumococcal conjugate vaccines (PCVs) introduction has directly and indirectly reduced pneumococcal pneumonia and invasive disease caused by PCV-covered serotypes among children and adults globally. In Japan, both PCV7 and PCV13 were introduced into the national immunization program (NIP) for children in 2013. However, the long-term impact of PCV use in children on adult pneumococcal pneumonia in Japan remains unclear. METHODS: We assessed serotypes isolated from adult pneumococcal pneumonia patients (in- and outpatients) in two multicenter observational studies in Japan: 2011-2014 and 2016-2020. The latter study period was divided into two periods to evaluate changes after PCV introduction in children. The Quellung reaction was used to determine serotypes. We evaluated trends of individual and vaccine-covered serotypes over three periods and assessed the difference in changes by patient group before and after the introduction of pediatric PCVs. RESULTS: A total of 650 patients were enrolled: 224, 322, and 104 in 2011-2014, 2016-2017, and 2018-2020, respectively. The median age was 73 years; 59.7% (388/650) were male; 86.9% (565/650) had comorbidities; and 10.2% (66/650) were nursing-home residents. The proportion of PCV13 serotypes decreased from 52.7% in 2011-2014 to 30.4% in 2016-2017 (p <0.001) after PCV13 introduction for children. However, PCV13, PCV15, and PCV20 serotypes still accounted for 38.5, 43.3, and 59.6% of total pneumococcal pneumonia in 2018-2020, respectively. Decline of PCV13 serotypes was more marked in patients aged ≥65 (-23.5%; p <0.001) than those aged <65 (-12.3%; p = 0.104) from 2011-2014 to 2016-2020. The proportion of PPSV23 non-PCV13 serotypes didn't change over time. CONCLUSIONS: The proportion of adult pneumococcal pneumonia caused by PCV13 serotypes in Japan declined after pediatric PCVs introduction into NIP, possibly due to indirect effects of pediatric PCVs. However, use of new PCVs in Japanese adults may potentially prevent additional pneumococcal pneumonia cases. Now, pneumococcal vaccination strategy for older adults requires discussion.

High prevalence of multiple serotypes of pneumococci in patients with pneumonia and their associated risk factors.

BACKGROUND: Multiple serotypes of pneumococci have epidemiological and clinical implications, such as the emergence of non-vaccine serotypes and the acquisition of antimicrobial resistance. Prevalence of multiple serotypes of pneumococci in adults and their risk factors are not known. METHODS: We enrolled adult patients from age ≥15 years with radiologically confirmed pneumonia in four hospitals across Japan. Pneumococcal pneumonia was defined with a pneumococcal bacterial density of ≥104/mL in sputum by lytA quantitative PCR, and serotypes were determined. Pneumonias with a single serotype were categorised as single-serotype pneumococcal pneumonia and with two or more serotypes as multiple-serotype pneumococcal pneumonia. Multivariable logistic regression was used to assess the risk factors. RESULTS: 3470 patients (median age 77 years, IQR 65-85) were enrolled. Pneumococcal pneumonia was identified in 476 (18.3%, n=2605) patients. Multiple serotypes were detected in 42% of them. Risk of having multiple serotypes was low among patients who had received 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccines (adjusted OR 0.51 (95% CI 0.27 to 0.94)). Proportion of non-PCV7 PPSV23 serotypes in overall distribution of multiple serotypes was 67.4% (n=324/481) compared with 46.4% (n=128/276) in that of single serotypes (p=0.001). Serotypes 5, 9N/9L, 10A, 12/22/46, 17F and 35F were associated with multiple-serotype pneumonia, and serotypes 6A/6B, 23F, 11 and 6C/6D were associated with single-serotype pneumonia. Proportion of more invasive serotypes (serotypes 1, 5, 7F, 8) was significantly higher in multiple-serotype pneumonia (p=0.001). CONCLUSIONS: Multiple serotypes of pneumococci are common in sputum of adult patients with pneumonia. The risk of multiple-serotype pneumococcal pneumonia is lower than that of single-serotype pneumococcal pneumonia among PPSV23-vaccinated patients. TRIAL REGISTRATION NUMBER: UMIN000006909.

Definitive and Indeterminate Pseudomonas aeruginosa Infection in Adults with Community-acquired Pneumonia: A Prospective Observational Study.

Rationale: Pneumonia due to Pseudomonas aeruginosa (PA) is associated with high mortality and requires antipseudomonal treatment. Because PA can colonize the respiratory tract, the diagnosis of pathogenic PA involvement is challenging. Objectives: To determine the prevalence of definitive and indeterminate PA infection in community-acquired pneumonia, to describe the clinical and microbiological profiles, and to estimate the burden of unnecessary antipseudomonal drug prescriptions. Methods: We prospectively enrolled 2,701 patients with community-acquired pneumonia. Using stringent criteria for diagnosing PA pneumonia, we generated the following three groups: 1) definitive PA, 2) indeterminate PA, and 3) non-PA pneumonia. Results: The prevalence of definitive PA pneumonia was 0.9% (n = 25), and that of indeterminate PA pneumonia was 4.9% (n = 131). Considerable clinical differences were observed among the groups. Patients with definitive PA pneumonia were more likely to have a history of tuberculosis and chronic obstructive pulmonary disease/bronchiectasis and had a higher 30-day mortality (28%) than patients with non-PA pneumonia. Patients with indeterminate PA pneumonia were more likely to have comorbidities than patients with non-PA pneumonia. More than half of the patients with indeterminate PA and 25% of the patients with non-PA pneumonia were treated with an antipseudomonal drug. No patients with definitive PA pneumonia had multidrug resistance. Conclusions: In this population, the prevalence of community-acquired pneumonia due to PA was low. The clinical features and 30-day mortality rates of patients with indeterminate PA pneumonia were different from those of patients with definitive PA pneumonia. Most of the prescribed antipseudomonal drugs for patients with community-acquired pneumonia were potentially unnecessary.

1g versus 2 g daily intravenous ceftriaxone in the treatment of community onset pneumonia - a propensity score analysis of data from a Japanese multicenter registry.

BACKGROUND: Community-onset pneumonia (COP) is a combined concept of community acquired pneumonia and the previous classification of healthcare-associated pneumonia. Although ceftriaxone (CRO) is one of the treatment choices for COP, it is unclear whether 1 or 2 g CRO daily has better efficacy. We compared the effectiveness of 1 g with 2 g of CRO for COP treatment. We hypothesized that 1 g CRO would show non-inferiority over 2 g CRO. METHODS: This study was an analysis of prospectively registered data of the patients with COP from four Japanese hospitals (the Adult Pneumonia Study Group-Japan: APSG-J). We included subjects who were initially treated solely with 1 or 2 g of CRO. The propensity score was estimated from the 33 pre-treatment variables, including age, sex, weight, pre-existing comorbidities, prescribed drugs, risk factors for aspiration pneumonia, vital signs, laboratory data, and a finding from chest xrays. The primary endpoint was the cure rate, for which a non-inferiority analysis was performed with a margin of 0.05. In addition, we performed three sensitivity analyses; using data limited to the group in which CRO solely was used until the completion of treatment, using data limited to inpatient cases, and performing a generalized linear mixed-effect logistic regression analysis to assess the primary outcome after adjusting for random hospital effects. RESULTS: Of the 3817 adult subjects with pneumonia who were registered in the APSG-J study, 290 and 216 were initially treated solely with 1 or 2 g of CRO, respectively. Propensity score matching was used to extract 175 subjects in each group. The cure rate was 94.6 and 93.1% in the 1 and 2 g CRO groups, respectively (risk difference 1.5%; 95% confidence interval - 3.1 to 6.0; p = 0.009 for non-inferiority). The results of the sensitivity analyses were consistent with the primary result. CONCLUSIONS: The propensity score-matched analysis of multicenter cohort data from Japan revealed that the cure rate for COP patients treated with 1 g daily CRO was non-inferior to that of patients treated with 2 g daily CRO.

Ceftriaxone versus ampicillin/sulbactam for the treatment of aspiration-associated pneumonia in adults.

Aim: To compare hospital mortality in patients with aspiration-associated pneumonia treated with ceftriaxone (CTRX) and in those treated with ampicillin/sulbactam (ABPC/SBT). Methods: From a Japanese multicentre observational study cohort of patients with pneumonia, those diagnosed with pneumonia and having at least one aspiration-related risk factor were selected. Propensity score-matching analysis was used to balance baseline characteristics of the participants and compare hospital mortality of patients treated with CTRX and those treated with ABPC/SBT. Results: Hospital mortality did not significantly differ between patients treated with CTRX and those treated with ABPC/SBT (6.6 vs 10.7%, risk difference -4.0, 95% CI [-9.4, 1.3]; p = 0.143). Conclusion: Further studies are needed to compare CTRX and ABPC/SBT treatments in patients with aspiration-associated pneumonia.

Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE).

BACKGROUND: The pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described. METHODS: The first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype. RESULTS: A total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p < 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49-4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02-2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes. CONCLUSIONS: The occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.

Severe Community-acquired Pneumonia Caused by Acinetobacter baumannii Successfully Treated with the Initial Administration of Meropenem Based on the Sputum Gram Staining Findings.

A 62-year-old man with diabetes mellitus and a two-day history of fever and dyspnea presented at our hospital. He was diagnosed with community-acquired pneumonia (CAP), septic shock, and respiratory failure. Sputum Gram staining revealed Gram-negative coccobacilli. Based on the Gram staining findings and history, Acinetobacter baumannii was considered as one of the causative organisms of his CAP. Consequently, he was successfully treated with the initial administration of meropenem. We suggest that A. baumannii should be considered as one of the possible causative organisms of CAP based on a fulminant clinical course, and the presence of Gram-negative coccobacilli.

Case Report: Concurrent Sympatric Scrub Typhus and Japanese Spotted Fever in Japan.

Scrub typhus and Japanese spotted fever-both rickettsial diseases-are endemic and notifiable in Japan and may cause a fatal outcome without prompt treatment. Here we present the first case of a concurrent sympatric infection of both diseases with grade II evidence. A 67-year-old woman, after a single event of potential exposure to the pathogens, presented with a 12-day history of fever, pharyngeal pain, papulo-erythematous rash, and pronounced fatigue. Her erythematous rash was distributed on her trunk and extremities, palms, and soles and eventually progressed to purpura. Fever persisted until doxycycline was administered on day 12. A significant > 4-fold increase in immunoglobulin G and immunoglobulin M titers against multiple serotypes of Orientia tsutsugamushi and Rickettsia japonica were revealed by indirect immunoperoxidase assays. These clinical and serological data, even in the absence of molecular or isolation evidence, provided grade II evidence that this was a concurrent infection of sympatric scrub typhus and Japanese spotted fever.

Distinguishing Japanese Spotted Fever and Scrub Typhus, Central Japan, 2004- 2015.

Japanese spotted fever (JSF) and scrub typhus (ST) are endemic to Japan and share similar clinical features. To document the clinical and epidemiologic characteristics that distinguish these 2 rickettsial diseases, during 2004-2015 we recruited 31 JSF patients, 188 ST patients, and 97 nonrickettsial disease patients from the southern Boso Peninsula of Japan. JSF occurred during April-October and ST during November-December. Patients with JSF and ST were significantly older and more likely to reside in wooded areas than were patients with nonrickettsial diseases. Spatial analyses revealed that JSF and ST clusters rarely overlapped. Clinical findings more frequently observed in JSF than in ST patients were purpura, palmar/plantar rash, hyponatremia, organ damage, and delayed defervescence after treatment. Although their clinical features are similar, JSF and ST differ in seasonality, geographic distribution, physical signs, and severity. Because a considerable percentage of patients did not notice rash and eschar, many rickettsial diseases might be underdiagnosed in Japan.

Six underlying health conditions strongly influence mortality based on pneumonia severity in an ageing population of Japan: a prospective cohort study.

BACKGROUND: Mortality prediction of pneumonia by severity scores in patients with multiple underlying health conditions has not fully been investigated. This prospective cohort study is to identify mortality-associated underlying health conditions and to analyse their influence on severity-based pneumonia mortality prediction. METHODS: Adult patients with community-acquired pneumonia or healthcare-associated pneumonia (HCAP) who visited four community hospitals between September 2011 and January 2013 were enrolled. Candidate underlying health conditions, including demographic and clinical characteristics, were incorporated into the logistic regression models, along with CURB (confusion, elevated urea nitrogen, tachypnoea, and hypotension) score as a measure of disease severity. The areas under the receiver operating characteristic curves (AUROC) of the predictive index based on significant underlying health conditions was compared to that of CURB65 (CURB and age ≥ 65) score or Pneumonia severity index (PSI). Mortality association between disease severity and the number of underlying health conditions was analysed. RESULTS: In total 1772 patients were eligible for analysis, of which 140 (7.9%) died within 30 days. Six underlying health conditions were independently associated: home care (adjusted odds ratio, 5.84; 95% confidence interval, CI, 2.28-14.99), recent hospitalization (2.21; 1.36-3.60), age ≥ 85 years (2.15; 1.08-4.28), low body mass index (1.99, 1.25-3.16), neoplastic disease (1.82; 1.17-2.85), and male gender (1.78; 1.16-2.75). The predictive index based on these conditions alone had a significantly or marginally higher AUROC than that based on CURB65 score (0.78 vs 0.66, p = 0.02) or PSI (0.78 vs 0.71, p = 0.05), respectively. Compared to this index, the AUROC of the total score consisting of six underlying health conditions and CURB score (range 0-10) did not improve mortality predictions (p = 0.3). In patients with one or less underlying health conditions, the mortality was discretely associated with severe pneumonia (CURB65 ≥ 3) (risk ratio: 7.24, 95%CI: 3.08-25.13), whereas in patients with 2 or more underlying health conditions, the mortality association with severe pneumonia was not detected (risk ratio: 1.53, 95% CI: 0.94-2.50). CONCLUSIONS: Mortality prediction based on pneumonia severity scores is highly influenced by the accumulating number of underlying health conditions in an ageing society. The validation using a different cohort is necessary to generalise the conclusion.

Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza pneumonia among adults aged ≥65 years in Japan.

BACKGROUND: The effectiveness of inactivated influenza vaccine (IIV) against laboratory-confirmed influenza pneumonia in older adults remains to be established. METHODS: Pneumonia patients aged ≥65 years who visited a study hospital in Chiba, Japan, were prospectively enrolled from February 2012 to January 2014. Sputum samples were collected from participants and tested for influenza virus by polymerase chain reaction assays. Influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza pneumonia was estimated by a test-negative design. RESULTS: Among a total of 814 pneumonia patients, 42 (5.2%) tested positive for influenza: 40 were positive for influenza A virus, and two were positive for influenza B virus. The IVE against laboratory-confirmed influenza pneumonia was 58.3% (95% confidence interval, 28.8-75.6%). The IVE against influenza pneumonia hospital admission, severe pneumonia, and death was 60.2% (95% CI, 22.8-79.4%), 65.5% (95% CI, 44.3-78.7%), and 71% (95% CI, -62.9% to 94.8%), respectively. In the subgroup analyses, the IVE against influenza pneumonia was higher for patients with immunosuppressive conditions (85.9%; 95% CI, 67.4-93.9%) than for those without (48.7%; 95% CI, 2.7-73%) but did not differ by patients' statin use status. CONCLUSION: IIV effectively reduces the risk of laboratory-confirmed influenza pneumonia in older adults.

Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial.

It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, -10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4-6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

The impact of virus infections on pneumonia mortality is complex in adults: a prospective multicentre observational study.

BACKGROUND: Various viruses are known to be associated with pneumonia. However, the impact of viral infections on adult pneumonia mortality remains unclear. This study aimed to clarify the effect of virus infection on pneumonia mortality among adults stratified by virus type and patient comorbidities. METHODS: This multicentre prospective study enrolled pneumonia patients aged ≥15 years from September 2011 to August 2014. Sputum samples were tested by in-house multiplex polymerase chain reaction assays to identify 13 respiratory viruses. Viral infection status and its effect on in-hospital mortality were examined by age group and comorbidity status. RESULTS: A total of 2617 patients were enrolled in the study and 77.8% was aged ≥65 years. 574 (21.9%) did not have comorbidities, 790 (30.2%) had chronic respiratory disease, and 1253 (47.9%) had other comorbidities. Viruses were detected in 605 (23.1%) patients. Human rhinovirus (9.8%) was the most frequently identified virus, followed by influenza A (3.9%) and respiratory syncytial virus (3.9%). Respiratory syncytial virus was more frequently identified in patients with chronic respiratory disease (4.7%) than those with other comorbidities (4.2%) and without comorbidities (2.1%) (p = 0.037). The frequencies of other viruses were almost identical between the three groups. Virus detection overall was not associated with increased mortality (adjusted risk ratio (ARR) 0.76, 95% CI 0.53-1.09). However, influenza virus A and B were associated with three-fold higher mortality in patients with chronic respiratory disease but not with other comorbidities (ARR 3.38, 95% CI 1.54-7.42). Intriguingly, paramyxoviruses were associated with dramatically lower mortality in patients with other comorbidities (ARR 0.10, 95% CI 0.01-0.70) but not with chronic respiratory disease. These effects were not affected by age group. CONCLUSIONS: The impact of virus infections on pneumonia mortality varies by virus type and comorbidity status in adults.

A case of tracheo-innominate artery fistula successfully treated with endovascular stent of the innominate artery.

Tracheo-innominate artery fistula (TIF) is a rare but life-threatening complication of tracheostomy. We describe a 44-year-old man who was admitted for a pressure ulcer infection with a third tracheostomy in place. He showed massive hemoptysis from the TIF, followed by cardiopulmonary arrest. The cuff of the tube was hyperinflated; however, even a slight movement of the tube resulted in recurrent massive hemorrhage. Thus, an endovascular stent graft was placed. Our case shows that sentinel bleeding may be found prior to TIF, and an endovascular repair can be a lifesaving temporizing option, when the hemorrhage was not controlled by hyperinflating the cuff of the tube.

Serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study.

BACKGROUND: The serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal pneumonia has not been established in people aged 65 years or older. We assessed the effectiveness of PPV23 in this population. METHODS: For this multicentre, prospective study, we enrolled all individuals aged 65 years or older with community-onset pneumonia who visited four study hospitals in Japan between Sept 28, 2011, and Aug 23, 2014. Streptococcus pneumoniae was isolated from sputum and blood samples, and serotyped by the capsular Quellung method. Sputum samples were further tested by PCR assay to identify pneumococcal DNA, and positive samples were examined for 50 serotypes by a nanofluidic real-time PCR assay. Urine samples were tested by a urinary antigen test. Serotype-specific vaccine effectiveness was estimated using the test-negative design. FINDINGS: 2621 eligible patients visited the study hospitals, of whom 585 did not have sputum samples available and were excluded from our analysis. 419 (21%) of 2036 patients were positive for pneumococcal infection (232 by sputum culture, 317 by sputum PCR, 197 by urinary antigen test, and 14 by blood culture). 522 (26%) patients were judged to be vaccinated in the analyses. Effectiveness of PPV23 was 27·4% (95% CI 3·2 to 45·6) against all pneumococcal pneumonia, 33·5% (5·6 to 53·1) against PPV23 serotypes, and 2·0% (-78·9 to 46·3) against non-PPV23 serotypes. Although no significant differences between subgroups were seen, higher protection was noted in people younger than 75 years, women, and individuals with lobar pneumonia or health-care-associated pneumonia. INTERPRETATION: PPV23 showed low to moderate effectiveness against vaccine serotype pneumococcal pneumonia in people aged 65 years or older. To improve the current pneumococcal vaccination programme, the variability of PPV23 effectiveness in different groups of older people must be further investigated. FUNDING: Pfizer and Nagasaki University.

Recurrent pneumonia among Japanese adults: disease burden and risk factors.

BACKGROUND: In Japan and other societies with rapidly aging populations, recurrent pneumonia (RP) is a major clinical problem yet only limited information exists regarding the burden of this disease. METHODS: A prospective study of adult pneumonia was conducted to investigate the incidence of RP and potential risk factors. From February 1, 2012 to January 31, 2013, patients aged ≥ 15 years who were diagnosed with pneumonia were prospectively enrolled in a representative community hospital located in central Japan. Patients were followed for one-year to evaluate the recurrence of pneumonia and characteristics associated with RP. Cox proportional hazards models were constructed to compute adjusted hazard ratios (aHR) and ascertain risk factors significantly associated with RP. RESULTS: In total, 841 patients with a median age of 73 years (range 15-101 years) were enrolled totaling 1,048 person-years of observation with a median follow-up time of 475 days. A total of 137 patients had at least one recurrent episode with an incidence rate of 13.1 per 100 person-years (95% confidence interval: 11.1-15.5). In multivariate analysis, a past history of pneumonia (aHR 1.95, 95% CI: 1.35-2.8), chronic pulmonary disease (aHR 1.86, 1.24-2.78) and inhaled corticosteroid usage (aHR 1.78, 1.12-2.84) and hypnotic/sedative medication usage (aHR 2.06, 1.28-3.31) were identified as independent risk factors for recurrent pneumonia, whereas angiotensin converting enzyme-inhibitors usage was associated with a reduction of the risk of RP (aHR 0.22, 0.05-0.91). The detection of P. aeruginosa was significantly associated with RP even after adjusting for chronic pulmonary diseases (aHR = 2.37). CONCLUSIONS: Recurrent pneumonia constitutes a considerable proportion of the pneumonia burden in Japan. A past history of pneumonia, chronic pulmonary disease, inhaled corticosteroid and hypnotic/sedative medication usage and detection of P. aeruginosa were identified as independent risk factors for recurrent pneumonia and special attention regarding the use of medications in this vulnerable population is needed to reduce the impact of this disease in aging populations.

The burden and etiology of community-onset pneumonia in the aging Japanese population: a multicenter prospective study.

BACKGROUND: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world's most aged society. METHODS: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥ 15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. RESULTS: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥ 85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥ 65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). CONCLUSIONS: A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.