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In our study, the positivity of S. pneumoniae by sputum culture was only 9%. Considering the low sensitivity of sputum culture, we included urinary antigen test-positive cases for the standard estimation and further included PCR-positive cases for the maximum estimation. The true value must lie between these values. The proportion of bacteremia among pneumococcal BYL719 1217486-61-7 pneumonia cases was 6% in our study. A meta-analysis showed that approximately 25% of pneumococcal pneumonia is bacteremic ; our figure was lower than this estimate. However, our results showed that the incidence of bacteremic pneumococcal pneumonia among Japanese adults was 12 per 100,000 PY, a figure that was comparable with those reported for other countries, such as the United States and Australia. The findings suggest that pneumococcal pneumonia, either bacteremic or non-bacteremic, remains the leading target for pneumonia control programs in Japan. PPV23 reduces the risk of invasive pneumococcal diseases among adults; however, its effectiveness against pneumococcal pneumonia is still controversial, particularly for the elderly. The recently approved PCV13 is expected to prevent almost half of the pneumococcal pneumonia cases in the elderly ; however, the vaccine covers only 13 serotypes of pneumococcus, and its long-term effects remain unknown. In Japan, before the introduction of PCV7 for children in 2010, 85% of IPD isolates were PPV23 serotypes, and 62% were PCV13 serotypes. In the current study, 67% of the isolates were PPV23 serotypes, and 54% were PCV13 serotypes. The vaccination policy for pneumococcus has been dramatically changing in Japan. PCV7 for children was replaced by PCV13 in late 2013, and PPV23 was also included in the Ministry of Health, Labour and Welfare recommended vaccines for elderly people in late 2014. The proportion of vaccine-covered serotypes is known to decline after widespread use of PCV ; thus, these figures will decrease in coming years. The true efficacy of PCV13 for adult pneumonia among the Japanese population must be evaluated along with cost-effectiveness analyses before it is introduced into the national immunization program. A substantial proportion of pneumonia was associated with RVs. Recent studies suggest that RVs play crucial roles in the development of pneumonia, including severe cases ; however, their biological mechanisms remain largely unknown. RVs such as influenza, RSV, and human metapneumovirus cause outbreaks among the elderly in nursing homes, and these RVs are potential targets for vaccination. Currently, only seasonal influenza vaccines are available for adults, but their effects on pneumonia prevention have not yet been established. Further investigations are needed to clarify the public health impact of RV-associated pneumonia in aging societies. Our findings have important implications for effective pneumonia control programs in the aging society. The burden of pneumonia is higher in older people, and the pneumonia etiology largely varies by age group: the incidences of aspiration-, S. pneumoniae-, H. influenzae-, RV-, and PDR pathogen-associated pneumonia increase with age, while the incidence of atypical bacteria-associated pneumonia decreases. It must be noted that the proportion of pneumonia caused by unknown pathogens is higher among elderly people. This category most likely represents multifactorial conditions. Therefore, in coming decades, the pneumonia burden will likely increase, and its etiology will become more diverse. In this situation, the current etiologyspecific approach must have only a limited impact. A multidimensional approach integrating vaccination programs, clinical management guidelines, training for health care workers, and education for people must be needed; further studies are warranted. This study is the first to estimate the national burden of COP in Japan. Although pneumonia is a common disease, its true burden remains unclear, even in high-income countries. A number of studies have reported the incidence of adult pneumonia, but their estimates substantially varied from setting to setting. Several factors explain this variation. First, the definition of pneumonia differs among studies. Some studies have reported incidences of CAP that include outpatients and hospitalized patients, while other studies have reported hospitalized cases only. It was not clear whether these studies included HCAP cases. Additionally, the diagnosis of pneumonia is not standardized in clinical settings; thus, the burden estimates based on existing database are unreliable. Second, study designs vary. Pneumonia is a common disease, and it is not included in national surveillance. Cohort studies may not represent the entire population of a country, while hospital-based studies do not capture all the cases in the community.

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