Daisuke Kurai

Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality in adults aged 50-59 years at increased risk of severe RSV disease due to specific underlying conditions (i.e. '50-59 years at-increased-risk [AIR] population'), and in older adults aged ≥60 years (i.e. '≥60 years population'). A static multi-cohort Markov model estimated cost-effectiveness of adjuvanted RSVPreF3 vaccination versus no vaccination among the 50-59 years AIR and ≥60 years populations in Japan, over a five-year time horizon from a healthcare payer perspective. Japan-specific RSV epidemiology and healthcare resource utilization parameters were used; vaccine efficacy was derived from the phase 3 AReSVi-006 trial (NCT04886596). Adjuvanted RSVPreF3 vaccination was cost-effective: in the 50-59 years AIR population, 49,280 RSV cases were prevented and 4333 quality-adjusted life years (QALYs) gained, at an incremental cost-effectiveness ratio (ICER) of Japanese yen (JPY) 2,770,558/QALY; in the ≥60 years population, 2,111,080 RSV cases were prevented and 205,543 QALYs gained, at an ICER of JPY 2,613,241/QALY. Vaccination was more cost-effective when including productivity losses from RSV-ARI. Scenario and sensitivity analyses results were robust. RSV vaccination may provide substantial health benefits and be a cost-effective intervention to reduce RSV burden in adults in Japan.

Older adults (OA) are at risk of morbidity and mortality from respiratory syncytial virus (RSV), a major cause of seasonal acute respiratory illness. The first RSV vaccine for OA (RSVPreF3 OA) was recently launched in Japan. With the already large and growing OA population in Japan, and limited RSV treatments, prevention is key. The aim of this study was to assess the cost-effectiveness of introducing RSVPreF3 OA for Japanese adults aged ≥60 years. A static multicohort Markov model was adapted to assess the cost-effectiveness of a single dose of RSVPreF3 OA versus no vaccination over a three-year time horizon. Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty. RSVPreF3 OA vaccination prevented 1,008,499 cases and 6,840 deaths, with 109,119 quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio was Japanese yen (JPY) 4,180,084/QALY gained from a payer perspective and JPY 4,041,917/QALY gained from a societal perspective (with productivity loss from RSV disease), thus vaccination was considered cost-effective. Base case results were robust to changes in sensitivity and scenario analyses. RSVPreF3 OA vaccination for adults ≥60 years can provide substantial health benefits and is a cost-effective intervention to reduce the RSV burden in Japan.

Respiratory syncytial virus (RSV), a common respiratory pathogen, can lead to severe symptoms, especially in older adults (OA). A recently developed RSV prefusion F protein (RSVPreF3 OA) vaccine confers high protection against RSV lower respiratory tract disease (LRTD) over two full RSV seasons. The aim of this study was to assess the potential public health impact of RSVPreF3 OA vaccination in the Japanese OA population. A static Markov model was used to estimate the number of symptomatic RSV cases, hospitalizations and deaths in the Japanese population aged ≥ 60 years over a 3-year time horizon. Japan-specific RSV epidemiology and healthcare resource use parameters were used; vaccine efficacy was derived from a phase 3 randomized study (AReSVi-006, NCT04886596). Vaccination coverage was set to 50%. Without vaccination, >5 million RSV acute respiratory illness (ARI) would occur (2.5 million LRTD and 2.8 million upper respiratory tract infections) leading to ~ 3.5 million outpatient visits, >534,000 hospitalizations and ~ 25,500 RSV-related deaths over 3 years. Vaccination could prevent > 1 million RSV-ARI cases, 728,000 outpatient visits, 143,000 hospitalizations and 6,840 RSV-related deaths. RSVPreF3 OA vaccination is projected to have a substantial public health impact by reducing RSV-related morbidity and mortality in the OA population.

DNA gyrase plays important roles in genome replication in various bacteria, including Pseudomonasaeruginosa. The gyrA gene encodes the gyrase subunit A protein (GyrA). Mutations in GyrA are associated with resistance to quinolone-based antibiotics. We performed a detailed molecular evolutionary analyses of the gyrA gene and associated resistance to the quinolone drug, ciprofloxacin, using bioinformatics techniques. We produced an evolutionary phylogenetic tree using the Bayesian Markov Chain Monte Carlo (MCMC) method. This tree indicated that a common ancestor of the gene was present over 760 years ago, and the offspring formed multiple clusters. Quinolone drug-resistance-associated amino-acid substitutions in GyrA, including T83I and D87N, emerged after the drug was used clinically. These substitutions appeared to be positive selection sites. The molecular affinity between ciprofloxacin and the GyrA protein containing T83I and/or D87N decreased significantly compared to that between the drug and GyrA protein, with no substitutions. The rate of evolution of the gene before quinolone drugs were first used in the clinic, in 1962, was significantly lower than that after the drug was used. These results suggest that the gyrA gene evolved to permit the bacterium to overcome quinolone treatment.

Background: The frequency and clinical profile of respiratory syncytial virus (RSV)–acute respiratory disease (ARD) in older adults in Japan has not been well‐characterized.Methods: This was a multicenter prospective observational cohort study to evaluate the occurrence rate of ARD in 1000 older adult participants (≥65 years) for 52 weeks during the 2019 to 2020 season. A multiplex polymerase chain reaction panel was used for pathogen detection in nasopharyngeal swab from participants diagnosed with ARD. Symptoms and impact of ARD was assessed using the Respiratory Infection Intensity and Impact Questionnaire (RiiQ™). The study was registered at UMIN (https://www.umin.ac.jp/ctr/): UMIN000037891.Results: RSV–ARD was detected in 24/1000 (2.4%) participants and RSV‐lower respiratory tract disease in 8/1000 (0.8%) participants. The median duration of RSV–ARD was 18 days. All 24 participants had utilized the medical services of outpatient visits and only 1 (4.2%) participant was hospitalized for RSV–ARD. The most common viruses other than RSV that caused ARD (detected in >10 participants) were human rhinovirus/enterovirus, parainfluenza 3, coronavirus OC43, human metapneumovirus, and influenza A/H1. The most frequent symptoms of RSV–ARD were cough, sore throat, nasal congestion, and expectoration.Conclusions: RSV was reported as a major pathogen for respiratory infections in older adults in Japan.

During the ongoing coronavirus disease (COVID-19) pandemic, N95 filtering facepiece respirators (N95 respirators) are in short supply in many countries. Considering this, the Centers for Disease Control and Prevention suggested reusing N95 respirators and recommended the use of ultraviolet germicidal irradiation (UVGI) for sterilizing the respirators. However, only a few reports have described UVGI protocols for sterilizing the N95 respirators for reuse. Therefore, in this study, we aimed to develop and evaluate a novel method for the reuse of N95 respirators after sterilization by UVGI. Before conducting the study, the function of N95 respirators after multiple UVGI with a total dose of up to 10 J (1 J/cm² or more per dose) was assessed by measuring the particle collection efficiency and ventilation resistance. The participants used N95 respirators during work if they passed the fit test. After use, the respirators were sterilized using UVGI (1 J/cm²) and stored in a breathable paper bag for a week. The procedure was repeated up to three times after confirming the successful results of the fit tests. The particle collection efficiency without UVGI was 96.7%, while those after one, five, and 10 cycles of UGVI were 96.8%, 97.2%, and 97.2%, respectively. Ventilation resistance without UVGI was 42 Pa, and 43 Pa, 42 Pa, and 41 Pa after one, five, and 10 cycles of UVGI, respectively, which satisfied the Japanese national certification standard DS2. All 43 participants passed the fit test before the first reuse, and 39 participants (90.7%) completed the entire study protocol. The results of this study showed that N95 respirators could be used safely after repeated UVGI treatment. This study developed a novel method for reusing the N95 respirators. A few cycles of UV radiation N95 masks retain their functionalities and can be reused with proper UVGI.

A surge in the demand for N95 filtering facepiece respirators (N95 respirators) due to the worldwide spread of coronavirus disease 2019 (COVID-19) has resulted in a global shortage of N95 respirators. This study was performed to evaluate the clinical validation of reusing N95 respirators following stringent fit test protocols. After passing the first fit test, we prospectively enrolled healthcare workers who used N95 respirators for two hours per shift (duckbill-shaped HPR-R/HPR-S, dome-shaped Hi-Luck 350, and three-panel flat-fold respirators 9211) in settings such as bronchoscopy or respiratory specimen sampling. These procedures were repeated for up to three weeks, with the fit test performed every week. At each timing of the fit test, we used a fit-testing system for quantitatively evaluating particle leakage. A total of 41 participants were enrolled, including 24 doctors and 17 nurses, of whom 25 were women. The pass rate of successful reuse over three observational weeks using four fit tests was 85.4%, which was comparable among the three types of N95 respirators. Six (14.6%) participants failed the fit test, while no participants dropped out of protocol due to either N95 respirator damage or contamination. Among the six dropped out participants, four reused the duckbill-shaped type and two reused the three-panel flat-fold type. All participants using the cup-shaped type mask successfully completed the protocol. However, the passing rate of this study was not statistically different among the three types of N95 respirators. This study shows that N95 respirators can be safely reused for a short period irrespective of their type, as quantitatively assessed by fit tests.

Treatment of Candidemia has become increasingly complicated as more and more non-albicans Candida species are being isolated in recent years. We launched an investigation of the species, the MIC value, and the state of administration of antifungal drugs for all the cases with Candida spp. confirmed by blood cultures for the 7-year period from 2012 to 2018 at our hospital. In total, 192 cases were found and 206 strains of Candida species were isolated. Overall, 49.5% of the 206 isolated strains were Candida albicans (102 strains), followed by Candida glabrata (40 strains, 19.4%), and Candida parapsilosis (38 strains, 18.4%). The most frequently used antifungal drug for the initial dose was MCFG (120 cases, 59.2%), while the most frequently switched antifungal agent was L-AMB. Cases with an inappropriate end-of-treatment time represented 58.7% of all the cases. We investigated the Candidemia situation at our hospital for a period of seven years. We believe that it is important for medical institutions to gather detailed data on candidemia at their own hospitals. Likewise, the hospital's Infection Control Team/Antimicrobial Stewardship Team should inform the physicians-in-charge about the appropriate diagnosis and treatment based on the data obtained.

Introduction: A reversed halo sign (RHS) has diverse differential diagnoses such as cryptogenic organizing pneumonia, fungal, bacterial and mycobacterial infections, and systemic and neoplastic diseases. However, no report has been described regarding an RHS associated with infective endocarditis (IE). Case presentation: A 43‐year‐old man was transferred to our hospital because of persistent pyrexia, chest pain with multiple cavitary lung lesions for a month. He was diagnosed with tricuspid native valve IE caused by massive vegetations in the context of CA‐MRSA (staphylococcal cassette chromosome mec type II, sequence type 91, clonal complex 509) infection with multiple pulmonary septic emboli, manifesting as an atypical RHS. Conclusion: The present case showed huge tricuspid native valve IE associated with community‐acquired meticillin‐resistant Staphylococcus aureus (CA‐MRSA), which was analysed successfully by multilocus sequence typing.