Kanagawa Prefectural Institute of Public Health

Escherichia coli O157 and O26 are well-known Shiga toxin-producing E. coli (STEC) serotypes, but other serotypes such as O91, O103, O111, O121, O145, and O165 have also emerged as important public health concerns. PCR-based methods, such as multilocus variable-number tandem-repeat analysis (MLVA), are commonly used for rapid genotyping of STEC strains. However, MLVA requires analysis of numerous loci, some of which are serotype-specific, limiting its applicability across multiple STEC serotypes. In this study, we developed a PCR-based open reading frame typing (POT) method for genotyping diverse STEC serotypes. By detecting 22 ORFs using two multiplex PCR assays, STEC genotypes were determined based on the presence or absence of specific ORFs. Most STEC serotypes, except for O121, were classified with high discriminatory power (Simpson's index: 0.95-0.98). STEC-POT represents a rapid, cost-effective, and broadly applicable molecular typing tool. It facilitates timely outbreak detection and enhances public health surveillance by enabling rapid molecular epidemiological investigations.

Pediatric acute hepatitis of unknown etiology (AHUE) has been reported globally since April 2022. The purpose of the present study was to investigate the impact of coronavirus disease 2019 (COVID-19) pandemic on the incidence of AHUE in Japan. A nationwide survey of AHUE was conducted in 2510 pediatric hospitals by the Japan Pediatric Society. We retrospectively reviewed AHUE cases, defined by the World Health Organization's working case definition, and compared the incidence, clinical characteristics, and causative pathogens before the COVID-19 pandemic period (pre-pandemic, January 2017 to December 2019) and during the pandemic period (pandemic, January 2020 to June 2022). In total, 707 cases (450 pre-pandemic, 257 pandemic) were reported. The median age was 3years (interquartile range (IQR): 1-9years), and 43.8% were female. The number of AHUE cases decreased significantly in the pandemic period (102.8 cases/year) compared with the pre-pandemic period (150.0 cases/year). Investigations of pathogens causing AHUE demonstrated that the most common cause was unknown, accounting for 64% and 75% of cases in the pre-pandemic and pandemic periods, respectively. Among those whose pathogens were identified, the most common pathogens were Epstein-Barr virus (9.6%), cytomegalovirus (6.2%), and influenza (4.0%) in the pre-pandemic, and 7.0%, 3.5%, and 0.4%, respectively, in the pandemic period. SARS-CoV-2 and adenovirus were only 2.7% and 1.9%, respectively, in the pandemic period. The number of AHUE cases decreased during the COVID-19 pandemic compared with the pre-pandemic period, and no increase in adenovirus-associated disease or severe cases was observed in Japan.

Streptococcus pyogenes is involved in a wide range of diseases, including pharyngitis and life-threatening invasive infections. Increasing prevalence of antimicrobial resistance (AMR) has been reported worldwide in various bacteria, limiting the use of antibiotics in infection cases. The present study investigated the AMR of most prevalent S. pyogenes emm types, including emm89 strains in Japan. A total of 368 previously identified S. pyogenes isolates (311 emm89 strains and 57 of other emm types), which were previously isolated from patients with invasive and non-invasive infections throughout Japan, were used in the analyses. The minimum inhibitory concentrations of seven antibiotics, including penicillin-G, azithromycin (AZM) and clindamycin, were determined, and whole-genome sequences of AMR-associated genes were screened. We identified 47 resistant strains, of which 91.49% (43/47) were resistant to AZM and/or clindamycin. A strong correlation was observed between non-invasive phenotypes and AMR. Whole-genome analysis indicated the wide distribution of three AMR-related genes, ermT, folP and lmrP, among the emm89 strains. Additionally, tetO was detected in tetracycline-resistance and soxS and mel was detected in chloramphenicol-resistance only in emm4 strains. The high prevalence of S. pyogenes resistance to AZM and/or clindamycin poses a threat to public health in Japan; thus, the development of next-generation antimicrobial therapies is imperative.

Influenza viruses can cause zoonotic infections that pose public health risks. Surveillance of influenza A and B viruses is conducted globally; however, information on influenza C and D viruses is limited. Longitudinal monitoring of influenza C virus in humans has been conducted in several countries, but there has been no long-term monitoring of influenza D virus in humans. The public health risks associated with the influenza D virus therefore remain unknown. We established a duplex real-time RT-PCR to detect influenza C and D viruses and analyzed respiratory specimens collected from 2144 patients in Japan with respiratory diseases between January 2018 and March 2023. We isolated viruses and conducted hemagglutination inhibition tests to examine antigenicity and focus reduction assays to determine susceptibility to the cap-dependent endonuclease inhibitor baloxavir marboxil. We detected three influenza C viruses belonging to the C/Kanagawa- or C/Sao Paulo-lineages, which recently circulated globally. None of the specimens was positive for the influenza D virus. The C/Yokohama/1/2022 strain, isolated from the specimen with the highest viral RNA load and belonging to the C/Kanagawa-lineage, showed similar antigenicity to the reference C/Kanagawa-lineage strain and was susceptible to baloxavir. Our duplex real-time RT-PCR is useful for the simultaneous detection of influenza C and D viruses from the same specimen. Adding the influenza D virus to the monitoring of the influenza C virus would help in assessing the public health risks posed by this virus.

高いエネルギー分解能をもつ無機半導体放射線検出器は，素粒子・原子核実験などの分野で使用されているが，高純度な単結晶構造を必要とし柔軟性がなく高価で大型化が難しい。本研究は，結晶構造をもたない有機材料に着目した新しい放射線検出器の開発を行った。放射線感度を高めるために，n型半導体の性質をもつ二酸化チタンを混合して有機無機ハイブリッドセンサを試作した。本論文では，二酸化チタンの含有量や粒子径の違いによるセンサ性能への影響や特徴について述べる。

As coronavirus disease 2019 (COVID-19) outbreaks in healthcare facilities are a serious public health concern, we performed a case-control study to investigate the risk of COVID-19 infection in healthcare workers. We collected data on participants' sociodemographic characteristics, contact behaviors, installation status of personal protective equipment, and polymerase chain reaction testing results. We also collected whole blood and assessed seropositivity using the electrochemiluminescence immunoassay and microneutralization assay. In total, 161 (8.5%) of 1,899 participants were seropositive between August 3 and November 13, 2020. Physical contact (adjusted odds ratio 2.4, 95% confidence interval 1.1-5.6) and aerosol-generating procedures (1.9, 1.1-3.2) were associated with seropositivity. Using goggles (0.2, 0.1-0.5) and N95 masks (0.3, 0.1-0.8) had a preventive effect. Seroprevalence was higher in the outbreak ward (18.6%) than in the COVID-19 dedicated ward (1.4%). Results showed certain specific risk behaviors of COVID-19; proper infection prevention practices reduced these risks.

In order to adopt "screening analysis" in drinking water quality testing, which performs qualitative and quantitative analysis based on information registered in a database without measuring standard materials at the time of each testing, a validation test was conducted to evaluate the difference on the chromatogram data analysis by analysts. In the validation test, chromatograms of 6 water samples were analyzed using the same database and software by 16 analysts in 13 laboratories. Peak identification was performed based on Retention time (RT), (qualifier and target ion) QT ratio, and degree of matching of mass spectra, and if necessary, peak shapes in water samples were compared with those in calibration curve samples. Large differences were observed in the detection of pesticides among the analysts. There were two main reasons for the disagreement. The first is that the judgement of peak detection at low concentrations near the quantification limit of each pesticide, particularly below the concentration at three times of quantification limit, differed depending on the analyst. The other reason was that some analysts made clear misidentifications and identified wrong peaks close to the predicted retention time, despite the QT ratio and mass spectrum didn't match that in the database. In addition, there were some cases where the quantified values were reported by misidentifying the peaks of degradation products and metabolites, even when the peak detection was correctly judged. In order to use screening analysis practically by drinking water quality testing laboratories, it is important to conduct a validation test like this study in advance to use screening analysis and to coordinate criteria for peak identification and quantification among data analysts.

In Japan, large-scale mumps epidemics recur every 4-6 years because of low vaccination coverage. This study aimed to describe the seroprevalence of mumps in the Japanese population and identify the age groups most affected. The prevalence of anti-mumps antibodies was evaluated based on 1000 serum samples obtained from the Japanese National Serum Reference Bank. These samples consisted of 50 sera for each of 10 different age groups, collected during 2007-2008 (pre-epidemic period) and 2012-2013 (post-epidemic period). Seropositivity was lowest in the 6-11 months subgroup (3% and 0% in pre- and post-epidemic periods, respectively) and highest in the 10-14 years group (66% and 72% in pre- and post-epidemic periods, respectively). A comparison of anti-mumps antibody prevalence throughout the two periods considered revealed a large rise in seropositivity among the 2004-2008 birth cohort, using that of the 1-4 years group as representative in the pre-epidemic period (from 22% in pre- to 58% in post-epidemic periods;p = 0.0002). These results indicate that most people likely gain antibodies to the mumps virus during their childhood, especially during the first epidemic that they experience after their second year of life. Therefore, children should be vaccinated against mumps soon after their first birthday for effective prevention.