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Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis. To clarify the epidemiology of HEV and characterize the genetic diversity of the virus in Japan, nationwide enhanced surveillance and molecular characterization studies of HEV in Japan were undertaken from 2014 to 2021. In total, 2770 hepatitis E cases were reported, of which 88% were domestic cases, while only 4.1% represented cases following infection abroad. In addition, 57% of domestic infections occurred in males aged in their 40s–70s. For domestic cases, infection via pork meat consumption continued to be the most reported route. Analysis of the 324 sequences detected between 2016 and 2021 showed that the majority of domestic HEV strains belong to Genotype 3a (G3a) and G3b. In contrast, six of eight cases of G1 HEV reflected infection abroad. Our results suggest that HEV is circulating widely in Japan, with genotypes G3a and G3b being most prevalent. Continued surveillance is necessary to monitor future trends and changes in the epidemiology of HEV in Japan. [ABSTRACT FROM AUTHOR]

During a coronavirus infection, the spike protein undergoes sequential structural transitions triggered by its receptor and the host protease at the interface between the virus and cell membranes, thereby mediating membrane fusion. After receptor binding, the heptad repeat motif (HR1/HR2) within the viral spike protein bridges the viral and cellular membranes; however, the intermediate conformation adopted by the spike protein when drawing the viral and cellular membranes into close proximity remains unclear due to its transient and unstable nature. Here, we experimentally induced conformational changes in the spike protein of a murine coronavirus by incubating the virus with its receptor, followed by exposure to trypsin. We then treated the virus/receptor complex with proteinase K to probe the tightly packed core structure of the spike protein. The conformations of the spike protein were predicted from the sizes of the protease digestion products detected by western blot analysis. Upon receptor binding, two bands (each showing different reactivity with a fusion-inhibiting HR2-peptide) were detected; we propose that these bands correspond to the packed and unpacked HR1/HR2 motifs. After trypsin-mediated triggering, measurement of temperature and time dependency revealed that packing of the remaining unpacked HR1/HR2 motifs and assembly of three HR1 motifs in a trimer occur almost simultaneously. Thus, the trimeric spike protein adopts an asymmetric-unassembled conformation after receptor binding, followed by direct assembly into the post-fusion form triggered by the host protease. This biochemical study provides mechanistic insight into the previously unknown intermediate structure of the viral fusion protein.IMPORTANCEDuring infection by an enveloped virus, receptor binding triggers fusion between the cellular membrane and the virus envelope, enabling delivery of the viral genome to the cytoplasm. The viral spike protein mediates membrane fusion; however the molecular mechanism underlying this process is unclear. This is because using structural biology methods to track the transient conformational changes induced in the unstable spike trimer is challenging. Here, we harnessed the ability of protease enzymes to recognize subtle differences on protein surfaces, allowing us to detect structural differences in the spike protein before and after conformational changes. Differences in the size of the degradation products were analyzed by western blot analysis. The proposed model explaining the conformational changes presented herein is a plausible candidate that provides valuable insight into unanswered questions in the field of virology.

In Japan, as elsewhere, the COVID-19 pandemic affected the notification trends of respiratory syncytial virus (RSV) infection. Here, we describe the epidemiological trends of RSV cases among children reported during 2018-2021 in Japan, based on the national surveillance system. Compared to 2018 and 2019, 2020 saw an unprecedented decrease in RSV notifications per sentinel site. However, 2021 experienced an unseasonably early and high peak in week 28 (peak week in 2018 and 2019: week 37) with a large resurgence in notifications, nationwide and across regions. Regarding age, compared to 2018 and 2019, the number and proportion of cases aged 2, 3, and ≥4-years increased substantially in 2021 but the number of cases aged <1 year decreased slightly. Furthermore, in 2021, the ratio of notifications per site from outpatient clinics to hospitals increased, suggesting a proportionate increase in clinically milder case diagnoses. Notably, RSV-attributed deaths from vital statistics also dropped substantially in 2020 and rebounded in 2021, but were fewer than in 2018 or 2019. While RSV incidence likely declined in 2020 (possibly from COVID-19 countermeasures) and increased in 2021, notifications in 2021 appeared to be associated with milder presentations. Given unpredictable RSV epidemiology, continuous monitoring and pluralistic assessments are imperative.

Background: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the novel coronavirus disease 2019 (COVID-19) pandemic. This article aimed to describe those among travelers to Japan., Methods: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts-both by number and per arrival-were calculated by disease comparing those from the pandemic period (April 2020-March 2021) to the pre-pandemic period (April 2016-March 2020)., Results: A total of 3,524 imported infectious disease cases were diagnosed during the study period, including 3,439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95% confidence interval [CI], 41.5-78.7), malaria (21.7; 95% CI, 10.5-33.0), and typhoid fever (9.3; 95% CI, 1.9-16.8)., Conclusion: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance.

Background: The CD4 cell count of patients during diagnosis and distribution of CD4 cell counts in the patient population are important to understand infection-diagnosis interval and incidence rate of human immunodeficiency virus (HIV) infection, respectively. However, this information has not been published in Japan. This study aimed to describe the change in CD4 cell count trends and clarify the change in patients' characteristics in association with the CD4 cell count information., Methods: A descriptive study was conducted to analyze the medical records of patients with HIV who visited one of the largest acquired immunodeficiency syndrome (AIDS) core hospitals in western Japan. The basic characteristics, CD4 cell counts, viral loads, and diagnosis-treatment intervals between the first (2003-2010) and second (2011-2017) halves of the study duration were compared., Results: The distribution of CD4 cell counts significantly changed between 2003-2010 and 2011-2017 (χ 2 = 20.42, P < 0.001). The proportion of CD4 cell count <200 cells/mm 3 increased (38.8% in 2003 to 45.9% in 2017), whereas CD4 cell count ≥500 cells/mm 3 decreased (19.4% in 2003 to 12.2% in 2017). Moreover, the distributions of age groups, history of HIV screening test, patient outcomes, HIV viral load, and diagnosis-treatment interval also significantly changed (χ 2 = 25.55, P < 0.001; χ 2 = 8.37, P = 0.015; χ 2 = 6.07, P = 0.014; χ 2 = 13.36, P = 0.020; χ 2 = 173.76, P < 0.001, respectively)., Conclusion: This study demonstrated the fundamental trends of the HIV epidemic in Osaka, Japan between 2003-2010 and 2011-2017 and indicated that the incidence rate of HIV was decreasing in Japan.

Background: Coronavirus disease 2019 (COVID-19) continues to be a major global health burden. This study aims to estimate the all-cause excess mortality occurring in the COVID-19 outbreak in Japan, 2020, by sex and age group., Methods: Daily time series of mortality for the period January 2015-December 2020 in all 47 prefectures of Japan were obtained from the Ministry of Health, Labour and Welfare, Japan. A two-stage interrupted time-series design was used to calculate excess mortality. In the first stage, we estimated excess mortality by prefecture using quasi-Poisson regression models in combination with distributed lag non-linear models, adjusting for seasonal and long-term variations, weather conditions and influenza activity. In the second stage, we used a random-effects multivariate meta-analysis to synthesize prefecture-specific estimates at the nationwide level., Results: In 2020, we estimated an all-cause excess mortality of -20 982 deaths [95% empirical confidence intervals (eCI): -38 367 to -5472] in Japan, which corresponded to a percentage excess of -1.7% (95% eCI: -3.1 to -0.5) relative to the expected value. Reduced deaths were observed for both sexes and in all age groups except those aged <60 and 70-79 years., Conclusions: All-cause mortality during the COVID-19 outbreak in Japan in 2020 was decreased compared with a historical baseline. Further evaluation of cause-specific excess mortality is warranted., (© The Author(s) 2021. Published by Oxford University Press on behalf of the International Epidemiological Association.)