Fatal SARS-CoV-2 Infection among Children, Japan, January-September 20221.

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases.

Effects of coronavirus disease 2019 on the spread of respiratory-transmitted human-to-human bacteria.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has necessitated significant changes in medical systems, social behaviours, and non-pharmaceutical interventions (NPIs). We aimed to determine the effect of the COVID-19 pandemic on changes in the epidemiology of respiratory-transmitted bacteria that have been unexplored. METHODS: We utilised a comprehensive national surveillance database from 2018 to 2021 to compare monthly number of patients with four respiratory-transmitted human-to-human bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes) before and after the COVID-19 pandemic, stratified by specimen sources and age groups. RESULTS: The incidence of detected patients with S. pneumoniae, H. influenzae, and S. pyogenes from both respiratory and blood cultures significantly decreased from 2019 to 2020. In 2021, the incidence of detected patients with the respiratory-transmitted bacterial species, except for S. pyogenes, from respiratory cultures, increased again from April to July, primarily affecting the 0-4-year age group. CONCLUSIONS: Our comprehensive national surveillance data analysis demonstrates the dynamic changes and effects of NPIs on respiratory-transmitted bacteria during the COVID-19 pandemic, with variations observed among species, specimen sources, and age groups.

Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence, Japan, 2023.

We assessed SARS-CoV-2 seroprevalence in Japan during July-August 2023, with a focus on 2 key age groups, 0-15 and >80 years. We estimated overall seroprevalence of 45.3% for nucleocapsid antibodies and 95.4% for spike antibodies and found notable maternally derived spike antibodies in infants 6-11 months of age (90.0%).

Correction: Unique characteristics of new complete blood count parameters, the Immature Platelet Fraction and the Immature Platelet Fraction Count, in dengue patients.

[This corrects the article DOI: 10.1371/journal.pone.0258936.].

Unveiling the role of preceding seasonal influenza in the development of bacteremic pneumococcal pneumonia in older adults before the COVID-19 pandemic in Japan.

OBJECTIVE: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. METHODS: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID-19 pandemic (2020-2022). RESULTS: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic (P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. CONCLUSION: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults.

Identifying the population susceptible to rubella in Japan, 2020: Fine-scale risk mapping.

BACKGROUND: Rubella remains a public health challenge in Japan, impeding the attainment of herd immunity. Despite vaccination efforts since 1976, persistent outbreaks reveal a susceptibility gap in male adults born before 1995. Seroepidemiological surveys are pivotal in evaluating population immunity and identifying at-risk groups. METHODS: This study aims to pinpoint high-risk areas for potential rubella outbreaks in Japan by merging seroepidemiological data from 2020 with population census information. Various data sources, including spatial demographic data, reported rubella and congenital rubella syndrome (CRS) cases, and traveler lodging statistics, were employed. Geospatial information for Japan's 230,300 small geographic areas was analyzed, and HI (hemagglutination inhibition) titers were examined by age and sex. Seroconversion was defined as an HI titer ≥ 1:32 or 1:16, indicating protective immunity. Geospatial maps illustrated the distribution of susceptible individuals per square kilometer, emphasizing high-risk urban areas like Tokyo and Osaka. Demographic shifts in the working-age population were assessed. RESULTS: Susceptible individuals cluster in densely populated urban centers, persisting despite demographic changes. The study highlights areas at risk of increased susceptibility, particularly with an HI titer cut-off of 1:16. Foreign travelers pose potential rubella importation risks as travel volume to Japan rises. To prevent epidemics and congenital rubella syndrome burden, achieving and sustaining herd immunity in high-risk areas is crucial. CONCLUSIONS: This study offers a comprehensive assessment of vulnerability in densely populated Japanese regions. Integrating population statistics with seroepidemiological data enhances our understanding of population immunity, guiding resource allocation for supplementary vaccination planning. To avert rubella epidemics, high-risk locations must bolster indirect protection through herd immunity, ultimately preventing congenital rubella syndrome.

Usefulness of a pluralistic approach in sentinel surveillance: seasonal influenza activity based on case counts per sentinel site in the National Epidemiological Surveillance of Infectious Diseases Program and test counts, case counts, and test positivity from the National Hospital Organization.

In Japan, based on the National Epidemiological Surveillance of Infectious Diseases (NESID) Program, influenza cases from ~5,000 sentinel sites are monitored weekly as part of influenza surveillance (as number of influenza cases/sentinel site). One limitation is that the number of influenza tests conducted is not reported. Separately, the National Hospital Organization (NHO), with ~140 hospitals, routinely publishes three indicators: number of influenza tests, influenza-positive case counts, and test positivity. We used NESID and NHO data from April 2011 to June 2022 to assess the usefulness of multiple indicators to monitor influenza activity. Temporal trends of the NHO and NESID indicators were similar, and NHO indicator levels well-correlated with those of the NESID indicator. Influenza positivity in the NHO data, however, showed an earlier rise and peak time compared to the NESID indicator. Importantly, through the non-epidemic summer periods and the coronavirus disease 2019 pandemic, a sizable number of influenza tests continued to be done at NHO hospitals, with results showing considerably low case counts and test positivity. These data show that a relatively small number of sentinel sites is sufficient to monitor influenza activity nationally, and, that utilizing multiple indicators can increase our confidence in situational awareness and data interpretations.

Changes in Place of Death among Patients with Dementia during the COVID-19 Pandemic in Japan: A Time Series Analysis.

BACKGROUND: A key measure of the effectiveness of end-of-life care is the place of death. The COVID-19 pandemic affected end-of-life care and the circumstances of patients with dementia. METHODS: This observational, retrospective cohort study used Japanese national data to examine the numbers and locations of reported deaths among patients with dementia older than 65 years during the COVID-19 pandemic. Locations were grouped as medical institutions, nursing facilities, homes, or all the above. The quasi-Poisson regression model known as the Farrington algorithm was employed. RESULTS: Between December 30, 2019, and January 29, 2023, 279,703 patients who died of causes related to dementia were reported in Japan. A decline was seen in early 2020, followed by increased numbers of deaths in homes, medical facilities, and nursing homes beginning in October 2020, December 2020, and March 2021, respectively. In 2021, the percentage of excess deaths at home peaked at 35.2%, while in 2022, those in medical facilities and nursing homes peaked at 18.8% and 16.6%, respectively. In 2022, the percentage of excess deaths in nursing homes exceeded that of other locations. CONCLUSIONS: The results suggest a change in the preferred place of death, along with pandemic-related visitation restrictions among healthcare facilities. Excess deaths also suggest strained medical resources and limited access to care. Methodological limitations include data from a limited period (2017 onwards) and post-2020 data used to estimate data after 2021, albeit with weighting. Considering these findings, physicians should reconfirm preferred places of death among older patients with dementia.

A description of a pre-emptive typhoid Vi capsular polysaccharide vaccination campaign after the 2015 earthquake in Nepal and vaccine effectiveness evaluation.

BACKGROUND: A 7.8 R scale earthquake hit Nepal in April 2015 and caused about 9000 deaths along with damage to infrastructure, including the water and sewage system. Bhaktapur was one of the highly affected districts. A typhoid vaccination campaign (pre-emptive) was carried out among children who were living in the temporary shelters in this district. The assessment of vaccine effectiveness after a pre-emptive typhoid vaccine campaign following an earthquake has previously not been attempted in Nepal. OBJECTIVE: To describe the pre-emptive typhoid Vi capsular polysaccharide vaccination campaign and an evaluation of the vaccine effectiveness. METHODS: We conducted a pre-emptive typhoid Vi capsular polysaccharide vaccination campaign among children between 2 and 15 years of age dwelling in 23 temporary shelters in Bhaktapur district after the earthquake. Surveillance of clinical typhoid was carried out from 2014 to 2017 in Siddhi Memorial Hospital, the only hospital for children in the district. We calculated vaccine effectiveness using a case-control study design (clinical typhoid as cases and chest x-ray confirmed pneumonia as controls). RESULTS: Three thousand nine hundred sixteen children of age 2-15 years residing in the 23 temporary shelters in Bhaktapur received the typhoid Vi capsular polysaccharide vaccine between July and December 2015. 2193 children of age 2-15 years were admitted to the hospital during the study period and 260 (11.9%) were diagnosed with clinical typhoid. The numbers of children admitted with clinical typhoid decreased over the study period (105 in 2014 and 47 in 2017; P = 0.001). Overall vaccine effectiveness was calculated at 52% (95% CI -46 to 85%), and it was 87% (95% CI -25 to 99) among children less than 5 years of age. CONCLUSIONS: We successfully conducted a pre-emptive vaccination campaign against typhoid after the 2015 Nepal earthquake. The pre-emptive vaccination campaign appeared to be more effective among children less than 5 years of age. Further studies are needed to assess the effectiveness of pre-emptive use of typhoid vaccines in the emergency situations. We highlight the challenges of calculating vaccine effectiveness of a typhoid vaccine in an emergency setting.

Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Epidemiologic Trends and Distributions of Imported Infectious Diseases Among Travelers to Japan Before and During the COVID-19 Pandemic, 2016 to 2021: A Descriptive Study.

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.

Macacine alphaherpesvirus 1 (B Virus) Infection in Humans, Japan, 2019.

Two human patients with Macacine alphaherpesvirus 1 infection were identified in Japan in 2019. Both patients had worked at the same company, which had a macaque facility. The rhesus-genotype B virus genome was detected in cerebrospinal fluid samples from both patients.

Infectious virus shedding duration reflects secretory IgA antibody response latency after SARS-CoV-2 infection.

Infectious virus shedding from individuals infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is used to estimate human-to-human transmission risk. Control of SARS-CoV-2 transmission requires identifying the immune correlates that protect infectious virus shedding. Mucosal immunity prevents infection by SARS-CoV-2, which replicates in the respiratory epithelium and spreads rapidly to other hosts. However, whether mucosal immunity prevents the shedding of the infectious virus in SARS-CoV-2-infected individuals is unknown. We examined the relationship between viral RNA shedding dynamics, duration of infectious virus shedding, and mucosal antibody responses during SARS-CoV-2 infection. Anti-spike secretory IgA antibodies (S-IgA) reduced viral RNA load and infectivity more than anti-spike IgG/IgA antibodies in infected nasopharyngeal samples. Compared with the IgG/IgA response, the anti-spike S-IgA post-infection responses affected the viral RNA shedding dynamics and predicted the duration of infectious virus shedding regardless of the immune history. These findings highlight the importance of anti-spike S-IgA responses in individuals infected with SARS-CoV-2 for preventing infectious virus shedding and SARS-CoV-2 transmission. Developing medical countermeasures to shorten S-IgA response time may help control human-to-human transmission of SARS-CoV-2 infection and prevent future respiratory virus pandemics.

Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis.

OBJECTIVES: The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022. STUDY ELIGIBILITY CRITERIA: We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant. DATA EXTRACTION AND SYNTHESIS: Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach. RESULTS: This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14-30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61-90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91-120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death. CONCLUSION: The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies. PROSPERO REGISTRATION NUMBER: CRD42023376698.

Evaluating the COVID-19 vaccination program in Japan, 2021 using the counterfactual reproduction number.

Japan implemented its nationwide vaccination program against COVID-19 in 2021, immunizing more than one million people (approximately 1%) a day. However, the direct and indirect impacts of the program at the population level have yet to be fully evaluated. To assess the vaccine effectiveness during the Delta variant (B.1.617.2) epidemic in 2021, we used a renewal process model. A transmission model was fitted to the confirmed cases from 17 February to 30 November 2021. In the absence of vaccination, the cumulative numbers of infections and deaths during the study period were estimated to be 63.3 million (95% confidence interval [CI] 63.2-63.6) and 364,000 (95% CI 363-366), respectively; the actual numbers of infections and deaths were 4.7 million and 10,000, respectively. Were the vaccination implemented 14 days earlier, there could have been 54% and 48% fewer cases and deaths, respectively, than the actual numbers. We demonstrated the very high effectiveness of COVID-19 vaccination in Japan during 2021, which reduced mortality by more than 97% compared with the counterfactual scenario. The timing of expanding vaccination and vaccine recipients could be key to mitigating the disease burden of COVID-19. Rapid and proper decision making based on firm epidemiological input is vital.

Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan.

BACKGROUND: Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation. METHODS: A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses. RESULTS: 13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4. CONCLUSIONS: Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection.

Impact of the COVID-19 pandemic on cancer death locations in Japan: an analysis up to February 2023 on excess mortality.

IntroductionThe Covid-19 pandemic has significantly impacted end-of-life decisions for cancer patients in Japan, with disparities existing between preferred and actual care settings. Our study investigates the potential shifts in cancer death locations during the pandemic and if there were excess cancer deaths.MethodsUtilizing national mortality data from the Ministry of Health, Labour, and Welfare from January 2012 to February 2023, we identified cancer deaths using ICD-10 codes. We assessed death locations, including medical institutions, nursing facilities, and homes. The Farrington algorithm was employed to estimate expected death counts, and the differences between observed and expected counts were denoted as excess deaths.ResultsFrom January 2018 to February 2023, there was consistently increase in the weekly observed cancer deaths. The presence of a definitive excess during the pandemic period remains uncertain. The percentage of deaths in medical institutions declined from 83.3% to 70.1% , while home deaths increased from 12.1% to 22.9%. Between April 2020 and February 2023, deaths in medical institutions frequently fell below the 95% prediction lower limit. Home deaths consistently exceeded the 95% prediction upper limit, with significant excess deaths reported annually.ConclusionOur study found a shift in cancer death locations from medical institutions to homes in Japan during the COVID-19 pandemic. Our study did not confirm an overall increase in cancer deaths during this period. As with global trends, the profound shift from hospitals to homes in Japan calls for a comprehensive exploration to grasp the pandemic's multifaceted impact on end-of-life cancer care decisions.