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.

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%).

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.

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.

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.

Coronavirus Disease 19 (COVID-19) Vaccine Effectiveness Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Delta-Dominant and Omicron-Dominant Periods in Japan: A Multicenter Prospective Case-control Study (Factors Associated with SARS-CoV-2 Infection and the Effectiveness of COVID-19 Vaccines Study).

BACKGROUND: Although several coronavirus disease 2019 (COVID-19) vaccines initially showed high efficacy, there have been concerns because of waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period compared with unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received messenger RNA (mRNA)-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% confidence interval [CI], 82-93) 14 days to 3 months after dose 2 and 87% (95% CI, 38-97) 3 to 6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI, 37-70) 14 days to 3 months since dose 2, 52% (95% CI, 40-62) 3 to 6 months after dose 2, 49% (95% CI, 34-61) 6+ months after dose 2, and 74% (95% CI, 62-83) 14+ days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (ie, mask wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan, where most are infection-naïve, and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

Infection-Induced SARS-CoV-2 Seroprevalence among Blood Donors, Japan, 2022.

A nationwide survey of SARS-CoV-2 antinucleocapsid seroprevalence among blood donors in Japan revealed that, as of November 2022, infection-induced seroprevalence of the population was 28.6% (95% CI 27.6%-29.6%). Seroprevalence studies might complement routine surveillance and ongoing monitoring efforts to provide a more complete real-time picture of COVID-19 burden.

SARS-CoV-2 Variants and Age-Dependent Infection Rates among Household and Nonhousehold Contacts.

To determine the effects of age and variants of concern on transmission of SARS-CoV-2, we analyzed infection rates among close contacts over 4 periods in Toyama Prefecture, Japan. Among household contacts, odds of infection were 6.2 times higher during the period of the Omicron variant than during previous periods, particularly among children and adolescents.

Invasive Haemophilus influenzae disease among adults in Japan during 2014-2018.

PURPOSE: We describe the epidemiology of invasive Haemophilus influenzae disease (IHD) among adults in Japan. METHODS: Data for 200 adult IHD patients in 2014-2018 were analyzed. The capsular type of H. influenzae was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable Haemophilus influenzae (NTHi) was identified by PCR. RESULTS: The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15-64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5% were aged ≥ 65 years. About one-fourth of patients were associated with immunocompromising condition. The major presentations were pneumonia, followed by bacteremia, meningitis and other than pneumonia or meningitis (other diseases). The case fatality rate (CFR) was 21.2% for all cases, and was significantly higher in the ≥ 65-year group (26.1%) than in the 15-64-year group (7.5%) (p = 0.013). The percentage of cases with pneumonia was significantly higher in the ≥ 65-year group than in the 15-64-year group (p < 0.001). The percentage of cases with bacteremia was significantly higher in the 15-64-year group than in the ≥ 65-year group (p = 0.027). Of 200 isolates, 190 (95.0%) were NTHi strains, and the other strains were encapsulated strains. 71 (35.5%) were resistant to ampicillin, but all were susceptible to ceftriaxone. CONCLUSION: The clinical presentations of adult IHD patients varied widely; about three-fourths of patients were age ≥ 65 years and their CFR was high. Our findings support preventing strategies for IHD among older adults, including the development of NTHi vaccine.

Impact of airline network on the global importation risk of mpox, 2022.

From 1 January 2022 to 4 September 2022, a total of 53 996 mpox cases were confirmed globally. Cases are predominantly concentrated in Europe and the Americas, while other regions are also continuously observing imported cases. This study aimed to estimate the potential global risk of mpox importation and consider hypothetical scenarios of travel restrictions by varying passenger volumes (PVs) via airline travel network. PV data for the airline network, and the time of first confirmed mpox case for a total of 1680 airports in 176 countries (and territories) were extracted from publicly available data sources. A survival analysis technique in which the hazard function was a function of effective distance was utilised to estimate the importation risk. The arrival time ranged from 9 to 48 days since the first case was identified in the UK on 6 May 2022. The estimated risk of importation showed that regardless of the geographic region, most locations will have an intensified importation risk by 31 December 2022. Travel restrictions scenarios had a minor impact on the global airline importation risk against mpox, highlighting the importance to enhance local capacities for the identification of mpox and to be prepared to carry out contact tracing and isolation.

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.

Haplotype networks of SARS-CoV-2 infections in the Diamond Princess cruise ship outbreak.

The Diamond Princess cruise ship was put under quarantine offshore Yokohama, Japan, after a passenger who disembarked in Hong Kong was confirmed as a coronavirus disease 2019 case. We performed whole-genome sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly from PCR+ clinical specimens and conducted a phylogenetic analysis of the outbreak. All tested isolates exhibited a transversion at G11083T, suggesting that SARS-CoV-2 dissemination on the Diamond Princess originated from a single introduction event before the quarantine started. Although further spreading might have been prevented by quarantine, some progeny clusters could be linked to transmission through mass-gathering events in the recreational areas and direct transmission among passengers who shared cabins during the quarantine. This study demonstrates the usefulness of haplotype network/phylogeny analysis in identifying potential infection routes.

Unprecedented increase in syphilis cases among heterosexual men and women in Japan, 2021-2022.

Based on national surveillance data, we describe an unprecedented increase in syphilis case reports in Japan, with a surge in 2021-2022 reaching 10141 cases in Week 42, 2022, a 1.7-fold increase over the same period in 2021. This already represented the highest annual case count in nearly half a century; by Week 52, 2022, the number reached 12 966, far surpassing the 7978 cases in 2021. Predominantly affecting heterosexual men and young women, the proportionate increase in primary and secondary syphilis cases suggests a true increase in incidence. The syphilis surge during the pandemic poses a serious public health concern and underscores the importance of adequate testing and preventive measures.

Effectiveness of Messenger RNA Coronavirus Disease 2019 Vaccines Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infections During the Delta Variant Epidemic in Japan: Vaccine Effectiveness Real-time Surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: Although high vaccine effectiveness of messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines has been reported in studies in several countries, data are limited from Asian countries, especially against the Delta (B.1.617.2) variant. METHODS: We conducted a multicenter test-negative case-control study in patients aged ≥16 years visiting hospitals or clinics with signs or symptoms consistent with COVID-19 from 1 July to 30 September 2021, when the Delta variant was dominant (≥90% of SARS-CoV-2 infections) nationwide in Japan. Vaccine effectiveness of BNT162b2 or mRNA-1273 against symptomatic SARS-CoV-2 infections was evaluated. Waning immunity among patients aged 16-64 years was also assessed. RESULTS: We enrolled 1936 patients, including 396 test-positive cases and 1540 test-negative controls for SARS-CoV-2. The median age was 49 years, 53.4% were male, and 34.0% had underlying medical conditions. Full vaccination (receiving 2 doses ≥14 days before symptom onset) was received by 6.6% of cases and 38.8% of controls. Vaccine effectiveness of full vaccination against symptomatic SARS-CoV-2 infections was 88.7% (95% confidence interval [CI], 78.8%-93.9%) among patients aged 16-64 years and 90.3% (95% CI, 73.6%-96.4%) among patients aged ≥65 years. Among patients aged 16-64 years, vaccine effectiveness was 91.8% (95% CI, 80.3%-96.6%) within 1-3 months after full vaccination, and 86.4% (95% CI, 56.9%-95.7%) within 4-6 months. CONCLUSIONS: mRNA COVID-19 vaccines had high effectiveness against symptomatic SARS-CoV-2 infections in Japan during July-September 2021, when the Delta variant was dominant nationwide.

Age-Dependent Effects of COVID-19 Vaccine and of Healthcare Burden on COVID-19 Deaths, Tokyo, Japan.

COVID-19 vaccine effectiveness against death in Japan remains unknown. Furthermore, although evidence indicates that healthcare capacity influences case-fatality risk (CFR), it remains unknown whether this relationship is mediated by age. With a modeling study, we analyzed daily COVID-19 cases and deaths during January-August 2021 by using Tokyo surveillance data to jointly estimate COVID-19 vaccine effectiveness against death and age-specific CFR. We also examined daily healthcare operations to determine the association between healthcare burden and age-specific CFR. Among fully vaccinated patients, vaccine effectiveness against death was 88.6% among patients 60-69 years of age, 83.9% among patients 70-79 years of age, 83.5% among patients 80-89 years of age, and 77.7% among patients >90 years of age. A positive association of several indicators of healthcare burden with CFR among patients >70 years of age suggested an age-dependent effect of healthcare burden on CFR in Japan.

Social and Behavioral Factors Associated with Lack of Intent to Receive COVID-19 Vaccine, Japan.

Persons in Japan who did not intend to receive COVID-19 vaccines after widespread rollout were less likely than others to engage in preventive measures or to be afraid of getting infected or infecting others. They were also not less likely to engage in potentially high-risk behaviors, suggesting similar or higher exposure risks.

High prevalence of multiple serotypes of pneumococci in patients with pneumonia and their associated risk factors.

BACKGROUND: Multiple serotypes of pneumococci have epidemiological and clinical implications, such as the emergence of non-vaccine serotypes and the acquisition of antimicrobial resistance. Prevalence of multiple serotypes of pneumococci in adults and their risk factors are not known. METHODS: We enrolled adult patients from age ≥15 years with radiologically confirmed pneumonia in four hospitals across Japan. Pneumococcal pneumonia was defined with a pneumococcal bacterial density of ≥104/mL in sputum by lytA quantitative PCR, and serotypes were determined. Pneumonias with a single serotype were categorised as single-serotype pneumococcal pneumonia and with two or more serotypes as multiple-serotype pneumococcal pneumonia. Multivariable logistic regression was used to assess the risk factors. RESULTS: 3470 patients (median age 77 years, IQR 65-85) were enrolled. Pneumococcal pneumonia was identified in 476 (18.3%, n=2605) patients. Multiple serotypes were detected in 42% of them. Risk of having multiple serotypes was low among patients who had received 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccines (adjusted OR 0.51 (95% CI 0.27 to 0.94)). Proportion of non-PCV7 PPSV23 serotypes in overall distribution of multiple serotypes was 67.4% (n=324/481) compared with 46.4% (n=128/276) in that of single serotypes (p=0.001). Serotypes 5, 9N/9L, 10A, 12/22/46, 17F and 35F were associated with multiple-serotype pneumonia, and serotypes 6A/6B, 23F, 11 and 6C/6D were associated with single-serotype pneumonia. Proportion of more invasive serotypes (serotypes 1, 5, 7F, 8) was significantly higher in multiple-serotype pneumonia (p=0.001). CONCLUSIONS: Multiple serotypes of pneumococci are common in sputum of adult patients with pneumonia. The risk of multiple-serotype pneumococcal pneumonia is lower than that of single-serotype pneumococcal pneumonia among PPSV23-vaccinated patients. TRIAL REGISTRATION NUMBER: UMIN000006909.

A seroepidemiological study across age groups before and after the 2010-2011 mumps epidemic in Japan.

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.

Respiratory virus detection in the upper respiratory tract of asymptomatic, community-dwelling older people.

BACKGROUND: The prevalence of virus positivity in the upper respiratory tract of asymptomatic community-dwelling older people remains elusive. Our objective was to investigate the prevalence of respiratory virus PCR positivity in asymptomatic community-dwelling older people using saliva samples and nasopharyngeal and oropharyngeal swabs. METHODS: We analyzed 504 community-dwelling adults aged ≥ 65 years who were ambulatory and enrolled in a cross-sectional study conducted from February to December 2018 in Nagasaki city, Japan. Fourteen respiratory viruses were identified in saliva, nasopharyngeal and oropharyngeal samples using multiplex PCR assays. RESULTS: The prevalences of PCR positivity for rhinovirus, influenza A, enterovirus and any respiratory virus were 12.9% (95% CI: 10.1-16.1%), 7.1% (95% CI: 5.1-9.8%), 6.9% (95% CI: 4.9-9.5%) and 25.2% (95% CI: 21.5-29.2%), respectively. Rhinovirus was detected in 21.5% of subjects, influenza A in 38.9% of subjects, enterovirus in 51.4% of subjects and any virus in 32.3% of subjects using only saliva sampling. CONCLUSIONS: The prevalences of several respiratory viruses were higher than the percentages reported previously in pharyngeal samples from younger adults. Saliva sampling is a potentially useful method for respiratory virus detection in asymptomatic populations.

Diphtheria in Metro Manila, the Philippines 2006-2017: A Clinical, Molecular, and Spatial Characterization.

BACKGROUND: Diphtheria is a vaccine-preventable disease that persists as a global health problem. An understanding of the pattern of disease is lacking in low- and middle-income countries such as the Philippines. METHODS: We conducted a retrospective review of the clinical, microbiological, and epidemiological features of patients admitted with a clinical diagnosis of diphtheria to an infectious disease referral hospital in Metro Manila, the Philippines, between 2006 and 2017. Cases were mapped and the distribution was compared with population density. Corynebacterium diphtheriae isolates from between 2015 and 2017 were examined by multilocus sequence typing (MLST). RESULTS: We studied 267 patients (range:12-54 cases/year) admitted between 2006 and 2017. The case fatality rate (CFR) was 43.8% (95% confidence interval, 37.8-50.0%). A higher number of cases and CFR was observed among children <10 years. Mortality was associated with a delayed admission to hospital and a lack of diphtheria antitoxin. Between 2015 and 2017 there were 42 laboratory-confirmed cases. We identified 6 multilocus sequence types (STs). ST-302 was the most common (17/34, 48.6%), followed by ST67 (7/34, 20%) and ST458 (5/34, 14%). Case mapping showed a wide distribution of diphtheria patients in Metro Manila. Higher case numbers were found in densely populated areas but with no apparent clustering of ST types. CONCLUSIONS: Our analysis indicates that diphtheria remains endemic in Metro Manila and that the infection is frequently fatal in young children. Improved vaccine coverage and a sustainable supply of diphtheria antitoxin should be prioritized.