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.

Rapid response to a COVID-19 outbreak at a nightclub in Kagoshima prefecture, Japan, in the early phase of the COVID-19 pandemic, June and July 2020: A descriptive epidemiological study.

INTRODUCTION: During COVID-19 pandemic in Japan, nightclubs were identified as high-risk locations for COVID-19 outbreaks, but an outbreak investigation in this setting is challenging because of the anonymous and opportunistic nature of interactions. METHODS: The joint rapid response team collected epidemiological data, conducted descriptive epidemiology to determine the characteristics of cases associated with the nightclub, and implemented countermeasures. Polymerase chain reaction (PCR) tests were performed by the Local Institute of Public Health, Kagoshima University, and several commercial laboratories. RESULTS: Between June 15 and July 20, 2020, 121 individuals tested positive for SARS-CoV-2 (59 confirmed and 62 asymptomatic) of whom 8 were nightclub staff who had no travel history of outside Kagoshima, 66 were guests, and 47 were subsequent contacts. The median age was 32 years (interquartile range: 24-43 years). One individual showed severe symptoms but there were no fatal. The epidemic curve showed one peak on June 30 and July 1 with a limited number of cases subsequently. Of the 121 cases, 116 and 5 were in individuals living in and outside Kagoshima Prefecture, respectively. Haplotype network analysis showed 5 genome-wide single-nucleotide variants between the isolates before and during this outbreak. CONCLUSIONS: There is a possibility that unidentified guests from outside Kagoshima Prefecture could infect staff who could subsequently spread the virus to guests and other staff, who were mainly a younger population. The rapid outbreak response enabled onward transmission in the community to be minimized. This outbreak investigation could provide insights for effective responses to challenging situations in future pandemic.

Enhanced measures, including PCR-based screening and syndromic surveillance for nosocomial outbreaks of the COVID-19 Omicron variant, using descriptive epidemiology and whole-genome sequencing in a Japanese tertiary care hospital.

INTRODUCTION: In this study, we aimed to analyze the effectiveness of enhanced preventive measures against nosocomial COVID-19 Omicron outbreaks based on those encountered. METHODS: We introduced PCR-based screening and syndromic surveillance, in addition to standard and transmission-based precautions, during a COVID-19 outbreak in three wards of Kagoshima University Hospital, a Japanese tertiary care hospital, in February 2022, amid the Omicron variant endemic. Furthermore, we analyzed the descriptive epidemiology and whole-genome sequencing (WGS) of positive SARS-CoV-2 PCR samples from this outbreak. RESULTS: PCR-based screening tests were conducted following the identification of three cases through syndromic surveillance. As a result, 30 individuals tested positive for SARS-CoV-2, including 13 inpatients, five attendant family members, and 12 healthcare workers across the three wards. Notably, no new infections were observed within eight days following the implementation of preventive measures. Among the SARS-CoV-2 genomes analyzed (n = 16; 53.3%), all strains were identified as belonged to BA.1.1 variant. Detailed analysis of descriptive and molecular epidemiology, incorporating single-nucleotide polymorphism analysis of WGS and clarification of transmission links, considering two potential entry routes to the hospital. CONCLUSIONS: Introduction of additional preventive measures, including PCR-based screening and syndromic surveillance, in addition to WGS and descriptive epidemiology, is useful for the early intervention of nosocomial outbreaks and for revealing the transmission route of the COVID-19 Omicron variant.

National Surveillance of Pediatric Acute Hepatitis of Unknown Etiology, Japan, October 2021-December 2022.

Pediatric acute hepatitis of unknown etiology has been reported globally since April 2022. In Japan, 139 possible cases with onset dates after October 2021 were reported as of December 2022. Three patients required liver transplants, but none died. Rates of adenovirus positivity (11/125, 9%) were lower than those for other countries.

SARS-CoV-2 Infection in Wrestlers after International Tournaments, April 2021.

Epidemiologic and genomic investigation of SARS-CoV-2 infections in members of Japan's national wrestling team after participation in international tournaments in 2021 revealed multiple lineages of SARS-CoV-2 not reported in Japan. The attack rate among wrestlers was high. Results suggest possible transmission during matches. We recommend early case detection and response practices.

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.

Seroepidemiology of hepatitis A virus infection in Japan: An area of very low endemicity.

The incidence of hepatitis A virus (HAV) infection has declined significantly worldwide, including in Japan. A nationwide seroepidemiological study on hepatitis A in Japan has taken place almost every 10 years since 1973, and the last study was performed in 2003. In the present study, we describe the latest seroepidemiological pattern of hepatitis A in Japan using 7867 serum specimens obtained from healthy individuals collected between 2013 and 2017, approximately 10 years after the last study. Among them, 223 were anti-HAV positive. About 68% of individuals aged 60 years and older had anti-HAV antibodies, whereas only 1.1% of those aged below 60 years old had immunity; thus, almost all individuals younger than 60 years of age were HAV susceptible. In comparison with previous investigations, the susceptible population has increased and aged. According to data from the National Epidemiological Surveillance of Infectious Diseases (NESID) program, between 1989 and 2016, the proportion of patients with hepatitis A aged 60 years and older continuously increased with each year. The NESID data also suggested that recently, typical large foodborne outbreaks of hepatitis A have become rare, and cases tend to be reported among at-risk groups; overseas travelers contributed to 25% of hepatitis A cases, and in 2018, the first nationwide hepatitis A outbreak that affected mostly men who have sex with men was reported. The purpose of this study was to determine the current status of HAV infection in Japan, based on both seroepidemiology and the national surveillance data from the NESID.

Atypical diarrhoeagenic Escherichia coli in milk related to a large foodborne outbreak.

A foodborne outbreak related to milk cartons served in school lunches occurred in June 2021, which involved more than 1,800 cases from 25 schools. The major symptoms were abdominal pain, diarrhoea, vomiting, and fever. Although major foodborne toxins and pathogens were not detected, a specific Escherichia coli strain, serotype OUT (OgGp9):H18, was predominantly isolated from milk samples related to the outbreak and most patients tested. The strains from milk and patient stool samples were identified as the same clone by core genome multilocus sequence typing and single-nucleotide polymorphism analysis. The strain was detected in milk samples served for two days related to the foodborne outbreak at a rate of 69.6% and levels of less than ten most probable number/100 mL but not on days unrelated to the outbreak. The acid tolerance of the strain for survival in the stomach was similar to that of enterohaemorrhagic E. coli O157:H7, and the same inserts in the chu gene cluster in the acid fitness island were genetically revealed. The pathogenicity of the strain was not clear; however, it was indicated that the causative pathogen was atypical diarrhoeagenic E. coli OUT (OgGp9):H18.

Trends in CD4+ Cell Counts, Viral Load, Treatment, Testing History, and Sociodemographic Characteristics of Newly Diagnosed HIV Patients in Osaka, Japan, From 2003 through 2017: A Descriptive Study.

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 (χ2 = 20.42, P < 0.001). The proportion of CD4 cell count <200 cells/mm3 increased (38.8% in 2003 to 45.9% in 2017), whereas CD4 cell count ≥500 cells/mm3 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 (χ2 = 25.55, P < 0.001; χ2 = 8.37, P = 0.015; χ2 = 6.07, P = 0.014; χ2 = 13.36, P = 0.020; χ2 = 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.

Proactive Engagement of the Expert Meeting in Managing the Early Phase of the COVID-19 Epidemic, Japan, February-June 2020.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Excess All-Cause Deaths during Coronavirus Disease Pandemic, Japan, January-May 20201.

To provide insight into the mortality burden of coronavirus disease (COVID-19) in Japan, we estimated the excess all-cause deaths for each week during the pandemic, January-May 2020, by prefecture and age group. We applied quasi-Poisson regression models to vital statistics data. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the 1-sided prediction interval. A total of 208-4,322 all-cause excess deaths at the national level indicated a 0.03%-0.72% excess in the observed number of deaths. Prefecture and age structure consistency between the reported COVID-19 deaths and our estimates was weak, suggesting the need to use cause-specific analyses to distinguish between direct and indirect consequences of COVID-19.

Clinical Characteristics and Risk Factors for Severe Outcomes of Novel Coronavirus Infection, January-March 2020, Japan.

BACKGROUND: Notifications of novel coronavirus infections increased in early 2020 in Japan. We described characteristics of novel coronavirus infection cases and analyzed risk factors for severe outcomes. METHODS: Cases were persons with laboratory-confirmed novel coronavirus infection reported under national surveillance between January and March 2020. Clinical characteristics were described, and risk factors of (1) intensive care unit [ICU] admission and (2) invasive ventilation/death were analyzed using Poisson regression. RESULTS: Among the 516 cases analyzed, median age was 60 years (range: 1-97 years) and 285 (55%) were male. Common symptoms/signs were fever (375/475, 79%), cough (353/465, 76%), and pneumonia (245/387, 63%). Ten (2%) cases died. Of the 348 cases with data, 50 (14%) required invasive ventilation. Adjusted for each other, male gender and 1-year increase in age were associated with ICU admission (risk ratio [RR] 4.18; 95% confidence interval [CI], 1.69-10.32 and RR 1.05; 95% CI, 1.03-1.08, respectively) and invasive ventilation/death (RR 2.79; 95% CI, 1.49-5.21 and RR 1.06; 95% CI, 1.04-1.08, respectively). Diabetes, dyslipidemia, hyperuricemia, and lung diseases were also associated with severe outcomes. Of the 80 cases asymptomatic at hospitalization, 40 developed symptoms and five of them >70 years of age required invasive ventilation. CONCLUSIONS: The early stage of the novel coronavirus epidemic in Japan disproportionately affected the elderly. Older age, male gender, and underlying conditions were associated with severe outcomes. Notably, some elderly case-patients who were asymptomatic at diagnosis and promptly hospitalized still went on to develop severe disease, indicating the importance of careful monitoring of certain populations.

Factors associated with knowledges and attitudes about measles and rubella immunization in a non-health care occupational setting in Japan.

INTRODUCTION: Elimination of measles and rubella has been achieved in several countries and some regions. After verified measles elimination, some countries have reported outbreaks among adults in occupational settings such as health care institution and school setting. Studies have reported that knowledge and attitude for measles and/or rubella are significantly associated with immunization uptake in adults, but few studies have been conducted in settings other than health care facilities and schools. METHODS: We conducted a cross-sectional study among 134 office employees during a routine health checkup in June 17-20, 2014, to examine the association between willingness to receive immunization and knowledge and attitudes. RESULTS: Approximately 75% had a protective level of antibody for measles (PA≥1:256) and rubella (HI ≥ 32 IU/mL). After adjustment for sex, age and immune status, the attitudes that immunization prevents measles (adjusted odds ratio [aOR] = 7.8, 95% confidence interval [95%CI]: 2.5-24.7) and prevents infection and transmission to others (aOR = 4.0, 95%CI: 1.4-11.4). Knowing that males are the vulnerable group for rubella infection (aOR = 5.8, 95%CI: 2.4-13.9), attitude that immunization prevents rubella infection (aOR = 7.9, 95%CI: 2.4-26.5), and prevents infection and transmit to others (aOR = 6.7, 95%CI: 2.2-20.1) were significantly associated with willingness to receive immunization after adjustment for sex, age, and immune status. CONCLUSIONS: Studies have shown that physicians and other health care workers are important source of information for promotion of immunization. Thus, we recommend that physicians educate and promote immunization for measles and/or rubella to adults working in offices during routine health checks.

Increase in congenital syphilis cases and challenges in prevention in Japan, 2016-2017.

In Japan, the increase in congenital syphilis (CS) notifications has become a public health concern. We conducted a case series study to describe the characteristics of CS patients and their mothers. Of the 13 mothers who consented to participate, seven had regular prenatal care visits, including four who had tested negative at their first trimester syphilis screening. Only three mothers noted that their partners were tested, with all three partners being diagnosed with syphilis. Raising awareness for syphilis prevention during pregnancy, partner testing, and considering additional syphilis testing at the third trimester of pregnancy during times of increased syphilis prevalence is imperative.

Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine against Invasive Pneumococcal Disease in Adults, Japan, 2013-2017.

The decline in the proportion of pneumococcal conjugate vaccine (PCV)-covered serotypes among adult invasive pneumococcal disease (IPD) patients might change the overall effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) because its effectiveness differs according to serotype. Using the indirect cohort method, we calculated the effectiveness of PPSV23 against IPD among adults in Japan to assess the impact of the national pediatric PCV program. Clinical and epidemiologic information and pneumococcal isolates were collected from IPD patients >20 years of age through enhanced IPD surveillance during April 2013-December 2017. Adjusted effectiveness against PPSV23-serotype IPD was 42.2%. Despite a substantial decline in the proportion of 13-valent PCV serotypes during the study period (45% to 31%), the change in effectiveness for PPSV23-serotype IPD was limited (47.1% to 39.3%) and only marginal in the elderly population (39.9% to 39.4%). The pediatric PCV program had limited impact on PPSV23 effectiveness against IPD in adults.

Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020.

In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly.

Clusters of Coronavirus Disease in Communities, Japan, January-April 2020.

We analyzed 3,184 cases of coronavirus disease in Japan and identified 61 case-clusters in healthcare and other care facilities, restaurants and bars, workplaces, and music events. We also identified 22 probable primary case-patients for the clusters; most were 20-39 years of age and presymptomatic or asymptomatic at virus transmission.

Estimating nationwide cases of sexually transmitted diseases in 2015 from sentinel surveillance data in Japan.

BACKGROUND: The rates of newly diagnosed cases of sexually transmitted diseases, including genital chlamydial infection and gonorrhea, are important for prevention and control of these diseases. However, nationwide rates are not reported in Japan. METHODS: We used the number of cases of sexually transmitted diseases reported by nationwide sentinel surveillance in 2015, together with the number of all disease outpatients in September 2014 at all medical institutions, drawn from the Survey of Medical Institutions of Japan. The number of cases of sexually transmitted diseases in the total population was estimated using the ratio estimation method with the number of all disease outpatients as auxiliary information. This method is currently used for estimating influenza cases from sentinel surveillance data in Japan. RESULTS: The estimated number of newly diagnosed cases per 100,000 population in 2015 in Japan was 244 (95% confidence interval 211-277) for genital chlamydial infection, 87 (95% confidence interval 74-100) for genital herpes, 61 (95% confidence interval 29-93) for condyloma acuminatum, and 89 (95% confidence interval 64-113) for gonorrhea. CONCLUSION: We estimated the nationwide number of newly diagnosed cases of sexually transmitted diseases in Japan from sentinel surveillance data. This provides useful information for public health policy-making.

Characteristics and Outcomes of Influenza-Associated Encephalopathy Cases Among Children and Adults in Japan, 2010-2015.

Background: Influenza-associated encephalopathy (IAE) can result in severe neurologic disease with high mortality. Most IAE cases are reported among children worldwide. Understanding of IAE among adults is limited. Methods: Data were collected on IAE cases reported through the National Epidemiological Surveillance of Infectious Diseases database in Japan from 2010 through 2015. IAE cases were stratified by age category and analyzed using descriptive statistics to assess differences in characteristics and outcomes. Results: Among 385 IAE cases, median age at diagnosis was 7 years (range, 0-90), and 283 (74%) were aged <18 years. Mean seasonal incidence of IAE cases among children and adults (aged ≥18 years) was 2.83 and 0.19 cases per 1000000 population, respectively. IAE incidence did not vary by predominant influenza A virus subtype. IAE frequency was highest in school-aged (5-12 years) children (38%), followed by children aged 2-4 years (21%) and adults aged 18-49 years (11%). The proportion of cases with seizures was more common in children. There were more cases with cerebrospinal fluid pleocytosis among adults than in children (P < .01), especially among those aged 18-49 (17%) and 50-64 (19%) years. Case fatality proportion was highest in those aged 40-64 (17%) and ≥65 (20%) years. Conclusions: We found differences in the clinical features of IAE between adults and children in Japan. Although IAE incidence was higher in children, mortality was higher in adults. Efforts are needed to prevent and improve survival of patients with IAE, especially in adults.

Rapid Increase in Reports of Syphilis Associated With Men Who Have Sex With Women and Women Who Have Sex With Men, Japan, 2012 to 2016.

BACKGROUND: In Japan, syphilis reports have recently increased rapidly. However, unlike other developed countries where men who have sex with men (MSM) were associated with the rise, the increase in Japan has been attributed more to men who have sex with women (MSW) and women who have sex with men (WSM). We report on this increase based on surveillance data. METHODS: Syphilis is a notifiable disease requiring all laboratory-confirmed cases to be reported; stage and sex of the sex partner(s) suspected as the infection source are also reported. Focusing on primary and secondary (P&S) cases, we describe the temporal, demographic, and geographic distributions of reported cases in 2012 through 2016. RESULTS: A total of 7040 (64.0%) of 10,997 cases were P&S; the annual rate of increase was greatest for P&S and the proportion of P&S increased over time. Among P&S cases (1609 MSM, 2768 MSW, and 1323 WSM), MSW and WSM each surpassed MSM cases in 2016. Men were older with a wider age distribution (median, 37 years; interquartile range, 28-46 years) relative to women (median, 26 years; interquartile range, 21-34 years). Among women, 20- to 24-year-olds consistently had the highest reporting rate, reaching 9.0 per 100,000 in 2016. Congenital syphilis reports increased from 0.4 in 2012 to 1.4 per 100,000 live births in 2016. Although Tokyo prefecture had the highest reporting rate (3.98 per 100,000 person-years), the proportionate contribution from Tokyo decreased in 2016. CONCLUSIONS: Reports on P&S syphilis increased yearly among MSW and WSM. Young women seem to be at particular risk, and with increased reports of congenital syphilis, syphilis prevention and control is currently a public health priority in Japan.