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%).

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.

Testosterone bounce predicts favorable prognoses for prostate cancer patients treated with degarelix.

BACKGROUND: To clarify the clinical roles of changes in testosterone (T) levels with a cut-off level of 20 ng/dL as predictive factors for prostate cancer patients treated with degarelix acetate. METHODS: A total of 120 prostate cancer patients who received hormone therapies with gonadotropin-releasing hormone antagonist degarelix acetate were retrospectively analyzed. The predictive values of nadir T levels, max T levels, T bounce, and other clinical factors were evaluated for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). T bounce was defined as satisfying both nadir serum T levels of <20 ng/dL and max serum T levels of ≥20 ng/dL during hormone therapies. RESULTS: In 120 prostate cancer patients, 16 (13%) patients did not achieve nadir T < 20 ng/dL, and 76 (63%) patients had max T ≥ 20 ng/dL. The median times to nadir T and max T are 108 and 312 days, respectively. T bounce was shown in 60 (50%) patients and is associated with favorable prognoses both for OS (p = 0.0019) and CSS (p = 0.0013) but not for PFS (p = 0.92). While in the subgroup analyses of the patients with the progression of the first-line hormone therapies, T bounce predicts favorable OS (p = 0.0015) and CSS (p = 0.0013) after biochemical recurrence. CONCLUSIONS: The present study revealed that T bounce with cut-off levels of 20 ng/dL is a promising biomarker that predicts OS and CSS for prostate cancer patients treated with degarelix acetate.

Chest Compression-Associated Internal Thoracic Artery Injury During Cardiopulmonary Resuscitation: Incidence, Injury Patterns and Efficacy of Transcatheter Arterial Embolization.

PURPOSE: To investigate the incidence and patterns of chest compression-associated internal thoracic artery injury (CAI) during cardiopulmonary resuscitation and identify the embolization techniques used to treat hemorrhage. MATERIALS AND METHODS: A retrospective study was conducted in the patients who underwent transcatheter arterial embolization (TAE) for life-threatening hemorrhage caused by CAI at two tertiary care centers between May 2013 and December 2019. Data on background characteristics, imaging findings, embolization and outcomes were collected from the medical records. RESULTS: Among 385 patients in whom circulation returned after resuscitation, there were 9 patients (2.3%) who required TAE for CAI. Eight of 9 patients had acute myocardial infarction, and all had been started on extracorporeal membrane oxygenation before TAE. Seven patients had unilateral, and two had bilateral internal thoracic artery injuries. Main trunk injury of internal thoracic artery was seen in 27%, while branch injury in 73%. Six patients (67%) had multiple injuries in the internal thoracic artery territory, and five (56%) had injuries to other vessels. In all cases, we embolized the main trunk of the internal thoracic artery using n-butyl 2-cyanoacrylate and coils (n = 8), a gelatin sponge only (n = 2), or coils and a gelatin sponge (n = 1). TAE was technically successful in all, without any complication. The 30-day mortality rate was 44%. CONCLUSIONS: CAI needing hemostatic intervention occurred in 2.3% of patients after successful cardiopulmonary resuscitation. Branch injury was more common than main trunk injury, and multiple vessel injuries were common. TAE appears to be safe and effective for controlling life-threatening hemorrhage.

A child with TSC2/PKD1 contiguous gene deletion syndrome successfully treated with tolvaptan for rapidly enlarging renal cysts.

Tolvaptan, a vasopressin receptor antagonist, has been shown to be effective in the treatment of renal cysts in ADPKD. However, tolvaptan is not indicated for pediatric patients, and reports of its use are rare, making its efficacy and adverse reactions unclear. Herein, we present the case of an 11-year-old girl who had vitiligo from birth. She was diagnosed with West syndrome at 6 months of age and tuberous sclerosis at 2 years of age. At the age of 6 years, an abdominal magnetic resonance imaging (MRI) revealed multiple bilateral renal cysts, and she was diagnosed with ADPKD. Abdominal MRI scans performed at 10 years and 11 years showed rapid renal cyst enlargement, and the renal prognosis was judged to be poor. The patient was treated with tolvaptan to delay cyst exacerbation. There were no apparent adverse events after the initiation of treatment, and the MRI performed 12 months after treatment initiation showed that renal cyst enlargement was suppressed. The results suggest that tolvaptan may be effective in pediatric patients with severe ADPKD who have rapidly enlarging renal cysts, although evaluation of renal cyst enlargement and side effects should be continued.

Holiday effect on childbirth: A population-based analysis of 21,869,652 birth records, 1979-2018.

Maternity and neonatal services always have to operate 24 hours a day and 7 days a week, and require well preparedness to guarantee safe deliveries for both mothers and babies. However, the evidence of holiday effect from large-scale data is still insufficient from the obstetrics perspective. We analyzed data of over 21 million births in Japan from January 1, 1979, to December 31, 2018. We revealed that the number of births is lower on holidays, and especially among high-risk births such as low birthweight and preterm births. The frequency of high-risk birth has been increasing over the study period, and the variation by the day of week and between holiday and non-holiday have become more prevalent in recent years.

Survey on chest CT findings in COVID-19 patients in Okinawa, Japan: differences between the delta and omicron variants.

To investigate the frequency of pneumonia and chest computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) during the fifth Delta variant-predominant and sixth Omicron variant-predominant waves of the COVID-19 pandemic in Okinawa, Japan. A survey on chest CT examinations for patients with COVID-19 was conducted byhospitals with board-certified radiologists who provided treatment for COVID-19 pneumonia in Okinawa Prefecture. Data from 11 facilities were investigated. Indications for chest CT; number of COVID-19 patients undergoing chest CT; number of patients with late-onset pneumonia, tracheal intubation, and number of deaths; and COVID-19 Reporting and Data System classifications of initial chest CT scans were compared by the chi-squared test between the two pandemic waves (Delta vs. Omicron variants). A total of 1944 CT scans were performed during the fifth wave, and 1178 were performed during the sixth wave. CT implementation rates, which were the number of patients with COVID-19 undergoing CT examinations divided by the total number of COVID-19 cases in Okinawa Prefecture during the waves, were 7.1% for the fifth wave and 2.1% for the sixth wave. The rates of tracheal intubation and mortality were higher in the fifth wave. Differences between the distributions of the CO-RADS classifications were statistically significant for the fifth and sixth waves (p < 0.0001). In the fifth wave, CO-RADS 5 (typical of COVID-19) was most common (65%); in the sixth wave, CO-RADS 1 (no findings of pneumonia) was most common (50%). The finding of "typical for other infection but not COVID-19" was more frequent in the sixth than in the fifth wave (13.6% vs. 1.9%, respectively). The frequencies of pneumonia and typical CT findings were higher in the fifth Delta variant-predominant wave, and nontypical CT findings were more frequent in the sixth Omicron variant-predominant wave of the COVID-19 pandemic in Okinawa, Japan.

Familial focal segmental glomerulosclerosis with Alport-like glomerular basement changes caused by paired box protein 2 gene variant.

Paired box protein 2 (PAX2) gene variant causes renal coloboma syndrome (MIM#120330). Further, they are associated with focal segmental glomerulosclerosis and characterized by basement membrane changes similar to Alport syndrome.Herein, we report an 8-year-old boy who presented with proteinuria and decreased renal function. His paternal uncle has focal segmental glomerulosclerosis and renal failure, and his paternal grandmother has renal failure and is receiving peritoneal dialysis. Further, his father has stage 2 chronic kidney disease. At 3 years of age, his serum creatinine-estimated glomerular filtration rate was 40-50 mL/min/1.73 m2. At 8 years of age, his renal function further decreased and he had proteinuria (urinary protein/Cr 3.39 g/g Cr). Renal histopathology showed oligonephronia and focal segmental glomerulosclerosis. A partial basket-weave pattern, similar to Alport syndrome, was also observed on a transmission electron microscope, and low-vacuum scanning electron microscopy revealed coarse meshwork changes in the glomerular basement membrane. Genetic analysis revealed a PAX2 heterozygous variant (NM_003987.4:c.959C  >  G), a nonsense variant in which the serine at position 320 changes to a stop codon, in our patient and his father. PAX2 is a transcription factor that is important for the podocyte variant. However, podocytes with PAX2 gene variants may cause abnormal basement membrane production and repair, thereby resulting in Alport-like changes.

Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis.

Hepatitis is an inflammation of the liver caused by the inadequate elimination of reactive oxygen species (ROS) derived from Kupffer cells. Edaravone is clinically used as an antioxidant but shows poor liver distribution. Herein, we report on the design of a Kupffer cell-oriented nanoantioxidant based on a disulfide cross-linked albumin nanoparticle containing encapsulated edaravone (EeNA) as a therapeutic for the treatment of hepatitis. Since the edaravone is bound to albumin, this results in a soluble and stable form of edaravone in water. Exchanging the intramolecular disulfide bonds to intermolecular disulfide bridges of albumin molecules allowed the preparation of a redox responsive albumin nanoparticle that is stable in the blood circulation but can release drugs into cells. Consequently, EeNA was fabricated by the nanoscale self-assembly of edaravone and albumin nanoparticles without the additives that are contained in commercially available edaravone preparations. EeNA retained its nanostructure under serum conditions, but the encapsulated edaravone was released efficiently under intracellular reducing conditions in macrophages. The EeNA was largely distributed in the liver and subsequently internalized into Kupffer cells within 60 min after injection in a concanavalin-A-induced hepatitis mouse. The survival rate of the hepatitis mice was significantly improved by EeNA due to the suppression of liver necrosis and oxidative stress by scavenging excessive ROS. Moreover, even through the postadministration, EeNA showed an excellent hepatoprotective action as well. In conclusion, EeNA has the potential for use as a nanotherapeutic against various types of hepatitis because of its Kupffer cell targeting ability and redox characteristics.

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.

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.

National seroepidemiological study of COVID-19 after the initial rollout of vaccines: Before and at the peak of the Omicron-dominant period in Japan.

Background: Based on routine surveillance data, Japan has been affected much less by COVID-19 compared with other countries. To validate this, we aimed to estimate SARS-CoV-2 seroprevalence and examine sociodemographic factors associated with cumulative infection in Japan. Methods: A population-based serial cross-sectional seroepidemiological investigation was conducted in five prefectures in December 2021 (pre-Omicron) and February-March 2022 (Omicron [BA.1/BA.2]-peak). Anti-nucleocapsid and anti-spike antibodies were measured to detect infection-induced and vaccine/infection-induced antibodies, respectively. Logistic regression was used to identify associations between various factors and past infection. Results: Among 16 296 participants (median age: 53 [43-64] years), overall prevalence of infection-induced antibodies was 2.2% (95% CI: 1.9-2.5%) in December 2021 and 3.5% (95% CI: 3.1-3.9%) in February-March 2022. Factors associated with past infection included those residing in urban prefectures (Tokyo: aOR 3.37 [95% CI: 2.31-4.91], Osaka: aOR 3.23 [95% CI: 2.17-4.80]), older age groups (60s: aOR 0.47 [95% CI 0.29-0.74], 70s: aOR 0.41 [95% CI 0.24-0.70]), being vaccinated (twice: aOR 0.41 [95% CI: 0.28-0.61], three times: aOR 0.21 [95% CI: 0.12-0.36]), individuals engaged in occupations such as long-term care workers (aOR: 3.13 [95% CI: 1.47-6.66]), childcare workers (aOR: 3.63 [95% CI: 1.60-8.24]), food service workers (aOR: 3.09 [95% CI: 1.50-6.35]), and history of household contact (aOR: 26.4 [95% CI: 20.0-34.8]) or non-household contact (aOR: 5.21 [95% CI:3.80-7.14]) in February-March 2022. Almost all vaccinated individuals (15 670/15 681) acquired binding antibodies with higher titers among booster dose recipients. Conclusions: Before Omicron, the cumulative burden was >10 times lower in Japan (2.2%) compared with the US (33%), the UK (25%), or global estimates (45%), but most developed antibodies owing to vaccination.

Protective effect of previous infection and vaccination against reinfection with BA.5 Omicron subvariant: a nationwide population-based study in Japan.

Background: The Omicron variant of SARS-CoV-2 was reported to evade immunity derived from vaccination and previous infection. A better understanding of hybrid immunity informs effective infection control strategies. Since the reinfection risk was not well-assessed in East Asia, this study aims to evaluate the risk of infection with Omicron subvariant BA.5 among previously infected individuals in Japan. Methods: All notified cases were extracted from the Japanese national COVID-19 surveillance database including 20,297,335 records up to 25 September 2022. Reinfection with BA.5 was defined as the infection notified during the BA.5 dominated period with any prior SARS-CoV-2 infection. The protective effect of prior infections against reinfections with BA.5 was estimated by applying a case-population design and the protective effect of vaccination was estimated by a multivariable Cox regression adjusting for age, sex, variants of prior infection, and the time since the last vaccination. Findings: Among 19,830,548 SARS-CoV-2 first infections, 233,424 (1.2%) were reinfected with BA.5. The protective effect against BA.5 reinfection of prior infection with Wuhan strain was 46%, Alpha variant was 35%, Delta variant was 41%, and BA.1/BA.2 subvariant was 74%. The reduced risk of BA.5 reinfection by 7%, 33%, and 66% was associated with two, three, and four doses of vaccination, respectively, compared with one-dose vaccination. Interpretation: The prior infections with Omicron subvariant BA.1/BA.2 protected BA.5 reinfection more than pre-Omicron variants. Increased frequency of vaccination led to more protection from reinfection with BA.5. Up-to-date vaccination may be encouraged to prevent future reinfection among the previously infected population. Funding: None.

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.

Impact of the Coming-of-Age Day and ceremony on the risk of SARS-CoV-2 transmission in Japan: A natural-experimental study based on national surveillance data.

BACKGROUND: Quantifying the impact on COVID-19 transmission from a single event has been difficult due to the virus transmission dynamics, such as lag from exposure to reported infection, non-linearity arising from the person-to-person transmission, and the modifying effects of non-pharmaceutical interventions over time. To address these issues, we aimed to estimate the COVID-19 transmission risk of social events focusing on the Japanese Coming-of-Age Day and Coming-of-Age ceremony in which "new adults" practice risky behavior on that particular day. METHODS: Using national surveillance data in Japan in 2021 and 2022, we conducted difference-in-differences regression against COVID-19 incidences by setting "new adults" cases as the treatment group and the cases 1 year younger or older than these "new adults" as the control group. In addition, we employed a triple differences approach to estimate the risk of holding the Coming-Age ceremony by using a binary variable regarding the presence or absence of the ceremony in each municipality. RESULTS: We estimated the relative risks (RRs) of the Coming-of-Age Day as 1.27 (95% confidence interval [CI] 1.02-1.57) in 2021 and 3.22 (95% CI 2.68-3.86) in 2022. The RR of the Coming-of-Age ceremony was also large, estimated as 2.83 (1.81-4.43) in 2022. CONCLUSIONS: When planning large social events, it is important to be aware of the unique risks associated with these gatherings, along with effective public health messages to best communicate these risks.

Epidemiology of coronavirus disease 2019 (COVID-19) in Japan during the first and second waves.

Following the emergence and worldwide spread of coronavirus disease 2019 (COVID-19), each country has attempted to control the disease in different ways. The first patient with COVID-19 in Japan was diagnosed on 15 January 2020, and until 31 October 2020, the epidemic was characterized by two large waves. To prevent the first wave, the Japanese government imposed several control measures such as advising the public to avoid the 3Cs (closed spaces with poor ventilation, crowded places with many people nearby, and close-contact settings such as close-range conversations) and implementation of "cluster buster" strategies. After a major epidemic occurred in April 2020 (the first wave), Japan asked its citizens to limit their numbers of physical contacts and announced a non-legally binding state of emergency. Following a drop in the number of diagnosed cases, the state of emergency was gradually relaxed and then lifted in all prefectures of Japan by 25 May 2020. However, the development of another major epidemic (the second wave) could not be prevented because of continued chains of transmission, especially in urban locations. The present study aimed to descriptively examine propagation of the COVID-19 epidemic in Japan with respect to time, age, space, and interventions implemented during the first and second waves. Using publicly available data, we calculated the effective reproduction number and its associations with the timing of measures imposed to suppress transmission. Finally, we crudely calculated the proportions of severe and fatal COVID-19 cases during the first and second waves. Our analysis identified key characteristics of COVID-19, including density dependence and also the age dependence in the risk of severe outcomes. We also identified that the effective reproduction number during the state of emergency was maintained below the value of 1 during the first wave.

Phenomenological and mechanistic models for predicting early transmission data of COVID-19.

Forecasting future epidemics helps inform policy decisions regarding interventions. During the early coronavirus disease 2019 epidemic period in January-February 2020, limited information was available, and it was too challenging to build detailed mechanistic models reflecting population behavior. This study compared the performance of phenomenological and mechanistic models for forecasting epidemics. For the former, we employed the Richards model and the approximate solution of the susceptible-infected-recovered (SIR) model. For the latter, we examined the exponential growth (with lockdown) model and SIR model with lockdown. The phenomenological models yielded higher root mean square error (RMSE) values than the mechanistic models. When using the numbers from reported data for February 1 and 5, the Richards model had the highest RMSE, whereas when using the February 9 data, the SIR approximation model was the highest. The exponential model with a lockdown effect had the lowest RMSE, except when using the February 9 data. Once interventions or other factors that influence transmission patterns are identified, they should be additionally taken into account to improve forecasting.

The Therapeutic Effect of Human Serum Albumin Dimer-Doxorubicin Complex against Human Pancreatic Tumors.

Human serum albumin (HSA) is a versatile drug carrier with active tumor targeting capacity for an antitumor drug delivery system. Nanoparticle albumin-bound (nab)-technology, such as nab-paclitaxel (Abraxane®), has attracted significant interest in drug delivery research. Recently, we demonstrated that HSA dimer (HSA-d) possesses a higher tumor distribution than HSA monomer (HSA-m). Therefore, HSA-d is more suitable as a drug carrier for antitumor therapy and can improve nab technology. This study investigated the efficacy of HSA-d-doxorubicin (HSA-d-DOX) as next-generation nab technology for tumor treatment. DOX conjugated to HSA-d via a tunable pH-sensitive linker for the controlled release of DOX. Lyophilization did not affect the particle size of HSA-d-DOX or the release of DOX. HSA-d-DOX showed significantly higher cytotoxicity than HSA-m-DOX in vitro. In the SUIzo Tumor-2 (SUIT2) human pancreatic tumor subcutaneous inoculation model, HSA-d-DOX could significantly inhibit tumor growth without causing serious side effects, as compared to the HSA binding DOX prodrug, which utilized endogenous HSA as a nano-drug delivery system (DDS) carrier. These results indicate that HSA-d could function as a natural solubilizer of insoluble drugs and an active targeting carrier in intractable tumors with low vascular permeability, such as pancreatic tumors. In conclusion, HSA-d can be an effective drug carrier for the antitumor drug delivery system against human pancreatic tumors.

Projecting a second wave of COVID-19 in Japan with variable interventions in high-risk settings.

An initial set of interventions, including the closure of host and hostess clubs and voluntary limitation of non-household contact, probably greatly contributed to reducing the disease incidence of coronavirus disease (COVID-19) in Japan, but this approach must eventually be replaced by a more sustainable strategy. To characterize such a possible exit strategy from the restrictive guidelines, we quantified the next-generation matrix, accounting for high- and low-risk transmission settings. This matrix was used to project the future incidence in Tokyo and Osaka after the state of emergency is lifted, presenting multiple 'post-emergency' scenarios with different levels of restriction. The effective reproduction numbers (R) for the increasing phase, the transition phase and the state-of-emergency phase in the first wave of the disease were estimated as 1.78 (95% credible interval (CrI): 1.73-1.82), 0.74 (95% CrI: 0.71-0.78) and 0.63 (95% CrI: 0.61-0.65), respectively, in Tokyo and as 1.58 (95% CrI: 1.51-1.64), 1.20 (95% CrI: 1.15-1.25) and 0.48 (95% CrI: 0.44-0.51), respectively, in Osaka. Projections showed that a 50% decrease in the high-risk transmission is required to keep R less than 1 in both locations-a level necessary to maintain control of the epidemic and minimize the risk of resurgence.

Identifying geographic areas at risk of rubella epidemics in Japan using seroepidemiological data.

OBJECTIVE: Even with relatively high vaccination coverage, Japan experienced rubella epidemics in 2012-2014 and 2018-2019, which were fueled by untraced imported cases. We aimed to develop a risk map for rubella epidemics in Japan by geographic location via analysis of seroepidemiological data and accounting for the abundance of foreign visitors. METHODS: Geographic age distribution and seroprevalence were used to compute the age- and sex-dependent next-generation matrix in each region. We computed the probability of a major epidemic using the assumed number of untraced imported rubella cases proportionally modeled to the number of foreign travelers. RESULTS: Risks of a major epidemic were high in areas with capital cities, while areas with a greater fraction of older people yielded smaller effective reproduction numbers, a lower volume of foreign travelers, and thus a lower probability of a major epidemic. The volume of susceptible adult males was larger in urban geographic regions, having a greater number of foreign travelers than remote areas. CONCLUSIONS: Our findings are consistent with the observation of multiple large clusters of rubella cases in urban areas during 2012-2014 and 2018-2019. Should a future rubella epidemic occur, it will likely be in geographic areas with capital cities.