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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.

Objectives: To reconstruct age-structured case counts of COVID-19 using sentinel reporting, which replaced universal reporting of COVID-19 from May 2023 in Japan. Methods: Using COVID-19 sentinel data stratified by discrete age groups in selected prefectures and referring to universal case count data up to May 8, 2023, we fitted a statistical model to handle weekly growth rates as a function of age and time so as to convert sentinel data to case counts after cessation of universal reporting. Results: The age distribution of cases in sentinel reporting was significantly biased toward younger age groups compared to universal reporting. When comparing the epidemic size of the 9th wave (May 8 to September 18, 2023) to the 8th wave (October 3, 2022 to April 10, 2023), using the wave-on-wave ratio of total cumulative sentinel cases led to a significant underestimation of the wave-on-wave in Tokyo (0.975, vs 1.461 by universal reporting) and Okinawa (1.299, vs 1.472). The estimates of growth rates, scaling factors between universal and sentinel cases, and expected universal case count showed robustness to changes in the ending week of the data period. Conclusion: Our model quantified COVID-19 dynamics, comparably to universal reporting that ended in May 2023, enabling detailed and up-to-date health burden analysis using sentinel reports. The cumulative incidence was greater than that suggested from sentinel data in Tokyo, Nara, and Okinawa. Per-population burdens among children were particularly high in Osaka and Nara, indicating a strong bias in sentinel reporting toward pediatric cases.

Background: Stringent public health and social measures against COVID-19 infection were implemented to avoid an overwhelming hospital caseload and excessive number of deaths, especially among elderly people. We analyzed population-level immunity and predicted mortality, calculated as the potential number of deaths on a given calendar date in Japan, to develop a science-based exit strategy from stringent control measures. Methods: Immune proportions were inferred by age group using vaccination coverage data and the estimated number of naturally infected individuals. Immunity against symptomatic illness and death were estimated separately, allowing for inference of the immune fraction that was protected against either COVID-19-related symptomatic infection or death. By multiplying the infection fatality risk by age group for the immune fraction, the potential number of deaths was obtained. Results: Accounting for a second and third dose of messenger RNA vaccine in the present-day population, approximately 155,000 potential deaths would be expected among people aged ≥ 60 years if all individuals were infected at the very end of 2022. A fourth dose (i.e., second booster) with a coverage identical to that of the third dose could reduce mortality by 60%. In all examined settings, the largest number of deaths occurred among people aged 80 years and older. Conclusions: Our estimates can help policymakers understand the mortality impact of the COVID-19 epidemic in a quantitative manner and the critical importance of timely immunization so as to assist in decision making.

Many countries struggled with suppressing the incidence of COVID-19 caused by SARS-CoV-2 Omicron variant (B.1.1.529). As the epidemic size of COVID-19 in 2022 became bigger than earlier years in Japan, the present study aimed to estimate life expectancy at birth at the end of 2022, using provisional death datasets in Aichi and Fukui prefectures. We collected monthly death count from 2019 to the end of 2022, computing the period life table. While the life expectancy at birth in Aichi, 2019 was 84.6 years, it was very slightly extended to 84.7 years in 2020 and 2021, followed by a shortening for nearly 0.4 years in 2022. In Fukui, monotonous extension pattern was seen, i.e., 85.5 years in 2019, 85.6 in 2020, followed by 85.8 and 86.2 years in 2021 and 2022, respectively. Although decades-long trend of extending life expectancy at birth was partly discontinued from 2020 due to the pandemic at the national level, we have shown that the pandemic impact was still small in Japan by the end of 2022. First Omicron wave occurred shortly after primary series vaccination, and even real time booster program was underway during that wave. Different demographic consequences between Aichi and Fukui are explained by differential epidemic sizes prior to vaccination.

Background: A highly pathogenic avian influenza (HPAI) A (H5N1) virus has been detected in domestic and wild animals worldwide. The incidence of HPAI infections in sea mammals has been increasing, as is the number of stranded marine mammals linked to H5N1 viral clade 2.3.4.4(b). In this study, we investigated a stranding event involving dolphins and human–dolphin contact, and investigated the potential risk of animal-to-human H5N1 transmission with a survey of exposure on the Tsurigasaki coast, Japan. Methods: We performed a non-random, convenient-sample-based, survey on Tsurigasaki beach where around 30 melon-headed whales were stranded on April 3, 2023. Face-to-face (n = 25) and telephone (n = 1) interviews among surfers took place on April 7 and 8. A nasal swab for quick antigen testing was taken from those who wished to be tested (n = 13), to detect infections with influenza A virus. Results: Although there was no confirmatory diagnosis of H5N1 in either humans or dolphins (while n = 3 dolphins were autopsied), we found that a large number of surfers had touched the dolphins with their bare hands while attempting to rescue them, and that some surfers were directly exposed to dolphin blood and body fluids in the ocean. Conclusions: The adequate communication of risk is required to minimize the threat of viral transmission at this particular human–animal interface. Administrative and legal responses to cross-species transmission, including guidelines via one health frameworks, a rapid evaluation process of ethical approval, and the systematic involvement of experts in infectious disease, must be urgently formulated.

Objectives: Elucidating the infection dynamics that lead to severe respiratory syncytial virus (RSV) pneumonia and hospitalization among young children are critical. We explored the role of infection parity as well as age in months for RSV-associated hospitalization among young children in Japan. Methods: We used a sequential transmission catalytic model to capture the transmission mechanisms of RSV among infants in an endemic state. We investigated data on the age-dependent seroprevalence and incidence rate of hospitalization in Japan, and jointly estimated the age-specific risk of hospitalization during primary RSV infection and relative risk of hospitalization during secondary infection in children aged

ABSTRACT: Objectives: COVID-19 vaccination in Japan started on February 17, 2021. Because the timing of vaccination and the risk of severe COVID-19 greatly varied with age, the present study aimed to monitor the age-specific fractions of the population who were immune to SARS-CoV-2 infection after vaccination. Methods: Natural infection remained extremely rare, accounting for less than 5% of the population by the end of 2021; thus, we ignored natural infection-induced immunity and focused on vaccine-induced immunity. We estimated the fraction of the population immune to infection by age group using vaccination registry data from February 17, 2021, to October 17, 2021. We accounted for two important sources of delay: (i) reporting delay and (ii) time from vaccination until immune protection develops. Results: At the end of the observation period, the proportion of individuals still susceptible to SARS-CoV-2 infection substantially varied by age and was estimated to be ≥90% among people aged 0–14 years, in contrast to approximately 20% among the population aged ≥65 years. We also estimated the effective reproduction number over time using a next-generation matrix while accounting for differences in the proportion immune to infection by age. Conclusion: The COVID-19 immune landscape greatly varied by age, and a substantial proportion of young adults remained susceptible. Vaccination contributed to a marked decrease in the reproduction number.

Objectives: To explore a potential country-based ecological link between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) infection and an apparent current global outbreak of severe hepatitis of unknown etiology among children. Methods: We examined country-level statistical associations between reported detection of one or more unexplained severe hepatitis cases in children and the cumulative number of Omicron (B.1.1.529) cases in 38 Organisation for Economic Co-operation and Development (OECD) member countries plus Romania. Results: At least one focal hepatitis case was detected in 12 of the 39 countries included in our analysis. Numbers of confirmed Omicron cases reported in these 12 countries ranged from 4.4 to 11.9 million. Among the remaining 27 countries, this measure ranged from 0.5 to 5.5 million cases. Countries which reported focal hepatitis cases experienced higher precedent population burdens of Omicron cases relative to those which did not report any such hepatitis cases (p=0.013). Conclusion: Prior exposure to Omicron variant (B.1.1.529) may be associated with an increased risk for severe hepatitis among children, indicating a critical need to conduct cofactor studies.

ABSTRACT: Background: Following an outbreak of coronavirus disease 2019 (COVID-19) on the cruise ship Diamond Princess, passengers and crew were followed-up to determine prognosis. This study examined the epidemiological determinants of COVID-19 natural history using these follow-up data. Methods: Infection status, diagnosis, clinical symptoms and prognosis were analysed for all passengers and crew members on the Diamond Princess. In addition, the risk of infection associated with exposure within cabin rooms, as well as the risks of various clinical manifestations of disease, along with their epidemiological determinants, were analysed. Results: The adjusted odds ratio (aOR) of infection for individuals tested by polymerase chain reaction on or after 12 February 2020 compared with individuals tested before this date was 0.53 [95% confidence interval (CI) 0.39–0.72], reflecting decreased transmission during onboard quarantine. Among infected individuals, older age was associated with elevated odds of symptomatic illness (aOR 1.01, 95% CI 1.00–1.02), severe disease (aOR 1.08, 95% CI 1.05–1.12) and death (aOR 1.12, 95% CI 1.05–1.21). Conclusions: Severe COVID-19 disease, death and symptomatic illness were more frequent among older individuals on the Diamond Princess. Older elderly cases (age ≥80 years) had the highest risks of severe disease and death. Inter-room transmission was prevented successfully by the onboard quarantine.

Objectives: The effective reproduction number (Rt) has been critical for assessing the effectiveness of countermeasures during the coronavirus disease 2019 (COVID-19) pandemic. Conventional methods using reported incidences are unable to provide timely Rt data due to the delay from infection to reporting. Our study aimed to develop a framework for predicting Rt in real time, using timely accessible data — i.e. human mobility, temperature, and risk awareness. Methods: A linear regression model to predict Rt was designed and embedded in the renewal process. Four prefectures of Japan with high incidences in the first wave were selected for model fitting and validation. Predictive performance was assessed by comparing the observed and predicted incidences using cross-validation, and by testing on a separate dataset in two other prefectures with distinct geographical settings from the four studied prefectures. Results: The predicted mean values of Rt and 95% uncertainty intervals followed the overall trends for incidence, while predictive performance was diminished when Rt changed abruptly, potentially due to superspreading events or when stringent countermeasures were implemented. Conclusions: The described model can potentially be used for monitoring the transmission dynamics of COVID-19 ahead of the formal estimates, subject to delay, providing essential information for timely planning and assessment of countermeasures.

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infections have been associated with substantial presymptomatic transmission, which occurs when the generation interval—the time between infection of an individual with a pathogen and transmission of the pathogen to another individual—is shorter than the incubation period—the time between infection and symptom onset. We collected a dataset of 257 SARS-CoV-2 transmission pairs in Japan during 2020 and jointly estimated the mean incubation period of infectors (4.8 days, 95 % CrI: 4.4–5.1 days), mean generation interval to when they infect others (4.3 days, 95 % credible interval [CrI]: 4.0–4.7 days), and the correlation (Kendall’s tau: 0.5, 95 % CrI: 0.4–0.6) between these two epidemiological parameters. Our finding of a positive correlation and mean generation interval shorter than the mean infector incubation period indicates ample infectiousness before symptom onset and suggests that reliance on isolation of symptomatic COVID-19 cases as a focal point of control efforts is insufficient to address the challenges posed by SARS-CoV-2 transmission dynamics.

Summary: Background: In Japan, vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initiated on 17 February 2021, mainly using messenger RNA vaccines and prioritizing health care professionals. Whereas nationwide vaccination alleviated the coronavirus disease 2019 (COVID-19)-related burden, the population impact has yet to be quantified in Japan. We aimed to estimate the numbers of COVID-19 cases and deaths prevented that were attributable to the reduced risk among vaccinated individuals via a statistical modeling framework. Methods: We analyzed confirmed cases registered in the Health Center Real-time Information-sharing System on COVID-19 (3 March–30 November 2021) and publicly reported COVID-19-related deaths (24 March–30 November 2021). The vaccination coverage over this time course, classified by age and sex, was extracted from vaccine registration systems. The total numbers of prevented cases and deaths were calculated by multiplying the daily risk differences between unvaccinated and vaccinated individuals by the population size of vaccinated individuals. Findings: For both cases and deaths, the averted numbers were estimated to be the highest among individuals aged 65 years and older. In total, we estimated that 564,596 (95% confidence interval: 477,020–657,525) COVID-19 cases and 18,622 (95% confidence interval: 6522–33,762) deaths associated with SARS-CoV-2 infection were prevented owing to vaccination during the analysis period (i.e., fifth epidemic wave, caused mainly by the Delta variant). Female individuals were more likely to be protected from infection following vaccination than male individuals whereas more deaths were prevented in male than in female individuals. Interpretation: The vaccination program in Japan led to substantial reductions in the numbers of COVID-19 cases and deaths (33% and 67%, respectively). The preventive effect will be further amplified during future pandemic waves caused by variants with shared antigenicity. Funding: This project was supported by the Japan Science and Technology Agency; the Japan Agency for Medical Research and Development; the Japan Society for the Promotion of Science; and the Ministry of Health, Labour and Welfare.

Background: The number of coronavirus disease 2019 (COVID-19) cases was expected to increase during the Tokyo Olympic Games because of the increased physical contact within and between the domestic population and international participants of the Games. The rapid rise of the Delta variant (B.1.617) in Japan meant that hosting the Olympic Games without any restrictions was likely to lead to an increase in cases. We aimed to quantitatively assess possible COVID-19 response strategies for the Olympic Games, comparing the prevalence of severe cases and the cumulative number of COVID-19 deaths via scenario analysis. Methods: We used a discrete-time deterministic compartmental model structured by age group. Parameters were calibrated using the age-stratified COVID-19 incidence data in Osaka. Numerical simulations incorporated the planned Olympics Games and nationwide COVID-19 vaccination into the proposed model, alongside various subjects and types of countermeasures. Results: Our model-informed approach suggested that having spectators at the Tokyo Olympic Games could lead to a surge in both cases and hospitalization. Projections for the scenario that explicitly incorporated the spread of the Delta variant (i.e., time-dependent increase in the relative transmissibility) showed that imposing stringent social distancing measures (Rt=0.7) for more than 8 weeks from the end of the Olympic Games might be required to suppress the prevalence of severe cases of COVID-19 to avoid overwhelming the intensive care unit capacity in Tokyo. Conclusions: Our modeling analyses guided an optimal choice of COVID-19 response during and after the Tokyo Olympic Games, allowing the epidemic to be brought under control despite such a large mass gathering.

Objectives: End-of-outbreak declarations are an important component of outbreak response because they indicate that public health and social interventions may be relaxed or lapsed. Our study aimed to assess end-of-outbreak probabilities for clusters of coronavirus disease 2019 (COVID-19) cases detected during the first wave of the COVID-19 pandemic in Japan. Methods: A statistical model for end-of-outbreak determination, which accounted for reporting delays for new cases, was computed. Four clusters, representing different social contexts and time points during the first wave of the epidemic, were selected and their end-of-outbreak probabilities were evaluated. Results: The speed of end-of-outbreak determination was most closely tied to outbreak size. Notably, accounting underascertainment of cases led to later end-of-outbreak determinations. In addition, end-of-outbreak determination was closely related to estimates of case dispersionk and the effective reproduction number Re. Increasing local transmission (Re>1) leads to greater uncertainty in the probability estimates. Conclusions: When public health measures are effective, lowerRe (less transmission on average) and larger k (lower risk of superspreading) will be in effect, and end-of-outbreak determinations can be declared with greater confidence. The application of end-of-outbreak probabilities can help distinguish between local extinction and low levels of transmission, and communicating these end-of-outbreak probabilities can help inform public health decision making with regard to the appropriate use of resources.

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.

R(t), the actual average number of secondary cases per primary case at calendar time t, is epidemiologically useful in assessing transmission dynamics in a population with varying susceptibility levels. However, a technical limitation of existing methods of estimating R(t) is the reliance on the daily number of cases with illness onset and the distribution of the serial interval, although the estimator of R(t) should be calculated as the ratio of newly infected cases at time t to the total number of potentially infectious people at the same time. Using historical data of a smallpox outbreak in Tokyo City, Japan, approximately 100 years ago, we propose a new method to compute R(t) that can be estimated using information on illness onset. Our method decomposes the mechanism of transmission into two distinct pieces of information: the frequency of secondary transmission relative to disease age and the probability density function of the incubation period. Employing a piecewise constant model, our maximum likelihood estimates of R(t) dropped below unity (0.6; 95% confidence interval: 0.5–0.7) for the period from Day 64 to Day 79, indicating that the epidemic was under control in this period. R(t) was continuously below one through the remaining days. The model prediction captured the overall observed pattern of the epidemic well. Our method is appropriate for acute infectious diseases other than smallpox for which variations in infectivity relative to disease age should be considered to correctly estimate the transmission potential, such as the ongoing global epidemic of coronavirus disease 2019 (COVID-19).

Objectives: Very few infectious disease physicians exist in Japan. A concerted infection control intervention program involving an antimicrobial stewardship team and multiple components was designed and implemented in multiple hospitals from 2010. Here, we aimed to retrospectively evaluate the intervention program’s effectiveness. Methods: The frequencies of methicillin resistant Staphylococcus aureus (MRSA) and drug-resistant Pseudomonas aeruginosa were monitored in four acute-care hospitals. The primary goal of the program was to accelerate the speed of decline of such resistance. A quasi-experimental study design was used to detect accelerated rates of increases in drug susceptibility, comparing time before and after the intervention. Results: Both MRSA and drug-resistant P. aeruginosa exhibited decreasing trends (p

Background: The epidemiological importance of asymptomatic individuals who would never develop illness, compared to those who eventually develop symptoms, has yet to be fully clarified. Methods: The very first cluster data in Tokyo and Kanagawa (n = 36) were analyzed. Movement of all close contact was restricted for 14 days and they underwent laboratory testing with polymerase chain reaction. The reproduction numbers of symptomatic and asymptomatic cases were estimated. Results: The reproduction number for symptomatic cases was estimated to be 1.2 (95% confidence interval (CI): 0.5–2.9). The relative infectiousness of asymptomatically infected cases was estimated to be 0.27 (95% CI: 0.03–0.81) of symptomatic cases. Conclusion: The relative transmissibility of asymptomatic cases is limited. Observing clusters starting with symptomatic transmission might be sufficient for the control.

The incubation period, or the time from infection to symptom onset, of COVID-19 has usually been estimated by using data collected through interviews with cases and their contacts. However, this estimation is influenced by uncertainty in the cases’ recall of exposure time. We propose a novel method that uses viral load data collected over time since hospitalization, hindcasting the timing of infection with a mathematical model for viral dynamics. As an example, we used reported data on viral load for 30 hospitalized patients from multiple countries (Singapore, China, Germany, and Korea) and estimated the incubation period. The median, 2.5, and 97.5 percentiles of the incubation period were 5.85 days (95 % CI: 5.05, 6.77), 2.65 days (2.04, 3.41), and 12.99 days (9.98, 16.79), respectively, which are comparable to the values estimated in previous studies. Using viral load to estimate the incubation period might be a useful approach, especially when it is impractical to directly observe the infection event.

Objective: To estimate the ascertainment rate of novel coronavirus disease (COVID-19). Methods: The epidemiological dataset of confirmed cases with COVID-19 in Japan as of February 28, 2020 was analyzed. A statistical model was constructed to describe the heterogeneity of the reporting rate by age and severity. We estimated the number of severe and non-severe cases, accounting for under-ascertainment. Results: The ascertainment rate of non-severe cases was estimated at 0.44 (95% confidence interval 0.37–0.50), indicating that the unbiased number of non-severe cases would be more than twice the reported count. Conclusions: Severe cases are twice as likely to be diagnosed and reported when compared to other cases. Considering that reported cases are usually dominated by non-severe cases, the adjusted total number of cases is also approximately double the observed count. This finding is critical in interpreting the reported data, and it is advised that the mild case data for COVID-19 should always be interpreted as under-ascertained [Au?1].

Objective: To estimate the serial interval of novel coronavirus (COVID-19) from information on 28 infector-infectee pairs. Methods: We collected dates of illness onset for primary cases (infectors) and secondary cases (infectees) from published research articles and case investigation reports. We subjectively ranked the credibility of the data and performed analyses on both the full dataset (n = 28) and a subset of pairs with highest certainty in reporting (n = 18). In addition, we adjust for right truncation of the data as the epidemic is still in its growth phase. Results: Accounting for right truncation and analyzing all pairs, we estimated the median serial interval at 4.0 days (95% credible interval [CrI]: 3.1, 4.9). Limiting our data to only the most certain pairs, the median serial interval was estimated at 4.6 days (95% CrI: 3.5, 5.9). Conclusions: The serial interval of COVID-19 is close to or shorter than its median incubation period. This suggests that a substantial proportion of secondary transmission may occur prior to illness onset. The COVID-19 serial interval is also shorter than the serial interval of severe acute respiratory syndrome (SARS), indicating that calculations made using the SARS serial interval may introduce bias. Keywords: Coronavirus, Outbreak, Illness onset, Generation time, Statistical model, Epidemiology, Viruses

During an Ebola virus disease (EVD) outbreak, the analysis and forecasting of the incidence in real time is challenged by reporting of cases, especially the reporting delay. It should be remembered that the latest count of cases is likely underestimated in real time, and moreover, the effective reproduction number, i.e. the average number of secondary cases generated by a single primary case at a given point in time, is also underestimated without proper adjustment. The present study aimed to adjust the reporting delay to appropriately estimate the latest incidence and obtain short-term forecasts from weekly reporting data of EVD in North Kivu, the Democratic Republic of the Congo (DRC). A semi-structured modeling approach was taken, accounting for reporting delay which can depend on time. The mean reporting delay was estimated at 11.6 days (95% CI: 11.3, 11.9) and the standard deviation was estimated to have changed from 26 November 2019 from 8.5–6.0 days. Nowcasting was successfully implemented by account for the time-dependent reporting delay: it mostly contained future observed values within the 95% confidence intervals, but there were failures when the reported incidence abruptly changed over time. Forecasting was also exercised in a similar manner to the nowcasting, while we imposed an extrapolation approach to the effective reproduction number for two future weeks. Moving average of the reproduction numbers for a few weeks prior the latest time of observation outperformed other extrapolations. The information that we can gain from real time (i.e. sequential) update of “situation report” can be considerably improved by integrating the proposed nowcasting and forecasting to the surveillance system. Keywords: Reporting delay, Nowcasting, Forecasting, Prediction, Effective reproduction number

Objectives: A rubella epidemic has been ongoing in Japan since August 2018. In the present study, we aimed to predict the likely size of a congenital rubella syndrome (CRS) epidemic during 2018–19. Methods: The expected number of CRS cases was estimated using an integral equation based on age-specific incidence of rubella among adult women, the time delay from gestational age of infection to diagnosis of CRS, and distribution of the mothers’ age at delivery. We used epidemic data during 2012–14 to parameterize the model and applied this in the prediction for 2018–19. Results: In analyzing the 2012–14 epidemic data, the mean delay from the mother’s infection to diagnosis was estimated at 24.2 weeks (95% confidence interval (CI): 20.7, 28.1). Applying the parameterized model, together with the more than 480 rubella cases in women in 2018 as well as delayed mother’s age at delivery in 2017, we determined that the expected number of CRS cases would be 9.7 (95% CI: 6.5, 12.5) cases. As the epidemic is ongoing, the cumulative number of CRS cases could potentially reach 96.8 (95% CI: 65.3, 125.5) cases, if rubella cases in adult women rose to 10 times the number by week 49 in 2018. Conclusions: CRS is expected to occur an average of 24 weeks following the mother’s infection with rubella virus. Accounting for an increase to 650 cases in women by week 5 in 2019, the expected number of CRS cases during 2018–19 has already exceeded 13 cases, as of week 5 in 2019. Keywords: Rubella virus, Statistical model, Forecasting, Outbreak, Epidemiology, Prediction, Japan

Circulating lymphocytes infiltrate into local foci at the inflammatory phase of acute wound healing for activation of the immune system and express an immune checkpoint protein programmed cell death 1 (PD-1) at the resolution phase for inactivation of the immune system. Conversely, the PD-1 expression was still found even on circulating lymphocytes of the elder patients with chronic tonsillitis at the palliative stage. Recently, an adhesion G protein coupled receptor 56 (GPR56) was reported to at least work as a proliferation factor for infiltrated lymphocytes into local foci at the resolution phase of acute wound healing. To preliminary examine a similar role of PD-1 and GPR56 at local foci at chronic inflammation, palate tonsils were prepared from small amounts of patients with chronic tonsillitis and tonsillar hypertrophy. A positive relationship of RNA expression might be observed between PD-1 and GPR56 in the elder patients with chronic tonsillitis. In regard to immunohistopathological findings, there were huge and small amounts of PD-1 and GPR56 expression at the marginal zone of lymphoid follicles of palate tonsils with chronic tonsillitis. Moreover, the positive relationship of RNA expression between PD-1 and GPR56 confirmed in large numbers of the elder patients with chronic tonsillitis. Probably, GPR56 participates in a supplement of PD-1+ lymphocytes to circulating bloods of the elder patients with chronic tonsillitis through a lymphocyte cell maintenance system at the marginal zone of the lymphoid follicles of palate tonsils.

Background: On April 7, 2020, the Japanese government declared a state of emergency regarding the novel coronavirus (COVID-19). Given the nation-wide spread of the coronavirus in major Japanese cities and the rapid increase in the number of cases with untraceable infection routes, large-scale monitoring for capturing the current epidemiological situation of COVID-19 in Japan is urgently required. Methods: A chatbot-based healthcare system named COOPERA (COvid-19: Operation for Personalized Empowerment to Render smart prevention And AN care seeking) was developed to surveil the Japanese epidemiological situation in real-time. COOPERA asked questions regarding personal information, location, preventive actions, COVID-19 related symptoms and their residence. Empirical Bayes estimates of the age-sex-standardized incidence rate and disease mapping approach using scan statistics were utilized to identify the geographical distribution of the symptoms in Tokyo and their spatial correlation r with the identified COVID-19 cases. Findings: We analyzed 353,010 participants from Tokyo recruited from 27th March to 6th April 2020. The mean (SD) age of participants was 42.7 (12.3), and 63.4%, 36.4% or 0.2% were female, male, or others, respectively. 95.6% of participants had no subjective symptoms. We identified several geographical clusters with high spatial correlation (r = 0.9), especially in downtown areas in central Tokyo such as Shibuya and Shinjuku. Interpretation: With the global spread of COVID-19, medical resources are being depleted. A new system to monitor the epidemiological situation, COOPERA, can provide insights to assist political decision to tackle the epidemic. In addition, given that Japan has not had a strong lockdown policy to weaken the spread of the infection, our result would be useful for preparing for the second wave in other countries during the next flu season without a strong lockdown. Funding: The present work was supported in part by a grant from the Ministry of Health, Labour and Welfare of Japan (H29-Gantaisaku-ippan-009).

Background: In the absence of widespread testing, symptomatic monitoring efforts may allow for understanding the epidemiological situation of the spread of coronavirus disease 2019 (COVID-19) in Japan. We obtained data from a social networking service (SNS) messaging application that monitors self-reported COVID-19 related symptoms in real time in Fukuoka Prefecture, Japan. We aimed at not only understanding the epidemiological situation of COVID-19 in the prefecture, but also highlighting the usefulness of symptomatic monitoring approaches that rely on self-reporting using SNS during a pandemic, and informing the assessment of Japan's emergency declaration over COVID-19. Methods: We analysed symptoms data (fever over 37.5° and a strong feeling of weariness or shortness of breath), reported voluntarily via SNS chatbot by 227,898 residents of Fukuoka Prefecture during March 27 to May 3, 2020, including April 7, when a state of emergency was declared. We estimated the spatial correlation coefficient between the number of the self-reported cases of COVID-19 related symptoms and the number of PCR confirmed COVID-19 cases in the period (obtained from the prefecture website); and estimated the empirical Bayes age- and sex-standardised incidence ratio (EBSIR) of the symptoms in the period, compared before and after the declaration. The number of symptom cases was weighted by age and sex to reflect the regional population distribution according to the 2015 national census. Findings: Of the participants, 3.47% reported symptoms. There was a strong spatial correlation of 0.847 (p

Objectives: The characteristics of disease in North Korea, including severe malnutrition and infectious disease risks, have not been openly and widely analyzed. This study was performed to estimate the risks of infectious diseases among refugees from North Korea. Methods: A literature review of clinical studies among North Korean defectors was conducted to statistically estimate the risks of infectious diseases among North Korean subjects. Results: A total of six groups of data from five publications covering the years 2004 to 2014 were identified. Tuberculosis and viral hepatitis appeared to be the two most common infectious diseases, especially among adult refugees. When comparing the risks of infectious diseases between North Korean and Syrian refugees, it is critical to remember that Plasmodium vivax malaria has been endemic in North Korea, while cutaneous leishmaniasis has frequently been seen among Syrian migrants. Conclusions: Valuable datasets from health surveys of defectors were reviewed. In addition to tuberculosis and viral hepatitis, which were found to be the two most common infectious diseases, a special characteristic of North Korean defectors was Plasmodium vivax malaria. This needs to be added to the list of differential diagnoses for pyretic patients.

Objectives: Despite the verification of measles elimination, Japan experienced multiple generations of measles transmission following importation events in 2016. The purpose of the present study was to analyze the transmission dynamics of measles in Japan, 2016, estimating the transmission potential in the partially vaccinated population. Methods: All diagnosed measles cases were notified to the government, and the present study analyzed two pieces of datasets independently, i.e., the transmission tree of the largest outbreak in Osaka (n = 49) and the final size distribution of all importation events (n = 23 events). Branching process model was employed to estimate the effective reproduction number Rv, and the analysis of transmission tree in Osaka enabled us to account for the timing of introducing contact tracing and case isolation. Results: Employing a negative binomial distribution for the offspring distribution, the model with time-dependent decline in Rv due to interventions appeared to best fit to the transmission tree data with Rv of 9.20 (95% CI (confidence interval): 2.08, 150.68) and the dispersion parameter 0.32 (95% CI: 0.07, 1.17) before interventions were introduced. The relative transmissibility in the presence of interventions from week 34 was estimated at 0.005. Analyzing the final size distribution, models for subcritical and supercritical processes fitted equally well to the observed data, and the estimated reproduction number from both models did not exclude the possibility that Rv > 1. Conclusions: Our results likely reflect the highly contagious nature of measles, indicating that Japan is at risk of observing multiple generations of measles transmission given imported cases. Considering that importation events may continue in the future, supplementary vaccination of adults needs to be considered.

Objectives: There has been a growing concern over Zika virus (ZIKV) infection, particularly since a probable link between ZIKV infection during pregnancy and microcephaly in the baby was identified. The present study aimed to estimate a theoretical risk of microcephaly during pregnancy with ZIKV infection in Northeastern Brazil in 2015. Methods: Temporal distributions of microcephaly, reported dengue-like illness and dengue seropositive in Brazil were extracted from secondary data sources. Using an integral equation model and a backcalculation technique, we estimated the risk of microcephaly during pregnancy with Zika virus infection. Results: If the fraction of Zika virus infections among a total of seronegative dengue-like illness cases is 30%, the risk of microcephaly following infection during the first trimester was estimated at 46.7% (95% CI: 9.1, 84.2), comparable to the risk of congenital rubella syndrome. However, the risk of microcephaly was shown to vary widely from 14.0% to 100%. The mean gestational age at delivery with microcephaly was estimated at 37.5 weeks (95% CI: 36.9, 39.3). Conclusions: The time interval between peaks of reported dengue-like illness and microcephaly was consistent with cause–outcome relationship. Our modeling framework predicts that the incidence of microcephaly is expected to steadily decline in early 2016, Brazil.

Objectives: There have been errors in determining the end of the Ebola virus disease (EVD) epidemic when adhering to the criteria of the World Health Organization. The present study aimed to review and learn from all known recrudescence events in West Africa occurring in 2014â2016. Methods: Background mechanisms of five erroneous declarations in Guinea, Liberia, and Sierra Leone during 2014â2016 were reviewed. Results: Three cases of recrudescence were suspected to have been caused by sexual contact with survivors, one to be due to international migration, and one was linked to a potentially immunocompromised mother. The three sexual transmission events involving survivorsâthe first two in Liberia and one in Sierra Leoneârequired 164 days, >150 days, and approximately 180 days, respectively, from discharge of the survivors to confirmation of the recrudescent case. Conclusions: The events of recrudescence were associated with relatively uncommon routes of transmission other than close contact during burial or care-giving, including sexual transmission, possible immunocompromise, and migration. Recognition of the sexual transmission risk among survivors could potentially involve discrimination, which may lead to under-ascertainment. Keywords: Ebola virus disease, Survivors, Sexually transmitted infections, Epidemic, Decision-making

Objectives: Zika virus has spread internationally through countries in the South Pacific and Americas. The present study aimed to estimate the basic reproduction number, R0, of Zika virus infection as a measurement of the transmission potential, reanalyzing past epidemic data from the South Pacific. Methods: Incidence data from two epidemics, one on Yap Island, Federal State of Micronesia in 2007 and the other in French Polynesia in 2013–2014, were reanalyzed. R0 of Zika virus infection was estimated from the early exponential growth rate of these two epidemics. Results: The maximum likelihood estimate (MLE) of R0 for the Yap Island epidemic was in the order of 4.3–5.8 with broad uncertainty bounds due to the small sample size of confirmed and probable cases. The MLE of R0 for French Polynesia based on syndromic data ranged from 1.8 to 2.0 with narrow uncertainty bounds. Conclusions: The transmissibility of Zika virus infection appears to be comparable to those of dengue and chikungunya viruses. Considering that Aedes species are a shared vector, this finding indicates that Zika virus replication within the vector is perhaps comparable to dengue and chikungunya.

Objectives: A large cluster of the Middle East respiratory syndrome (MERS) linked to healthcare setting occurred from May to July 2015 in the Republic of Korea. The present study aimed to estimate the case fatality ratio (CFR) by appropriately taking into account the time delay from illness onset to death. We then compare our estimate against previously published values of the CFR for MERS, i.e., 20% and 40%. Methods: Dates of illness onset and death of the MERS outbreak in the Republic of Korea were extracted from secondary data sources. Using the known distribution of time from illness onset to death and an integral equation model, we estimated the delay-adjusted risk of MERS death for the South Korean cluster. Results: Our most up-to-date estimate of CFR for the MERS outbreak in South Korea was estimated at 20.0% (95% confidence intervals (CI): 14.6, 26.2). During the course of the outbreak, estimate of the CFR in real time appeared to have decreased and become significantly lower than 40%. Conclusions: The risk of MERS death in Korea was consistent with published CFR. The estimate decreased with time perhaps due to time-dependent increase in case ascertainment. Crude ratio of cumulative deaths to cases underestimates the actual risk of MERS death because of time delay from illness onset to death.

Objectives: A rubella epidemic occurred in Japan from 2012-14, involving more than 15,000 cases. The present study aimed to estimate the immunizing effect of the epidemic, analyzing seroepidemiological data that were collected over time and age. Methods: Annual nationwide cross-sectional surveys were conducted from July to September, collecting serum from at least 5,400 individuals. The proportions seropositive were estimated before (2012), during (2013) and after (2014) the epidemic. Results: While the cases were mainly seen among men aged from 30-49 years, no significant increase was observed in the proportion seropositive in the corresponding age group. Even after the epidemic, age-standardized proportion seropositive of the total population remained 79.3% (95% confidence interval (CI): 75.2, 83.4) and that among males was as small as 76.7% (95% CI: 73.8, 79.6). Conclusions: Susceptible pockets remain in Japan, exposing the country to risk of additional rubella epidemics.