Infection control and COVID-19 outbreak training at elderly care facilities.

Fatalities caused by pneumonia and underlying diseases from COVID-19 infection show the highest relative frequency among elderly people. Long-term care facilities for elderly people have continued to be the areas most vulnerable to COVID-19. We examined the effectiveness of training for infection control and COVID-19 at elderly care facilities. After sending questionnaires to all long-term elderly care facilities in Ibaraki prefecture, Japan during January 18-29, 2022, we received useful responses from 98 facilities. Using logistic regression, we regressed a dummy variable for outbreak experience to dummy variables representing routine but partial training, routine training for all staff members, long-term care facilities for elderly people, numbers of nurses, and numbers of residents. Outbreak experiences of two types were inferred, as represented by a dummy variable for a COVID-19 outbreak at the facility, and by a dummy variable for outbreak experience at the facility before COVID-19 was found. Multivariate analysis indicated routine training for all staff members as the most effective, in fact the only effective, countermeasure against COVID-19 outbreak.

Waning COVID-19 vaccine effectiveness in Japan.

As of the end of November, 2021, the rate of completion for second-dose COVID-19 vaccine administration was almost 80% in Japan. We evaluated waning COVID-19 vaccine effectiveness in Japan, controlling for mutated strains, the Olympic Games, and countermeasures. The effective reproduction number R(t) was regressed on current vaccine coverage and data of a certain number of days prior, as well as shares of mutated strains, and an Olympic Games dummy variable along with data of temperature, humidity, mobility, and countermeasures. The study period was February, 2020 through November 4, as of November 25, 2021. Estimation results indicate that vaccine coverage of more than 90 days prior raises R(t) significantly. Especially, vaccine coverage with 90 or 120 days prior cancelled vaccine effectiveness completely. Results indicate significant waning of vaccine effectiveness from 90 days after the second dose.

Association of bleeding symptoms during influenza infection and administered drugs.

On March 1, 2019, the Ministry of Health, Labour and Welfare added bleeding symptoms to adverse reaction package inserts as a possible adverse event for a new anti-influenza drug, baloxavir marboxil, because 13 patients with bleeding symptoms were identified among influenza patients taking the drug. Nevertheless, aspects of the epidemiology of bleeding symptoms among influenza patients remain unclear. This study elucidated bleeding symptoms among influenza patients and hospitalized patients as severe cases. A survey was administered to all physicians in Japan during the 2019-2020 season for reporting of bleeding symptoms in influenza patients. The survey elicited information about outcomes, assuming associated underlying diseases and drugs in addition to administered drugs including acetaminophen and anti-influenza (antiviral) drugs. We received reports of 63 cases with bleeding symptoms, including 5 cases of hospitalized patients. Among all patients, 54% had been administered oseltamivir; 10% had been administered baloxavir marboxil. Among hospitalized patients, all had been administered acetaminophen; 40% of them had been administered oseltamivir, and one patient had been administered baloxavir marboxil. Accumulation of bleeding symptom cases is expected to be necessary to evaluate the association.

Attenuation of antibody titer of measles and rubella virus among university students of department of healthcare providers during 2015-2018 in Japan.

BACKGROUND: In Japan, measles elimination was confirmed in March 2015. Nevertheless, some outbreaks with cases imported from abroad were reported even after certification. A large rubella outbreak has been occurring since 2017. This study examines measurement of the speed of attenuation of antibody titer for a measles virus comparison with rubella virus. METHOD: Student subjects born from April 2, 1996 through April 1, 2000 were selected at Ibaraki Prefectural University of Health Sciences for this study: 177 for measles and 114 for rubella. They had available dates of additional immunization and antibodies in the following period and were judged as requiring additional immunization. We used enzyme immunoassay for IgG antibody testing. We regressed post-antibody titers of measles or rubella on pre-antibody titers and functions of duration between inoculation to post-evaluation. Functions of duration were selected according to the adjusted coefficient of determination. RESULTS: For measles, only a linear term of duration or log of duration was found to be significant without the quadratic terms. For rubella, we selected a five-order linear model which indicated that titer after vaccination would converge to 19.2. DISCUSSION: Results demonstrate that measles antibody decreased monotonically. If the pre-antibody titer was 15, vaccination raised titer quickly to 26; then it attenuated by 0.014 per day. Antibody titer is expected to be less than 16, which is the protection level of titer, after 704 days. For rubella, however, when pre-vaccination titer was evaluated at its average, the lower limit was 19.2. Therefore, protection can be maintained for a long time. This difference might reflect some circumstances of outbreaks of the respective diseases. CONCLUSION: This report describes the speed of attenuation and the epidemiological situation. The speed of attenuation can be expected to rise. Therefore, additional vaccination every several years might be necessary to maintain a protection level if a disease is almost eliminated.

Study Elucidating Disinfection at Nursery Schools in Ibaraki, Japan.

Control of infectious diseases requires switching from usual hygiene such as water wiping and cleaning, to control measures including appropriate and aggressive disinfection using 70% alcohol and/or hypochlorous acid depending on the pathogen. Nevertheless, some nursery schools might not understand or select proper disinfectant methods. A survey was administered by the local government of Ibaraki prefecture, Japan in January 2018 to all 456 nursery schools in Ibaraki prefecture. The surveyed items were the number of nursery teachers, usual manual hygiene among children, usual disinfection for lavatories, diaper changing spaces, tables used by children for meals, and classroom floors when there was no vomiting in the facilities and no outbreak in surrounding area. Moreover, it asked about disinfection procedures if children vomited during a community outbreak of gastroenteritis infection. We defined proper use for usual disinfection of a lavatory or diaper changing space as chlorine-based disinfectant including hypochlorous acid or 70% alcohol according to guidelines. Overall, 403 nursery schools responded to the survey. All nursery schools implemented usual hand hygiene. Association between proper disinfection and the size of nursery schools was not significant. Moreover, association between proper disinfection and nursery schools with nurse presence was not found to be significant.

Evaluating Apple Inc Mobility Trend Data Related to the COVID-19 Outbreak in Japan: Statistical Analysis.

BACKGROUND: In Japan, as a countermeasure against the COVID-19 outbreak, both the national and local governments issued voluntary restrictions against going out from residences at the end of March 2020 in preference to the lockdowns instituted in European and North American countries. The effect of such measures can be studied with mobility data, such as data which is generated by counting the number of requests made to Apple Maps for directions in select countries/regions, sub-regions, and cities. OBJECTIVE: We investigate the associations of mobility data provided by Apple Inc and an estimate an an effective reproduction number R(t). METHODS: We regressed R(t) on a polynomial function of daily Apple data, estimated using the whole period, and analyzed subperiods delimited by March 10, 2020. RESULTS: In the estimation results, R(t) was 1.72 when voluntary restrictions against going out ceased and mobility reverted to a normal level. However, the critical level of reducing R(t) to <1 was obtained at 89.3% of normal mobility. CONCLUSIONS: We demonstrated that Apple mobility data are useful for short-term prediction of R(t). The results indicate that the number of trips should decrease by 10% until herd immunity is achieved and that higher voluntary restrictions against going out might not be necessary for avoiding a re-emergence of the outbreak.

Estimated effectiveness of school closure and voluntary event cancellation as COVID-19 countermeasures in Japan.

BACKGROUND: As countermeasures against the COVID-19 outbreak, sports and entertainment events were canceled (VEC) in Japan for two weeks from 26 February through 13 March. Moreover, most schools were closed (SC). OBJECTIVE: For this study, we estimated the basic reproduction number (R0) and SC and VEC effects. METHOD: After constructing a susceptible-infected-recovered model with three age classes, we used data of symptomatic patients in Japan for 14 January through 24 March. The SC and VEC effects were incorporated into the model through changes in contact patterns and contact frequencies among age classes. RESULTS: Results suggest R0 as 2.56, with 95% CI of [2.51, 2.96] before SC and VEC. The respective effects of SC and VEC were estimated as 0.4 (95% CI [0.3, 0.5]) and 0.5 (95% CI [0.3, 0.7]). CONCLUSION: The estimated R0 is similar to those found from other studies of China and Japan. Significant reduction of contact frequency has been achieved by SC and VEC. Nevertheless, its magnitude was insufficient to contain the outbreak.

Effects of voluntary event cancellation and school closure as countermeasures against COVID-19 outbreak in Japan.

BACKGROUND: To control the COVID-19 outbreak in Japan, sports and entertainment events were canceled and schools were closed throughout Japan from February 26 through March 19. That policy has been designated as voluntary event cancellation and school closure (VECSC). OBJECT: This study assesses VECSC effectiveness based on predicted outcomes. METHODS: A simple susceptible-infected-recovered model was applied to data of patients with symptoms in Japan during January 14 through March 26. The respective reproduction numbers for periods before VECSC (R0), during VECSC (Re), and after VECSC (Ra) were estimated. RESULTS: Results suggest R0 before VECSC as 2.534 [2.449, 2.598], Re during VECSC as 1.077 [0.948, 1.228], and Ra after VECSC as 4.455 [3.615, 5.255]. DISCUSSION AND CONCLUSION: Results demonstrated that VECSC can reduce COVID-19 infectiousness considerably, but after VECSC, the value of the reproduction number rose to exceed 4.0.

Risk factors affecting the failure to complete treatment for patients with latent tuberculosis infection in Tokyo, Japan.

OBJECTIVE: The treatment completion rate for all latent tuberculosis infection (LTBI) patients in Tokyo was 83.6% in 2014: somewhat lower than the targeted goal of 85%. This study examines the association between risk factors and LTBI patients' failure to complete treatment. METHODS: We collected data related to the treatment of LTBI patients who were reported to public health centers in Tokyo from January 2014 through December 2014. Data included potential risk factors affecting treatment, treatment results, and patient characteristics. We used Fisher's exact test to evaluate risk factors affecting failure to complete treatment. The failure rate was defined as the incompletion rate of treatment. RESULTS: Of 1060 notified cases, 877 had completed treatment; 116 had not completed treatment. Of these 116 cases, failure to complete treatment in 52 cases was attributable to side effects of anti-tuberculosis drugs. Reasons other than side effects were given for 64 cases. Another 67 cases could not be followed up. In all, 941 cases were analyzed, excluding cases lost to follow-up and cases for which patients had not completed treatment because of anti-tuberculosis drug side effects. Failure rates among foreign-born patients (26.9%) were significantly much higher than those among Japan-born patients (3.9%). Statistical tests indicated no presumed potential risk factor as significant. However, "no supporter for foreign-born LTBI patients" was marginally significant. CONCLUSION: Only "no supporter for foreign-born LTBI patients" was found to be marginally significant. More data must be accumulated to assess the risk factors affecting LTBI treatment.

Higher Incidence of Syphilis among Patients with HIV Infection: Population Study using Surveillance Data of Tokyo, Japan.

In Japan, the reported cases of syphilis have been increasing since 2011 especially in large cities such as Tokyo. The objective of this study was to evaluate the risk of HIV infection for syphilis co-infection on the population of Tokyo, Japan. We analyzed data of syphilis cases obtained from additional surveillance by the Tokyo Metropolitan Government in 2018, including those with human immunodeficiency virus (HIV) infection as well as data of HIV/acquired immunodeficiency syndrome (AIDS) cases during 1985-2017. We calculated the incidence of symptomatic syphilis cases among HIV-infected or non-HIV-infected individuals. Similarly, we calculated the incidence of syphilis, including asymptomatic cases, among each population. The relative risk of HIV infection for syphilis, including or excluding asymptomatic syphilis cases, was estimated. The relative risk was calculated by dividing the incidence of syphilis in the HIV-infected population by that in the non-HIV-infected population. Of the 1,775 syphilis cases reported in 2018, 172 cases were infected with HIV, 575 cases were uninfected, and the remainder were either unknown or not reported. The cumulative number of HIV/AIDS cases during 1985-2017 in Tokyo was 9,629; among them, 172 were co-infected with syphilis. The relative risk of HIV infection for syphilis was estimated as 423.29 if asymptomatic syphilis cases were included, and 372.37 if they were excluded. These results showed an extremely high risk of HIV infection. Since many syphilis cases have unknown or unreported HIV infection status, reduction of these cases might contribute to more reliable estimation of HIV infection risk.

Negative effect on immune response of repeated influenza vaccination and waning effectiveness in interseason for elderly people.

BACKGROUND: Through test negative designs for visiting a doctor because of influenza-like illness, many studies have found decreasing efficacy of repeated vaccination. Furthermore, waning effectiveness during interseason periods has been reported. This study was conducted to confirm negative effects of repeated vaccination in individuals with the same vaccine strain and to measure waning effects. METHODS: Our cohort includes 66 participants older than 65 years old recruited from an outpatient department of one hospital. All were vaccinated, with hemagglutination inhibition (HI) antibody titers measured from 2001/02 season through the 2003/04 season. HI antibody titers were measured three times in one season: pre-vaccination, post-vaccination, and post-epidemic. To test negative effects of immune response to the repeated vaccination, differences between protection rates and differences between response rates were analyzed for individuals in the two consecutive seasons. For the test of waning effectiveness, we measured the difference in geometric mean titers of HI antibody between post-epidemic results and pre-vaccination results obtained in the following season. RESULTS: Protection rates were 40-55% in A/New Caledonia/20/99 and ≥75% in A/Panama/2007/99 by repeated vaccination. In A/New Caledonia/20/99 and A/Panama/2007/99 in the 2003/04 season, significant decreases were found in protection rates from the earlier seasons, although the rate for A/Panama/2007/99 in the 2002/03 season increased significantly from that of the prior season. The respective response rates in the 2003/04 season in A/New Caledonia/20/99, and in the 2002/03 and 2003/04 seasons in A/Panama/2007/99 decreased significantly from those of earlier seasons. Regarding waning effectiveness, antibody titers for A/New Caledonia/20/99 in 2003/04 season, and A/Panama/2007/99 in 2002/03 and 2003/04 seasons decreased significantly to 37.0-66.7%. CONCLUSION: Results show significant negative effects of immune response by repeated vaccination and show significant waning effectiveness during the interseason for individuals with the same strain of influenza type A. The proportion of elderly people with HI antibody titers of ≥1:40 might be maintained by repeated influenza vaccination.

Association of moderately abnormal behavior and administered neuraminidase inhibitors.

Our earlier study investigated the incidence of severe abnormal behavior associated with neuraminidase inhibitors (NIs), but some studies have specifically examined the association of oseltamivir use and moderately abnormal behavior. Therefore, this study was undertaken to assess associations between moderately abnormal behavior and administered drugs. All cases of patients with influenza who exhibited moderately abnormal behavior were reported to us by physicians of all sentinel clinics and hospitals for influenza throughout Japan. Open Data of the National Database of Electronic Medical Claims include the numbers of patients diagnosed as having influenza who were prescribed NI. Incidence by NI was tested using Fisher's exact test. We received 518 moderately abnormal cases in 5-9-year-olds and 207 moderately abnormal behavior cases in 10-19-year-olds. The incidence among NI ranged from 193 per one million influenza patients in laninamivir among 10-19-year-olds to 1021 for peramivir among 5-9-year-olds. Estimation results revealed the order of risk among NIs as peramivir, oseltamivir, zanamivir and laninamivir in moderate abnormal behavior. Because of data limitations, risk among patients with and without NI cannot be compared.

Syndromic surveillance using ambulance transfer data in Tokyo, Japan.

Bioterrorism attacks become more probable when important high-profile international or political events are held, such as G7 summit meetings or mass gathering events including Olympic and Paralympic games and FIFA World Cup tournaments. Outbreaks of infectious disease and widespread incidents of food poisoning are also public health concerns at such times. In Japan, the Tokyo Metropolitan Government operates Ambulance Transfer Syndromic Surveillance (ATSS), which can help monitor such incidents. The present study presents and assesses the ATSS framework. During the study period of October 2017 through November 2018, we monitored 33 areas for symptoms of 9 categories: vomiting/nausea, dizziness, palpitation, unconsciousness, breathing disorder, fever, spasm/paralysis, collapse/weakness, and bloody emesis/nasal hemorrhage. Among all symptoms, we found 9929 low-level aberrations, 2537 medium-level aberrations, and 577 high-level aberrations, with respective frequencies of 9.2%, 2.3%, and 0.5%. Of those, Tokyo Metropolitan Institute of Public Health reported the information to Tokyo Metropolitan Government 28 times during the period. Of the 28 identified clusters, Tokyo Metropolitan Government judged the necessity for investigating 7. All of those were investigated at hospitals by the jurisdictional public health center. Because ATSS covers almost the entire Tokyo metropolitan area, with about 13.8 million residents, it is definitely the largest syndromic surveillance in the world.

Determinants of Vaccination Coverage for the Second Dose of Measles-Rubella Vaccine in Tokyo, Japan.

In Japan, some measles outbreaks were initiated by a tourist from oversea and foreign workers recently. Moreover, rubella outbreak emerged since July 2018 mainly in the South Kanto, and the outbreak is currently ongoing in 2019. It is important to maintain a high measles-rubella combined vaccine (MR) coverage for measles-rubella control. Vaccination coverage for the second dose of MR (MR2) is 90.8% in Tokyo in 2016, which was the third worst among all prefectures in Japan. The purpose of this study was to clarify determinant factors of vaccination coverage for MR2 in Tokyo. Data were obtained for 49 wards and cities in Tokyo in 2016. We regressed vaccination coverage of MR2 on the times of notification by mail, the proportion of households receiving welfare payments, and the proportion of non-Japanese elementary school students. In addition to the simplest specification, five factors were included separately as explanatory variables: the proportion of public health nurses; the ratio of the number of pediatric medical facilities to the number of preschool and elementary school children; the moving-in rate; the proportion of households with a single parent; and the proportion of households with husband and wife both working. Results show that a high proportion of households receiving welfare payments, notification by two or more letters, and moving-in rate or a lower proportion of non-Japanese elementary school students improve coverage. In conclusion, the health authorities can exert efforts to reduce burden of time spent for vaccination and provide sufficient information to improve coverage.

Cost-effectiveness analysis of (Nursery) School Absenteeism Surveillance System.

BACKGROUND: Our earlier report reported that the (Nursery) School Absenteeism Surveillance System ((N)SASSy) can decrease numbers of patients. This study evaluates (N)SASSy's cost-effectiveness. METHODS: A social perspective is taken for economic evaluation. For simplicity, 8,000 yen is assumed for direct medical costs. We assume the home health care duration to be 6 days, with 30 000 yen as the indirect opportunity cost of family nursing. Benefit-cost ratios are used as indicators of cost-effectiveness. RESULTS: By multiplying the disease burden per patient by the reduced number of patients, the (N)SASSy effect was estimated as 206.9 billion yen, with 95% confidence interval of [67.3,346.6] billion yen. The total cost attributable to (N)SASSy throughout Japan is expected to be 2.63 billion yen. The benefit-cost ratio is expected to be approximately 60. CONCLUSIONS: The estimated benefit-cost ratio is much higher than that for the routine immunization of children.

Association of influenza outbreak in each nursery school and community in a ward in Tokyo, Japan.

In nursery schools, influenza outbreaks have occurred every year. However, influenza characteristics of its diffusion among nursery schools, within each nursery school, and among classes of different ages in nursery schools remains unclear. This paper presents an examination of these matters using the Nursery School Absenteeism Surveillance System (NSASSy). All nursery schools in ward A in Tokyo introduced to the NSASSy in 2015. The study period was November 2015 through March 2016. The data of influenza patients were extracted from NSASSy. We examined four definitions of 'starting date of community outbreak' (SDCO) of influenza: 1) the first recorded day of influenza patients (SDCO1), 2) the last day of influenza patients recorded for two consecutive days (SDCO2), 3) three consecutive days (SDCO3), and 4) four consecutive days (SDCO4). We evaluated those four definitions by duration of the initial case at each nursery school from SDCO and evaluated the proportion of nursery schools at which the initial case occurred before SDCO. The average durations of initial cases at respective nursery schools from SDCO1-4 were 40.3, 26.3, 23.1 and 13.3 days. The respective proportions of nursery schools at which the initial case occurred before SDCO1-4 were 3.1%, 6.4%, 9.4% and 40.6%. Results demonstrate that SDCO3 is an appropriate definition of SDCO. Robustness checks for other areas, seasons, and population size constitute the next challenge for research in this area.

Infection Control in Nursery Schools and Schools Using a School Absenteeism Surveillance System.

Infection control in nursery schools and schools is important for community health and the health of children. In Japan, caregivers of children or students usually report the absence due to illness to their attending nurseries or schools, including symptoms and diagnosed diseases. The (Nursery) School Absenteeism Surveillance System, (N)SASSy, covers about 60% of schools and 40% of nurseries in Japan. In this paper, we evaluated the benefits of (N)SASSy as an infection control measure by a public health center. Mito Public Health Center (MPHC) covers 58 nurseries and 186 schools, as of May 2015, and called the nurseries and/or schools to confirm the situation, in case of aberration detected through (N)SASSy. The outcome was defined as the proportion of cluster avoidance by advice from MPHC. A cluster was identified, when the number of patients at the same facility with the same symptom or diagnosed disease was greater than ten during the prior seven days. During the study period (April 2015-March 2016), MPHC advised 85 times, and clusters were avoided 82 times (96.5%). The proportion of cluster avoidance was 100% for fever, enterohemorrhagic Escherichia coli infection, respiratory syncytial virus infection, or streptococcal pharyngitis infection. The proportion of cluster avoidance for diarrhea, vomiting or gastroenteritis infection, mumps, hand-foot-mouth disease (HFMD), and influenza was 78.8, 50.0, 20.0, and 6.7%, respectively. In conclusion, advice from a public health center given by phone based on information from (N)SASSy will be helpful for reducing the number of clusters of infectious diseases, except for HFMD and influenza.

Association of severe abnormal behavior and acetaminophen with/without neuraminidase inhibitors.

BACKGROUND: Even though abnormal behavior related with influenza and neuraminidase inhibitors (NI) has been discussed, the risks of acetaminophen and co-administration of NI and acetaminophen have not been examined. This study assesses those risks. MATERIALS AND METHODS: All cases of patients with influenza who present with severe abnormal behavior are reported by physicians of all clinics and hospitals throughout Japan. The numbers of people diagnosed as having influenza, whether prescribed NI and acetaminophen or not, were extracted from the National Database of Electronic Medical Claims (NDBEMC). The study period was from September 2009 to March 2016. RESULTS: We found two consistent results among four combinations of age class and severity. The one was that patients who did not use NI or acetaminophen showed significantly higher incidence of abnormal behavior than zanamivir with acetaminophen, another one was that patients with oseltamivir only has higher incidence than zanamivir with acetaminophen. Concerning about acetaminophen, the use of it significantly decrease risk for severe and the most severe instances in 5-9-year-old patients with laninamivir and the severe instances in 10-19-year-old patients with zanamivir. DISCUSSION: We also demonstrated that acetaminophen alone or co-administered with NI does not seem to raise the risk of abnormal behavior in influenza patients.

Prescription surveillance for early detection system of emerging and reemerging infectious disease outbreaks.

Based on prescriptions filled at external pharmacies, prescription surveillance (PS) in Japan has been reporting the estimated numbers of influenza and varicella patients and people prescribed certain drugs since 2009. Every morning, this system estimates the numbers of patients from the numbers of prescriptions filled nationwide for neuraminidase inhibitors, anti-herpes virus drugs, antibiotic drugs, antipyretic analgesics, and multi-ingredient cold medications. Moreover, it can detect "unexplained" infectious diseases that are not explained as infectious diseases monitored by other surveillance systems. Such "unexplained" infectious diseases might be emerging and re-emerging infectious diseases including bioterrorism attacks, which are reportedly difficult to diagnose, at least in early outbreak stages. To ascertain the system's potential benefits, this study examined schemes to detect "unexplained" infectious diseases using PS information. The numbers of patients prescribed the respective drugs are first regressed on the known infectious diseases, time trends, and dummies for day-of-the-week, holidays, and days following a holiday. Known infectious diseases are defined as covered by the National Official Sentinel Surveillance for Infectious Diseases under the Infection Control Law. After the numbers of patients from PS are compared with the predicted numbers of patients, their probabilities of occurrence are calculated. We examined the system's prospective operation from January 2017 through July 2018. The criterion we used to define aberrations varied, from 0.01 to 10-7. For criteria of 0.01 and 10-7 we found 254 and 15 aberrations, respectively. We confirmed its feasibility and effectiveness.