External quality assessment survey for SARS-CoV-2 nucleic acid amplification tests in clinical laboratories in Tokyo, 2021.

INTRODUCTION: Nucleic acid amplification tests (NAATs) play a pivotal role in clinical laboratories for diagnosing COVID-19. This study aimed to elucidate the accuracy of these tests. METHODS: In 2021, an external quality assessment of NAATs for SARS-CoV-2 was conducted in 47 laboratories in Tokyo, Japan. In open testing, where the laboratories knew that the samples were intended for the survey, a simulated nasopharyngeal swab suspension sample was used, featuring a positive sample A with a viral concentration of 50 copies/µL, positive sample B with 5 copies/µL, and a negative sample. Laboratories employing real-time RT-PCR were required to report cycle threshold (Ct) values. In blind testing, where the samples were processed as normal test samples, a positive sample C with 50 copies/µL was prepared using a simulated saliva sample. RESULTS: Of the 47 laboratories, 41 were engaged in open testing. For sample A, all 41 laboratories yielded positive results, whereas for sample B, 36 laboratories reported positive results, 3 laboratories reported "test decision pending", 1 laboratory reported "suspected positive", and 1 laboratory did not respond. All 41 laboratories correctly identified the negative samples as negative. The mean Ct values were 32.2 for sample A and 35.2 for sample B. In the blind test, six laboratories received samples. Sample C was identified as positive by five laboratories and negative by one laboratory. CONCLUSIONS: The nature of the specimen, specifically the saliva, may have influenced the blind test outcomes. The identified issues must be meticulously investigated and rectified to ensure accurate results.

A study of quality assessment in SARS-CoV-2 pathogen nucleic acid amplification tests performance; from the results of external quality assessment survey of clinical laboratories in the Tokyo Metropolitan Government external quality assessment program in 2020.

INTRODUCTION: The Tokyo Metropolitan Government (TMG) conducted an external quality assessment (EQA) survey of pathogen nucleic acid amplification tests (NAATs) as a TMG EQA program for SARS-CoV-2 for clinical laboratories in Tokyo. METHODS: We diluted and prepared a standard product manufactured by Company A to about 2,500 copies/mL to make a positive control and distribute it with a negative control. The participants reported the use of the NAATs methods for SARS-CoV-2, the name of the real-time RT-PCR kit, the name of the detection device, the target gene(s), nucleic acid extraction kit, Threshold Cycle value in the case of RT-PCR and the Threshold time value and Differential calculation value in the case of Loop-Mediated Isothermal Amplification (LAMP) method. RESULTS: As a result, 17 laboratories using fully automated equipment and 34 laboratories using the RT-PCR method reported generally appropriate results in this EQA survey. On the other hand, among the laboratories that adopted the LAMP method, there were a plurality of laboratories that judged positive samples to be negative. CONCLUSION: The false negative result is considered to be due to the fact that the amount of virus genome contained in the quality control reagent used this time was below the detection limit of the LAMP method combined with the rapid extraction reagent for influenza virus. On the other hand, false positive results are considered to be due to the non-specific reaction of the NAATs. The EQA program must be continued for the proper implementation of the pathogen NAATs.

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.

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.

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.

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.

Radioactive iodine (RAI) therapy for distantly metastatic differentiated thyroid cancer (DTC) in juvenile versus adult patients.

In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent characteristics and favorable prognosis are observed in comparison with many other carcinomas. However, recurrence is frequent, necessitating additional treatment, including radioactive iodine (RAI) therapy. In this report, the probability of recurrence, prognostic factors, treatment, and outcomes in both juvenile- and adult-onset DTC were analyzed and compared. At our institution, a total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection. The patients included 23 in their teens, 118 in their twenties, and 1412 in their thirties or older. The risk factors for distant metastases for DTC were male gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node metastases from PTC, and the presence of more than two distant metastatic foci. Patients with the highest risk underwent RAI ablation in line with institutional guidelines. Although the overall outcome in our juvenile patients was excellent, during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3% achieved complete remission, 4.35% partial remission, and 4.35% stable disease, with no disease-related deaths. Among the 118 patients in their twenties to thirties, 1 (0.8%) experienced progressive disease and disease-related death. A younger age at diagnosis and less radical primary surgery without subsequent RAI ablation are factors strongly predictive of distant metastases in patients with juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with high- and intermediate-risk juvenile DTC.

Biological differential diagnosis of follicular thyroid tumor and Hürthle cell tumor on the basis of telomere length and hTERT expression.

BACKGROUND: The most difficult thyroid tumors to diagnose by histology are follicular carcinomas (FTCs) and Hürthle cell carcinomas (HCCs). Telomere alteration and human telomerase reverse transcriptase (hTERT) expression have been observed in most human cancers and are known to be a feature of malignancy. The purpose of this study was to clarify whether hTERT protein expression and telomere alteration could be applicable biological markers for distinguishing FTC from HCC. METHODS: We investigated a total of 78 thyroid tumor cases, including 14 FTCs, 47 follicular adenomas (FTAs), 5 HCCs, and 12 Hürthle cell adenomas (HCAs). hTERT protein expression was examined by immunohistochemistry, and telomere length was determined by tissue quantitative fluorescence in situ hybridization. RESULTS: Positivity for hTERT protein expression was observed in 86 % of FTCs and 49 % of FTAs. Telomeres in FTCs were significantly shorter than those in FTAs. All HCCs and HCAs (100 %) expressed hTERT protein. Telomeres in HCCs were significantly shorter than those in HCAs. CONCLUSIONS: Our results suggest that hTERT protein expression and telomere shortening would be applicable as biological markers to distinguish FTC from FTA. Previous studies have suggested that follicular tumor and Hürthle cell tumor should be classified biologically as distinct tumors. All Hürthle cell tumors expressed hTERT protein and HCCs had markedly shortened telomeres, suggesting that follicular tumor and Hürthle cell tumor might be biologically distinct entities.

Therapeutic strategy for low-risk thyroid cancer in Kanaji Thyroid Hospital.

It is well-known that differentiated thyroid carcinoma (DTC) has a generally indolent character and shows a favorable prognosis in comparison with many other carcinomas. The therapeutic strategy for patients with DTC in Japan has differed from that in Western countries. Total thyroidectomy followed by radioactive iodine (RAI) ablation has been standard in Western countries, whereas limited hemi-thyroidectomy and subtotal thyroidectomy has been extensively accepted in Japan. Papillary thyroid carcinoma (PTC) accounts for over 90% of all thyroid cancers in Japan. The majority of patients with PTC are categorized into a low-risk group on the basis of the recent risk-group classification schemes, and they show excellent outcomes. Several management guidelines for thyroid cancers have been published in Western countries. However, the optimal therapeutic options for PTC remain controversial, and high-level clinical evidence aimed at resolving these issues is lacking. Moreover, as socioeconomic differences in medical care exist, conventional policies for the treatment of PTC have differed between Japan and other countries. This review focuses on the special features of treatment in Japan for patients with low-risk DTC involving subtotal thyroidectomy without adjuvant therapies, rather than total thyroidectomy with RAI, with the aim of preserving quality of life. At our institution in Japan, we have had extensive experience with RAI treatment for high-risk DTC patients, and this represents a very rare situation. Here we introduce the therapeutic strategy for low-risk thyroid cancer in Japan, including the measures adopted at our institution.

The 2011 measles outbreak in Tokyo. An analysis of surveillance data.

OBJECTIVES: The study was conducted with the intention of establishing a strategy to eliminate measles on the basis of an analysis of the epidemiological profile of measles cases reported in Tokyo during the year 2011. METHODS: We investigated measles cases reported to the Tokyo Metropolitan Government in 2011, recorded as part of the National Epidemiological Surveillance of Infectious Diseases. Factors analyzed included age, vaccination status for each patient, cases for which records were discarded after laboratory confirmation, genotype of the measles virus and relationships between dates of specimen collection and results of polymerase chain reaction (PCR) and IgM antibody tests. RESULTS: A total of 178 measles cases were reported in Tokyo during 2011, and the majority of cases (128, 71.9%) were reported during the peak period from epiweeks 13 to 24. The largest age group reported was one to four years of age (40, 22.5%) followed by groups of 20-29 and 30-39 years of age (both 34, 19.1%). Most cases were sporadic, with only six outbreaks occurring. Even then, the numbers of cases for each outbreak was less than five. More than half of the patients in all age groups, except for the 1-4-year-old group, had not been vaccinated or did not have a record of vaccination. Genotypes D4 and D9 of measles virus were detected in most cases. However, genotype D5, which had been circulating in Japan before 2008, was not detected. CONCLUSION: Imported viruses were the cause of measles cases reported in Tokyo during 2011. The disease control was better than that in 2007 and 2008 because of the swift and appropriate responses to the occurrences. It is also possible that there has been an increase in the proportion of people with immunity to measles. Increasing the rate of immunization, performing effective surveillance, and confirming suspicious measles cases by using molecular methods are important for achieving the elimination of measles.

Epidemiology of Syphilis in Tokyo from 2019 to 2022: a Descriptive Epidemiological Study.

In recent years, the incidence of syphilis in Tokyo has increased. This descriptive epidemiological study aimed to elucidate the status of syphilis within the city. Data regarding age, sex, disease stage, and presumed sexual partners of patients with syphilis reported in Tokyo were compiled and analyzed. A total of 9,419 patients with syphilis were diagnosed between 2019 and 2022. A sharp rise was observed in the number of reported cases from 2021 to 2022. Between 2020 and 2022, the number of women in their 20s who developed syphilis rapidly increased by more than 3-fold. Furthermore, the number of pregnant women with syphilis increased the end of 2022. Despite a rapid increase in the number of young women with syphilis, the incidence of congenital syphilis has remained stable. This stability may be attributed to the early detection of syphilis during pregnancy, facilitated by the high rate of antenatal checkups in Tokyo. However, the growing incidence of syphilis among young women could potentially lead to a rise congenital syphilis cases in the future. Therefore, public health strategies should include educational initiatives targeting high-risk populations and adolescents, along with early and appropriate testing and treatment to prevent the progression of syphilis.

Multisource surveillance conducted by the Tokyo Metropolitan Government during the Tokyo 2020 Olympic and Paralympic Games.

The Tokyo 2020 Olympic and Paralympic Games (the Games) were held from 23 July to 5 September 2021 in Tokyo, Japan, after a 1-year delay due to the coronavirus disease (COVID-19) pandemic. The Tokyo Metropolitan Government was responsible for monitoring and responding to infectious disease outbreaks other than COVID-19 during the Games. A multisource surveillance system was used from 1 July to 12 September 2021 for the early detection and rapid response to infectious diseases. This included routine notifiable disease surveillance, sentinel surveillance, syndromic surveillance, cluster surveillance, ambulance transfer surveillance and the Tokyo Infectious Alert system. Daily reports were disseminated summarizing the data collected from the multisource surveillance system. No case of infectious disease under the Tokyo Metropolitan Government system required a response during the Games. The multisource surveillance was useful for providing intelligence during the Games and, if required, could contribute to the early detection and rapid response to outbreaks during other mass gatherings. The system could be improved to overcome the challenges implied by the findings of this multisource surveillance.

Genetic Characteristics of the Virus Detected in the First Mpox Imported Case in Tokyo, Japan.

Mpox, caused by the mpox virus (MPXV), produces symptoms similar to those of smallpox when transmitted to humans. Since 1970, this disease has been endemic, particularly in Africa. However, since May 2022, the number of patients without a history of travel to endemic areas has increased rapidly globally. Under these circumstances, in July 2022, two different real-time PCR methods were used on specimens brought to the Tokyo Metropolitan Institute of Public Health. MPXV was detected in the skin samples, and it was inferred that the virus was a West African strain. Furthermore, a more detailed analysis of the genetic characteristics of the detected MPXV using next-generation sequencing revealed that the MPXV detected in Tokyo was strain B.1, which corresponds to the same strain that is prevalent in Europe and the USA. This suggests that mpox reported for the first time in Japan was imported and related to outbreaks in Europe and the USA. Therefore, it is necessary to continue monitoring outbreaks in Japan in conjunction with global epidemics.

[Relationship between BCG immunization coverage and the immunization delivery system in the Tama area of Tokyo].

PURPOSE: The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. METHODS: The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. RESULTS: Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj. OR 48.17 CI 29.62-79.75 in Group 4; and OR 4.24 CI 2.86-6.31, adj. OR 15.61 CI 9.05-27.26 in Group 5. The univariate analysis and multivariate regression analysis revealed an influence of the BCG immunization delivery manner on the BCG immunization coverage. CONCLUSION: The choice of BCG immunization delivery manner is very important to raise the BCG immunization coverage. The BCG immunization given on the occasion of the mass health check-up and the high-frequent immunization service are thought to improve the BCG immunization coverage.

[The possibility of outbreak control by real-time surveillance with PCR method perfomed immediately--a case study of hand foot and mouth disease outbreak in a day care facility for children].

OBJECT: We examined the relationship between syndromic surveillance and laboratory confirmation, at an early stage of an outbreak of hand foot and mouth disease and RS virus infection. METHOD: We observed the epidemiological situation from a surveillance system at a day care facility for young children in Tokyo from one week before onset of the indicator until one month thereafter. For laboratory diagnosis, we collected a rectal swab or a nasal swab from one patient in the early stage of the outbreak. RESULT: A total of 20 patients, comprising 12 1-year-old, 5 2-year-old and 3 3-year-old children, were found to have hand foot and mouth disease on August 1st, 2011. From a rectal swab from one HFMD patient, enterovirus genome was detected and identified as coxsackievirus type A6 (CA6) with PCR sequencing. The CA6 had 99% identity to CA6 (Genbank No AB663318) in the VP4 coding region. RS virus also was detected from a nasal swab. DISCUSSION: The establishment of a surveillance system at day care facilities for children can monitor infectious diseases among young children promptly. Laboratory confirmation, even though from only one patient as shown in this study, can provide critical information regarding the causative agent of the outbreak. This method is easy to conduct and could be used for activating appropriate countermeasures. CONCLUSION: We believe that the combination of the timeliness of a surveillance system at day care facility for children and the convenience of laboratory diagnosis of even one patient can detect the causative pathogen, and thus enable the activation of countermeasures before an outbreak become widespread.

Melanin-producing medullary thyroid carcinoma with transformation to melanoma: A case report.

Only one case of melanoma arising from melanin-producing medullary thyroid carcinoma (MTC) has been reported previously. In the present study, a second such case was reported and compared with the previous one. The patient was an 86-year-old male who presented with a right anterior neck mass. Ultrasound revealed a nodule measuring 49x48x40 mm in the right lobe of the thyroid. The levels of serum calcitonin (2,298 pg/ml) and carcinoembryonic antigen (CEA; 27.0 ng/ml) were markedly elevated. Aspiration cytology revealed suspected malignant anaplastic thyroid carcinoma and total thyroidectomy without neck nodal dissection was performed. On gross observation, the nodule was well encapsulated, soft, solid and black. Light microscopy indicated that the nodule was composed mainly of large, occasionally huge, pleomorphic cells with a solid or alveolar growth pattern. On immunohistochemistry, these cells were positive for melan-A and S-100 protein, and negative for thyroid transcription factor 1, calcitonin, chromogranin A and CEA. In the subcapsular area, melanin-producing MTC was intimately intermingled with the pleomorphic cells. No primary site of the melanoma was detectable in other organs. At three years after surgery, the patient died due to metastasis of the melanoma to the brain. The previously reported case had no detectable recurrence or distant metastasis up to 11 years after surgery. In comparison with that case, the present case had a similar morphology but the outcome was poorer. Thus, the prognosis of melanoma that transforms from MTC appears to remain uncertain.

Effectiveness and cost-effectiveness of influenza vaccination for elderly people.

For elderly people who have low incidence of influenza, calculation of credible vaccine effectiveness (VE) sometimes becomes difficult. Currently, VE for elderly people is insufficient to ascertain the precise efficacy specifically. Cost-effectiveness of influenza vaccination of elderly people is discussed widely in terms of topics and areas. This report describes research results demonstrating influenza vaccination effectiveness among elderly people based on recent findings. Newly available influenza vaccination for elderly people appears to be cost-effective compared with that of trivalent inactiveted influenza vaccine. Overall, for all influenza virus types, it remains unclear whether influenza vaccination shows high VE. A decreasing effect of repeated vaccination was confirmed partially by test negative design and a serological study of cohorts. However, some studies have found no such decreasing effect. Measurement of VE and subsequent analysis of the cost-effectiveness of influenza vaccination for elderly people requires long-term monitoring using serological studies and test negative design.

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.

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.