Tuberculosis in older adults: case studies from four countries with rapidly ageing populations in the western pacific region.

BACKGROUND: The Western Pacific Region has one of the fastest-growing populations of older adults (≥ 65 years) globally, among whom tuberculosis (TB) poses a particular concern. This study reports country case studies from China, Japan, the Republic of Korea, and Singapore reflecting on their experiences in managing TB among older adults. FINDINGS: Across all four countries, TB case notification and incidence rates were highest among older adults, but clinical and public health guidance focused on this population was limited. Individual country reports illustrated a range of practices and challenges. Passive case finding remains the norm, with limited active case finding (ACF) programs implemented in China, Japan, and the Republic of Korea. Different approaches have been trialled to assist older adults in securing an early diagnosis, as well as adhering to their TB treatment. All countries emphasised the need for person-centred approaches that include the creative application of new technology and tailored incentive programs, as well as reconceptualisation of how we provide treatment support. The use of traditional medicines was found to be culturally entrenched among older adults, with a need for careful consideration of their complementary use. TB infection testing and the provision of TB preventive treatment (TPT) were underutilised with highly variable practice. CONCLUSION: Older adults require specific consideration in TB response policies, given the burgeoning aging population and their high TB risk. Policymakers, TB programs and funders must invest in and develop locally contextualised practice guidelines to inform evidence-based TB prevention and care practices for older adults.

Trend and treatment outcomes of latent tuberculosis infection among migrant persons in Japan: retrospective analysis of Japan tuberculosis surveillance data.

BACKGROUND: Screening for latent tuberculosis infection (LTBI) among migrant population has become a critical issue for many low tuberculosis (TB) burden countries. Evidence regarding effectiveness of LTBI programs are limited, however, partly because of paucity of national data on treatment outcomes for LTBI. In Japan, notification of LTBI is mandatory, and its treatment outcome is reported as part of Japan's national TB surveillance system. We thus conducted a detailed analysis of LTBI among foreign-born persons, to update the epidemiological trend of newly notified LTBI between 2007 and 2018, and to examine the treatment regimen and outcome of those notified in 2016 and 2017, focusing specifically on the potential risk factors for lost to follow-up. METHODS: We extracted and analyzed the data of newly notified LTBI patients from the Japan Tuberculosis Surveillance System to examine the overall trend of notification and by age groups and modes of detection between 2007 and 2018, and the cohort data for treatment regimen and outcomes of foreign-born persons notified with LTBI in 2016 and 2017. Trends and proportions were summarized descriptively, and logistic regression analysis was conducted to identify potential risk factors for lost to follow-up. Comparisons were made with the Japan-born patients where appropriate, using chi-squared tests. RESULTS: Both the number and proportion of LTBI among foreign-born persons have been constantly increasing, reaching 963 cases in 2018. Cohort analysis of the surveillance data indicated that the proportion of those on shorter regimen was higher among the foreign- than Japan-born patients (5.5% vs. 1.8%, p < 0.001). The proportion of those who have been lost to follow-up and transferred outside of Japan combined was higher among the foreign- than Japan-born patients (12.0% vs, 8.2%, p < 0.001). Risk factors for lost to follow-up were being employed on a temporal basis, and job status unknown (adjusted odds ratios 3.11 and 4.09, 95% confidence intervals 1.34-7.26 and 1.60-10.48, respectively). CONCLUSIONS: Migrant population face greater risk of interrupting LTBI treatment, and interventions to improve adherence are a critical component of programmatic management of LTBI. Further studies are needed to explore the cultural and socioeconomic situation in which foreign-born persons undergo LTBI treatment in Japan.

Prediction of Local Transmission of Mycobacterium tuberculosis Isolates of a Predominantly Beijing Lineage by Use of a Variable-Number Tandem-Repeat Typing Method Incorporating a Consensus Set of Hypervariable Loci.

Strain genotyping based on the variable-number tandem repeat (VNTR) is widely applied for identifying the transmission of Mycobacterium tuberculosis A consensus set of four hypervariable loci (1982, 3232, 3820, and 4120) has been proposed to improve the discrimination of Beijing lineage strains. Herein, we evaluated the utility of these four hypervariable loci for tracing local tuberculosis transmission in 981 cases over a 14-month period in Japan (2010 to 2011). We used six different VNTR systems, with or without the four hypervariable loci. Patient ages and weighted standard distances (a measure of the dispersion of genotype-clustered cases) were used as proxies for estimating local tuberculosis transmission. The highest levels of isolate discrimination were achieved with VNTR systems that incorporated the four hypervariable loci (i.e., the Japan Anti-Tuberculosis Association [JATA]18-VNTR, mycobacterial interspersed repetitive unit [MIRU]28-VNTR, and 24Beijing-VNTR). The clustering rates by JATA12-VNTR, MIRU15-VNTR, JATA15-VNTR, JATA18-VNTR, MIRU28-VNTR, and 24Beijing-VNTR systems were 52.2%, 51.0%, 39.0%, 24.1%, 23.1%, and 22.0%, respectively. As the discriminative power increased, the median weighted standard distances of the clusters tended to decrease (from 311 to 80 km, P < 0.001, Jonckheere-Terpstra trend test). Concurrently, the median ages of patients in the clusters tended to decrease (from 68 to 60 years, P < 0.001, Jonckheere-Terpstra trend test). These findings suggest that strain typing using the four hypervariable loci improves the prediction of active local tuberculosis transmission. The four-locus set can therefore contribute to the targeted control of tuberculosis in settings with high prevalence of Beijing lineage strains.

Treatment outcome of multidrug-resistant tuberculosis in Japan - the first cross-sectional study of Japan tuberculosis surveillance data.

BACKGROUND: Multidrug resistant-tuberculosis (MDR-TB) is a major global health concern. Its treatment requires toxic medications, is longer and costlier than drug-susceptible TB, and often results in productivity losses and poor outcomes. In Japan, a TB middle-burden country, reports on treatment outcome of MDR-TB patients have only been institution-based. We thus sought to shed some light on the nationwide treatment status and outcome of MDR-TB patients in Japan. METHODS: Characteristics and treatment status and outcome of MDR-TB patients notified between 2011 and 2013 were evaluated using the data from the Japan TB Surveillance (JTBS) system. Since the treatment outcome from the surveillance data was not directly linked to any clinical records or drug susceptible test results, we also analyzed the treatment duration of MDR-TB cases in an attempt to validate our results. RESULTS: Between 2011 and 2013, a total of 172 MDR-TB patients had been notified to the JTBS as MDR-TB. 68.6% (118/172) were males and 70.9% (122/172) were Japan-born - however, over the study period, the proportions of foreign-born, of those in the age group 15-64 years old and of new cases have increased. The overall treatment completion rate was 57.0%, however, when restricted to patients aged 64 years old and below, the rate improved to 71.6%. Treatment duration of 29.2% of those patients who had been recorded as "treatment completed" in fact fell short of the 540 days, the minimum duration as recommended by the Japanese guideline. CONCLUSIONS: Increasing proportion of new cases, and of younger age groups among the MDR-TB patients indicate new transmissions. Better strategies for early detection and containment of MDR-TB are urgently needed. The overall treatment completion rate was 57.0% over the three-year study period. However, when restricting the result to those aged 64 years old and below, the rate improved to 71.6%, which was comparable to similarly industrialized countries. Due to the limitations of the JTBS data, a comprehensive survey of all MDR-TB patients may be necessary to provide more concrete evidence for decision-making.

Evaluation of "international transfer-out" among foreign-born pulmonary tuberculosis patients in Japan - what are the implications for a cross-border patient referral system?

BACKGROUND: Tuberculosis (TB) patients crossing borders pose a serious challenge to global TB control efforts. The objectives of our study were firstly, to evaluate the trend and size of foreign-born pulmonary TB patients, who had been notified and initiated treatment in Japan but have transferred out of the country while still on treatment; and secondly, to conduct a detailed analysis of these patients and identify possible risk factors for international transfer-out, and discuss policy implications for a cross-border patient referral system for foreign-born TB patients in Japan. METHODS: We conducted a cross-sectional study whereby aggregated cohort data of pulmonary TB cases newly notified to the Japan TB Surveillance system between 1 January 2011 and 31 December 2015 were analyzed. Multinomial logistic regression analysis was conducted to identify and compare the risk factors for international transfer-out. RESULTS: Among the 668 foreign-born patients whose treatment outcome had been evaluated as "transferred- out", 51.3% has in fact moved to outside Japan between 2011 and 2015. The proportion of such international transfer-out of total foreign-born patients who had transferred out has more than doubled during the study period, from 23.3% in 2011 to 57.7% in 2015. Some of the risk factors for international transfer-out were being a full-time worker (Relative risk [RR] 2.86, 95% confidence interval [CI] 2.04, 3.99), being diagnosed within 0 to 2 years of arriving to Japan (RR 8.78, 95% CI 4.30,17.90) and within 3 to 5 years (RR 7.53, 95% CI 3.61, 15.68), sputum smear positive (RR 1.95, 95% CI 1.53, 2.48), and coming from Indonesia (RR 1.86, 95% CI 1.13, 3.03). CONCLUSIONS: Providing continuity of care for mobile population is one of the keys to achieving the WHO's End TB Strategy targets for 2030, and results of our study indicate that a cross-border referral system should be an integral part of TB control among foreign-born persons in Japan.

[COMPARISON OF TUBERCULOSIS SURVEILLANCE SYSTEMS IN JAPAN AND LOW-INCIDENCE COUNTRIES: INSTITUTIONAL DESIGN].

[Objective] To compare the tuberculosis (TB) surveillance systems of Japan and low TB-incidence western countries in terms of institutional design. [Method] We conducted a descriptive comparative study for TB surveillance systems in Japan, the Netherlands, the United Kingdom, and the United States. The following information was collected from self-administrated question- naires and relevant published data: 1) TB notification, 2) TB registration, 3) quality assurance and data protection mechanisms, 4) linkage with other surveillance, and 5) data disclosure. [Result] The basic structure common to all countries sur- veyed was that TB notifications were reported quickly through an online system, as required by law. TB registration data, which included detailed demographic and clinical informa- tion, was shared via the database and available to all admin- istrative levels. In addition, aggregated data reports were published periodically. Information related to TB genotype and data quality assurance, for example, detection of duplication of records, was available in surveillance systems in countries other than Japan. [Conclusion] We propose that developing a sharing mechanism for TB genotype and ensuring better quality assurance would strengthen the Japanese TB surveillance system.

[COMPARISON OF TUBERCULOSIS SURVEILLANCE SYSTEMS IN JAPAN AND LOW-INCIDENCE COUNTRIES: REPORTING DATA ITEMS].

[Objective] To compare the tuberculosis (TB) surveillance systems of Japan and low TB-incidence western countries in terms of reported data items. [Method] We conducted a descriptive comparative study for TB surveillance systems in Japan, the Netherlands, the United Kingdom, and the United States. Data items reported by the surveillance systems were collected and summarized by the categories prepared by the authors. Additionally, relevant published data were collected. [Result] The data items collected in each country surveyed was around 40 categories, among which 21 categories were common to the all surveyed countries. Regarding data items collected from the surveyed countries other than Japan, information related to risk factors such as drug addiction, imprisonment history, and history of residence in nursing home; TB genotype; and contact investigation were available in the surveillance system. In Japan, treatment outcomes are automatically determined by a preset algorithm, which leads to high percentage of outcomes not being evaluated. [Conclusion] Potential suggestions for the Japanese TB surveillance system are reconsidering risk factor items, collecting and evaluating contact investigation information through the surveillance system, adding genotype information, and introducing manual assessment of treatment outcome.

[THE POTENTIAL ROLE OF SOCIAL NETWORK ANALYSIS IN TUBERCULOSIS CONTACT INVESTIGATION].

[Aim] To explore the possible role of social network analysis (SNA) in identifying infected contacts and visualizing data in a tuberculosis (TB) contact investigation. [Method] We analyzed TB contact investigation data from an outbreak in a Japanese language school in Tokyo, Japan, in 20XX. Information on places which the index case and his contacts commonly shared was collected in line with the data collected routinely in contact investigation. Average hours of exposure to the index case were calculated for each contact by using SNA software, and the relationship to the index case via commonly shared places was visualized as a sociogram. Statistical analysis was performed to. compare the exposure hours and TB infection statuses, between those . infected, including active TB and latent TB infection (LTBI), and non- infected contacts. [Result] The data on the index TB case and 41 contacts, of whom 5 and 10 were diagnosed with active TB and LTBI, were analyzed. Contacts with active TB and LTBI had 12.5 and 11.5 times longer median hours of exposure, which were significantly longer compared to non-infected contacts. The sociogram summarized the network of index TB case, contacts characterized by exposure hours and infection statuses, and the places shared by the index case and the contacts. [Discussion] SNA analysis was considered to be useful in prioritizing contacts in a TB contact investigation, in assisting interpretation of indeterminate Interferon-Gamma release assay test results, in estimating places where transmission occurred, and visualizing data accrued in TB contact inves- tigations.

[A SYSTEMATIC REVIEW ON THE PREVALENCE AND INCIDENCE OF LATENT TUBERCULOSIS INFECTION AMONG PRISON POPULATION].

SETTING: We conducted a systematic review of literatures on the prevalence and incidence of latent tuberculosis infection in correctional settings, with the aim of offering one of the resources to guide establishment of policies on screening for and treating LTBI among prisoners in Japan. OBJECTIVE: Using the keywords "latent tuberculosis AND (prison OR jail OR correctional)" and "tuberculosis infection AND (prison OR jail OR correctional)", we conducted a systematic review of relevant literatures on PubMed and secondary searches from the reference list of primary sources. We limited our search to those original articles published since 1980, and in English. RESULTS: 55 articles were identified, and 15 were subject to the systematic review. Of the 12 articles on prevalence of LTBI, 5 were from middle and high-burden and 7 from low-burden countries. The average prevalence of LTBI among middle and high-burden countries was 73.0%, and among low-burden countries, 40.3%. "Duration of incarceration" and "history of previous incarceration" were identified as risk factors for high LTBI prevalence which were specific to the prison population. Incidence of LTBI among the high-burden country was 61.8 per 100 person years, while 5.9 and 6.3 in the two reports from low-burden countries. CONCLUSION: Prevalence and incidence of LTBI were higher than the general population, both in middle/high- and low-burden countries. The fact that "duration of incarceration" and "history of previous incarceration" were identified as risk factors indicate that high prevalence of LTBI among prison population is not just attributable to the characteristics of prisoners themselves, but also to the possibility of TB infection occurring in prison settings.

[FACTORS ASSOCIATED WITH CHANGES IN THE NUMBER OF LATENT TUBERCULOSIS INFECTION NOTIFICATIONS IN JAPAN: NATIONWIDE SURVEY FINDINGS].

PURPOSE: To investigate factors contributing to the drastic increase and subsequent decrease in latent tuberculosis infection (LTBI) notifications in 2011 (n = 10,046) and 2012 (n = 8,771), respectively, in Japan. METHODS: We conducted cross-sectional surveys in all 495 health centers in Japan in 2012 and 2013 using a semi-structured questionnaire that contained questions regarding the number of contacts listed for contact investigation, interferon-gamma release assay (IGRA) results, and incident of possible false positive IGRA results. RESULTS: Both the numbers and proportion of patients investigated using IGRA tended to increase from 2009 to 2012. However, the numbers and proportion of IGRA-positive patients, as well as that of those with borderline IGRA results, increased in 2011 and have decreased since 2012. In the 2012 survey, only 34 health centers (8%) reported questionable IGRA results. DISCUSSION: The removal of the age limit for LTBI treatment in 2010 may have contributed to the increase in the number of LTBI notifications in 2011, as the increase was particularly remarkable in the elderly age group. The increase in the proportion of positive and borderline IGRA results was likely partly due to expanded IGRA coverage that included more medical staff and the older population, which have a relatively high prevalence of tuberculosis infection, as well as a change from second-generation to third-generation QuantiFERON (QFT®) IGRA that offered increased sensitivity. The decrease in the number of outbreak incident cases and infectious patients may have contributed to the decrease in the number of LTBI notifications in 2012. CONCLUSION: Factors such as the increase in the number of patients undergoing IGRA, increase in the number of positive or borderline results due to QFT changes, and decrease in the number of tuberculosis outbreak incidents and infectious patients likely contributed to the increase and decrease in the number of LTBI notifications in 2011 and 2012, respectively.

Factors associated with health-related quality of life among pulmonary tuberculosis patients in Manila, the Philippines.

PURPOSE: Health-related quality of life (HRQOL) among pulmonary tuberculosis (PTB) patients has not been investigated in the Philippines. This study aimed to describe HRQOL among PTB patients and to determine factors that are associated with HRQOL. METHODS: A cross-sectional survey was conducted at 10 public health centers and 2 non-government organization clinics in District I, Tondo, Manila. Face-to-face interviews using a structured questionnaire including Short Form-8, Duke-UNC Functional Social Support Questionnaire, and Medical Research Council (MRC) dyspnea scale were performed with 561 PTB patients from September to November 2012. RESULTS: HRQOL among PTB patients was generally impaired. Factors associated with lower physical component summary were exposure to secondhand smoke (SHS) (P = 0.038), positive sputum smear result (P = 0.027), not working (P = 0.038), lower education level (P < 0.01), number of symptoms (P < 0.01), number of adverse drug reactions (ADRs) (P < 0.01), higher score on the MRC dyspnea scale (P < 0.01), and low perceived social support (P = 0.027). Lower body mass index (P = 0.016), non-SHS exposure (P = 0.033), number of symptoms (P < 0.01), number of ADRs (P < 0.01), low perceived social support (P < 0.01), and negative perception for waiting time in the clinic (P = 0.026) were identified to be factors significantly associated with lower mental component summary. CONCLUSION: Socioeconomic status including SHS exposure and low perceived social support, in addition to clinical factors, may be associated with poor HRQOL. Further study would be needed to assess our findings.

A molecular epidemiologic analysis of Mycobacterium tuberculosis among Filipino patients in a suburban community in the Philippines.

BACKGROUND: The Philippines is designated as one of the high tuberculosis (TB) burden countries by WHO. We conducted a molecular epidemiologic analysis of Mycobacterium tuberculosis isolates collected from patients consulting at the health clinics in the city of Santa Rosa, Laguna, a suburban community in the Philippines. METHODS: A total of 116 M. tuberculosis isolates were characterized and genotyped using spoligotyping and 15 loci of variable number of tandem repeats of mycobacterial interspersed repetitive units (15 MIRU-VNTR). The strains were then compared with the international spoligotyping database (SpolDB4). Cluster analyses were done using 15 MIRU-VNTR and spoligotyping. RESULTS: Majority of the patients with pulmonary tuberculosis were young (18-29 year age group at 41.4%) and male (62.1%). 86/116 (74.1%) were sputum-smear positive and 43/116 (37.1%) had severe pulmonary tuberculosis. When the genotyping results were compared to the SpolDB4, there were 10 identified Spoligo-International-Types (SITs) with SIT 19 as the predominant SIT (89/116, 76.7%). 10 out of 116 (8.6%) did not match any SIT in the SpolDB4. The distribution of strains according to major M. tuberculosis clades was as follows: EAI2_Manilla (101/116, 87.1%; U 2/116, 1.7%; LAM2 1/116, 0.9%; EAI3_Ind 1/116, 0.9%; MANU2 1/116, 0.9%. Using univariate and multivariate analysis, there was no significant association shown between the EAI2_Manilla clade and SIT with patient characteristics such as sex and age groups as well as bacillary load based on sputum-smear positivity and severity of pulmonary tuberculosis. Using logistic regression, no patient characteristic, as well as bacillary load or severity of TB, were significant predictors for clade or SIT. Based on the molecular typing method used, spoligotyping identified 4 clusters and 20 genotypes (16 unique strains) with a Hunter-Gaston discrimination index (HGDI) of 0.409. 15 MIRU-VNTR identified 16 clusters and 69 genotypes (53 unique strains) with an HGDI of 0.960. The combination of spoligotyping and 15 MIRU-VNTR identified 11 clusters and 79 genotypes (68 unique strains) with the highest HGDI at 0.970. High case rate of TB among young people in this community suggests the high transmission rate of infection. However, in the absence of significant association between clustering and age, the interpretation of observed high cluster rate warrants caution, and requires further molecular and epidemiological observation. CONCLUSION: This is the first molecular epidemiology study to show the distribution of genotypes of the M. tuberculosis strains, systematically and prospectively sampled, of the patient population in a suburban community in the Philippines. The combination of spoligotyping and 15 MIRU-VNTR identified 11 clusters and 79 genotypes (68 unique strains) with the highest HGDI at 0.970. High case rate of TB among young people in this community suggests the high transmission of infection. However, in the absence of significant association between clustering and age, the interpretation of observed high cluster rate warrants caution, and requires further molecular and epidemiological observation.

Epidemiology of latent tuberculosis infection in Japan-born and foreign-born children in Japan.

Objective: This study aims to compare the epidemiology of notifications of latent tuberculosis infection (LTBI) among Japan-born and foreign-born children in Japan between 2010 and 2020, and to assess the language used during LTBI case interviews with parents or caregivers of foreign-born children with LTBI during 2019. Methods: Our study consisted of two parts: (1) an analysis of national data from the Japan Tuberculosis Surveillance (JTBS) system on the epidemiology of LTBI among Japan-born and foreign-born children in Japan, and (2) a survey of staff at public health centres that had registered at least one foreign-born child aged ≤ 14 years with LTBI. Data were extracted from the JTBS system for all children aged ≤ 14 years who were newly notified as having LTBI between 2010 and 2020, and analysed to determine trends, characteristics and treatment outcomes. Staff at relevant public health centres completed a self-administered survey. Results: A total of 7160 Japan-born and 320 foreign-born children were notified as having LTBI between 2010 and 2020. Compared with Japan-born children, foreign-born children notified as having LTBI were more likely to be older, have their mother or sibling as their source of infection and have LTBI detected via a routine school health check. At case interviews, the use of language interpretation services was limited, even when both parents were non-Japanese. No interview was directly conducted with children themselves, not even with school-aged children. Discussion: Foreign-born children and their parents may be unfamiliar with the system of testing for TB infection and the diagnosis of LTBI in Japan in school settings. Public health centres are required to provide education to patients and their families and care that takes into account cultural and linguistic differences. However, the provision of language support during case interviews may need strengthening.

A Study on the Health-Related Issues and Behavior of Vietnamese Migrants Living in Japan: Developing Risk Communication in the Tuberculosis Response.

Ensuring a healthy lifestyle for the increasing number of Vietnamese migrants living in Japan is a key public health issue, including infectious disease responses such as tuberculosis (TB). To develop risk communication in relation to the TB response, this study aimed to explore the health issues and health-related behaviors of Vietnamese migrants living in Japan using a mixed method. A survey was conducted on Vietnam-born migrants, aged 18 years and over, in Tokyo. The survey consisted of questions on the following components: (1) demographics; (2) health-related issues and behavior; and (3) health-seeking behavior, information, and communication. A total 165 participants participated in the survey. The majority of the participants were young adults. 13% of the participants responded that they were concerned about their health. Moreover, 22% and 7% of the participants reported weight loss and respiratory symptoms, respectively. 44% of the participants answered they had no one to consult about their health in Japan when they needed it, and 58% answered they had no awareness of any Vietnamese-language health consultation services. Logistic regression analysis revealed that people who contact family members living in Vietnam or overseas using social networking services (SNSs) when they needed to consult someone about their health (adjusted odds ratio (AOR) = 6.09, 95% confidence interval (CI) 1.52-24.43) were more likely to present with one or more of the typical TB symptoms, compared to those who did not consult someone in this manner. Current smokers (OR = 3.08, 95% CI 1.15-8.23) were more likely to have health problems compared to non-smokers. The key informant interviews revealed that individual factors, the health system, and socio-environmental factors may hinder Vietnamese migrants' health-seeking and health-information-seeking behaviors in Japan. TB risk communication approaches for migrants need to be developed considering their health-related behaviors while addressing their health needs.

Tuberculosis in older adults: challenges and best practices in the Western Pacific Region.

The Western Pacific has one of the fastest-growing older adult populations globally, and tuberculosis (TB) remains one of the foremost infectious causes of disease and death in the region. Older adults are at higher risk of TB due to immunosenescence, comorbidities, and increased institutionalisation. Atypical symptoms and reduced access to health services may delay care-seeking and TB diagnosis, while co-morbidity and increased risk of adverse drug reactions complicate TB treatment. Post-TB sequelae and socioeconomic challenges may decrease the quality of life after TB treatment completion. Despite their high disease burden and special challenges, there is a lack of regionally coordinated policies and guidelines to manage TB among older adults. Routine TB screening at aged-care facilities, age-friendly infrastructure and services, awareness of atypical TB features, integration of TB and non-communicable diseases services, and person-centred approaches to treatment support could improve TB management among older adults. Addressing these challenges and adopting the best practices identified should inform policy formulation and implementation. Funding: This project was funded by 1) the World Health Organization Regional Office for the Western Pacific, with financial contributions from the Government of the Republic of Korea through the Korean Disease Control and Prevention Agency and the Government of Japan through the Ministry of Health, Labour and Welfare, and 2) NUS Start-up Grant. The funders had no role in the paper design, collection, analysis, and interpretation of data and in writing of the paper.

[Medical service systems for tuberculosis in low-incidence countries].

OBJECTIVES: Currently, Japan has a near low incidence of tuberculosis (TB); the incidence is below 20/100,000. Considering this incidence, the medical service provision system needs to be restructured and related policies need to be revised. The Revised National Guidelines for TB Control, issued in May 2011 by the Ministry of Health, Labour, and Welfare, provided the policy towards achieving a low incidence of TB. This study aims to provide suggestions for restructuring the medical service system in Japan by analyzing the systems in selected countries with low incidence. METHOD: Between 2004 and 2010, we conducted tours to study TB control and medical services in the UK, the USA, Germany, The Netherlands, and Norway. In these tours, we visited the medical facilities, agencies implementing preventive activities, health departments of central and local governments, reference laboratories, technical agencies, non-governmental organizations, and other organizations involved in TB control in these countries. In addition, we collected information from published papers and related documents through the internet. This paper reports the policies and strategies adopted in these low-incidence countries, especially pertaining to medical service systems, directly observed treatment, short-course (DOTS) services, hospital beds and facilities, objectives and duration of hospitalization, and mechanisms for maintaining quality medical services. RESULTS: In all the visited countries, except Germany, TB patients were diagnosed and treated, as well as provided support such as DOTS, by a single organization or agency. In the US and Norway, DOTs was provided to all TB patients at chest centers and/or health centers. On the other hand, in the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) stated that DOT is not necessary for managing most active TB cases. In these countries there were 3 modes of treating infectious patients: home isolation, hospitalization for the first 2 weeks after initiating treatment, and hospitalization until smear examination results are negative. None of the countries had official standards for hospitalization. Measures to maintain service quality were integrating service providers, strengthening technical support, training and/or educating experts, and networking of personnel in charge. DISCUSSION: The study tours were conducted over 6 years, but no follow-up surveys were conducted. In each visit, we visited only a limited number of medical facilities, which may not be representative of that country. Obviously, this report does not aim to be a comparative study but to provide useful information for discussing the future direction of the medical service system in Japan. In Japan, TB is diagnosed and treated in hospitals and clinics, but contact surveys and other preventive activities are conducted in health centers. In this regard, Japan seems to be unique in that the ways to achieve collaboration among hospitals, health centers, and related organizations are emphasized in the revised National Guidelines for TB Control. Regardless of the DOT target group of a patient, healthcare providers in Japan are expected to ensure patient's adherence through patient-centered support in order to achieve successful treatment. In Japan, the central Government is expected to take responsibility to prevent infection. We suggest that the standards for lengths of hospital stay of TB patients should be revised such that the lengths are based on each patient's bacteriological condition and social setting. The revised National Guidelines for TB Control provide frameworks for ensuring the quality of medical services, but further discussions are warranted in order to plan and implement an effective strategy.

Characteristics and Treatment Outcomes among Migrants with Pulmonary Tuberculosis: A Retrospective Cohort Study in Japan, 2009-2018.

This study aimed to describe characteristics and treatment outcomes of overseas-born pulmonary tuberculosis (PTB) patients in Japan, and identify the factors associated with "treatment non-success". We conducted a retrospective analysis of overseas-born patients with drug-susceptible PTB using cohort data of PTB cases newly registered in the Japan tuberculosis (TB) surveillance system between 2009 and 2018. Overall, 9151 overseas-born PTB cases were included in this study, and 70.3% were aged 34 years old or younger. "Students of high school and higher" (28.6%) and "regular workers other than service related sectors" (28.5%) accounted for over half of the study population, and they have continued to increase. Overall, the treatment success rate was 67.1%. Transferred-out constituted the largest proportion (14.8%) among the treatment non-success rate (32.9%). Multiple logistic regression analysis revealed patients whose health insurance type was "others and unknown", including the uninsured (adjusted OR (AOR) = 3.43: 95% Confidence Intervals (CI) 2.57-4.58), those diagnosed as TB within "one year" (AOR = 2.61, 95% CI 1.97-3.46) and "1-5 years" (AOR = 2.44, 95% CI 1.88-3.17) of arrival in Japan, and males (AOR = 1.34, 95% CI 1.16-1.54), which were the main factors associated with treatment non-success. These findings imply that Japan needs to develop TB control activities considering the increasing trends of overseas-born PTB patients, the majority of whom are young and highly mobile. There is a need to pay greater attention to overseas-born PTB patients diagnosed within a short duration after entering Japan, who may be socially and economically disadvantaged for their treatment completion.

Factors associated with mortality among patients with culture-positive pulmonary tuberculosis in the urban poor population of Osaka City, Japan.

OBJECTIVE: To determine the characteristics associated with mortality in patients with culture-positive pulmonary tuberculosis (PTB) in Airin, Osaka City, Japan. METHODS: The characteristics of patients with culture-positive PTB registered between 2015 and 2018 in Airin, Osaka City, Japan, were compared between those who died of all causes before or during treatment and those who completed treatment. RESULTS: Of the 241 culture-positive PTB patients eligible for this study, 170 completed treatment, with negative sputum culture tests, and 62 died. The all-cause case fatality rate was 26.7% (62/232). Multivariate analysis showed that mortality was associated with age 370 years, having a positive sputum smear, a body mass index of < 18.5 and serious comorbidities such as cancer and heart and renal disease. Detection of tuberculosis (TB) by screening or in an outpatient department (OPD) for other diseases was inversely associated with mortality. DISCUSSION: Detection of PTB by chest X-ray screening and during regular visits to OPDs for other diseases was associated with non-fatal TB and might contribute to early case finding. Therefore, current active TB case finding and health education on regular visits to physicians for other diseases should be strengthened further for the urban poor population of Osaka City, Japan.

Clonal expansion of multidrug-resistant and extensively drug-resistant tuberculosis, Japan.

The emergence and spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has raised public health concern about global control of TB. To estimate the transmission dynamics of MDR and XDR TB, we conducted a DNA fingerprinting analysis of 55 MDR/XDR Mycobacterium tuberculosis strains isolated from TB patients throughout Japan in 2002. Twenty-one (38%) of the strains were classified into 9 clusters with geographic links, which suggests that community transmission of MDR/XDR TB is ongoing. Furthermore, the XDR M. tuberculosis strains were more likely than the non-XDR MDR strains to be clustered (71% vs. 24%; p = 0.003), suggesting that transmission plays a critical role in the new incidence of XDR TB. These findings highlight the difficulty of preventing community transmission of XDR TB by conventional TB control programs and indicate an urgent need for a more appropriate strategy to contain highly developed drug-resistant TB.