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.

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: 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.

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.

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.

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.

Characteristics of individuals with tuberculosis in an urban, poor population in Osaka City, Japan - a case-control study.

OBJECTIVE: To identify individual characteristics related to the development of pulmonary tuberculosis (PTB) among residents in the Airin area (Airin), Osaka City, Japan. METHODS: We conducted a retrospective case-control study of individual characteristics potentially related to the development of PTB by comparing PTB patients and residents without tuberculosis (TB) in Airin. The following binominal data of characteristics were compared: age (< 65 or > 65); body mass index (BMI) (< 18.5 or > 18.5); diabetes mellitus (diagnosed or not diagnosed); smoking (currently smoking any amount or not smoking); and alcohol use (currently drinking any amount or not drinking). RESULTS: We compared the individual characteristics of 192 PTB patients notified from January 2015 to December 2018 and 190 residents of supportive houses who attended a health education programme from April 2016 to March 2018.Univariable analysis showed that the following characteristics were significantly related with PTB: BMI < 18.5 (odds ratio [OR]: 6.54, 95% confidence interval [CI]: 3.58-11.97, P < 0.001) and current alcohol use (OR: 1.88; 95% CI: 1.24-2.85, P = 0.003). Multivariable analysis showed similar results: BMI < 18.5 (adjusted odds ratio [aOR]: 6.90, 95% CI: 3.72-12.79, P < 0.001) and current alcohol use (aOR: 2.15, 95% CI: 1.36-3.42, P = 0.001). DISCUSSION: Undernutrition and alcohol use are individual characteristics associated with PTB among residents in Airin, Osaka City. To strengthen the TB control programme further, it is suggested to develop new programmes for primary prevention.

Delay in health-care-seeking treatment among tuberculosis patients in Japan: what are the implications for control in the era of universal health coverage?

OBJECTIVE: To study the trends in and risk factors for patient delay (the time from the onset of symptoms to the initial doctor visit) in pulmonary tuberculosis (PTB) using three temporal categories - short (2 weeks to < 2 months), medium (2 months to < 6 months) and long (≥ 6 months) - and discuss implications for social protection measures. METHODS: A descriptive cross-sectional study was conducted by analysing Japanese TB surveillance data from patients with symptomatic PTB registered between 2007 and 2017 (n = 88 351). RESULTS: While the proportion of patients with short delay has decreased significantly (P < 0.001), the proportions of those with medium or long delays have decreased slightly (P = 0.0015 and P < 0.001, respectively). Not having health insurance, receiving public assistance, being a temporary worker, and having a history of homelessness were some of the risks identified for patient delay. Being male and working full-time were two risks specifically associated with long delay (for males, the adjusted odds ratio = 1.17, P < 0.05; for being a full-time worker, the adjusted odds ratio = 1.72, P < 0.05). DISCUSSION: Despite the implementation of universal health coverage decades ago, patient delay remains a challenge in Japan. Our study identified various risk factors, many of which could have been resolved if appropriate social protection measures were in place, indicating shortcomings in universal health coverage in Japan and the need for continued effort to ensure that no one is left behind.

Whole-genome sequencing-based epidemiological analysis of anti-tuberculosis drug resistance genes in Japan in 2007: Application of the Genome Research for Asian Tuberculosis (GReAT) database.

We investigated the lineages of Mycobacterium tuberculosis (Mtb) isolates from the RYOKEN study in Japan in 2007 and the usefulness of genotypic drug susceptibility testing (DST) using the Genome Research for Asian Tuberculosis (GReAT) database. In total, 667 isolates were classified into lineage 1 (4.6%), lineage 2 (0.8%), lineage 2/Beijing (72.1%), lineage 3 (0.5%), and lineage 4 (22.0%). The nationality, gender, and age groups associated with the isolates assigned to lineage 1 were significantly different from those associated with other lineages. In particular, isolates of lineage 1.2.1 (EAI2) formed sub-clusters and included a 2,316-bp deletion in the genome. The proportion of the isolates resistant to at least one anti-tuberculosis (TB) drug was 10.8%, as determined by either the genotypic or phenotypic method of DST. However, the sensitivities to isoniazid, streptomycin, and ethambutol determined by the genotypic method were low. Thus, unidentified mutations in the genome responsible for drug resistance were explored, revealing previously unreported mutations in the katG, gid, and embB genes. This is the first nationwide report of whole-genome analysis of TB in Japan.

Referral and treatment outcomes of tuberculosis patients who crossed the border from Japan to the philippines.

Background: The referral and treatment outcomes of tuberculosis (TB) patients referred from Japan to the Philippines have not yet been systematically reported. This study aimed to describe the cross-border referral process for TB patients referred from Japan to the Philippines. Methods: This is a retrospective descriptive review of the referral process between the two countries. The data on the pathways of Filipino patients with TB or latent TB infection initially treated in Japan from 2009 to mid-2018 were summarized. We calculated the proportion of the referred-and-accessed and that of the successfully treated in the health facilities in the Philippines. The Chi-square test or Fisher's exact test was applied to test significant differences between categorical data. Results: Among the 36 Filipino TB patients referred, 83.3% (30 patients) were successful in accessing any of the health facilities. Among these, 28 patients confirmed that they had started TB treatment in the Philippines. Age groups (P = 0.17), gender (P = 0.76), planned place of residence (P = 0.44), bacteriological results (P = 0.81), and TB patient types (P = 0.96) did not show any significant differences in the referred-and-access rate. The treatment success rate among the 23 TB patients (excluding five patients who were still receiving treatment as of writing) was 91.3%. However, only three out of five multidrug-resistant TB patients successfully started treatment. Conclusions: The current cross-border TB patient referral mechanism between Japan and the Philippines indicated successful results. However, it needs to be enhanced by strengthening the mechanism to track referral outcomes systemically.

Transmission of tuberculosis and predictors of large clusters within three years in an urban setting in Tokyo, Japan: a population-based molecular epidemiological study.

OBJECTIVE: Molecular epidemiology is a promising tool for understanding tuberculosis transmission dynamics but has not been sufficiently utilised in Asian countries including Japan. The aim of this study was to estimate the proportion of TB cases attributable to recent transmission and to identify risk factors of genotype clustering and the development of large clusters within 3 years in an urban setting in Japan. DESIGN AND SETTING: Long-term cross-sectional observational study combining the characteristics of patients with culture-positive TB notified in Shinjuku City, Tokyo (2002-2013), with genotype data of Mycobacterium tuberculosis. PRIMARY OUTCOME MEASURE: Genotype clustering rate and association between genotype clustering status and explanatory variables. RESULTS: Among 1025 cases, 515 were localised within 113 genotype clusters. The overall clustering rate was 39.2%. Significantly higher rates were found in patients aged <40 years (adjusted odds ratio (aOR)=1.73, 95% CI 1.23 to 2.44), native Japanese individuals (aOR=3.90, 95% CI 2.27 to 6.72), full-time workers (aOR=1.63, 95% CI 1.17 to 2.27), part-time/daily workers (aOR=2.20, 95% CI 1.35 to 3.58), individuals receiving public assistance (aOR=1.81, 95% CI 1.15 to 2.84) and homeless people (aOR=1.63, 95% CI 1.02 to 2.62). A significant predictor of large genotype clusters within 3 years was a registration interval ≤2 months between the first two cases in a cluster. CONCLUSION: Our results indicated that a large proportion of patients with culture-positive TB were involved in the recent TB transmission chain. Foreign-born persons still have a limited impact on transmission in the Japanese urban setting. Intensified public health interventions, including the active case finding, need to focus on individuals with socioeconomic risk factors that are significantly associated with tuberculosis transmission and clusters with shorter registration intervals between the first two cases.

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.

A situational analysis of latent tuberculosis infection among incarcerated population in Japan.

BACKGROUND: The World Health Organization recommends that systematic testing and screening of latent tuberculosis infection (LTBI) among the incarcerated population "should be considered", though based on evidence of either low or very low quality. However, in Japan, a TB middle-burden country, systematic screening for LTBI in correctional facilities is currently not conducted. As part of a larger study to determine the cost-effectiveness of LTBI screening in correctional facilities in Japan, this study was conducted to determine the situation of LTBI, including treatment outcome, among the incarcerated population in Japan, and provide the essential data for cost-effectiveness analysis. METHOD: A cross-sectional study was conducted between 2017 and 2018 with public health centers which have one or more correctional facilities under their jurisdiction. Questionnaire surveys were sent to collect information on their policy of managing LTBI patients notified from correctional facilities, including whether or not there was a standardized procedure for initiating LTBI treatment, and also to collect sociodemographic information and treatment outcome of LTBI patients who were notified from the respective correctional facilities in 2015 and 2016. RESULTS: The survey was sent to a total of 163 public health centers, out of which 133 (81.6%) responded. 8 of the 133 public health centers actively guided the correctional facilities regarding LTBI treatment initiation through a standardized procedure, while 115 either had not established such procedure or were unaware of how LTBI treatment was being initiated in the correctional facilities. A total of 91 LTBI patients were notified from the correctional facilities in 2015 and 2016, and the information of 89 were available for analysis. 82 were males, and 83 were Japan-born. Treatment outcome was known for 88 patients, of which 70 had completed treatment. Of the 18 who did not complete the treatment, 15 had been lost to follow-up upon release from the facilities. Among those who had been released whilst on treatment, the proportion of those who completed the treatment was higher in those patients who received pre-release visit by a public health nurse, than those who did not. CONCLUSIONS: LTBI treatment was often being initiated without consideration for the patients' prison term. The treatment completion rate within jail was high, indicating the possibility that incarcerated population can benefit for LTBI treatment. On the other hand, the completion rate decreased significantly among those who had been released while still on treatment. In order to optimize the benefit, initiation of LTBI must carefully be considered upon the patient's prison term, as well as coordination among the relevant organizations to ensure continuity of care after release.

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.

A combination of quantitative and qualitative methods in investigating risk factors for lost to follow-up for tuberculosis treatment in Japan - Are physicians and nurses at a particular risk?

BACKGROUND: The treatment success rate of pulmonary tuberculosis (PTB) patients aged 64 years and below in Japan, a tuberculosis (TB) middle-burden country with a notification of 13.9 per 100,000 populations in 2016, has been fluctuating around 70% for some years. In order to improve treatment outcome, it is critical to address those lost to follow-up (LTFU). The objective of the study therefore was to describe the characteristics of, and analyze the risk factors for those LTFU among pulmonary TB patients aged between 15 and 64, and discuss policy implications. METHODS: The study used a mixed method of quantitative and qualitative approach, and was conducted in two phases. The first involved analysis of cohort data from the national TB surveillance of PTB patients newly notified between 1 January 2006 and 31 December 2015. The second phase involved focus group (FGD) discussions with public health nurses, who are responsible for supporting TB patients' adherence to medication, on the possible reasons why some patients become lost to follow-up. RESULTS: Analysis of the surveillance data suggested that among all patients, positive sputum smear (adjusted odds ratio, [aOR] 0.52, 95% confidence interval [CI] 0.47-0.58) and cavitary lesion on chest x-ray (aOR 0.79, 95%CI 0.72-0.85) decreased the risk, while not requiring hospitalization increased the risk of LTFU (aOR 1.46, 95%CI 1.33-1.60). Among females, being a physician (aOR 2.07 95%CI 1.23-3.48) and nurse (aOR 1.18, 95%CI 1.91-1.37) were identified as additional risk factors for LTFU. The analysis of focus group discussions revealed three possible themes which may be useful in understanding why nurses and physicians were at a higher risk of becoming LTFU-firstly, the possibility that physicians and nurses were finding it difficult to make medication taking a routine, secondly, their low risk perception towards TB is affecting their adherence behavior, and thirdly, their unwillingness to accept DOTS was increasing their risk of becoming LTFU. CONCLUSIONS: The analysis of surveillance data and FGD transcripts indicated that patient education for those starting their treatment as an outpatient, and establishing DOTS that is both acceptable and realistic to physicians and nurses, may be two issues which need to be addressed urgently.

Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. METHODS: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1-3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. FINDINGS: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8-9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1-7·3), but no significant effect on mortality (aOR 0·7, 0·4-1·1) or acquired rifampicin resistance (aOR 0·1, 0·0-1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2-0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. INTERPRETATION: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. FUNDING: World Health Organization and Canadian Institutes of Health Research.

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.