Tuberculosis Surveillance System Research Articles

Multidrug-resistant tuberculosis in the United States, 2011-2016: patient characteristics and risk factors.

OBJECTIVE: To determine risk factors for multidrug-resistant tuberculosis (MDR-TB) and describe MDR-TB according to three characteristics: previous TB disease, recent transmission of MDR-TB, and reactivation of latent MDR-TB infection.SETTING and DESIGN: We used 2011-2016 surveillance data from the US National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service and used logistic regression models to estimate risk factors associated with MDR-TB.RESULTS: A total of 615/45 209 (1.4%) cases were confirmed as MDR-TB; 111/615 (18%) reported previous TB disease; 41/615 (6.7%) were attributed to recent MDR-TB transmission; and 449/615 (73%) to reactivation. Only 12/41 (29%) patients with TB attributed to recent transmission were known to be contacts of someone with MDR-TB. For non-US-born patients, the adjusted odds ratios of having MDR-TB were 32.6 (95%CI 14.6-72.6) among those who were known to be contacts of someone with MDR-TB and 6.5 (95%CI 5.1-8.3) among those who had had previous TB disease.CONCLUSION: The majority of MDR-TB cases in the United States were associated with previous TB disease or reactivation of latent MDR-TB infection; only a small proportion of MDR-TB cases were associated with recent transmission.

Implementing TB Surveillance in Nigeria: Best Practices, Challenges and Lessons Learnt

Introduction: TB Surveillance is a critical component of the global TB response. Comprehensive, accurate and timely information on TB is crucial for an effective TB control program hence the need for a robust tuberculosis surveillance system in all countries that contribute to the global burden of TB including Nigeria. Against this backdrop, an intervention was set in motion to triangulate the information from the health data reporting systems towards improving the overall surveillance system for TB in the country. Objectives: This article highlights the best practices, lessons learnt and challenges associated with the implementation of TB surveillance in Nigeria. In resource-limited settings such as Nigeria where health systems including health information management are sub-optimal, there is a heavy reliance on national and sub-national TB surveillance systems. TB data is mainly reported through the National Tuberculosis Control, however the integrated disease surveillance and response (IDSR) system also provides a platform for TB data collation through the LGA and State disease surveillance and notification officers. Conclusion: Implementing TB surveillance in Nigeria brought to fore the need for a wider engagement of all health facilities in TB control. As a dividend of the TB surveillance intervention, quality of care was improved in the private health sector through effective linkages to the commodity management system of the NTP and the national treatment guidelines. Strengthening community health surveillance system was identified as a critical element of Tuberculosis control. Also, the efficiency birthed by the integration of TB surveillance into the IDSR structure opened up other potential opportunities such as a unified capacity building of community informants on all notifiable diseases and the integration of reporting and risk communication for all health issues at the community level.

Measuring and addressing the childhood tuberculosis reporting gaps in Pakistan: The first ever national inventory study among children.

Tuberculosis in children may be difficult to diagnose and is often not reported to routine surveillance systems. Understanding and addressing the tuberculosis (TB) case detection and reporting gaps strengthens national routine TB surveillance systems. The present study aimed to measure the percentage of childhood TB cases that are diagnosed but not reported to the national surveillance system in Pakistan. The study design was cross sectional. The study was nationwide in 12 selected districts across Pakistan, each representing a cluster. Health facilities that diagnose and treat childhood TB from all sectors were mapped and invited to participate. Lists of child TB cases were created for the study period (April-June 2016) from all study facilities and compared against the list of child TB cases notified to the national TB surveillance system for the same districts and the same period. All public and private health facilities were mapped across 12 sampled districts in Pakistan and those providing health services to child TB cases were included in the study. From all private health facilities, 7,125 children were found with presumptive TB during the study period. Of them, 5,258 were diagnosed with tuberculosis: 11% were bacteriologically-confirmed and 89% clinically-diagnosed; only 4% were notified to National TB Control Program. An additional 1,267 children with TB were also registered in the National TB Control Program. Underreporting was measured to be 78%. This is the first nationwide childhood TB inventory study globally and confirmed that childhood TB underreporting is very high in Pakistan. TB surveillance in the country must be strengthened to address this, with particular attention to guiding and supporting general practitioners and pediatricians to notify their TB cases.

The risk of active tuberculosis among individuals living in tuberculosis-affected households in the Republic of Korea, 2015.

BackgroundIn the Republic of Korea (ROK), compared to other high-income countries, tuberculosis (TB) prevalence is relatively high. Active TB and latent TB infection (LTBI) surveillance of individuals living in TB-affected households has been conducted for several years. Although active case finding is an important strategy in low-prevalence, high-income countries, its effectiveness in a high prevalence setting is unclear. This study evaluated the risk of TB in household contact by calculating the incidence of TB among household contacts and comparing it with the general population of the ROK.MethodsA retrospective cohort study, including 36,133 household-contacts of 17,958 TB patients reported in 2015, was conducted. The data was extracted from the Korean National TB Surveillance System (web-based TB cases notification system, KNTSS). The Cox proportional hazard regression model was used to evaluate risk factors for incidence of TB. A P-value < .05 was considered statistically significant.ResultsIn this study, 319 (0.9%) of 36,133 household-contacts were reported as having TB within 1 year, which is a higher rate than the rate for the general population in the ROK. The rate of TB reported for contacts that had completed LTBI treatment (0.6%) was lower than for the LTBI group without treatment (4.6%). In multivariate analysis, age older than 65 (p < .001), being a spouse of a TB patient (p = .007), and LTBI without treatment (p = .013) were each a risk factor for TB incidence among contacts. Younger age (p < .001), presence of a cough (p < .001), testing positive for acid-fast bacilli (AFB; p < .001), and cavity on radiograph (p < .001) of the index patient were also statistically significant risk factors.ConclusionsIndividuals living in TB-affected households are at high risk of developing TB in the ROK and active case finding among them is a strategy effective in the early detection and prevention of TB.

Estimating the effect of the 2005 change in BCG policy in England: a retrospective cohort study, 2000 to 2015.

BackgroundIn 2005 in England, universal Bacillus Calmette–Guérin (BCG) vaccination of school-age children was replaced by targeted BCG vaccination of high-risk neonates.AimEstimate the impact of the 2005 change in BCG policy on tuberculosis (TB) incidence rates in England.MethodsWe conducted an observational study by combining notifications from the Enhanced Tuberculosis Surveillance system, with demographic data from the Labour Force Survey to construct retrospective cohorts relevant to both the universal and targeted vaccination between 1 January 2000 and 31 December 2010. We then estimated incidence rates over a 5-year follow-up period and used regression modelling to estimate the impact of the change in policy on TB.ResultsIn the non-United Kingdom (UK) born, we found evidence for an association between a reduction in incidence rates and the change in BCG policy (school-age incidence rate ratio (IRR): 0.74; 95% credible interval (CrI): 0.61 to 0.88 and neonatal IRR: 0.62; 95%CrI: 0.44 to 0.88). We found some evidence that the change in policy was associated with an increase in incidence rates in the UK born school-age population (IRR: 1.08; 95%CrI: 0.97 to 1.19) and weaker evidence of an association with a reduction in incidence rates in UK born neonates (IRR: 0.96; 95%CrI: 0.82 to 1.14). Overall, we found that the change in policy was associated with directly preventing 385 (95%CrI: −105 to 881) cases.ConclusionsWithdrawing universal vaccination at school age and targeting vaccination towards high-risk neonates was associated with reduced incidence of TB. This was largely driven by reductions in the non-UK born with cases increasing in the UK born.

Integrating data of veterinarians’ practices in assessing the cost effectiveness of three components of the bovine tuberculosis surveillance system by intradermal tuberculin testing in French cattle farms through a scenario-tree approach

Disease surveillance systems’ effectiveness relies on participants following prescribed practices. We developed a general method to improve a previous cost-effectiveness evaluation of three French screening program protocols for bovine tuberculosis (bTB) to account for the practices of participants by scenario tree modelling. This method relies on: 1) semi-directive interviews of participants to identify the variability of practices and potentially influential factors, and to understand the sociological context; 2) a quantitative survey, based on multiple-choice questions, to quantify various practices and identify significantly influential factors by multivariable regression analyses; 3) addition of the scenario-tree nodes corresponding to the practices and their influential factors and configuration of the new limbs according to the data of the quantitative survey.We used this approach to integrate data concerning veterinary practices and identify some failures to conform to regulatory guidelines regarding intradermal cervical comparative tuberculin test (SICCT) (testing and notification of non-negative results). Such nonconformities appeared to be mainly caused by cattle restraint issues and the perception of veterinarians of the bTB control program. Indeed, their perception of that program significantly influenced veterinarians’ practices. We modelled the influence of the SICCT practices on the SICCT results. The incorporation of these data led to a major decrease of the herd sensitivity estimations relative to the previous assessments that did not incorporate data of practices (15% to 42% decrease). This result shows the important impact of veterinarians’ practices and their influencing factors (such as perception of the bTB control program) on the effectiveness of the surveillance system.

Predictive factors for unfavourable treatment in MDR-TB and XDR-TB patients in Rio de Janeiro State, Brazil, 2000-2016.

The State of Rio de Janeiro stands out as having the second highest incidence and the highest mortality rate due to TB in Brazil. This study aims at identifying the factors associated with the unfavourable treatment of MDR/XDR-TB patients in that State. Data on 2269 MDR-TB cases reported in 2000-2016 in Rio de Janeiro State were collected from the Tuberculosis Surveillance System. Bivariate and multivariate logistic regressions were run to estimate the factors associated with unfavourable outcomes (failure, default, and death) and, specifically, default and death. The proportion of unfavourable outcomes was 41.9% among MDR-TB and 81.5% among XDR-TB. Having less than 8 years of schooling, and being an Afro-Brazilian, under 40 years old and drug user were associated with unfavourable outcome and default. Bilateral disease, HIV positive, and comorbidities were associated with death. XDR-TB cases had a 4.7-fold higher odds of an unfavourable outcome, with 29.3% of such cases being not treated for multidrug resistance in the past. About 30% of XDR-TB cases may have occurred by primary transmission. The high rates of failure and death in this category reflect the limitation of treatment options. This highlights the urgency to incorporate new drugs in the treatment.

Noncountable Tuberculosis Case Reporting, National Tuberculosis Surveillance System, United States, 2010-2014.

Supplemental federal funding is allocated to state and local tuberculosis (TB) programs using a formula that considers only countable cases reported to the National Tuberculosis Surveillance System (NTSS). Health departments submit reports of cases, which are countable unless another (US or international) jurisdiction has already counted the case or the case represents a recurrence of TB diagnosed ≤12 months after completion of treatment for a previous TB episode. Noncountable cases are a resource burden, so in 2009, NTSS began accepting noncountable case reports as an indicator of program burden. We sought to describe the volume and completeness of noncountable case reports. We analyzed 2010-2014 NTSS data to determine the number and distribution of noncountable cases reported. We also surveyed jurisdictions to determine the completeness of noncountable case reporting and obtain information on jurisdictions' experience in reporting noncountable cases. In addition, we prepared a hypothetical recalculation of the funding formula to evaluate the effect of including noncountable cases on funding allocations. Of 54 067 TB case reports analyzed, 1720 (3.2%) were noncountable; 47 of 60 (78.3%) jurisdictions reported ≥1 noncountable case. Of 60 programs surveyed, 34 (56.7%) responded. Of the 34 programs that responded, 24 (70.6%) had not reported all their noncountable cases to NTSS, and 11 (32.4%) stated that reporting noncountable cases was overly burdensome, considering the cases were not funded. Complete data on noncountable TB cases help support estimates of programmatic burden. Ongoing training and a streamlined reporting system to NTSS can facilitate noncountable case reporting.

A systematic review of BCG vaccination policies among high-risk groups in low TB-burden countries: implications for vaccination strategy in Canadian indigenous communities

BackgroundBacille Calmette-Guérin (BCG) vaccination against tuberculosis (TB) is widespread in high-TB-burden countries, however, BCG vaccination policies in low-burden countries vary. Considering the uncertainties surrounding BCG efficacy and the lower likelihood of TB exposure in low-incidence countries, most have discontinued mass vaccination, choosing instead a targeted vaccination strategy among high-risk groups. Given the increased risk of TB infection in Canadian Indigenous communities compared to the general Canadian population, these communities are a pertinent example of high-incidence groups in an otherwise low-burden country, warranting particular consideration regarding BCG vaccination strategy. This systematic review aims to synthesise and critically appraise the literature on BCG vaccination strategies in high-risk groups in low-incidence settings to provide policy considerations relevant to the Canadian Indigenous context.Methods: A literature search of the Medline and Embase databases was conducted, returning studies pertaining to BCG vaccine efficacy, TB incidence under specific vaccination policies, BCG-associated adverse events, and vaccination policy guidelines in low-burden countries. Study screening was tracked using the Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia), and data pertaining to the above points of interest were extracted.ResultsThe final review included 49 studies, spanning 15 countries. Although almost all of these countries had implemented a form of mass or routine vaccination previously, 11 have since moved to targeted vaccination of selected risk groups, in most cases due to the low risk of infection among the general population and thus the high number of vaccinations needed to prevent one case in the context of low-incidence settings. Regarding identifying risk groups for targeted screening, community-based (rather than individual risk-factor-based) vaccination has been found to be beneficial in high-incidence communities within low-incidence countries, suggesting this approach may be beneficial in the Canadian Indigenous setting.ConclusionsCommunity-based vaccination of high-incidence communities may be beneficial in the Canadian Indigenous context, however, where BCG vaccination is implemented, delivery strategies and potential barriers to achieving adequate coverage in this setting should be considered. Where an existing vaccination program is discontinued, it is crucial that an effective TB surveillance system is in place, and that case-finding, screening, and diagnostic efforts are strengthened in order to ensure adequate TB control. This is particularly relevant in Canadian Indigenous and other remote or under-served communities, where barriers to surveillance, screening, and diagnosis persist.

Risk Factors for and Trends in Isoniazid Monoresistance at Diagnosis of Tuberculosis-United States, 1993-2016.

Resistance to isoniazid (INH) only (monoresistance), with drug susceptibility to rifampin, pyrazinamide, and ethambutol at diagnosis of tuberculosis (TB) disease, can increase the length of treatment. To describe US trends in INH monoresistance and associated patient characteristics. We performed trend and cross-sectional analyses of US National Tuberculosis Surveillance System surveillance data. We used Joinpoint regression to analyze annual trends in INH monoresistance and logistic regression to identify patient characteristics associated with INH monoresistance. Culture-positive cases reported to National Tuberculosis Surveillance System during 1993-2016 with drug susceptibility test results to INH, rifampin, pyrazinamide, and ethambutol. (1) Trends in INH monoresistance; (2) odds ratios for factors associated with INH monoresistance. Isoniazid monoresistance increased significantly from 4.1% of all TB cases in 1993 to 4.9% in 2016. Among US-born patients, INH monoresistance increased significantly from 2003 onward (annual percentage change = 2.8%; 95% confidence interval: 1.4-4.2). During 2003-2016, US-born persons with INH-monoresistant TB were more likely to be younger than 65 years; to be Asian; to be human immunodeficiency virus-infected; or to be a correctional facility resident at the time of diagnosis. Among non-US-born persons, INH resistance did not change significantly during 1993-2016 (annual percentage change = -0.3%; 95% confidence interval: -0.7 to 0.2) and was associated with being aged 15 to 64 years; being Asian, black, or Hispanic; or having a previous history of TB. INH-monoresistant TB has been stable since 1993 among non-US-born persons; it has increased 2.8% annually among US-born persons during 2003-2016. Reasons for this increase should be further investigated.

Evaluation of the effectiveness of the surveillance system for tuberculosis in cattle in Spain

In Spain, the eradication of tuberculosis (TB) in cattle has had some setbacks and therefore we need to re-evaluate the current surveillance strategies. The Spanish cattle TB surveillance system consists of three components: a) routine skin testing, b) slaughterhouse surveillance, and c) pre-movement controls. Our objectives were to assess the effectiveness of the whole surveillance system and evaluate the relative contribution of each of those components, both at national and at the province level. The effectiveness was estimated based on both the sensitivity of detection per year and the time until detection. Moreover, we evaluated the impact of different factors on that effectiveness. We used a stochastic model that simulated the spread of Mycobacterium tuberculosis-complex (MTC) infection within cattle herds that was modified to incorporate the three components of TB surveillance. Input data, at the province level, on cattle movements off-farm or the frequency of the routine screening were provided by the Spanish Ministry for Agriculture, Fisheries and Food.Under the current conditions, 96.1% of Spanish herds were detected within one year after their infection (i.e. mean sensitivity of TB surveillance), although that detection took on average 178 days. The surveillance system effectiveness was highly dependent on the routine skin testing, responsible for the detection of almost 90% of the infected herds, while slaughterhouse surveillance and pre-movement controls contributed only to the identification of a small proportion of infected herds. We observed substantial differences in the effectiveness of the surveillance components among Spanish provinces, although in general, the sensitivities were high. The most influential factor on the efficiency of TB detection in Spain was, by far, the frequency of routine controls, followed by the sensitivity of the test used.In a context of reduced funding for cattle TB eradication, the frequency of testing should be adapted based on risk-based surveillance strategies, i.e. efforts should focus on herds more likely to be infected, but also in herds more likely to infect other herds. While slaughterhouse surveillance seems a cost-effective strategy, the use of pre-movement testing at least in areas of low incidence should be further evaluated.

First insights into the genetic characteristics and drug resistance of Mycobacterium tuberculosis population collected during the first national tuberculosis prevalence survey of Lao PDR (2010\u20132011)

BackgroundIn Lao People’s Democratic Republic (PDR), tuberculosis (TB) prevalence was estimated at 540/100,000 in 2011. Nevertheless, little is known about the genetic characteristics and anti-TB drug resistance of the Mycobacterium tuberculosis population. The main objective of this work was to study the genetic characteristics and drug resistance of M. tuberculosis population collected during the first National TB Prevalence Survey (TBPS) of Lao PDR (2010–2011).MethodsTwo hundred and twenty two isolates collected during TBPS (2010–2011) were analyzed with the GenoType MTBDRplus test for M. tuberculosis identification and drug resistance detection. Then, 206 of the 222 isolates were characterized by spoligotyping and MIRU-VNTR typing.ResultsAmong the 222 M. tuberculosis isolates, 11 were mono-resistant to isoniazid and 2 were resistant to isoniazid and rifampicin (MDR-TB), using the GenoType MTBDRplus test. Among the 202 genetically characterized isolates, the East African-Indian (EAI) family was predominant (76.7%) followed by the Beijing (14.4%) and T (5.5%) families. EAI isolates came from all the country provinces, whereas Beijing isolates were found mainly in the northern and central provinces. A higher proportion of Beijing isolates was observed in people younger than 35 years compared to EAI. Moreover, the percentage of drug resistance was higher among Beijing (17.2%) than EAI (5.2%) isolates, and the two MDR-TB isolates belonged to the Beijing family. Combined analysis of the MIRU-VNTR and spoligotyping results (n = 202 isolates) revealed an estimated clustering rate of 11% and the occurrence of mini-outbreaks of drug-resistant TB caused by Beijing genotypes.ConclusionsThe EAI family, the ancient and endemic family in Asia, is predominant in Lao PDR whereas the prevalence of Beijing, the most harmful M. tuberculosis family for humans, is still low, differently from neighboring countries. However, its association with drug resistance, its presence in young patients and its potential association with recent transmission suggest that the Beijing family could change TB epidemiological pattern in Lao PDR. Therefore, efficient TB control and surveillance systems must be maintained and reinforced to prevent the emergence of highly transmissible and drug-resistant strains in Lao PDR, as observed in neighboring countries.

Multidrug-resistant tuberculosis in Lisbon: unfavourable treatment and associated factors, 2000-2014.

SETTING: The incidence of tuberculosis (TB) has been decreasing in Portugal. Lisbon concentrates the largest number of cases of multidrug-resistant (MDR) TB in the country. This study aims at identifying clinical and demographic factors associated with unfavourable treatment results of patients with MDR-TB in the city.METHOD: The data on 265 MDR-TB cases, notified from 2000 to 2014 in the District of Lisbon, were collected from the Tuberculosis Surveillance System. Unfavourable cases were classified as failure, loss to follow-up (LTFU) and death. Bivariate and multivariate logistic regressions were undertaken to estimate the factors associated with unfavourable outcomes, LTFU and death.RESULTS: The proportion of unfavourable outcomes was 30.5%. These were associated mostly with being male, foreign-born and resistant to kanamycin. Death was associated with being human immunodeficiency virus-positive and resistant to kanamycin. Being foreign-born had a 4.46-fold higher odds of a LTFU outcome than did being Portuguese-born. The foreign-born patients were mostly African immigrants.CONCLUSION: The main finding in this study is that foreign-born patients are associated with a higher probability of unfavourable outcomes than Portuguese-born patients. Therefore, foreign-born patients need more careful monitoring in the control of MDR-TB.

Incidence of Tuberculosis in Chinese Adults with Type 2 Diabetes: A Retrospective Cohort Study in Shanghai

Background: Both type 2 diabetes mellitus (T2DM) and tuberculosis (TB) bring heavy disease burden around the world. Their causal relationship, however, remains unclear. In this study, we estimated incidence of TB in Chinese T2DM patients and evaluated the effect of glucose level on TB risk based on the management data in Shanghai. Methods: A retrospective cohort study was built based on the diabetes management system in Shanghai and included 240 692 adults aged 35 or above, diagnosed with T2DM between January 1, 2010 and December 31, 2015 and free of TB at diagnosis. Baseline information was from the system which was routinely collected for each patient at diagnosis of T2DM. Incident TB cases were identified through record-linkage with the Shanghai TB Surveillance System and Mandatory Notification System using the unique identification card number of each individual. Incidence of TB in all diabetes patients and by subgroups were calculated and compared. Multivariable Cox regression models with restricted cubic splines were used to evaluate the association of fast plasma glucose (FPG) level with the risk of TB. Findings: A total of 439 incident TB cases were identified in the cohort after an average of 3·83 years of follow-up. The overall incidence was 51·3/100 000 in diabetes patients and remained higher than that in general population from 2010 to 2015, with range from 44·5 to 76·4/100 000 vs. 28·1 to 31·0/100 000. The incidence was higher in men than in women (86·2 vs. 22·1 per 100 000), and was highest in patients with body mass index (BMI) <18·5 kg/m2 (215·2/100 000) or FPG≥10 mmol/L (143·2/100 000). The risk of TB was observed increasing with FPG increasing, particularly among those with normal BMI. Interpretation: Our results suggest that the risk of TB may increase as FPG increasing in normally weighted diabetes patients. Individualized screening strategy should be provided in Chinese diabetes patients to prevent and control TB. Funding Statement: The Three-year Action Plan on Public Health, Phase Ⅳ, Shanghai, China (15GWZK0801); The Study on Comprehensive Prevention and Treatment Model of Tuberculosis, Shanghai, China (2018ZX10715012). Declaration of Interests: The authors declared that there is no conflict of interest. Ethics Approval Statement: This study was approved by the Ethical Review Committee of Shanghai Municipal Center for Disease Control and Prevention. Since this was a retrospective study and all patients’ information used was routinely collected through the management system and the TB mandatory notification system, the requirement for informed consent was exempted by the committee mentioned above.

Effectiveness of pre-entry active tuberculosis and post-entry latent tuberculosis screening in new entrants to the UK: a retrospective, population-based cohort study

Evaluating interventions that might lead to a reduction in tuberculosis in high-income countries with a low incidence of the disease is key to accelerate progress towards its elimination. In such countries, migrants are known to contribute a large proportion of tuberculosis cases to the burden. We assessed the effectiveness of screening for active tuberculosis before entry to the UK and for latent tuberculosis infection (LTBI) post-entry for reduction of tuberculosis in new-entrant migrants to the UK. Additionally, we investigated the effect of access to primary care on tuberculosis incidence in this population. We did a retrospective, population-based cohort study of migrants from 66 countries who were negative for active tuberculosis at pre-entry screening between Jan 1, 2011, and Dec 31, 2014, and eligible for LTBI screening. We used record linkage to track their first contact with primary care, uptake of LTBI screening, and development of active tuberculosis in England, Wales, and Northern Ireland. To assess the effectiveness of the pre-entry screening programme, we identified a control group of migrants who were not screened for active tuberculosis using the specific code for new entrants to the UK registering in primary care within the National Health Service patient registration data system. Our primary outcome was development of active tuberculosis notified to the National Enhanced Tuberculosis Surveillance System. Our cohort comprised 224 234 migrants who were screened for active tuberculosis before entry to the UK and a control group of 118 738 migrants who were not. 103 990 (50%) migrants who were screened for active tuberculosis registered in primary care; all individuals in the control group were registered in primary care. 1828 tuberculosis cases were identified during the cohort time, of which 31 were prevalent. There were 26 incident active tuberculosis cases in migrants with no evidence of primary care registration, and 1771 cases in the entire cohort of migrants who registered in primary care (n=222 728), giving an incidence rate of 174 (95% CI 166-182) per 100 000 person-years. 672 (1%) of 103 990 migrants who were screened for active tuberculosis went on to develop tuberculosis compared with 1099 (1%) of 118 738 not screened for active tuberculosis (incidence rate ratio [IRR] 1·49, 95% CI 1·33-1·67; p<0·0001). 2451 (1%) of the 222 728 migrants registered in primary care were screened for LTBI, of whom 421 (17%) tested positive and 1961 (80%) tested negative; none developed active tuberculosis within the observed time period. Migrants settling in the least deprived areas had a decreased risk of developing tuberculosis (IRR 0·74, 95% CI 0·62-0·89; p=0·002), and time from UK arrival to primary care registration of 1 year or longer was associated with increased risk of active tuberculosis (2·96, 2·59-3·38; p<0·0001). Pre-entry tuberculosis screening, early primary care registration, and LTBI screening are strongly and independently associated with a lower tuberculosis incidence in new-entrant migrants. National Institute for Health Research (NIHR) Health Protection Research Unit in Respiratory Infections and NIHR Imperial Biomedical Research Centre.

Clinical profiles of early and tuberculosis-related mortality in South Korea between 2015 and 2017: a cross-sectional study

BackgroundAlthough the incidence of tuberculosis (TB) has decreased in South Korea, the mortality rate remains high. TB mortality is a key indicator for TB control interventions. The purpose of this study was to assess early and TB-related mortality during anti-TB treatment and describe the associated clinical characteristics.MethodsA multicenter cross-sectional study was performed across South Korea. Patients with pulmonary TB who died during anti-TB treatment and whose records were submitted to the national TB surveillance system between 2015 and 2017 were enrolled. All TB deaths were categorized based on cause (TB-related or non-TB-related) and timing (early or late). We identified statistical associations using the frequency table, chi-square test, and binary logistic regression.ResultsOf 5595 notifiable mortality cases, 3735 patients with pulmonary TB were included in the analysis. There were 2541 (68.0%) male patients, and 2935 (78.6%) mortality cases were observed in patients older than 65 years. There were 944 (25.3%) cases of TB-related death and 2545 (68.1%) cases of early death. Of all cases, 187 (5.0%) patients were diagnosed post-mortem and 38 (1.0%) patients died on the first day of treatment. Low body mass index (adjusted odds ratio (aOR) = 1.26; 95% confidence interval (CI) = 1.08–1.48), no reported illness (aOR = 1.36; 95% CI = 1.10–1.68), bilateral disease on chest X-ray (aOR = 1.30; 95% CI = 1.11–1.52), and positive acid-fast bacilli smear result (aOR = 1.30; 95% CI = 1.11–1.52) were significantly associated with early death, as well as TB-related death. Acute respiratory failure was the most common mode of non-TB-related death. Malignancy was associated with both late (aOR = 0.71; 95% CI = 0.59–0.89) and non-TB-related (aOR = 0.35; 95% CI = 0.26–0.46) death.ConclusionsA high proportion of TB death was observed in elderly patients and attributed to non-TB-related causes. Many TB-related deaths occurred during the intensive phase, particularly within the first month. Further studies identifying risk factors for different causes of TB death at different phases of anti-TB treatment are warranted for early targeted intervention in order to reduce TB mortality.

Epidemiology of tuberculosis among children and adolescents in the USA, 2007–17: an analysis of national surveillance data

Understanding tuberculosis epidemiology among children and adolescents informs treatment and prevention efforts, and efforts to eliminate disparities in tuberculosis incidence and mortality. We sought to describe the epidemiology of children and adolescents with tuberculosis disease in the USA, including tuberculosis incidence rates by parental country of birth and for US territories and freely associated states, which have not been previously described. We analysed data for children aged younger than 15 years and adolescents aged 15-17 years with tuberculosis disease reported to the National Tuberculosis Surveillance System during 2007-17, and calculated tuberculosis incidence rates using population estimates from the US Census Bureau. During 2010-17, 6072 tuberculosis cases occurred among children and adolescents; of these, 5175 (85%) of 6072 occurred in the 50 US states or the District of Columbia and 897 (15%) of 6072 in US-affiliated islands. In US states, 3520 (68%) of 5175 cases occurred among US-born people overall, including 2977 (76%) of 3896 children and 543 (42%) of 1279 adolescents. The incidence rate among children and adolescents was 1·0 per 100 000 person-years during 2007-17 and declined 47·8% (95% CI -51·4 to -44·1) during this period. We observed disproportionately high tuberculosis rates among children and adolescents of all non-white racial or ethnic groups, people living in US-affiliated islands, and children born in or with parents from tuberculosis-endemic countries. Overall, tuberculosis incidence among children and adolescents in the USA is low and steadily declining, but additional efforts are needed to eliminate disparities in incidence and mortality. US Centers for Disease Control and Prevention.

Exploring the effects of BCG vaccination in patients diagnosed with tuberculosis: Observational study using the Enhanced Tuberculosis Surveillance system

BackgroundBacillus Calmette–Guérin (BCG) is one of the most widely-used vaccines worldwide. BCG primarily reduces the progression from infection to disease, however there is evidence that BCG may provide additional benefits. We aimed to investigate whether there is evidence in routinely-collected surveillance data that BCG vaccination impacts outcomes for tuberculosis (TB) cases in England. MethodsWe obtained all TB notifications for 2009–2015 in England from the Enhanced Tuberculosis surveillance system. We considered five outcomes: All-cause mortality, death due to TB (in those who died), recurrent TB, pulmonary disease, and sputum smear status. We used logistic regression, with complete case analysis, to investigate each outcome with BCG vaccination, years since vaccination and age at vaccination, adjusting for potential confounders. All analyses were repeated using multiply imputed data. ResultsWe found evidence of an association between BCG vaccination and reduced all-cause mortality (aOR:0.76 (95%CI 0.64–0.89), P:0.001) and weak evidence of an association with reduced recurrent TB (aOR:0.90 (95%CI 0.81–1.00), P:0.056). Analyses using multiple imputation suggested that the benefits of vaccination for all-cause mortality were reduced after 10 years. ConclusionsWe found that BCG vaccination was associated with reduced all-cause mortality in people with TB although this benefit was less pronounced more than 10 years after vaccination. There was weak evidence of an association with reduced recurrent TB.

Whole-genome sequencing for rapid, reliable and routine investigation of Mycobacterium tuberculosis transmission in local communities.

Contact investigations following the diagnosis of active tuberculosis (TB) are paramount for the control of the disease. Epidemiological data are very powerful for contact tracing but might be delayed and/or difficult to integrate, especially in the setting of multiple contact-tracing investigations. The aim of this study was to address the added-value of whole-genome sequencing (WGS) to routine local TB surveillance systems. From November 2016 to July 2017, the local TB surveillance system identified three clusters that could constitute a unique larger outbreak. Epidemiological and clinical information were integrated with WGS genotyping data of Mycobacterium tuberculosis strains obtained using a simple DNA extraction method coupled with sequencing using an Illumina MiSeq platform and an in-house bioinformatics pipeline for single nucleotide polymorphism (SNP) analysis. Epidemiological investigations identified three putative TB clusters potentially interrelated including eight patients with active TB. Seven M. tuberculosis isolates were available and analysed by WGS. Using a 5-SNP threshold to define recent transmission, WGS-based genotyping supported the occurrence of the three clusters as well as a link between clusters 1 and 2 (SNP ≤1), constituting a larger outbreak. This outbreak was clearly delineated by refuting a potential link with the third cluster (SNP >500). Genotyping data did not support the belonging of patient 7 to any studied cluster. This study illustrates the usefulness of WGS genotyping for routine TB surveillance systems in local communities to rapidly confirm or disprove epidemiological hypotheses and delineate TB clusters, especially in the context of multiple contact-tracing investigations.

Rifampin-resistant Tuberculosis in the United States, 1998-2014.

Monoresistance to rifamycins necessitates longer and more toxic regimens for tuberculosis (TB). We examined characteristics and mortality associated with rifampin-monoresistant (RMR) TB in the United States. We analyzed Mycobacterium tuberculosis culture-positive cases reported to the National TB Surveillance System (excluding California) between 1998 and 2014. We defined RMR TB found on initial drug susceptibility testing and possible acquired rifampin-resistant (ARR) TB. We assessed temporal trends in RMR TB. For both classifications of rifampin resistance, we calculated adjusted risk ratios (adjRRs) and 95% confidence intervals (CIs) for characteristics associated with mortality when compared with drug-susceptible TB in multivariable models using backward selection. Of 180 329 TB cases, 126 431 (70%) were eligible for analysis, with 359 (0.28%) of eligible cases reported as RMR. The percentage of RMR TB cases with HIV declined 4% annually between 1998 and 2014. Persons with HIV and prior TB were more likely to have RMR TB (adjRR, 25.9; 95% CI, 17.6-38.1), as were persons with HIV and no prior TB (adjRR, 3.1; 95% CI, 2.4-4.1) vs those without either characteristic, controlling for other statistically significant variables. RMR cases had greater mortality (adjRR, 1.4; 95% CI, 1.04-1.8), controlling for HIV and other variables. Persons with HIV had greater risk of ARR than persons without HIV (adjRR, 9.6; 95% CI, 6.9-13.3), and ARR was also associated with increased mortality, controlling for HIV and other variables. All forms of rifampin resistance were positively associated with HIV infection and increased mortality.