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Tuberculosis (TB) control programs prevent transmission of Mycobacterium tuberculosis by identifying and treating active cases of TB disease and ensuring that contacts of infectious cases are also identified, screened, and treated for active disease or latent infection. The chapter reviews the use of genotyping to investigate transmission as well as how genotyping methods have been applied to study transmission dynamics, lineage, recurrent TB disease, mixed infections, and laboratory contamination. A common outbreak investigation goal is to combine genotyping data with different sources of clinical, epidemiological, and programmatic data through partnerships that lead investigators to the best conclusions and public health action for control of recent transmission. Although spatial analyses of TB case distributions are common, they are heterogeneous in their methods and findings. The central problem with using genotype clustering to estimate recent transmission has been that clustered cases are not necessarily part of the same chain of transmission.

Setting Nearly 8% of adult tuberculosis (TB) cases in England, Wales and Northern Ireland (EW&NI) occur among health care workers (HCWs), the majority of whom are from high TB incidence countries. Objectives To determine if a TB cluster containing multiple HCWs was due to nosocomial transmission. Methods A cluster of TB cases notified in EW&NI from 2009 to 2014, with indistinguishable 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) profiles, was identified through routine national cluster review. Cases were investigated to identify epidemiological links, and occupational health (OH) information was collected for HCW cases. To further discriminate strains, typing of eight additional loci was conducted. Results Of the 53 cases identified, 22 were HCWs. The majority (n = 43), including 21 HCWs, were born in the Philippines. Additional typing split the cluster into three subclusters and seven unique strains. No epidemiological links were identified beyond one household and a common residential area. HCWs in this cluster received no or inadequate OH assessment. Conclusions The MIRU-VNTR profile of this cluster probably reflects common endemic strains circulating in the Philippines, with reactivation occurring in the UK. Furthermore, 32-locus typing showed that 24-locus MIRU-VNTR failed to distinguish strain diversity. The lack of OH assessment indicates that latent tuberculous infection could have been identified and treated, thereby preventing active cases from occurring.

Molecular technology to identify relatedness between Mycobacterium tuberculosis complex isolates, representative of possible tuberculosis (TB) transmission between individuals, continues to evolve. At the same time, tools to utilise this information for public health action to improve TB control should also be implemented. Public Health England developed the Strain Typing Module (STM) as an integral part of the web-based surveillance system used in the United Kingdom following the roll-out of prospective 24 loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) strain typing. The creation of such a system required data integration and linkage, bringing together laboratory results and patient notification information. The STM facilitated widespread access to patient strain typing and clustering results for the public health community working in TB control. In addition, the system provided a log of cluster review and investigation decision making and results. Automated real-time data linkage between laboratory and notification data are essential to allow routine use of genotyping results in TB surveillance and control. Outputs must be accessible by those working in TB control at a local level to have any impact in ongoing public health activity.

Background The incidence of TB has doubled in the last 20 years in London. A better understanding of risk groups for recent transmission is required to effectively target interventions. We investigated the molecular epidemiological characteristics of TB cases to estimate the proportion of cases due to recent transmission, and identify predictors for belonging to a cluster. Methods The study population included all culture-positive TB cases in London residents, notified between January 2010 and December 2012, strain typed using 24-loci multiple interspersed repetitive units-variable number tandem repeats. Multivariable logistic regression analysis was performed to assess the risk factors for clustering using sociodemographic and clinical characteristics of cases and for cluster size based on the characteristics of the first two cases. Results There were 10 147 cases of which 5728 (57%) were culture confirmed and 4790 isolates (84%) were typed. 2194 (46%) were clustered in 570 clusters, and the estimated proportion attributable to recent transmission was 34%. Clustered cases were more likely to be UK born, have pulmonary TB, a previous diagnosis, a history of substance abuse or alcohol abuse and imprisonment, be of white, Indian, black-African or Caribbean ethnicity. The time between notification of the first two cases was more likely to be

BACKGROUND: TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries.METHODS: We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends.FINDINGS: A total of 259,609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100,000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100,000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (pINTERPRETATION: To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years.

Objectives Tuberculosis (TB) is a serious re-emergent public health problem in the UK. In response to rising case incidence a National TB Strain-Typing Service based on molecular strain-typing was established. This facilitates early detection and investigation of clusters, targeted public health action, and prevention of further transmission. We review the added public health value of investigating molecular TB strain-typed (ST) clusters. Methods A structured questionnaire for each ST cluster investigated in England between 1 January 2010 and 30 June 2013 was completed. Questions related to epidemiological links and public health action and the perceived benefits of ST cluster investigation. Results There were 278 ST cluster investigations (CIs) involving 1882 TB cases. Cluster size ranged from 2 to 92. CIs identified new epidemiological links in 36% of clusters; in 18% STs were discordant refuting transmission thought to have occurred. Additional public health action was taken following 23% of CI. Conclusions We found positive benefits of TB molecular ST and CI, in identifying new epidemiological links between cases and taking public health action and in refuting transmission and saving resources. This needs to be translated to a decrease in transmission to provide evidence of public health value in this low prevalence high resource setting.

Background In the European Union and European Economic Area only 38% of multidrug-resistant tuberculosis patients notified in 2011 completed treatment successfully at 24 months’ evaluation. Socio-economic factors and patient factors such as demographic characteristics, behaviour and attitudes are associated with treatment outcomes. Characteristics of healthcare systems also affect health outcomes. This study was conducted to identify and better understand the contribution of health system components to successful treatment of multidrug-resistant tuberculosis. Methods We selected four European Union countries to provide for a broad range of geographical locations and levels of treatment success rates of the multidrug-resistant tuberculosis cohort in 2009. We conducted semi-structured interviews following a conceptual framework with representatives from policy and planning authorities, healthcare providers and civil society organisations. Responses were organised according to the six building blocks of the World Health Organization health systems framework. Results In the four included countries, Austria, Bulgaria, Spain, and the United Kingdom, the following healthcare system factors were perceived as key to achieving good treatment results for patients with multidrug-resistant tuberculosis: timely diagnosis of drug-resistant tuberculosis; financial systems that ensure access to a full course of treatment and support for multidrug-resistant tuberculosis patients; patient-centred approaches with strong intersectoral collaboration that address patients’ emotional and social needs; motivated and dedicated healthcare workers with sufficient mandate and means to support patients; and cross-border management of multidrug-resistant tuberculosis to secure continuum of care between countries. Conclusion We suggest that the following actions may improve the success of treatment for multidrug-resistant tuberculosis patients: deployment of rapid molecular diagnostic tests; development of context-specific treatment guidance and criteria for hospital admission and discharge in the European context; strengthening patient-centred approaches; development of collaborative mechanisms to ensure cross-border care, and development of long-term sustainable financing strategies. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4216-9) contains supplementary material, which is available to authorized users.

Objectives To describe the burden of TB in healthcare workers (HCWs) in the UK and determine whether HCWs are at increased risk of TB due to occupational exposure. Methods Retrospective cohort analysis of national UK TB surveillance and genotyping data between 2009 and 2013. The rate of TB in HCWs compared with non-HCWs to calculate incidence rate ratios stratified by country of birth. Results 2320 cases of TB in HCWs were notified in the study period, 85% were born abroad. The TB rate in HCWs was 23.4 (95% CI 22.5 to 24.4) per 100 000 compared with 16.2 (95% CI 16.0 to 16.3) per 100 000 in non-HCWs. After stratifying by country of birth, there was not an increased TB incidence in HCWs for the majority of countries of birth, including in the UK-born. Using combined genotyping and epidemiological data, only 10 confirmed nosocomial transmission events involving HCWs were identified between 2010 and 2012. Of these, only two involved transmission to patients. Conclusions The lack of an increased risk of TB after stratifying by country of birth, and the very few transmission events involving nosocomial transmission in the UK suggests that TB in HCWs in the UK is not generally acquired through UK occupational exposure. The majority of cases in foreign-born HCWs are likely to result from reactivation of latent TB infection (LTBI) acquired abroad, and is not likely to be prevented by BCG vaccination in the UK. Testing and treatment of LTBI in HCWs with exposure to high TB burden countries should be the focus of occupational health prevention activities.

Due to an increase in bovine tuberculosis in cattle in the United Kingdom, we investigated the characteristics of Mycobacterium bovis infection in humans and assessed whether extensive transmission of M. bovis between humans has occurred. A cross-sectional study linking demographic, clinical, and DNA fingerprinting (using 15-locus mycobacterial interspersed repetitive-unit–variable-number tandem-repeat [MIRU-VNTR] typing) data on cases reported between 2005 and 2008 was undertaken. A total of 129 cases of M. bovis infection in humans were reported over the period, with a decrease in annual incidence from 0.065 to 0.047 cases per 100,000 persons. Most patients were born pre-1960, before widespread pasteurization was introduced (73%), were of white ethnicity (83%), and were born in the United Kingdom (76%). A total of 102 patients (79%) had MIRU-VNTR typing data. A total of 31 of 69 complete MIRU-VNTR profiles formed eight distinct clusters. The overall clustering proportion determined using the n − 1 method was 33%. The largest cluster, comprising 12 cases, was indistinguishable from a previously reported West Midlands outbreak strain cluster and included those cases. This cluster was heterogeneous, having characteristics supporting recent zoonotic and human-to-human transmission as well as reactivation of latent disease. Seven other, smaller clusters identified had demographics supporting recrudescence rather than recent infection. A total of 33 patients had incomplete MIRU-VNTR profiles, of which 11 may have yielded 2 to 6 further small clusters if typed to completion. The incidence of M. bovis in humans in the United Kingdom remains low, and the epidemiology is predominantly that of reactivated disease.

Anti-tuberculosis drug regimens are efficacious, but drug intolerance can be severe and may impact on treatment completion rates. The Enhanced Tuberculosis Surveillance (ETS) system is a case register of all new notifications of tuberculosis in England, Wales and Northern Ireland. We conducted a cohort study to estimate the incidence of, and risk factors for, drug intolerance reported through ETS between 2001 and 2010 and to assess its relationship with treatment non-completion. Reports of drug intolerance were found for 868/67 547 (1.28%) patients in the cohort, and important risk factors were female sex, older age, later case report year and white ethnicity. Drug intolerance was associated with an approximate fivefold increased odds of treatment non-completion (p

To the Editor: Multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin, is an increasing problem globally [1]. Children are not usually included in global surveys of MDR-TB incidence and prevalence [2] due to the diagnostic challenges of paucibacillary TB [3]. Data on the burden of MDR-TB in children are, therefore, lacking globally [1, 4, 5] and no published data from the UK exist. The current World Health Organization (WHO) [6] and National Institute for Clinical Excellence (NICE) [7] TB guidelines for the management of MDR-TB do not explicitly address paediatric disease. As a consequence, the complex management of this condition is left to individual clinicians' judgment. In general, childhood TB is paucibacillary, most cases are treated on clinical grounds without drug susceptibility testing [2], and correct and timely diagnosis of childhood MDR-TB is therefore challenging. There are limited data on the pharmacokinetics, dosing and safety of the many second-line drugs used to treat MDR-TB in children [5]. Our group is the first to review the management of a paediatric cohort with MDR-TB in the UK, and represents the largest available dataset from children with culture-confirmed MDR-TB from western …

Introduction The incidence of nontuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW and NI) the reported rate of NTM more than doubled between 1996 and 2006. It is unclear if this trend has continued. We present an updated analysis with national NTM data from 2007 to 2012. Methods All individuals with culture positive NTM isolates between 2007–2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW and NI, were included. The annual incidence of NTM was calculated based on the year of the first positive NTM isolate from each individual. Results 21,024 individuals had NTM culture positive samples. Over the study period the incidence rose from 5.57 (n = 3126) to 7.63 (n = 4454) per 100,000 population. The majority were male (57%) and older (71% >50 years of age). 77% of individuals had a pulmonary isolate – and here the incidence increased from 3.97 to 6.05 per 100,000 population between 2007 and 2012. In those with extra-pulmonary samples it remained stable at 1.61 per 100,000 population. In patients Table 1 indicates the seven most frequently reported organisms; M. avium-intracellulare (MAI) accounted for 35% of isolates (75% in people >50 years). 78% of these were from pulmonary samples. 42% of M. abscessus isolates were in patients 60 years. Conclusion The incidence of NTM has continued to rise since the last national survey. This represents an almost ten-fold increase since 1995. The majority of these are pulmonary isolates (in particular MAI). Possible explanations include greater awareness amongst clinicians leading to increased sampling, improvements in laboratory techniques for speciation or laboratory reporting practices. However, such a large increase most likely reflects a genuine rise in NTM infection in the population. Given this change in culture confirmation, it is imperative that a comprehensive clinical database is set up to provide national monitoring of clinically significant infections, and establish the true burden of disease present in EW and NI.

United Kingdom (UK) guidelines recommend at least 18 months treatment for patients with multidrug-resistant tuberculosis (MDR-TB). Prior to 2008, data on treatment outcome were only available at 12 months and therefore the proportion completing treatment was unknown. This retrospective-prospective cohort study reports on treatment outcomes for MDR-TB patients notified between 2004 and 2007 and examines factors associated with successful outcomes. 70.6% (144/204) completed treatment in 24 months or more, 6.9% (14) stopped treatment, 6.9% (14) died, 7.8% (16) were lost to follow up, 0.5% (1) relapsed and 4.4% (9) were transferred overseas. Following adjustment for age, being non-UK born, non-compliance and having co-morbidities, treatment with a fluoroquinolone (OR 3.09; 95% CI 1.21-7.88; p

To the Editor: Described as a “template for success” by Hanekom et al. [1] the Beijing genotype of Mycobacterium tuberculosis has been associated with hypervirulence, drug resistance, evasion of the bacille Calmette–Guerin (BCG) vaccine and differential immunoregulation [1]. The genotype is itself diverse; accordingly the fact that specific traits have been associated with Beijing only in certain settings may be explained by the variation in the subtypes that predominate in each. We sought to explore the role that the Beijing genotype plays in the epidemiology of multidrug-resistant (MDR) tuberculosis (TB) in two very different epidemiological settings: England and Peru. In the UK nearly three quarters of TB disease occurs amongst migrants, which may result from latent M. tuberculosis infections acquired from high-burden countries of origin. Thus the distribution of lineages in the UK reflects a composite of the circulating strains in other nations. Whilst increasing levels of MDR-TB in the UK have triggered understandable concern, only a small fraction of cases of TB are MDR (in 2011 this was 1.0%) [2]. In contrast, the Peruvian TB epidemic is relatively “home-grown” and the prevalence of drug resistance is greater (in 2011 5.3% were MDR-TB) [2]. Our objectives were thus: 1) identify any association between the Beijing genotype and MDR in these two settings, and 2) to examine if trends in Beijing might explain changes in the prevalence of MDR-TB over time. Four datasets were used during this study: two English studies and two Peruvian studies. The English datasets were taken from Public Health England's Enhanced Tuberculosis Surveillance System and Mycobacterial Surveillance Network and were referred to as England 1 and England 2. England 1 consisted of 8 859 individuals diagnosed and 24-loci MIRU-VNTR (mycobacterial interspersed repetitive units variable number tandem repeats) strain-typed …

Introduction The London Borough of Newham consistently has the highest incidence of tuberculosis (TB) in the UK (≈120/100,000), with case numbers continuing to rise. We sought to investigate social risk factors for TB as compared with the general population in this borough. Methods Of 242 adult patients diagnosed with TB in 2012 at the Newham Chest Clinic 170 (70.3%) completed a structured interview assessing for social risk factors. Demographic data was obtained from hospital records. TB case data was compared with 2011 census data using Fisher’s exact test or t-tests as appropriate. Results Data directly comparable to 2011 census data is summarised in Table 1. Cases had a mean of 3.43 (95% CI 3.07–3.8) household contacts, 2.28 (1.41–3.16) non-household family contacts and 2.02 (1.71–2.33) close friends. Household and family contacts were almost exclusively of the same ethnicity as the cases, but with 18.4% of household contacts and 49.2% of family contacts being UK born, compared with 7.7% of cases. The majority of friends were of the same ethnicity (86%) with 18.4% UK born, 89.4% of cases had no close friends from a different ethnic group. None of the cohort reported alcohol or drug abuse or had been in prison in the last 5 years, one was currently homeless. Fifteen (8.8%) reported recent visitors from abroad and 61 (38.9% of foreign born) reported returning to their country of birth for greater than three weeks, with 75.4% having returned within the last two years, a further eleven had travelled to a high incidence country in the last ten years, six of whom were UK born travelling to their parents’ country of birth. Conclusions In this high incidence area of an otherwise low incidence country TB is significantly more common in those of South-Asian birth and ethnicity. It is more common in young adults who have lived in the UK between two and five years and work in unskilled jobs or are unemployed. This picture is likely driven by TB reactivation in new immigrants accompanied by a lack of social mixing and suggesting the influence of relative poverty in the development of TB.