Sarah R Anderson

Tuberculosis in London: a decade and a half of no decline

Background: London accounts for nearly half of the national burden of tuberculosis. The incidence of tuberculosis has more than doubled in London in the past 15 years. Methods: Data from the enhanced tuberculosis surveillance 1999–2003, the national tuberculosis surveys of 1993 and 1998, and tuberculosis notifications were compared and analysed. Results: In 2003, 3048 patients with tuberculosis were reported in London, 45% of the national total. This represents an incidence of 41.3/100 000, five times higher than the rest of England and Wales, and in parts of London the incidence of tuberculosis is nine times the national average. 75% of people with tuberculosis in London are born abroad; nearly half have lived in the UK for <5 years, but a third for >10 years. 86% are from an ethnic minority group, and the incidence is highest in black Africans at 283/100 000 compared with 141, 141 and 8/100 000 for Pakistanis, Indians and whites, respectively. In absolute terms, a third of patients with tuberculosis in London are from Africa and nearly a third from the Indian subcontinent. Specific groups affected also include the homeless, prisoners, and hard drug and alcohol users as well as the immunosuppressed. Conclusions: London reflects the worldwide rise in tuberculosis, with increasing incidence in ethnic minorities. Work has been carried out to combat this rise, but more is needed. Tuberculosis control and prevention strategies should be mindful of the changing epidemiology of tuberculosis in London, and provide information, diagnosis and treatment tailored to the specific needs of the capital and its at-risk groups.

Recent TB transmission, clustering and predictors of large clusters in London, 2010–2012: results from first 3 years of universal MIRU-VNTR strain typing

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 <90 days in large clusters. Conclusions Up to a third of TB cases in London may be due to recent transmission. Resources should be directed to the timely investigation of clusters involving cases with risk factors, particularly those with a short period between the first two cases, to interrupt onward transmission of TB.

A collaborative strategy to tackle tuberculosis in England

312 www.thelancet.com Vol 385 January 24, 2015 The UK has the second highest rate of tuberculosis among western European countries. Tuberculosis clinics in London manage more cases a year than those in all other western European capital cities put together. Rates of tuberculosis are now nearly fi ve times higher in the UK than in the USA. Lack of progress with tuberculosis control in the UK does not just represent a risk to domestic public health, but also an international embarrassment with examples of cases acquired in the UK leading to infections in other low-incidence countries. In recognition of this unacceptable trend, Public Health England has led a coalition of stakeholders to develop a forum, the national Tuberculosis Oversight Group, where innovation and good practice are shared between local, regional, and national health leaders. These discussions have led to local changes, with several areas establishing tuberculosis control boards and systematic cohort review, and the identifi cation of tuberculosis as a major priority for Public Health England. However, the implementation of improved tuberculosis control measures has not been universal, and there is still unacceptable variation in the quality of clinical and public health measures across England. A collaborative strategy to tackle tuberculosis in England There are some limitations to the study. First, the subtle eff ects of the HMGCR variants meant that the investigators had to use large numbers of cases and controls, and the associations between the variants and type 2 diabetes are not statistically beyond reproach—more cases and controls would help confi rm the fi ndings. Second, we cannot be certain that the variants operate directly and solely through the HMGCR gene, although there is some evidence that these variants alter splicing of HMGCR transcripts. Finally, genetic studies are not completely exempt from the confounders and biases of epidemiological studies—survival and index event biases can aff ect genetic studies, and further work with larger numbers of incident cases would provide more reassurance that the genetic associations with type 2 diabetes are real. However, the associations with body-mass index seem to be statistically robust and provide a mechanism downstream of the HMGCoA-reductase eff ect (increased body-mass index leading to increased insulin resistance, and to increased diabetes). In summary, Swerdlow and colleagues have used naturally occurring human genetic variation to provide another piece of evidence about the side-eff ects of statins, but have not cast any doubt on the evidence that the benefi ts of statins vastly outweigh their risks.

Tracking and responding to an outbreak of tuberculosis using MIRU-VNTR genotyping and whole genome sequencing as epidemiological tools

Background We describe an outbreak that contributed to a near doubling of the incidence of tuberculosis in Southampton, UK. We examine the importance of 24 locus mycobacterial interspersed repetitive unit variable number tandem repeat (MIRU-VNTR) genotyping in its identification and management and the role of whole genome sequencing (WGS) in tracing the spread of the strain. Methods Outbreak cases were defined as those diagnosed between January and December 2011 with indistinguishable 24 locus-MIRU-VNTR genotypes or, cases linked epidemiologically. A cluster questionnaire was administered by TB nurses to identify contacts and social settings. Results Overall, 25 patients fulfilled the case definition. No cases with this MIRU-VNTR genotype had been detected in the UK previously. Connections were found between all cases through household contacts or social venues including a football club, Internet cafe and barbers shop. Public health actions included extended contact tracing, venue screening and TB awareness-raising. The outbreak resulted in a high rate of transmission and high incidence of clinical disease among contacts. Conclusions This outbreak illustrates the value of combining active case-finding with prospective MIRU-VNTR genotyping to identify settings to undertake public health action. In addition WGS revealed that the VNTR-defined cluster was a single outbreak and that active TB transmission not reactivation was responsible for this outbreak in non-UK born individuals.

Reduction in tuberculosis incidence in the UK from 2011 to 2015: a population-based study

Background Following nearly two decades of increasing tuberculosis in the UK, TB incidence decreased by 32% from 2011 to 2015. Explaining this reduction is crucial to informing ongoing TB control efforts. Methods We stratified TB cases notified in the UK and TB cases averted in the UK through pre-entry screening (PES) between 2011 and 2015 by country of birth and time since arrival. We used population estimates and migration data to establish denominators, and calculated incidence rate ratios (IRRs) between 2011 and 2015. We calculated the contribution of changing migrant population sizes, PES and changes in TB rates to the reduction in TB notifications. Results TB IRRs fell in all non-EU migrant and UK-born populations between 2011 and 2015 (0.61; 95%  CI 0.59 to 0.64 and 0.78; 0.73 to 0.83 respectively), with the greatest decrease in recent non-EU migrants (0.54; 0.48 to 0.61). 61.9% of the reduction in TB notifications was attributable to decreases in TB rates, 33.4% to a fall in the number of recent/mid-term non-EU migrants and 11.4% to PES. A small increase in notifications in EU-born migrants offset the reduction by 6.6%. Conclusions Large decreases in TB rates in almost all populations accounted for the majority of the reduction in TB notifications, providing evidence of the impact of recent interventions to improve UK TB control. The particularly large decrease in TB rates in recent non-EU migrants provides evidence of the effectiveness of screening interventions that target this population. These findings will inform ongoing improvements to TB control.

P50 A summary of strain typing and clustering of TB in London in 2010 and an analysis of the associated risk factors

Since January 2010 prospective strain typing on all positive TB samples able to be cultured has occurred. Recent infection is presumed if the strain of TB isolated from the case is indistinguishable from one or more others in the population studied. Recently infected cases are likely to be part of clusters. All data are currently preliminary. In London from January to September 2010, 2679 cases were reported to the London TB Register, 36% of which were culture confirmed. Of those that were culture confirmed 37% were in a cluster. Adults were more likely to be culture confirmed than children (37% vs 23%). While children may be less likely to be culture confirmed, those who were culture confirmed were more likely to be clustered (and so recently infected). Comparing children (0–15 year olds) to young adults (16–24 year olds), 70% compared to 40% were clustered (OR 3.49, p=0.003). Overall more clustering was noted among males (39% vs 33%, OR 1.28, p=0.08), white (40%) and black-Caribbean (47%) ethnic groups, UK born cases (42% vs 36%), and those with pulmonary (45% vs 30%) and sputum smear positive disease (56% vs 38%). More clustering was seen with those who had social risk factors: history of drug use (46%), homelessness (49%), imprisonment (47%), and alcohol abuse (46%). The majority were in clusters with <5 cases and therefore did not reach the HPA cluster investigation threshold of =5 cases in 24 months. Data will be presented for the entirety of 2010, therefore numbers are subject to change.

Tuberculosis in London: A decade and a half of no decline in tuberculosis epidemiology and control

Background: London accounts for nearly half of the national burden of tuberculosis. The incidence of tuberculosis has more than doubled in London in the past 15 years. Methods: Data from the enhanced tuberculosis surveillance 1999–2003, the national tuberculosis surveys of 1993 and 1998, and tuberculosis notifications were compared and analysed. Results: In 2003, 3048 patients with tuberculosis were reported in London, 45% of the national total. This represents an incidence of 41.3/100 000, five times higher than the rest of England and Wales, and in parts of London the incidence of tuberculosis is nine times the national average. 75% of people with tuberculosis in London are born abroad; nearly half have lived in the UK for <5 years, but a third for >10 years. 86% are from an ethnic minority group, and the incidence is highest in black Africans at 283/100 000 compared with 141, 141 and 8/100 000 for Pakistanis, Indians and whites, respectively. In absolute terms, a third of patients with tuberculosis in London are from Africa and nearly a third from the Indian subcontinent. Specific groups affected also include the homeless, prisoners, and hard drug and alcohol users as well as the immunosuppressed. Conclusions: London reflects the worldwide rise in tuberculosis, with increasing incidence in ethnic minorities. Work has been carried out to combat this rise, but more is needed. Tuberculosis control and prevention strategies should be mindful of the changing epidemiology of tuberculosis in London, and provide information, diagnosis and treatment tailored to the specific needs of the capital and its at-risk groups.

Tuberculosis in London a decade and a half of no decline - TB epidemiology and control

Background: London accounts for nearly half of the national burden of tuberculosis. The incidence of tuberculosis has more than doubled in London in the past 15 years. Methods: Data from the enhanced tuberculosis surveillance 1999–2003, the national tuberculosis surveys of 1993 and 1998, and tuberculosis notifications were compared and analysed. Results: In 2003, 3048 patients with tuberculosis were reported in London, 45% of the national total. This represents an incidence of 41.3/100 000, five times higher than the rest of England and Wales, and in parts of London the incidence of tuberculosis is nine times the national average. 75% of people with tuberculosis in London are born abroad; nearly half have lived in the UK for <5 years, but a third for >10 years. 86% are from an ethnic minority group, and the incidence is highest in black Africans at 283/100 000 compared with 141, 141 and 8/100 000 for Pakistanis, Indians and whites, respectively. In absolute terms, a third of patients with tuberculosis in London are from Africa and nearly a third from the Indian subcontinent. Specific groups affected also include the homeless, prisoners, and hard drug and alcohol users as well as the immunosuppressed. Conclusions: London reflects the worldwide rise in tuberculosis, with increasing incidence in ethnic minorities. Work has been carried out to combat this rise, but more is needed. Tuberculosis control and prevention strategies should be mindful of the changing epidemiology of tuberculosis in London, and provide information, diagnosis and treatment tailored to the specific needs of the capital and its at-risk groups.

Prognostic value of interferon-γ release assays and tuberculin skin test in predicting the development of active tuberculosis (UK PREDICT TB): a prospective cohort study

Summary Background Tackling tuberculosis requires testing and treatment of latent tuberculosis in high-risk groups. The aim of this study was to estimate the predictive values of the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs) for the development of active tuberculosis in high-risk groups—ie, people in recent contact with active tuberculosis cases and from high-burden countries. Method In this prospective cohort study, we recruited participants from 54 centres (eg, clinics, community settings) in London, Birmingham, and Leicester in the UK. Participants were eligible if they were aged 16 years or older and at high risk for latent tuberculosis infection (ie, recent contact with someone with active tuberculosis [contacts] or a migrant who had arrived in the UK in the past 5 years from—or who frequently travelled to—a country with a high burden of tuberculosis [migrants]). Exclusion criteria included prevalent cases of tuberculosis, and participants who were treated for latent tuberculosis after a positive test result in this study. Each participant received three tests (QuantiFERON-TB Gold-In Tube, T-SPOT.TB, and a Mantoux TST). A positive TST result was reported using three thresholds: 5 mm (TST-5), 10 mm (TST-10), and greater than 5 mm in BCG-naive or 15 mm in BCG-vaccinated (TST-15) participants. Participants were followed up from recruitment to development of tuberculosis or censoring. Incident tuberculosis cases were identified by national tuberculosis databases, telephone interview, and review of medical notes. Our primary objective was to estimate the prognostic value of IGRAs compared with TST, assessed by the ratio of incidence rate ratios and predictive values for tuberculosis development. The study was registered with ClinicalTrials.gov, NCT01162265, and is now complete. Findings Between May 4, 2010, and June 1, 2015, 10 045 people were recruited, of whom 9610 were eligible for inclusion. Of this cohort, 4861 (50·6%) were contacts and 4749 (49·4%) were migrants. Participants were followed up for a median of 2·9 years (range 21 days to 5·9 years). 97 (1·0%) of 9610 participants developed active tuberculosis (77 [1·2%] of 6380 with results for all three tests). In all tests, annual incidence of tuberculosis was very low in those who tested negatively (ranging from 1·2 per 1000 person-years, 95% CI 0·6–2·0 for TST-5 to 1·9 per 1000 person-years, 95% CI 1·3–2·7, for QuantiFERON-TB Gold In-Tube). Annual incidence in participants who tested positively were highest for T-SPOT.TB (13·2 per 1000 person-years, 95% CI 9·9–17·4), TST-15 (11·1 per 1000 person-years, 8·3–14·6), and QuantiFERON-TB Gold In-Tube (10·1 per 1000 person-years, 7·4–13·4). Positive results for these tests were significantly better predictors of progression than TST-10 and TST-5 (eg, ratio of test positivity rates in those progressing to tuberculosis compared with those not progressing T-SPOT.TB vs TST-5: 1·99, 95% CI 1·68–2·34; p<0·0001). However, TST-5 identified a higher proportion of participants who progressed to active tuberculosis (64 [83%] of 77 tested) than all other tests and TST thresholds (≤75%). Interpretation IGRA-based or BCG-stratified TST strategies appear most suited to screening for potential disease progression among high-risk groups. Further work will be needed to assess country-specific cost-effectiveness of each screening test, and in the absence of highly specific diagnostic tests, cheap non-toxic treatments need to be developed that could be given to larger groups of people at potential risk. Funding National Institute for Health Research Health Technology Assessment Programme 08-68-01.

Tuberculosis in the European Union and European Economic Area: a survey of national tuberculosis programmes

How many European Union (EU) and European Economic Area (EEA) countries have national tuberculosis (TB) control plans/strategies, and what are the priority actions/populations and barriers to implementation? In order to answer this question, a survey of EU/EEA national TB programme leads was undertaken. The response rate was 100% (31 countries). 55% of countries reported having a national TB strategy, all of which were in implementation; five countries were preparing a strategy. 74% had a defined organisational TB control structure with central coordination and 19% had a costed programme budget; few organisational structures included patient/civil society representation. The most frequently mentioned priority TB control actions were: reaching vulnerable population groups (80%), screening for active TB in high-risk groups (63%), implementing electronic registries (60%), contact tracing and outbreak investigation (60%), and tackling multidrug-resistant TB (60%). Undocumented migrants were the most commonly (46%) identified priority population. Perceived obstacles to implementation included barriers related to care recipients (lack of TB knowledge, treatment seeking/adherence), care providers (including need for specialist training of nurses and doctors) and health system constraints (funding, communication between healthcare and social care systems). This survey has provided an insight into TB control programmes across the EU/EEA that will inform the development of a TB strategy toolkit for member states. There is a need for national TB control plans and investment in human resources to work towards TB elimination across the EU/EEA http://ow.ly/8gZG30m961Y