Jennifer A. Davidson

Epidemiology of Mycobacterium bovis Disease in Humans in England, Wales, and Northern Ireland, 2002-2014

Despite slightly increased cases in these areas, human infection with this cattle pathogen remains rare.

TB in healthcare workers in the UK: a cohort analysis 2009–2013

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.

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.

Acquired Resistance to Antituberculosis Drugs in England, Wales, and Northern Ireland, 2000–2015

Among tuberculosis (TB) patients, acquired resistance to anti-TB drugs represents a failure in the treatment pathway. To improve diagnosis and care for patients with drug-resistant TB, we examined the epidemiology and risk factors associated with acquired drug resistance during 2000–2015 among TB patients in England, Wales, and Northern Ireland. We found acquired resistance in 0.2% (158/67,710) of patients with culture-confirmed TB. Using multivariate logistic regression, we identified the following factors associated with acquired drug resistance: having pulmonary disease; initial resistance to isoniazid, rifampin, or both; a previous TB episode; and being born in China or South Africa. Treatment outcomes were worse for patients with than without acquired resistance. Although acquired resistance is rare in the study area, certain patient groups are at higher risk. Identifying these patients and ensuring that adequate resources are available for treatment may prevent acquisition of resistance, thereby limiting transmission of drug-resistant strains of mycobacteria.

A Quantitative Evaluation of MIRU-VNTR Typing Against Whole-Genome Sequencing for Identifying Mycobacterium tuberculosis Transmission: A Prospective Observational Cohort Study

Background Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR) typing is widely used in high-income countries to determine Mycobacterium tuberculosis relatedness. Whole-genome sequencing (WGS) is known to deliver greater specificity, but no quantitative prospective comparison has yet been undertaken. Methods We studied isolates from the English Midlands, sampled consecutively between 1 January 2012 and 31 December 2015. In addition to routinely performed MIRU-VNTR typing, DNA was extracted from liquid cultures and sequenced using Illumina technology. Demographic and epidemiological data for the relevant patients were extracted from the Enhanced Tuberculosis Surveillance system run by Public Health England. Closely related samples, defined using a threshold of five single nucleotide variants (SNVs), were compared to samples with identical MIRU-VNTR profiles, to samples from individuals with shared epidemiological risk factors, and to those with both characteristics. Findings 1999 patients were identified for whom at least one M. tuberculosis isolate had been MIRU-VNTR typed and sequenced. Comparing epidemiological risk factors with close genetic relatedness, only co-residence had a positive predictive value of over 5%. Excluding co-resident individuals, 18.6% of patients with identical MIRU-VNTR profiles were within 5 SNVs. Where patients also shared social risk factors and ethnic group, this rose to 48%. Only 8% of MIRU-VNTR linked pairs in lineage 1 were within 5 SNV, compared to 31% in lineage 4. Interpretation In the setting studied, this molecular epidemiological study shows MIRU-VNTR typing and epidemiological risk factors are poorly predictive of close genomic relatedness, assessed by SNV. MIRU-VNTR performance varies markedly by lineage. Funding Public Health England, Health Innovation Challenge Fund, NIHR Health Protection Research Unit Oxford, NIHR Oxford Biomedical Research Centre.

Understanding Tuberculosis Transmission in the United Kingdom: Findings From 6 Years of Mycobacterial Interspersed Repetitive Unit–Variable Number Tandem Repeats Strain Typing, 2010–2015

Genotyping provides the opportunity to better understand tuberculosis (TB) transmission. We utilized strain typing data to assess trends in the proportion of clustering and identify the characteristics of individuals and clusters associated with recent United Kingdom (UK) transmission. In this retrospective cohort analysis, we included all culture-confirmed strain-typed TB notifications from the UK between 2010 and 2015 to estimate the proportion of patients that clustered over time. We explored the characteristics of patients in a cluster using multivariable logistic regression. Overall, 58.5% of TB patients were concentrated in 2,701 clusters. The proportion of patients in a cluster decreased between 2010 (58.7%) and 2015 (55.3%) (P = 0.001). Being a clustered patient was associated with being male and UK-born, having pulmonary disease, having a previous TB diagnosis, and having a history of drug misuse or imprisonment. Our results suggest that TB transmission in the UK decreased between 2010 and 2015, during which time TB incidence also decreased. Targeted cluster investigation and extended contact tracing should be aimed at persons at risk of being in a transmission chain, including UK-born individuals with social risk factors in clusters with a high proportion of patients having pulmonary disease.