Creating a web-based electronic tool to aid tuberculosis (TB) cluster investigation: data integration in TB surveillance activities in the United Kingdom, 2013 to 2016.

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.

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.

Recent household transmission of tuberculosis in England, 2010-2012: retrospective national cohort study combining epidemiological and molecular strain typing data.

BACKGROUND: We estimate the proportion of tuberculosis (TB) in England due to recent household transmission, identify factors associated with being a household transmitter, and investigate the impact that identification of a case has on time to treatment of subsequent cases. METHODS: TB cases notified between 2010 and 2012 in England in the same household as another case were identified; 24 locus MIRU-VNTR strain typing (ST) was used to identify household cases with likely recent transmission. Treatment delay in index and subsequent cases was compared. Risk factors for being a household transmitter were identified in univariable and multivariable analyses. RESULTS: Overall, 7.7% (1849/24,060) of TB cases lived in a household with another case. We estimate that 3.9% were due to recent household transmission. ST data was unavailable for 67% (1242) of household pairs. For those with ST data, 64% (386) had confirmed, 11% probable (66) and 25% (155) refuted household transmission. The median treatment delay was 65 days for index cases and 37 days for subsequent asymptomatic cases. Risk factors for being a household transmitter included being under 25 years old, UK-born with Black African, Indian or Pakistani ethnicity, or born in Somalia or Romania. CONCLUSIONS: This study has a number of implications for household TB contact tracing in low incidence countries, including the potential to reduce the diagnostic delay for subsequent household cases and the benefit of using ST to identify when to conduct source contact tracing outside the household. As 25% of TB cases in households had discordant strains, households with multiple TB cases do not necessarily represent household transmission. The additional fact that 25% of index cases within households only had extra-pulmonary TB demonstrates that, if household contact tracing is limited to pulmonary TB cases (as recently recommended in UK guidelines), additional cases of active TB in households will be missed. Our finding that no lineage of TB was associated with recent household transmission and with no increased transmissibility in the Beijing lineage compared to others, suggests that the lineage need not impact contact tracing efforts. Improvements in contact tracing have the potential to reduce transmission of TB in low incidence countries.

Identifying areas and risk groups with localised Mycobacterium tuberculosis transmission in northern England from 2010 to 2012: spatiotemporal analysis incorporating highly discriminatory genotyping data.

BACKGROUND: Information on geographical variation in localised transmission of TB can inform targeting of disease control activities. The aim of this study was to estimate the proportion of TB attributable to localised transmission for the period 2010-2012 in northern England and to identify case characteristics associated with spatiotemporal-genotypical clusters. METHODS: We combined genotyping data with spatiotemporal scan statistics to define an indicator of localised TB transmission and identified factors associated with localised TB transmission thus defined in a multivariable logistics regression model. RESULTS: The estimated proportion of TB cases in northern England attributable to localised transmission was 10% (95% CI 9% to 12%). Clustered cases (cases which were spatiotemporally clustered with others of identical genotype) were on average younger than non-clustered cases (mean age 34 years vs 43 years; p value <0.05). Being UK born (adjusted OR (aOR) 3.6, 95% CI 2.9 to 6.0), presenting with pulmonary disease (aOR 2.2, 95% CI 1.3 to 3.6) and history of homelessness (aOR 2.8, 95% CI 1.2 to 6.8) or incarceration (aOR 2.6, 95% CI 1.2 to 5.9) were independently associated with being part of a spatiotemporal-genotypical cluster in a multivariable model. Belonging to an ethnic group other than white or mixed/other was also significantly associated with localised transmission. We identified localised transmission in 103/1958 middle super output areas mostly in urban areas. CONCLUSIONS: Incorporating highly discriminatory genotyping data into spatiotemporal analysis of TB incidence is feasible as part of routine surveillance and can provide valuable information on groups at greater risk and areas with localised transmission of TB, which could be used to inform control measures, such as intensified contact tracing.