Latent tuberculosis infection screening of adult close contacts in London: a cost-utility analysis

Background: The National Institute for Health and Care Excellence (NICE) guidelines in 2016 recommend tuberculin skin test (TST) at a 5 mm induration size cut-off for latent tuberculosis infection (LTBI) screening of adult close contacts of active tuberculosis (TB) cases. An alternative would be to use an interferon-gamma release assay (IGRA) which has a higher specificity, such as the QuantiFERON-TB Gold in Tube (QFT-GIT) or T-SPOT.TB (T-SPOT). We aimed to evaluate the cost-effectiveness of the screening and treatment of LTBI in adult close contacts with various combinations of these tests in a representative London cohort. Methods: Clinical data of adult close contacts of pulmonary TB cases who were recommended to receive TST and IGRA in a TB clinic in London between 2008 and 2010 were retrospectively reviewed. A Markov decision analytic model, using an NHS perspective and lifetime horizon, was used to compare costs and quality-adjusted life-years (QALYs) associated with 7 screening strategies followed by chemoprophylaxis: TST alone, IGRA (QFT-GIT or T-SPOT) alone, TST positive followed by IGRA, and TST negative followed by IGRA. Future costs and QALYs were discounted at 3.5% per year. Results: 381 asymptomatic close contacts aged 18 to 65 years were included in this study. The mean age was 35.2 years and the majority (75.3%) were BCG vaccinated. In the base-case analysis, QFT-GIT was the most cost-effective strategy with £6876 per QALY gained, compared to TST positive followed by QFT-GIT strategy. QFT-GIT alone averted 1.6 TB cases per 1000 contacts compared to TST positive followed by QFT-GIT. Conclusion: Of the considered testing strategies, the QFT-GIT alone is preferable for LTBI screening in adult close contacts of pulmonary TB cases in London

P109 The impact of tb nice guidance on resource capacity and contact screening outcomes: a retrospective, observational study within a central london tb centre

Introduction and objectives: Recently published NICE guidance has significantly expanded the approach to adult tuberculosis (TB) contact screening by recommending tuberculin skin testing (TST) for pulmonary and laryngeal contacts only, increasing the age threshold for screening and treatment to 65 years and defining a positive TST as induration ≥5 mm, regardless of BCG vaccination status. Interferon Gamma Release Assay (IGRA) is recommended only in situations where more evidence of infection is needed. Our institution has previously adopted an approach comprising a chest radiograph, TST and IGRA. The aim of our study was to evaluate the impact of NICE guidance on screening outcomes and resource capacity by applying the criteria to a well-defined historic cohort of TB contacts. Methods: This was a retrospective, observational study carried out at a central London teaching hospital. The study population comprised 593 consecutive, adult TB contacts screened between 1/1/2008 and 31/12/2010. Data was collected through a retrospective review of TST and IGRA tests. Results: Of the 593 contacts screened, 358 pulmonary contacts had TST and IGRA results. 56% had a TST ≥5 mm, regardless of BCG status, qualifying them for treatment as per the new NICE guidance. Of these, 61% were IGRA negative (discordant) and may therefore include false positive diagnoses, resulting in the potential for over treatment. In those with TST 5–14 mm, discordance rises to 84%. Conversely, 6% of those with TST < 5 mm are IGRA positive representing potentially missed cases. 16% of screened individuals were contacts of extra pulmonary TB. Not screening this group would reduce the demand for outpatient appointments by 151* in our cohort. In contrast, testing contacts > 35 years would require capacity for an additional 165* appointments. Furthermore, there were 162 additional LTBI cases in comparison to previous guidance requiring an additional 648* appointments. 72% of this group were IGRA negative. (*Approximate) Conclusions: Our results show the revised guidance will require increased resource capacity largely due to more patients being classified as having latent TB. In addition to workforce planning to meet these demands, further debate is needed to decide if this new approach truly reduces the incidence of active TB or results in unnecessary treatment

Engaging with civil society to improve access to LTBI screening for new migrants in England: a qualitative study

SETTING: The latent tuberculous infection (LTBI) programme in England, UK, offers testing and treatment to new migrants from high tuberculosis incidence countries. However, the rates of LTBI testing, treatment acceptance and completion are suboptimal and appropriate access should be improved. OBJECTIVE: To gain insight from the community, community-based organisations (CBOs) and public sector stakeholders on interventions that facilitate collaboration to improve health care outreach and delivery. DESIGN: Three stakeholder meetings and five focus group discussions were held using thematic analysis to identify themes arising from participants' perspectives. RESULTS: Four overarching themes emerged from the discussions. These were related to capacity of service providers, collaboration between stakeholders, migrant cultures and trust between migrants and service providers, and highlighted the complementary skill sets that different sectors bring to the collaboration, as well as the barriers that need to be surmounted. Stigma could be reduced by making LTBI testing routine. Community members could act as champions of health promotion to raise awareness on LTBI testing, and provide a bridge between communities and primary care services. CONCLUSION: Public service providers, community members and CBOs are willing to collaborate to support primary care delivery of testing for LTBI and other communicable and non-communicable diseases. Policy and commissioning support are needed to facilitate this collaboration

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institute for Health Research (NIHR) Health Protection Research Unit in Respiratory Infections and NIHR Imperial Biomedical Research Centre

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

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: National Institute for Health Research (NIHR) Health Protection Research Unit in Respiratory Infections and NIHR Imperial Biomedical Research Centre

Evaluation of prediagnosis emergency department presentations in patients with active tuberculosis:the role of chest radiography, risk factors and symptoms

Introduction London has a high rate of tuberculosis (TB) with 2572 cases reported in 2014. Cases are more common in non-UK born, alcohol-dependent or homeless patients. The emergency department (ED) presents an opportunity for the diagnosis of TB in these patient groups. This is the first study describing the clinico-radiological characteristics of such attendances in two urban UK hospitals for pulmonary TB (PTB) and extrapulmonary TB (EPTB). Methods We conducted a retrospective cohort study using the London TB Register (LTBR) and hospital records to identify patients who presented to two London ED's in the 6 months prior to their ultimate TB diagnosis 2011–2012. Results 397 TB cases were identified. 39% (154/397) had presented to the ED in the 6 months prior to diagnosis. In the study population, the presence of cough, weight loss, fever and night sweats only had prevalence rates of 40%, 34%, 34% and 21%, respectively. Chest radiography was performed in 76% (117/154) of patients. For cases where a new diagnosis of TB was suspected, 73% (41/56) had an abnormal radiograph, compared with 36% (35/98) of patients where it was not. There was an abnormality on a chest radiograph in 73% (55/75) of PTB cases and also in 40% (21/52) of EPTB cases where a film was requested. Conclusions A large proportion of patients with TB present to ED. A diagnosis was more likely in the presence of an abnormal radiograph, suggesting opportunities for earlier diagnosis if risk factors, symptoms and chest radiograph findings are combined

Much Ado About Leptoquarks: A Comprehensive Analysis

We examine the phenomenological implications of a 200 GeV leptoquark in light of the recent excess of events at HERA. Given the relative predictions of events rates in e^+p versus e^-p, we demonstrate that classes of leptoquarks may be excluded, including those contained in E_6 GUT models. It is shown that future studies with polarized beams at HERA could reveal the chirality of the leptoquark fermionic coupling and that given sufficient luminosity in each e^\pm_{L,R} channel the leptoquark quantum numbers could be determined. The implications of 200-220 GeV leptoquarks at the Tevatron are examined. While present Tevatron data most likely excludes vector leptoquarks and leptogluons in this mass region, it does allow for scalar leptoquarks. We find that while leptoquarks have little influence on Drell-Yan production, further studies at the Main Injector are possible in the single production channel. We investigate precision electroweak measurements as well as the process e^+e^-\to q\bar q at LEP II and find they provide no further restrictions on these leptoquark models. We then ascertain that cross section and polarization asymmetry measurements at the NLC provide the only direct mechanism to determine the leptoquark's electroweak quantum numbers. The single production of leptoquarks in \gamma e collisions by both the backscattered laser and Weisacker-Williams techniques at the NLC is also discussed. Finally, we demonstrate that we can obtain successful coupling constant unification in models with leptoquarks, both with or without supersymmetry. The supersymmetric case requires the GUT group to be larger than SU(5) such as flipped SU(5)\times U(1)_X.Comment: Corrected single production cross section at Tevatron, updated atomic parity violation constraints, 55 page

Interferon-gamma release assay (IGRA) conversion, reversion and implications for the diagnosis of latent tuberculosis infection using a multimodality approach: a retrospective, observational study within a central London TB centre

Introduction and Objectives Accurate diagnosis & management of latent tuberculosis infection (LTBI) among TB contacts is critical for both the health of infected individuals and prevention of disease transmission. Interferon gamma release assays (IGRAs) measure T cell release of interferon-gamma following stimulation by antigens not confounded by the BCG vaccination. The current NICE guidelines recommend their use following a positive TST. In addition some centres have moved to a single step IGRA test for LTBI. Our institution adopts a triple investigation approach comprising a chest radiograph (CXR), TST and IGRA on presentation followed by a rescreen if the TST & IGRA are discordant or if pulmonary contacts are screened prior to 6 weeks. The aim of our study was to evaluate the prevalence of IGRA conversion and reversion in rescreened asymptomatic TB contacts that attended our centre. Methods This was a retrospective, observational study carried out at a central London teaching hospital. The study population comprised 593 consecutive, adult TB contacts screened between 1 January 2008 and 31 December 2010. Data were collected through retrospective review of chest radiographs, TST & IGRA tests. Results Of 498 asymptomatic TB contacts screened, 460 had both an initial TST and IGRA performed (Abstract P13 figure 1). 81 (17.7%) contacts had discordant TST & IGRA results. 52 (64%) of these discordant cases had a positive TST & Negative IGRA; these patients would have been discharged under NICE guidelines however, our rescreen revealed 9 (17%) positive 2nd IGRAs that is, conversion. Three of these patients were under 35 and would therefore by eligible for chemoprophylaxis. Twenty-nine (36%) of the discordant cases had a negative TST and positive IGRA however, 8 (28%) of these IGRAs reverted to negative. It is important to note that if following a single-step IGRA screening protocol (ie, without a rescreen) these cases may have been commenced on chemoprophylaxis unnecessarily (four of these reversion cases were under the age of 35). Conclusions Our results show that adoption of either a sequential TST + ve/IGRA approach or single IGRA approach can result in a significant number of false negative LTBI diagnoses due to IGRA conversion. Conversely, we have also shown that an IGRA rescreen because of discordant TST/IGRA tests can improve LTBI diagnostic specificity and therefore reduce unnecessary chemoprophylaxis due to the effect of reversion

The impact of migration on the sexual health, behaviours and attitudes of Central and East European gay/bisexual men in London

Extensive social psychological research emphasises the importance of groups in shaping individuals' thoughts and actions. Within the child sexual abuse (CSA) literature criminal organisation has been largely overlooked, with some key exceptions. This research was a novel collaboration between academia and the UK's Child Exploitation and Online Protection Centre (CEOP). Starting from the premise that the group is, in itself, a form of social situation affecting abuse, it offers the first systematic situational analysis of CSA groups. In-depth behavioural data from a small sample of convicted CSA group-offenders (n =3) were analysed qualitatively to identify factors and processes underpinning CSA groups' activities and associations: group formation, evolution, identity and resources. The results emphasise CSA groups' variability, fluidity and dynamism. The foundations of a general framework are proposed for researching and assessing CSA groups and designing effective interventions. It is hoped that this work will stimulate discussion and development in this long-neglected area of CSA, helping to build a coherent knowledge-base