Prevalence of and risk factors for active tuberculosis in migrants screened before entry to the UK: a population-based cross-sectional study

SummaryBackgroundAn increasing number of countries with low incidence of tuberculosis have pre-entry screening programmes for migrants. We present the first estimates of the prevalence of and risk factors for tuberculosis in migrants from 15 high-incidence countries screened before entry to the UK.MethodsWe did a population-based cross-sectional study of applicants for long-term visas who were screened for tuberculosis before entry to the UK in a pilot programme between Oct 1, 2005, and Dec 31, 2013. The primary outcome was prevalence of bacteriologically confirmed tuberculosis. We used Poisson regression to estimate crude prevalence and created a multivariable logistic regression model to identify risk factors for the primary outcome.Findings476 455 visa applicants were screened, and the crude prevalence of bacteriologically confirmed tuberculosis was 92 (95% CI 84–101) per 100 000 individuals. After adjustment for age and sex, factors that were strongly associated with an increased risk of bacteriologically confirmed disease at pre-entry screening were self-report of close or household contact with an individual with tuberculosis (odds ratio 11·6, 95% CI 7·0–19·3; p<0·0001) and being an applicant for settlement and dependant visas (1·3, 1·0–1·6; p=0·0203).InterpretationMigrants reporting contact with an individual with tuberculosis had the highest risk of tuberculosis at pre-entry screening. To tackle this disease burden in migrants, a comprehensive and collaborative approach is needed between countries with pre-entry screening programmes, health services in the countries of origin and migration, national tuberculosis control programmes, and international public health bodies.FundingWellcome Trust, Medical Research Council, and UK National Institute for Health Research

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

Setting: The LTBI programme offers testing and treatment to new entrant migrants from high incidence countries in England. However, the rates of LTBI testing, treatment acceptance and completion are suboptimal and appropriate access must be improved. Objective: To gain insights 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 the participants’ perspectives. Results: Four overarching themes emerged from the discussions. These were capacity, collaboration, culture and trust. These highlighted the complementary skills sets different sectors bring to collaboration, as well as the barriers that need surmounting. Stigma could be reduced by making LTBI testing routine, and community members could act as champions for health promotion raising awareness on LTBI testing, and providing a bridge between communities and primary care services. Conclusion: Public service providers, community members and CBOs have a willingness 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 such workings

Tuberculosis in migrants moving from high-incidence to low-incidence countries: a population-based cohort study of 519 955 migrants screened before entry to England, Wales, and Northern Ireland.

BACKGROUND: Tuberculosis elimination in countries with a low incidence of the disease necessitates multiple interventions, including innovations in migrant screening. We examined a cohort of migrants screened for tuberculosis before entry to England, Wales, and Northern Ireland and tracked the development of disease in this group after arrival. METHODS: As part of a pilot pre-entry screening programme for tuberculosis in 15 countries with a high incidence of the disease, the International Organization for Migration screened all applicants for UK visas aged 11 years or older who intended to stay for more than 6 months. Applicants underwent a chest radiograph, and any with results suggestive of tuberculosis underwent sputum testing and culture testing (when available). We tracked the development of tuberculosis in those who tested negative for the disease and subsequently migrated to England, Wales, and Northern Ireland with the Enhanced Tuberculosis Surveillance system. Primary outcomes were cases of all forms of tuberculosis (including clinically diagnosed cases), and bacteriologically confirmed pulmonary tuberculosis. FINDINGS: Our study cohort was 519 955 migrants who were screened for tuberculosis before entry to the UK between Jan 1, 2006, and Dec 31, 2012. Cases notified on the Enhanced Tuberculosis Surveillance system between Jan 1, 2006, and Dec 31, 2013, were included. 1873 incident cases of all forms of tuberculosis were identified, and, on the basis of data for England, Wales, and Northern Ireland, the estimated incidence of all forms of tuberculosis in migrants screened before entry was 147 per 100 000 person-years (95% CI 140-154). The estimated incidence of bacteriologically confirmed pulmonary tuberculosis in migrants screened before entry was 49 per 100 000 person-years (95% CI 45-53). Migrants whose chest radiographs were compatible with active tuberculosis but with negative pre-entry microbiological results were at increased risk of tuberculosis compared with those with no radiographic abnormalities (incidence rate ratio 3·2, 95% CI 2·8-3·7; p<0·0001). Incidence of tuberculosis after migration increased significantly with increasing WHO-estimated prevalence of tuberculosis in migrants' countries of origin. 35 of 318 983 pre-entry screened migrants included in a secondary analysis with typing data were assumed index cases. Estimates of the rate of assumed reactivation tuberculosis ranged from 46 (95% CI 42-52) to 91 (82-102) per 100 000 population. INTERPRETATION: Migrants from countries with a high incidence of tuberculosis screened before being granted entry to low-incidence countries pose a negligible risk of onward transmission but are at increased risk of tuberculosis, which could potentially be prevented through identification and treatment of latent infection in close collaboration with a pre-entry screening programme. FUNDING: Wellcome Trust, UK National Institute for Health Research, UK Medical Research Council, Public Health England, and Department of Health Policy Research Programme

Initiation and completion of treatment for latent tuberculosis infection in migrants globally:a systematic review and meta-analysis

BACKGROUND: Latent tuberculosis infection (LTBI) is one of the most prevalent infections globally and can lead to the development of active tuberculosis disease. In many low-burden countries, LTBI is concentrated within migrant populations often because of a higher disease burden in the migrant's country of origin. National programmes consequently focus on screening and treating LTBI in migrants to prevent future tuberculosis cases; however, how effective these programmes are is unclear. We aimed to assess LTBI treatment initiation and outcomes among migrants, and the factors that influence both. METHODS: For this systematic review and meta-analysis, we searched Embase, MEDLINE, and Global Health, and manually searched grey literature from Jan 1, 2000, to April 21, 2020. We included primary research articles reporting on LTBI treatment initiation or completion, or both, in migrants and excluded articles in which data were not stratified by migrant status, or in which the data were related to outcomes before 2000. There were no geographical or language restrictions. All included studies were quality appraised using recognised tools depending on their design, and we assessed the heterogeneity of analyses using I2. We extracted data on the numbers of migrants initiating and completing treatment. Our primary outcomes were LTBI treatment initiation and completion in migrants (defined as foreign-born). We used random-effects meta-regression to examine the influence of factors related to these outcomes. The study is registered with PROSPERO (CRD42019140338). FINDINGS: 2199 publications were retrieved screened, after which 39 publications from 13 mostly high-income, low-burden countries were included in our analyses, with treatment initiation and completion data reported for 31 598 migrants positive for LTBI, with not all articles reporting the full pathway from initiation to completion. The pooled estimate for the true proportion of migrants testing positive who initiated treatment was 69% (95% CI 51-84; I2= 99·62%; 4409 of 8764). The pooled estimate for the true proportion of migrants on treatment in datasets, who subsequently completed it was 74% (95% CI = 66-81; I2= 99·19%; 15 516 of 25 629). Where data were provided for the entire treatment pathway, the pooled estimate for the true proportion of migrants who initiated and completed treatment after a positive test was only 52% (95% CI 40-64; I2= 98·90%; 3289 of 6652). Meta-regression showed that LTBI programmes are improving, with more recent reported data (2010-20) associated with better rates of treatment initiation and completion, with multiple complex factors affecting treatment outcomes in migrants. INTERPRETATION: Although our analysis highlights that LTBI treatment initiation and completion in migrants has improved considerably from 2010-20, there is still room for improvement, with drop out reported along the entire treatment pathway. The delivery of these screening and treatment programmes will require further strengthening if the targets to eradicate tuberculosis in low-incidence countries are to be met, with greater focus needed on engaging migrants more effectively in the clinic and understanding the diverse and unique barriers and facilitators to migrants initiating and completing treatment. FUNDING: European Society of Clinical Microbiology and Infectious Diseases, the Rosetrees Trust, the National Institute for Health Research, and the Academy of Medical Sciences

Treating latent TB in primary care: a survey of enablers and barriers among UK General Practitioners.

BACKGROUND: Treating latent tuberculosis infection (LTBI) is an important public health intervention. In the UK, LTBI treatment is delivered in secondary care. Treating LTBI in the community would move care closer to home and could increase uptake and treatment completion rates. However, healthcare providers' views about the feasibility of this in the UK are unknown. This is the first study to investigate perceived barriers and enablers to primary care-based LTBI treatment among UK general practitioners (GPs). METHODS: A national survey amongst 140 randomly sampled UK GPs practising in areas of high TB incidence was performed. GPs' experience and perceived confidence, barriers and enablers of primary care-based LTBI treatment were explored and multivariable logistic regression was used to determine whether these were associated with a GP's willingness to deliver LTBI treatment. RESULTS: One hundred and twelve (80 %) GPs responded. Ninety-three (83 %; 95 % CI 75 %-89 %) GPs said they would be willing to deliver LTBI treatment in primary care, if key perceived barriers were addressed during service development. The major perceived barriers to delivering primary care-based LTBI treatment were insufficient experience among GPs of screening and treating LTBI, lack of timely specialist support and lack of allied healthcare staff. In addition, GPs felt that appropriate resourcing was key to the successful and sustainable delivery of the service. GPs who reported previous experience of screening or treatment of patients with active or latent TB were almost ten times more likely to be willing to deliver LTBI treatment in primary care compared to GPs with no experience (OR: 9.98; 95 % CI 1.22-81.51). CONCLUSIONS: UK GPs support primary care-based LTBI treatment, provided they are given appropriate training, specialist support, staffing and financing

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review

Migrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit

Prevention and assessment of infectious diseases among children and adult migrants arriving to the European Union/European Economic Association: a protocol for a suite of systematic reviews for public health and health systems

Introduction The European Centre for Disease Prevention and Control is developing evidence-based guidance for voluntary screening, treatment and vaccine prevention of infectious diseases for newly arriving migrants to the European Union/European Economic Area. The objective of this systematic review protocol is to guide the identification, appraisal and synthesis of the best available evidence on prevention and assessment of the following priority infectious diseases: tuberculosis, HIV, hepatitis B, hepatitis C, measles, mumps, rubella, diphtheria, tetanus, pertussis, poliomyelitis (polio), Haemophilus influenza disease, strongyloidiasis and schistosomiasis. Methods and analysis The search strategy will identify evidence from existing systematic reviews and then update the effectiveness and cost-effectiveness evidence using prospective trials, economic evaluations and/or recently published systematic reviews. Interdisciplinary teams have designed logic models to help define study inclusion and exclusion criteria, guiding the search strategy and identifying relevant outcomes. We will assess the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethics and dissemination There are no ethical or safety issues. We anticipate disseminating the findings through open-access publications, conference abstracts and presentations. We plan to publish technical syntheses as GRADEpro evidence summaries and the systematic reviews as part of a special edition open-access publication on refugee health. We are following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols reporting guideline. This protocol is registered in PROSPERO: CRD42016045798

Trends in, and factors associated with, HIV infection amongst tuberculosis patients in the era of anti-retroviral therapy: a retrospective study in England, Wales and Northern Ireland

Background: HIV increases the progression of latent tuberculosis (TB) infection to active disease and contributed to increased TB in the UK until 2004. We describe temporal trends in HIV infection amongst patients with TB and identify factors associated with HIV infection. / Methods: We used national surveillance data of all TB cases reported in England, Wales and Northern Ireland from 2000 to 2014 and determined HIV status through record linkage to national HIV surveillance. We used logistic regression to identify associations between HIV and demographic, clinical and social factors. / Results: There were 106,829 cases of TB in adults (≥ 15 years) reported from 2000 to 2014. The number and proportion of TB patients infected with HIV decreased from 543/6782 (8.0%) in 2004 to 205/6461 (3.2%) in 2014. The proportion of patients diagnosed with HIV > 91 days prior to their TB diagnosis increased from 33.5% in 2000 to 60.2% in 2013. HIV infection was highest in people of black African ethnicity from countries with high HIV prevalence (32.3%), patients who misused drugs (8.1%) and patients with miliary or meningeal TB (17.2%). / Conclusions: There has been an overall decrease in TB-HIV co-infection and a decline in the proportion of patients diagnosed simultaneously with both infections. However, high rates of HIV remain in some sub-populations of patients with TB, particularly black Africans born in countries with high HIV prevalence and people with a history of drug misuse. Whilst the current policy of testing all patients diagnosed with TB for HIV infection is important in ensuring appropriate management of TB patients, many of these TB cases would be preventable if HIV could be diagnosed before TB develops. Improving screening for both latent TB and HIV and ensuring early treatment of HIV in these populations could help prevent these TB cases. British HIV Association guidelines on latent TB testing for people with HIV from sub-Saharan Africa remain relevant, and latent TB screening for people with HIV with a history of drug misuse, homelessness or imprisonment should also be considered