Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial.

BACKGROUND: The identification and treatment of LTBI is a key component of the WHO's strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care). METHODS: The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist. DISCUSSION: The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK. TRIAL REGISTRATION: NCT03069807, March 2017, registered retrospectively.

Till receipts--a new approach for investigating outbreaks? Evaluation during a large Salmonella Enteritidis phage type 14b outbreak in a North West London takeaway restaurant, September 2009.

Selecting suitable controls for outbreak investigations is often difficult and if done inappropriately will lead to biased inferences. Till receipts and other sales records are frequently available on food premises, but their applicability has not been fully explored. Using data from an investigation into a Salmonella outbreak affecting 66 individuals exposed in a London takeaway restaurant, this study aimed to evaluate the use of till receipts to assess associations between sales and illness. Cases identified through local case-finding were subjected to a standardised exposure questionnaire. Till receipts over the time period when cases arose were analysed. Estimated food exposures from sales were compared to case reported exposures and till receipts analysis showed strong association between illness and consumption of rotisserie chicken (odds ratio (OR): 2.75; confidence interval (CI): 1.7-4.5). Chicken sales immediately prior to food consumption for cases were compared to two control periods in an ecological case-crossover design. On average there was an estimated increase of 3.7 (CI: 2.2-5.2) extra chickens sold in the hour immediately prior to the consumption in the cases (p<0.0001) and the risk of becoming ill at busy times increased by 5% with each additional chicken quarter sold per hour (OR: 1.05; CI: 1.03-1.08). Microbiological and environmental investigations revealed Salmonella Enteritidis phage type (PT)14b in all available cases' stool samples, two environmental samples and leftover chicken from the takeaway. The feasibility of this novel approach to obtain exposure information in the population at risk has been demonstrated, and its limitations are discussed. Further validation is required, comparing results with those in a concurrent classic case-control study.

Tracking sickness through social networks - the practical use of social network mapping in supporting the management of an E. coli O157 outbreak in a primary school in London.

This paper describes the practical use of social network diagrams in the management of an outbreak of Escherichia coli O157 (VTEC) in a primary school in London. The diagrams were created during the outbreak to establish the extent and nature of person-to-person transmission in the cases and their contacts. The diagrams supported a tailored public health action, and hence aided in the control of the outbreak. We conclude that for selected infectious diseases, social network diagrams can provide a valuable tool in the management of an outbreak.

The serotype case-case design: a direct comparison of a novel methodology with a case-control study in a national Salmonella Enteritidis PT14b outbreak in England and Wales.

Societal and technological changes render traditional study designs less feasible for investigation of outbreaks. We compared results obtained from case-case and case-control designs during the investigation of a Salmonella Enteritidis PT14b (SE14b) outbreak in Britain to provide support for validation of this approach. Exposures of cases were compared to concurrent non-Enteritidis Salmonella cases and population controls recruited through systematic digit phone dialling. Infection with SE14b was associated with eating in oriental restaurants [odds ratio (OR) 35·8, 95% confidence interval (CI) 4·4-290·9] and consuming eggs away from home (OR 13·8, 95% CI 1·5-124·5) in the case-case study and was confirmed through a concurrent case-control study with similar effect estimates and microbiological findings of SE14b in eggs from a specific chicken flock on a Spanish farm. We found that the case-case design was feasible, quick and inexpensive, potentially minimized recall bias and made use of already interviewed cases with subtyping results. This approach has potential for use in future investigations.

Reducing the burden of TB among migrants to low TB incidence countries.

BACKGROUND: International migrants to low TB incidence countries are disproportionately affected by TB compared to the native population: migrants are at increased risk for TB transmission and TB disease due to a variety of personal, environmental and socio-economic determinants experienced during the four phases of migration (pre-departure, transit, arrival and early settlement, return travel).OBJECTIVE: To provide an up-to-date overview of the determinants that drive the TB burden among migrants, as well as effective and feasible interventions to address this for each migration phase.METHODS: We conducted a literature review by searching PubMed and the grey literature for articles and reports on determinants and interventions addressing migrant health and TB.RESULTS: Lowering the risk of TB transmission and TB disease among migrants would be most effective by improving the socio-economic position of migrants pre-, during and after migration, ensuring universal health coverage, and providing tailored and migrant-sensitive care and prevention activities.CONCLUSION: In addition to migrant-sensitive health services and cross-border collaboration between low TB incidence countries, there is a need for international financial and technical support for endemic countries.

A feasibility study evaluating the uptake, effectiveness and acceptability of routine screening of pregnant migrants for latent tuberculosis infection in antenatal care: a research protocol.

INTRODUCTION: Globally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake of routine screening of migrants for LTBI in the UK in primary care is low. Antenatal care is a novel setting which could improve uptake and can lend insight into the feasibility and acceptability of offering opt-out screening for LTBI. METHODS AND ANALYSIS: This is an observational feasibility study with a nested qualitative component. The setting will be the antenatal clinics in three hospitals in East London, UK . Inclusion criteria are pregnant migrant women aged 16-35 years attending antenatal clinics who are from countries with a TB incidence of greater than 150/100 000 including sub-Saharan Africa, and who have been in the UK for less than 5 years. Participants will be offered LTBI screening with an opt-out interferon gamma release assay blood test, and be invited to complete a questionnaire. Both participants and healthcare providers will be invited to participate in semistructured interviews or focus groups to evaluate understanding, feasibility and acceptability of routine opt-out LTBI screening. The primary analysis will focus on estimating the uptake of the screening programme along with the corresponding 95% CI. Secondary analysis will focus on estimating the test positivity. Qualitative analysis will evaluate the acceptability of offering routine opt-out LTBI screening to participants and healthcare providers. ETHICS AND DISSEMINATION: The study has received the following approvals: Health Research Authority (IRAS 247388) and National Health Service Ethics Committee (19/LO/0557). The results will be made available locally to antenatal clinics and primary care physicians, nationally to NHS England and Public Health England and internationally through conferences and journals. TRIAL REGISTRATION NUMBER: NCT04098341.

Country differences and determinants of yield in programmatic migrant TB screening in four European countries.

INTRODUCTION The WHO End TB Strategy emphasises early diagnosis and screening of TB in high-risk groups, including migrants. We analysed TB yield data from four large migrant TB screening programmes to inform TB policy.METHODS We pooled routinely collected individual TB screening episode data from Italy, the Netherlands, Sweden and the United Kingdom under the European Union Commission E-DETECT.TB grant, described characteristics of the screened population, and analysed TB case yield.RESULTS We collected data on 2,302,260 screening episodes among 2,107,016 migrants, mostly young adults aged 18-44 years (77.8%) from Asia (78%) and Africa (18%). There were 1,658 TB cases detected through screening, with substantial yield variation (per 100,000): 201.1 for Sweden (95% confidence intervals CI 111.4-362.7), 68.9 (95% CI 65.4-72.7) for the United Kingdom, 83.2 (95% CI 73.3-94.4) for the Netherlands and 653.6 (95% CI 445.4-958.2) in Italy. Most TB cases were notified among migrants from Asia (n = 1,206, 75/100,000) or Africa (n = 370, 76.4/100,000), and among asylum seekers (n = 174, 131.5/100,000), migrants to the Netherlands (n = 101, 61.9/100,000) and settlement visa migrants to the United Kingdom (n = 590, 120.3/100,000).CONCLUSIONS We found considerable variations in yield across programmes, types of migrants and country of origin. These variations may be partly explained by differences in migration patterns and programmatic characteristics.

Clinical standards for the diagnosis, treatment and prevention of TB infection.

BACKGROUND: Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, management of TB infection (TBI) and implementation of TPT.METHODS: A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.RESULTS: Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.CONCLUSION: This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.

National outbreak of Salmonella Enteritidis phage type 14b in England, September to December 2009: case-control study.

We conducted an unmatched retrospective case­control study to investigate an upsurge of non-travel-related sporadic cases of infection with Salmonella enterica subsp. enterica serotype Enteritidis phage type 14b with antimicrobial resistance to nalidixic acid and partial resistance to ciprofloxacin (S. Enteritidis PT 14b NxCp(L)) that was reported in England from 1 September to 31 December 2009. We analysed data from 63 cases and 108 controls to determine whether cases had the same sources of infection as those found through investigation of 16 concurrent local foodborne outbreaks in England and Wales. Multivariable logistic regression analysis adjusting for age and sex identified food consumption at restaurants serving Chinese or Thai cuisine (odds ratio (OR): 4.4; 95% CI: 1.3­14.8; p=0.02), egg consumed away from home (OR: 5.1; 95% CI: 1.3­21.2; p=0.02) and eating vegetarian foods away from home (OR: 14.6; 95% CI: 2.1­99; p=0.006) as significant risk factors for infection with S. Enteritidis PT 14b NxCp(L). These findings concurred with those from the investigation of the16 outbreaks, which identified the same Salmonella strain in eggs from a specified source outside the United Kingdom. The findings led to a prohibition of imports from this source, in order to control the outbreak.

The Barts Health NHS Trust COVID-19 cohort: characteristics, outcomes and risk scoring of patients in East London.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection.METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage.RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen.CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

Clostridium perfringens in London, July 2009: two weddings and an outbreak.

Food poisoning outbreaks caused by Clostridium perfringens enterotoxin occur occasionally in Europe but have become less common in recent years. This paper presents the microbiological and epidemiological results of a large C. perfringens outbreak occurring simultaneously at two weddings that used the same caterer. The outbreak involved several London locations and required coordination across multiple agencies. A case-control study (n=134) was carried out to analyse possible associations between the food consumed and becoming ill. Food, environmental and stool samples were tested for common causative agents, including enterotoxigenic C. perfringens. The clinical presentation and the epidemiological findings were compatible with C. perfringens food poisoning and C. perfringens enterotoxin was detected in stool samples from two cases. The case-control study found statistically significant associations between becoming ill and eating either a specific chicken or lamb dish prepared by the same food handler of the implicated catering company. A rapid outbreak investigation with preliminary real-time results and the successful collaboration between the agencies and the caterer led to timely identification and rectification of the failures in the food handling practices.

Pre-migration TB screening-the first step is always the hardest.

As the proportion of foreign-born persons among TB notifications continues to rise, Japan is preparing to introduce pre-migration TB screening for those coming from selected countries, who are intending to stay for more than 90 days. It has announced that the programme will commence in 2020. In this review, the authors examine the experiences from two countries which already have years of experience in operating pre-migration TB screening, namely the United Kingdom and Australia. The authors point out that both countries have developed strong health information system not only to collect and analyse screening results, but also to use the data to effectively monitor and evaluate the screening programme itself. The critical role which health information system plays within pre-migration screening is often overlooked. Here we argue that Japan, as with any other countries planning to introduce pre-migration screening for TB, must also plan for data management.

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

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. 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. Three stakeholder meetings and five focus group discussions were held using thematic analysis to identify themes arising from participants' perspectives. 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. 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. .

Investigating a tuberculosis cluster among Filipino health care workers in a low-incidence country.

SETTING: Nearly 8% of adult tuberculosis (TB) cases in England, Wales and Northern Ireland (EW&NI) occur among health care workers (HCWs), the majority of whom are from high TB incidence countries. OBJECTIVES: To determine if a TB cluster containing multiple HCWs was due to nosocomial transmission. METHODS: A cluster of TB cases notified in EW&NI from 2009 to 2014, with indistinguishable 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) profiles, was identified through routine national cluster review. Cases were investigated to identify epidemiological links, and occupational health (OH) information was collected for HCW cases. To further discriminate strains, typing of eight additional loci was conducted. RESULTS: Of the 53 cases identified, 22 were HCWs. The majority (n = 43), including 21 HCWs, were born in the Philippines. Additional typing split the cluster into three subclusters and seven unique strains. No epidemiological links were identified beyond one household and a common residential area. HCWs in this cluster received no or inadequate OH assessment. CONCLUSIONS: The MIRU-VNTR profile of this cluster probably reflects common endemic strains circulating in the Philippines, with reactivation occurring in the UK. Furthermore, 32-locus typing showed that 24-locus MIRU-VNTR failed to distinguish strain diversity. The lack of OH assessment indicates that latent tuberculous infection could have been identified and treated, thereby preventing active cases from occurring.

Effectiveness and cost-effectiveness of screening migrants for active tuberculosis and latent tuberculous infection.

With the advent of the World Health Organization End TB strategy, there has been renewed interest in screening for active tuberculosis (TB), and particularly latent tuberculous infection (LTBI). In low-incidence countries, a high proportion of TB cases are notified among migrants, which often occurs due to LTBI reactivation. We aimed to review the effectiveness and cost-effectiveness of screening migrants for active TB LTBI to inform and support the TB elimination strategy in low-incidence countries. We carried out a narrative review of English language articles published between 1 January 2000 and 31 June 2016 using the PubMed database. All studies that described the effectiveness or cost-effectiveness of active TB or LTBI screening among migrants were included. We identified 55 studies, and included 40 for the effectiveness of screening, 11 for cost-effectiveness and 4 that reported both. Screening for active TB can be effective and cost-effective depending on the setting, target group and screening approach. Pre-entry screening programmes have some impact on the epidemiology of the receiving countries. The effectiveness and cost-effectiveness of LTBI screening as predicted in mathematical models is also highly setting-specific, with best potential results achieved if screening is restricted to high-risk groups and/or to migrants from high-burden countries.

Capacity strengthening through pre-migration tuberculosis screening programmes: IRHWG experiences.

Effective tuberculosis (TB) prevention and care for migrants requires population health-based approaches that treat the relationship between migration and health as a progressive, interactive process influenced by many variables and addressed as far upstream in the process as possible. By including capacity building in source countries, pre-migration medical screening has the potential to become an integral component of public health promotion, as well as infection and disease prevention, in migrant-receiving nations, while simultaneously increasing capabilities in countries of origin. This article describes the collaborative experiences of five countries (Australia, Canada, New Zealand, United Kingdom and the United States of America, members of the Immigration and Refugee Health Working Group [IRHWG]), with similar pre-migration screening programmes for TB that are mandated. Qualitative examples of capacity building through IRHWG programmes are provided. Combined, the IRHWG member countries screen approximately 2 million persons overseas every year. Large-scale pre-entry screening programmes undertaken by IRHWG countries require building additional capacity for health care providers, radiology facilities and laboratories. This has resulted in significant improvements in laboratory and treatment capacity, providing availability of these facilities for national public health programmes. As long as global health disparities and disease prevalence differentials exist, national public health programmes and policies in migrant-receiving nations will continue to be challenged to manage the diseases prevalent in these migrating populations. National TB programmes and regulatory systems alone will not be able to achieve TB elimination. The management of health issues resulting from population mobility will require integration of national and global health initiatives which, as demonstrated here, can be supported through the capacity-building endeavours of pre-migration screening programmes.

Tuberculosis and latent tuberculous infection screening of migrants in Europe: comparative analysis of policies, surveillance systems and results.

Migration patterns into and within Europe have changed over the last decade. In 2015, European Union (EU) countries received over 1.2 million asylum requests, more than double the number registered in the previous year. This review compares the published literature on policies for tuberculosis (TB) and latent tuberculous infection (LTBI) screening in EU and European Free Trade Association (EFTA) countries with the existing TB/LTBI screening programmes for migrants in 11 EU/EFTA countries based on a survey of policy and surveillance systems. In addition, we provide a systematic review of the literature on the yield of screening migrants for active TB and LTBI in Europe. Published studies provide limited information about screening coverage and the yield of screening evaluations in EU/EFTA countries. Furthermore, countries use different screening strategies and settings, and different definitions for coverage and yield of screening for active TB and LTBI. We recommend harmonising case definitions, reporting standards and policies for TB/LTBI screening. To achieve TB elimination targets, a European platform for multi-country data collection and analysis, sharing of countries' policies and practices, and harmonisation of migrant screening strategies is needed.

Latent tuberculous screening of recent migrants attending language classes: a cohort study and cost analysis.

SETTING: England's national tuberculosis (TB) strategy recommends testing for and treatment of latent tuberculous infection (LTBI) among new migrants. Programmatic testing occurs in primary care, which may be inaccessible for some individuals. Current strategies could therefore be complemented by screening in other settings. OBJECTIVE: To investigate the feasibility and effectiveness of LTBI screening in a community college. DESIGN: A cohort study using observational data collected during the pilot study. Eligible students from high-incidence countries provided consent and were tested with a single-step interferon-gamma release assay (IGRA) and enrolled. We used single and multivariable analyses to estimate screening effectiveness and to explore different subgroups. We included costs from a UK National Health Service perspective. RESULTS: Screening uptake was 75% and treatment completion was 85%. Of 440 students, 71 (16%) were LTBI-positive; two had active TB. There was an association of positivity with age and incidence in the country of origin. Three incidence thresholds met our criteria for screening: countries with >40, >100 and >200 cases per 100 000 population, plus students from sub-Saharan Africa. CONCLUSION: We found that LTBI screening can be offered effectively in a community college, and could be a complement to primary care-based programmes in low-incidence countries.