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

Examining the epidemiology of tuberculosis in migrants to the UK to inform evidence-based screening policies

Background: In high-income countries an increasing proportion of all tuberculosis cases are detected in migrants. Understanding the epidemiology of tuberculosis in migrants to inform evidence-based screening policies is a priority. Methods: A systematic review and meta-analysis of pre-entry screening for tuberculosis was undertaken (chapter 2). Data from a pilot pre-entry programme in migrants to the UK was described, and risk factors for prevalent cases examined (chapter 3). The accuracy of a novel method for identifying individuals between two datasets was studied (chapter 4). This linkage method was used to combine data from migrants screened pre-entry to the UK tuberculosis register including molecular strain typing data. The linked datasets enabled estimates of the incidence of tuberculosis to be calculated, and risk factors were identified (chapters 5 and 6). Results: The systematic review identified 15 studies and found that culture confirmation increased with WHO prevalence in the country of origin. The crude prevalence of bacteriologically confirmed tuberculosis identified by UK pre-entry screening was 92 per 100,000 population screened. Migrants reporting a history of contact with a case of tuberculosis, and those from higher prevalence countries were at greatest risk. Compared to a gold standard of NHS number, probabilistic linkage identified individuals in two datasets with high sensitivity and specificity. The estimated incidence of tuberculosis notified in the UK in migrants screened pre-entry was 194 per 100,000 person years at risk. Migrants with a chest radiograph classified as suspected tuberculosis and those from higher prevalence countries had a higher risk post- migration. Compared to other non-UK born individuals, migrants screened pre-entry were less likely to be the first case in a cluster of tuberculosis. Conclusions: This thesis generated new knowledge that improves our understanding of the epidemiology of tuberculosis in migrants to the UK. Based on these findings, evidence-based screening recommendations were made

Accuracy of Probabilistic Linkage Using the Enhanced Matching System for Public Health and Epidemiological Studies

The Enhanced Matching System (EMS) is a probabilistic record linkage program developed by the tuberculosis section at Public Health England to match data for individuals across two datasets. This paper outlines how EMS works and investigates its accuracy for linkage across public health datasets

A rapid review and meta-analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections in community settings [version 1; peer review: awaiting peer review]

Background: Cross-sectional studies indicate that up to 80% of active SARS-CoV-2 infections may be asymptomatic. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically appropriate studies in community settings. / Methods: We searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published before 25/08/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold/genome copy number values and/or duration of viral shedding by symptom status, and age of asymptomatic versus (pre)symptomatic cases. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis. / Results: We screened 1138 studies and included 21. The pooled asymptomatic proportion of SARS-CoV-2 infections was 23% (95% CI 16%-30%). When stratified by testing context, the asymptomatic proportion ranged from 6% (95% CI 0-17%) for household contacts to 47% (95% CI 21-75%) for non-outbreak point prevalence surveys with follow-up symptom monitoring. Estimates of viral load and duration of viral shedding appeared to be similar for asymptomatic and symptomatic cases based on available data, though detailed reporting of viral load and natural history of viral shedding by symptom status were limited. Evidence into the relationship between age and symptom status was inconclusive. / Conclusion: Asymptomatic viral shedding comprises a substantial minority of SARS-CoV-2 infections when estimated using methodologically appropriate studies. Further investigation into variation in the asymptomatic proportion by testing context, the degree and duration of infectiousness for asymptomatic infections, and demographic predictors of symptom status are warranted

Migration health research in the United Kingdom: A scoping review

Background: One in seven people living in the United Kingdom (UK) is an international migrant, rendering migrants an important population group with diverse and dynamic health and healthcare needs. However, there has been no attempt to map contemporary trends within migration health research conducted in the UK. The aim of this scoping review was to describe trends within migration health research and identify gaps for future research agendas. Methods: PubMed and Embase were systematically searched for empirical research with a primary focus on the concepts “health” and “migrants” published between 2001 and 2019. Findings were analysed using the UCL-Lancet Commission on Migration and Health Conceptual Framework for Migration and Health. Results: In total, 399 studies were included, with almost half (41.1%; 164/399) published in the last five years of the study period between 2015 and 2019 and a third (34.1%; 136/399) conducted in London. Studies included asylum seekers (14.8%; 59/399), refugees (12.3%; 49/399), and undocumented migrants or migrants with insecure status (3.5%; 14/399), but most articles (74.9%; 299/399) did not specify a migrant sub-group. The most studied health topics were specific disease outcomes such as infectious diseases (24.1% of studies) and mental health (19.1%) compared to examining systems or structures that impact health (27.8%), access to healthcare (26.3%), or specific exposures or behaviours (35.3%). Conclusions: There has been a growing interest in migration health. Ensuring a diverse geographic distribution of research conducted in the UK and disaggregation by migrant sub-group is required for a nuanced and region-specific understanding of specific health needs, interventions and appropriate service delivery for different migrant populations. More research is needed to understand how migration policy and legislation intersect with both the social determinants of health and access to healthcare to shape the health of migrants in the UK

Seasonality and immunity to laboratory-confirmed seasonal coronaviruses (HCoV-NL63, HCoV-OC43, and HCoV-229E): results from the Flu Watch cohort study [version 1; peer review: 2 approved with reservations]

Background: There is currently a pandemic caused by the novel coronavirus SARS-CoV-2. The intensity and duration of this first wave in the UK may be dependent on whether SARS-CoV-2 transmits more effectively in the winter than the summer and the UK Government response is partially built upon the assumption that those infected will develop immunity to reinfection in the short term. In this paper we examine evidence for seasonality and immunity to laboratory-confirmed seasonal coronavirus (HCoV) from a prospective cohort study in England. Methods: In this analysis of the Flu Watch cohort, we examine seasonal trends for PCR-confirmed coronavirus infections (HCoV-NL63, HCoV-OC43, and HCoV-229E) in all participants during winter seasons (2006-2007, 2007-2008, 2008-2009) and during the first wave of the 2009 H1N1 influenza pandemic (May-Sep 2009). We also included data from the pandemic and ‘post-pandemic’ winter seasons (2009-2010 and 2010-2011) to identify individuals with two confirmed HCoV infections and examine evidence for immunity against homologous reinfection. Results: We tested 1,104 swabs taken during respiratory illness and detected HCoV in 199 during the first four seasons. The rate of confirmed HCoV infection across all seasons was 390 (95% CI 338-448) per 100,000 person-weeks; highest in the Nov-Mar 2008/9 season at 674 (95%CI 537-835). The highest rate was in February at 759 (95% CI 580-975). Data collected during May-Sep 2009 showed there was small amounts of ongoing transmission, with four cases detected during this period. Eight participants had two confirmed infections, of which none had the same strain twice

Hospital-based preventative interventions for people experiencing homelessness in high-income countries: A systematic review

BACKGROUND: People experiencing homelessness have significant unmet needs and high rates of unplanned care. We aimed to describe preventative interventions, defined in their broadest sense, for people experiencing homelessness in a hospital context. Secondary aims included mapping outcomes and assessing intervention effectiveness. METHODS: We searched online databases (MEDLINE, Embase, PsycINFO, HMIC, CINAHL, Web of Science, Cochrane Library) from 1999–2019 and conducted backward and forward citation searches to 31 December 2020 (PROSPERO CRD42019154036). We included quantitative studies in emergency and inpatient settings measuring health or social outcomes for adults experiencing homelessness in high income countries. We assessed rigour using the “Quality Assessment Tool for Quantitative Studies” and summarised findings using descriptive quantitative methods, a binomial test, a Harvest Plot, and narrative synthesis. We used PRISMA and SWiM reporting guidelines. FINDINGS: Twenty-eight studies identified eight intervention types: care coordination (n=18); advocacy, support, and outreach (n=13); social welfare assistance (n=13); discharge planning (n=12); homelessness identification (n=6); psychological therapy and treatment (n=6); infectious disease prevention (n=5); and screening, treatment, and referrals (n=5). The evidence strength was weak (n=16) to moderate (n=10), with two high quality randomised controlled trials. We identified six outcome categories with potential benefits observed for psychosocial outcomes, including housing (11/13 studies, 95%CI=54.6–98.1%, p=0.023), healthcare use (14/17, 56.6–96.2%, p=0.013), and healthcare costs (8/8, 63.1–100%, p=0.008). Benefits were less likely for health outcomes (4/5, 28.3–99.5%, p=0.375), integration with onward care (2/4, 6.8–93.2%, p=1.000), and feasibility/acceptability (5/6, 35.9–99.6%, p=0.219), but confidence intervals were very wide. We observed no harms. Most studies showing potential benefits were multi-component interventions. INTERPRETATION: Hospital-based preventative interventions for people experiencing homelessness are potentially beneficial, but more rigorous research is needed. In the context of high needs and extreme inequities, policymakers and healthcare providers may consider implementing multi-component preventative interventions. FUNDING: SL is supported by an NIHR Clinical Doctoral Research Fellowship (ICA-CDRF-2016-02-042). JD is supported by an NIHR School of Public Health Research Pre-doctoral Fellowship (NU-004252). RWA is supported by a Wellcome Clinical Research Career Development Fellowship (206602)

Household transmission of seasonal coronavirus infections: Results from the Flu Watch cohort study [version 1; peer review: 1 approved, 2 approved with reservations]

Background: In the context of the current coronavirus disease 2019 (COVID-19) pandemic, understanding household transmission of seasonal coronaviruses may inform pandemic control. We aimed to investigate what proportion of seasonal coronavirus transmission occurred within households, measure the risk of transmission in households, and describe the impact of household-related factors of risk of transmission. Methods: Using data from three winter seasons of the UK Flu Watch cohort study, we measured the proportion of symptomatic infections acquired outside and within the home, the household transmission risk and the household secondary attack risk for PCR-confirmed seasonal coronaviruses. We present transmission risk stratified by demographic features of households. Results: We estimated that the proportion of cases acquired outside the home, weighted by age and region, was 90.7% (95% CI 84.6- 94.5, n=173/195) and within the home was 9.3% (5.5-15.4, 22/195). Following a symptomatic coronavirus index case, 14.9% (9.8 - 22.1, 20/134) of households experienced symptomatic transmission to at least one other household member. Onward transmission risk ranged from 11.90% (4.84-26.36, 5/42) to 19.44% (9.21-36.49, 7/36) by strain. The overall household secondary attack risk for symptomatic cases was 8.00% (5.31-11.88, 22/275), ranging across strains from 5.10 (2.11-11.84, 5/98) to 10.14 (4.82- 20.11, 7/69). Median clinical onset serial interval was 7 days (IQR= 6-9.5). Households including older adults, 3+ children, current smokers, contacts with chronic health conditions, and those in relatively deprived areas had the highest transmission risks. Child index cases and male index cases demonstrated the highest transmission risks. Conclusion: Most seasonal coronaviruses appear to be acquired outside the household, with relatively modest risk of onward transmission within households. Transmission risk following an index case appears to vary by demographic household features, with potential overlap between those demonstrating the highest point estimates for seasonal coronavirus transmission risk and COVID-19 susceptibility and poor illness outcomes