Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis.

BACKGROUND: The World Health Organization End TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. METHODS: We pooled individual TB screening episode data from Italy, the Netherlands, Sweden and the UK, and analysed predictors and interactions for TB case yield using multivariable logistic regression models. RESULTS: Between 2005 and 2018 in 2 302 260 screening episodes among 2 107 016 migrants to four countries, the programmes identified 1658 TB cases (yield 72.0 (95% CI 68.6-75.6) per 100 000). In logistic regression analysis, we found associations between TB screening yield and age (≥55 years: OR 2.91 (95% CI 2.24-3.78)), being an asylum seeker (OR 3.19 (95% CI 1.03-9.83)) or on a settlement visa (OR 1.78 (95% CI 1.57-2.01)), close TB contact (OR 12.25 (95% CI 11.73-12.79)) and higher TB incidence in the country of origin. We demonstrated interactions between migrant typology and age, as well as country of origin. For asylum seekers, the elevated TB risk remained similar above country of origin incidence thresholds of 100 per 100 000. CONCLUSIONS: Key determinants of TB yield included close contact, increasing age, incidence in country of origin and specific migrant groups, including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in the country of origin. The high, country of origin-independent TB risk in asylum seekers above a 100 per 100 000 threshold could reflect higher transmission and re-activation risk of migration routes, with implications for selecting populations for TB screening.

Infectious disease testing of UK-bound refugees: a population-based, cross-sectional study.

BACKGROUND: The UK, like a number of other countries, has a refugee resettlement programme. External factors, such as higher prevalence of infectious diseases in the country of origin and circumstances of travel, are likely to increase the infectious disease risk of refugees, but published data is scarce. The International Organization for Migration carries out and collates data on standardised pre-entry health assessments (HA), including testing for infectious diseases, on all UK refugee applicants as part of the resettlement programme. From this data, we report the yield of selected infectious diseases (tuberculosis (TB), HIV, syphilis, hepatitis B and hepatitis C) and key risk factors with the aim of informing public health policy. METHODS: We examined a large cohort of refugees (n = 18,418) who underwent a comprehensive pre-entry HA between March 2013 and August 2017. We calculated yields of infectious diseases stratified by nationality and compared these with published (mostly WHO) estimates. We assessed factors associated with case positivity in univariable and multivariable logistic regression analysis. RESULTS: The number of refugees included in the analysis varied by disease (range 8506-9759). Overall yields were notably high for hepatitis B (188 cases; 2.04%, 95% CI 1.77-2.35%), while yields were below 1% for active TB (9 cases; 92 per 100,000, 48-177), HIV (31 cases; 0.4%, 0.3-0.5%), syphilis (23 cases; 0.24%, 0.15-0.36%) and hepatitis C (38 cases; 0.41%, 0.30-0.57%), and varied widely by nationality. In multivariable analysis, sub-Saharan African nationality was a risk factor for several infections (HIV: OR 51.72, 20.67-129.39; syphilis: OR 4.24, 1.21-24.82; hepatitis B: OR 4.37, 2.91-6.41). Hepatitis B (OR 2.23, 1.05-4.76) and hepatitis C (OR 5.19, 1.70-15.88) were associated with history of blood transfusion. Syphilis (OR 3.27, 1.07-9.95) was associated with history of torture, whereas HIV (OR 1521.54, 342.76-6754.23) and hepatitis B (OR 7.65, 2.33-25.18) were associated with sexually transmitted infection. Syphilis was associated with HIV (OR 10.27, 1.30-81.40). CONCLUSIONS: Testing refugees in an overseas setting through a systematic HA identified patients with a range of infectious diseases. Our results reflect similar patterns found in other programmes and indicate that the yields for infectious diseases vary by region and nationality. This information may help in designing a more targeted approach to testing, which has already started in the UK programme. Further work is needed to refine how best to identify infections in refugees, taking these factors into account.

Access of non-specialist sexual health services by men who have sex with men: do they differ from those attending specialist services?

OBJECTIVES: Men who have sex with men (MSM) bear a disproportionate burden of STIs. While routine STI surveillance data suggest MSM regularly access specialist genitourinary medicine (GUM) clinics for their sexual healthcare, the extent to which MSM attend non-specialist sexual health services (SHSs) is unclear. METHODS: We used data from the GUM Clinic Activity Data Set (GUMCADv2), the national STI surveillance system, to compare the characteristics, service usage and STI outcomes of MSM accessing specialist and non-specialist (non-GUM) SHSs in England in 2014. Pearson's χ2, Student's t-test and logistic regression analysis were used. RESULTS: Where sexual orientation was recorded (92%), 11% (4552/41 597) of non-GUM attendances were among MSM compared with 28% (280 466/999 331) of GUM attendances (p<0.001). Compared with those attending GUM services, MSM attending non-GUM services were younger (mean age: 30.2 years vs 37.7 years; p<0.001) and were more likely to be of mixed ethnicity (4.9% vs 3.5%; p<0.001), to have had a full sexual health screen (chlamydia, gonorrhoea, syphilis and HIV tests) (48.0% vs 37.0%; p<0.001) and to be diagnosed with chlamydia (7.4% vs 4.1%; p<0.001) and gonorrhoea (8.5% vs 6.5%: p<0.001). MSM attending non-GUM services had slightly lower HIV test uptake (87.0% vs 95.0%; p=0.157) and were less likely to be diagnosed with HIV (0.5% vs 0.8%; p=0.019), compared with those attending GUM clinics. CONCLUSIONS: Non-specialist SHSs play an important role in the care of MSM and should ensure services meet their needs.

Prevalence and characteristics of gastrointestinal infections in men who have sex with men diagnosed with rectal chlamydia infection in the UK: an 'unlinked anonymous' cross-sectional study.

INTRODUCTION: Gastrointestinal infections (GII) can cause serious ill health and morbidity. Although primarily transmitted through faecal contamination of food or water, transmission through sexual activity is well described, especially among men who have sex with men (MSM). METHODS: We investigated the prevalence of GIIs among a convenience sample of MSM who were consecutively diagnosed with rectal Chlamydia trachomatis (CT) at 12 UK genitourinary medicine clinics during 10 weeks in 2012. Residual rectal swabs were coded, anonymised and tested for Shigella, Campylobacter, Salmonella, shiga toxin-producing Escherichia coli and enteroaggregative E. coli (EAEC) using a real-time PCR. Results were linked to respective coded and anonymised clinical and demographic data. Associations were investigated using Fisher's exact tests. RESULTS: Of 444 specimens tested, overall GII prevalence was 8.6% (95% CI 6.3% to 11.6%): 1.8% (0.9% to 3.6%) tested positive for Shigella, 1.8% (0.9% to 3.6%) for Campylobacter and 5.2% (3.5% to 7.7%) for EAEC. No specimens tested positive for Salmonella or other diarrhoeagenic E. coli pathotypes. Among those with any GII, 14/30 were asymptomatic (2/7 with Shigella, 3/6 with Campylobacter and 9/17 with EAEC). Shigella prevalence was higher in MSM who were HIV-positive (4.7% (2.1% to 10.2%) vs 0.5%(0.1% to 3.2%) in HIV-negative MSM; p=0.01). CONCLUSIONS: In this small feasibility study, MSM with rectal CT appeared to be at appreciable risk of GII. Asymptomatic carriage may play a role in sexual transmission of GII.

Impact of SARS-CoV-2 infection on patients with systemic lupus erythematosus in England prior to vaccination: a retrospective observational cohort study.

OBJECTIVES: Determine the prevaccination healthcare impact of COVID-19 in patients with systemic lupus erythematosus (SLE) in England. DESIGN: Retrospective cohort study of adult patients with SLE from 1 May to 31 October 2020. SETTING: Clinical Practice Research Datalink (CPRD) Aurum and Hospital Episode Statistics (HES) databases from general practitioners across England combining primary care and other health-related data. PARTICIPANTS: Overall, 6145 adults with confirmed SLE diagnosis ≥1 year prior to 1 May 2020 were included. Most patients were women (91.0%), white (67.1%), and diagnosed with SLE at age <50 (70.8%). Patients were excluded if they had a COVID-19 diagnosis before 1 May 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographics and clinical characteristics were compared. COVID-19 severity was determined by patient care required and procedure/diagnosis codes. COVID-19 cumulative incidence, hospitalisation rates, lengths of stay and mortality rates were determined and stratified by SLE and COVID-19 severity. RESULTS: Of 6145 patients, 3927 had mild, 1288 moderate and 930 severe SLE at baseline. The majority of patients with moderate to severe SLE were on oral corticosteroids and antimalarial treatments. Overall, 54/6145 (0.88%) patients with SLE acquired and were diagnosed with COVID-19, with 45 classified as mild, 6 moderate and 3 severe COVID-19. Cumulative incidence was higher in patients with severe SLE (1.4%) compared with patients classified as mild (0.8%) or moderate (0.8%). Ten COVID-19-specific hospital admissions occurred (n=6 moderate; n=4 severe). Regardless of COVID-19 status, hospital admission rates and length of stay increased with SLE severity. Of 54 patients with SLE diagnosed with COVID-19, 1 (1.9%) COVID-19-related death was recorded in a patient with both severe SLE and severe COVID-19. CONCLUSIONS: SLE severity did not appear to impact COVID-19 outcomes in this study. The COVID-19 pandemic is evolving and follow-up studies are needed to understand the relationship between COVID-19 and SLE.

Prevalence and Patient Outcomes of Adult Primary Hypercholesterolemia and Dyslipidemia in the UK: Longitudinal Retrospective Study Using a Primary Care Dataset from 2009 to 2019.

Background: Guidelines for the management of dyslipidemias recommend intensive low-density lipoprotein (LDL-C) control through lifestyle advice and lipid-lowering drugs to reduce the risk of cardiovascular disease (CVD). Objective: This retrospective study aimed to characterize the adult primary care population with primary hypercholesterolemia (PH)/mixed dyslipidemia (MD). Methods: Data on adults with PH/MD between 1 January 2009 and 31 December 2019 in the UK were extracted from linked primary Clinical Practice Research Datalink (CPRD) and secondary care (Hospital Episode Statistics) datasets and analyzed. Results: A total of 279,221 patients met the inclusion criteria. Mean follow-up was 8.6 years. Crude prevalence of PH/MD increased from 13.5% in 2009 to 23.5% by 2019. The incidence decreased from 176 to 49 per 100,000 population. Mean age of the cohort was 58 years, baseline LDL-C was 4.32 mmol/L, 19.6% had atherosclerotic CVD, 30.1% diabetes, and 8.5% heterozygous familial hypercholesterolemia. Estimated LDL-C reductions of 40% and 50% were achieved in 2.6% and 2.3% of patients, respectively. Most received moderate-intensity statins as monotherapy (62.4%); high-intensity statins were used less frequently (24.3% as initial treatment). Less than 10% of patients received ezetimibe plus statins of different intensities. Conclusion: The prevalence of dyslipidemia doubled between 2009 and 2019, likely due to more systematic identification of PH/MD. A large proportion of patients with PH/MD are of high and very high CV risk, remain suboptimally treated in terms of lipid lowering, and may experience CV events with associated non-negligible clinical and economic sequelae. Despite intensive LDL-C-lowering recommendations, these do not translate in clinical practice to the wider population.

The burden of selected vaccine-preventable diseases on the secondary care health system in England: Results from a five-year administrative healthcare dataset.

OBJECTIVES: This study examined healthcare resource use (HCRU) for selected vaccine-preventable diseases (VPD) in secondary care in England. METHODS: The hospital episode statistics (HES) dataset covering all secondary care interactions within the English National Health Service (NHS) from 2015 to 2021 was used to identify and track HCRU for patients with a primary or secondary diagnosis for pertussis and Haemophilus influenzae type b (Hib), or a primary diagnosis only for hepatitis B, diphtheria, poliomyelitis, or tetanus. The first documented diagnosis during the study period (01/04/2015-31/03/2021) was the index event. RESULTS: 7,274 patients with a total of 5,554,343 patient-days (mean follow up 1,491 days) were included. The total number of hospital admissions was 27,092 and total inpatient cost was £4,987,770, with hepatitis B making up ∼80 % of this. Mean outpatient hospital appointments per patient were highest for tetanus (4.00), but total outpatient A&E cost burden was highest for Hib (£643,343 [mean per attendance £144.57]). For patients 0-9 years of age (n = 1,917), pertussis (n = 1,547) and Hib (n = 313) were by far the most commonly coded diseases. Hepatitis B was the most common disease in adults of working age and Hib was most prevalent in adults of retirement age. Surprisingly, poliomyelitis was observed in the database potentially due to historic diagnoses and/or coding inaccuracy. Other discrepancies with surveillance data were noted. CONCLUSIONS: VPDs impose a large burden on the NHS, but there is potential to reduce this and improve public health by optimising vaccination schedules, improving access and ensuring high coverage rates.

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.

Predicting STI Diagnoses Amongst MSM and Young People Attending Sexual Health Clinics in England: Triage Algorithm Development and Validation Using Routine Clinical Data.

BACKGROUND: Sexual health (SH) services increasingly need to prioritise those at greatest risk of sexually transmitted infections (STIs). We used SH surveillance data to develop algorithms to triage individuals attending SH services within two high-risk populations: men who have sex with men (MSM) and young people (YP). METHODS: Separate multivariable logistic regression models for MSM and YP were developed using surveillance data on demographics, recent sexual history, prior STI diagnoses and drug/alcohol use from five clinics in 2015-2016 to identify factors associated with new STI diagnoses. The models were prospectively applied in one SH clinic in May 2017 as an external validation. FINDINGS: 9530 YP and 1448 MSM SH episodes informed model development. For YP, factors associated with new STI diagnosis (overall prevalence: 10.6%) were being of black or mixed white/black ethnicity; history of chlamydia diagnosis (previous year); and multiple partners/new partner (previous 3-months). The YPs model had reasonable performance (c-statistic: 0.703), but poor discrimination when externally validated (c-statistic: 0.539). For MSM, being of South Asian ethnicity; being born in Europe (excluding the UK); and condomless anal sex or drug use (both in previous 3-months) were associated with STI diagnosis (overall prevalence: 22.0%). The MSM model had a c-statistic of 0.676, reducing to 0.579 on validation. INTERPRETATION: SH surveillance data, including limited behavioural data, enabled triage algorithms to be developed, but its implementation may be problematic due to poor external performance. This approach may be more suitable to self-triage, including online, ensuring patients are directed towards appropriate services. FUNDING: NIHR HTA programme (12/191/05).