National policies for delivering tuberculosis, HIV and hepatitis B and C virus infection services for refugees and migrants among Member States of the WHO European Region.

BACKGROUND/OBJECTIVE: Refugees and migrants to the World Health Organization (WHO) European Region are disproportionately affected by infections, including tuberculosis (TB), human immunodeficiency virus (HIV) and hepatitis B and C (HBV/HCV) compared with the host population. There are inequities in the accessibility and quality of health services available to refugees and migrants in the Region. This has consequences for health outcomes and will ultimately impact the ability to meet Regional infection elimination targets. METHODS: We reviewed academic and grey literature to identify national policies and guidelines for TB/HIV/HBV/HCV specific to refugees and migrants in the Member States of the WHO European Region and to identify: (i) evidence informing policy and (ii) barriers and facilitators to policy implementation. RESULTS: Relatively few primary national policy/guideline documents were identified which related to refugees and migrants and TB [14 of 53 Member States (26%), HIV (n = 15, 28%) and HBV/HCV (n = 3, 6%)], which often did not align with the WHO recommendations, and for some countries, violated refugees' and migrants' human rights. We found extreme heterogeneity in the implementation of the WHO- and European Centre for Disease Prevention and Control (ECDC)-advocated policies and recommendations on the prevention, diagnosis, treatment and care of TB/HIV/HBV/HCV infection among migrants across the Member States of the WHO European Region.There is great heterogeneity in implementation of WHO- and ECDC-advocated policies on the prevention, diagnosis, treatment and care of TB/HIV/HBV/HCV infection in refugees and migrants across the Member States in the Region. CONCLUSION: More transparent and accessible reporting of national policies and guidelines are required, together with the evidence base upon which these policy decisions are based. Political engagement is essential to drive the changes in national legislation to ensure equitable and universal access to the diagnosis and care for infectious diseases.

The impact, effectiveness and outcomes of targeted screening thresholds for programmatic latent tuberculosis infection testing in HIV.

BACKGROUND: Screening and treatment for latent tuberculosis infection (LTBI) are key for TB control. In the UK, the National Institute for Health and Care Excellence (NICE) and the British HIV Association (BHIVA) give conflicting guidance on which groups of people with HIV (PWH) should be screened, and previous national analysis demonstrated heterogeneity in how guidance is applied. There is an urgent need for a firmer clinical effectiveness evidence base on which to build screening policy. METHODS: We conducted a systematic, programmatic LTBI-screening intervention for all PWH receiving care in Leicester, UK. We compared yields (percentage IGRA positive) and number of tests required when applying the NICE and BHIVA testing strategies, as well as strategies targeting screening by TB incidence in patients' countries of birth. RESULTS: Of 1053 PWH tested, 118 were IGRA-positive (11.2%). Positivity was associated with higher TB incidence in country-of-birth [adjusted odds ratio, 50-149 cases compared with <50 cases/100 000: 11.6; 95% confidence interval (CI) 4.79-28.10)]. There was high testing uptake (1053/1069, 98.5%). Appropriate chemoprophylaxis was commenced in 100 of 117 (85.5%) patients diagnosed with LTBI, of whom 96 of 100 (96.0%) completed treatment. Delivering targeted testing to PWH from countries with TB incidence greater than 150 per 100 000 population or any sub-Saharan African country, would have correctly identified 89.8% of all LTBI cases while cutting tests required by 46.1% compared with NICE guidance, performing as well as BHIVA 2018 guidance. CONCLUSION: Targeting screening to higher risk PWH increases yield and reduces the number requiring testing. Our proposed 'PWH-LTBI streamlined guidance' offers a simplified approach, with the potential to improve national LTBI-screening implementation.

Risk factors associated with SARS-CoV-2 infection in a multiethnic cohort of United Kingdom healthcare workers (UK-REACH): A cross-sectional analysis.

BACKGROUND: Healthcare workers (HCWs), particularly those from ethnic minority groups, have been shown to be at disproportionately higher risk of infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) compared to the general population. However, there is insufficient evidence on how demographic and occupational factors influence infection risk among ethnic minority HCWs. METHODS AND FINDINGS: We conducted a cross-sectional analysis using data from the baseline questionnaire of the United Kingdom Research study into Ethnicity and Coronavirus Disease 2019 (COVID-19) Outcomes in Healthcare workers (UK-REACH) cohort study, administered between December 2020 and March 2021. We used logistic regression to examine associations of demographic, household, and occupational risk factors with SARS-CoV-2 infection (defined by polymerase chain reaction (PCR), serology, or suspected COVID-19) in a diverse group of HCWs. The primary exposure of interest was self-reported ethnicity. Among 10,772 HCWs who worked during the first UK national lockdown in March 2020, the median age was 45 (interquartile range [IQR] 35 to 54), 75.1% were female and 29.6% were from ethnic minority groups. A total of 2,496 (23.2%) reported previous SARS-CoV-2 infection. The fully adjusted model contained the following dependent variables: demographic factors (age, sex, ethnicity, migration status, deprivation, religiosity), household factors (living with key workers, shared spaces in accommodation, number of people in household), health factors (presence/absence of diabetes or immunosuppression, smoking history, shielding status, SARS-CoV-2 vaccination status), the extent of social mixing outside of the household, and occupational factors (job role, the area in which a participant worked, use of public transport to work, exposure to confirmed suspected COVID-19 patients, personal protective equipment [PPE] access, aerosol generating procedure exposure, night shift pattern, and the UK region of workplace). After adjustment, demographic and household factors associated with increased odds of infection included younger age, living with other key workers, and higher religiosity. Important occupational risk factors associated with increased odds of infection included attending to a higher number of COVID-19 positive patients (aOR 2.59, 95% CI 2.11 to 3.18 for ≥21 patients per week versus none), working in a nursing or midwifery role (1.30, 1.11 to 1.53, compared to doctors), reporting a lack of access to PPE (1.29, 1.17 to 1.43), and working in an ambulance (2.00, 1.56 to 2.58) or hospital inpatient setting (1.55, 1.38 to 1.75). Those who worked in intensive care units were less likely to have been infected (0.76, 0.64 to 0.92) than those who did not. Black HCWs were more likely to have been infected than their White colleagues, an effect which attenuated after adjustment for other known risk factors. This study is limited by self-selection bias and the cross sectional nature of the study means we cannot infer the direction of causality. CONCLUSIONS: We identified key sociodemographic and occupational risk factors associated with SARS-CoV-2 infection among UK HCWs, and have determined factors that might contribute to a disproportionate odds of infection in HCWs from Black ethnic groups. These findings demonstrate the importance of social and occupational factors in driving ethnic disparities in COVID-19 outcomes, and should inform policies, including targeted vaccination strategies and risk assessments aimed at protecting HCWs in future waves of the COVID-19 pandemic. TRIAL REGISTRATION: The study was prospectively registered at ISRCTN (reference number: ISRCTN11811602).

Community-based testing of migrants for infectious diseases (COMBAT-ID): impact, acceptability and cost-effectiveness of identifying infectious diseases among migrants in primary care: protocol for an interrupted time-series, qualitative and health economic analysis.

BACKGROUND: Migration is a major global driver of population change. Certain migrants may be at increased risk of infectious diseases, including tuberculosis (TB), HIV, hepatitis B and hepatitis C, and have poorer outcomes. Early diagnosis and management of these infections can reduce morbidity, mortality and onward transmission and is supported by national guidelines. To date, screening initiatives have been sporadic and focused on individual diseases; systematic routine testing of migrant groups for multiple infections is rarely undertaken and its impact is unknown. We describe the protocol for the evaluation of acceptability, effectiveness and cost-effectiveness of an integrated approach to screening migrants for a range of infectious diseases in primary care. METHODS AND ANALYSIS: We will conduct a mixed-methods study which includes an observational cohort with interrupted time-series analysis before and after the introduction of routine screening of migrants for infectious diseases (latent TB, HIV, hepatitis B and hepatitis C) when first registering with primary care within Leicester, UK. We will assess trends in the monthly number and rate of testing and diagnosis for latent TB, HIV, hepatitis B and hepatitis C to determine the effect of the policy change using segmented regression analyses at monthly time-points. Concurrently, we will undertake an integrated qualitative sub-study to understand the views of migrants and healthcare professionals to the new testing policy in primary care. Finally, we will evaluate the cost-effectiveness of combined infection testing for migrants in primary care. ETHICS AND DISSEMINATION: The study has received HRA and NHS approvals for both the interrupted time-series analysis (16/SC/0127) and the qualitative sub-study (16/EM/0159). For the interrupted time-series analysis we will only use fully anonymised data. For the qualitative sub-study, we will gain written, informed, consent. Dissemination of the results will be through local and national meetings/conferences as well as publications in peer-reviewed journals.

Cost-effectiveness of screening for HIV in primary care: a health economics modelling analysis.

BACKGROUND: Early HIV diagnosis reduces morbidity, mortality, the probability of onward transmission, and their associated costs, but might increase cost because of earlier initiation of antiretroviral treatment (ART). We investigated this trade-off by estimating the cost-effectiveness of HIV screening in primary care. METHODS: We modelled the effect of the four-times higher diagnosis rate observed in the intervention arm of the RHIVA2 randomised controlled trial done in Hackney, London (UK), a borough with high HIV prevalence (≥0·2% adult prevalence). We constructed a dynamic, compartmental model representing incidence of infection and the effect of screening for HIV in general practices in Hackney. We assessed cost-effectiveness of the RHIVA2 trial by fitting model diagnosis rates to the trial data, parameterising with epidemiological and behavioural data from the literature when required, using trial testing costs and projecting future costs of treatment. FINDINGS: Over a 40 year time horizon, incremental cost-effectiveness ratios were £22 201 (95% credible interval 12 662-132 452) per quality-adjusted life-year (QALY) gained, £372 207 (268 162-1 903 385) per death averted, and £628 874 (434 902-4 740 724) per HIV transmission averted. Under this model scenario, with UK cost data, RHIVA2 would reach the upper National Institute for Health and Care Excellence cost-effectiveness threshold (about £30 000 per QALY gained) after 33 years. Scenarios using cost data from Canada (which indicate prolonged and even higher health-care costs for patients diagnosed late) suggest this threshold could be reached in as little as 13 years. INTERPRETATION: Screening for HIV in primary care has important public health benefits as well as clinical benefits. We predict it to be cost-effective in the UK in the medium term. However, this intervention might be cost-effective far sooner, and even cost-saving, in settings where long-term health-care costs of late-diagnosed patients in high-prevalence regions are much higher (≥60%) than those of patients diagnosed earlier. Screening for HIV in primary care is cost-effective and should be promoted. FUNDING: NHS City and Hackney, UK Department of Health, National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care.

Patient population with multiple myeloma and transitions across different lines of therapy in the USA: an epidemiologic model.

PURPOSE: Multiple myeloma (MM) is a progressive, malignant neoplasia with a worldwide, age-standardized annual incidence of 1.5 per 100 000 individuals and 5-year prevalence around 230 000 patients. Main favorable prognostic factors are younger age, low/standard cytogenetic risk, and undergoing stem cell transplantation. Our aim was to estimate the size of the patient population with MM eligible to receive a new MM therapy at different lines of therapy in the USA. METHODS: We constructed a compartmental, differential equation model representing the flow of MM patients from diagnosis to death, via two possible treatment pathways and distinguished in four groups based on prognostic factors. Parameters were obtained from published references, available statistics, and assumptions. The model was used to estimate number of diagnosed MM patients and number of patient transitions from one line of therapy to the next over 1 year. Model output included 95% credible intervals from probabilistic sensitivity analyses. RESULTS: The base-case estimates were 80 219 patients living with MM, including 70 375 on treatment, 780 symptomatic untreated patients, and 9064 asymptomatic untreated patients. Over a 1-year period, the number of MM patients on treatment line 1 was estimated at 23 629 (credible intervals 22 236-25 029), and the number of transitions from treatment line 1 to treatment line 2 was estimated at 14 423. CONCLUSIONS: The size of the patient population with MM on different lines of therapy and in patient subgroups of interest estimated from this epidemiologic model can be used to assess the number of patients who could benefit from new MM therapies and their corresponding budgetary impact. Copyright © 2016 John Wiley & Sons, Ltd.

Mind the gaps: what's missing from current economic evaluations of universal HPV vaccination?

BACKGROUND: Since the original licensing of human papilloma virus (HPV) vaccination for women, evidence is accumulating of its effectiveness in preventing HPV-related conditions in men, and universal vaccination (vaccinating men and women) is now recommended in some countries. Several models of the cost-effectiveness of universal HPV vaccination have been published, but results have been mixed. This article assesses the extent to which economic studies have captured the range of values associated with universal HPV vaccination, and how this influences estimates of its cost-effectiveness. METHODS: Eight published economic evaluations of universal HPV vaccination were reviewed to identify which of the values associated with universal HPV vaccination were included in each analysis. RESULTS: Studies of the cost-effectiveness of universal HPV vaccination capture only a fraction of the values generated. Most studies focused on impacts on health and health system cost, and only captured these partially. A range of values is excluded from most studies, including impacts on productivity, patient time and costs, carers and family costs, and broader social values such as the right to access treatment. Further, those studies that attempted to capture these values only did so partially. DISCUSSION: Decisions to invest in universal HPV vaccination need to be based on a complete assessment of the value that it generates. This is not provided by existing economic evaluations. Further work is required to understand this value. First, research is required to understand how HPV-related health outcomes impact on society including, for instance, their impact on productivity. Second, consideration should be given to alternative approaches to capture this broader set of values in a manner useful to decisions-makers, such as multi-criteria decision analysis.

What do mathematical models tell us about the emergence and spread of drug-resistant HIV?

PURPOSE OF REVIEW: To discuss recent HIV epidemic models examining the transmission of antiretroviral (ARV) drug resistance. RECENT FINDINGS: A relatively small number of recent transmission models have investigated ARV resistance in the context of therapeutic, combined ART (cART); ARV-vaginal microbicides (ARV-VMB); and oral pre-exposure prophylaxis (PrEP). Models of cART use have highlighted potential concerns about future resistance transmission, particularly in resource-constrained settings, and have emphasized the benefits of viral load monitoring in limiting resistance spread. PrEP models have concluded that inadvertent use by HIV-infected individuals could increase resistance prevalence, and that risk compensation by PrEP users could limit their beneficial effects on HIV transmission. ARV-VMB models have demonstrated that whereas resistance can reduce prophylactic effectiveness in preventing HIV acquisition of female ARV-VMB users, it may concomitantly benefit users' male partners if the resistant strains that female users acquire are less transmissible than wild-type strains. The models have examined the balance between these two factors at the population level. SUMMARY: Recent HIV transmission models have adopted a wide assortment of structures and assumptions to explore drug resistance in the context of different ARV interventions in various settings. There is a need for future work emphasizing the simultaneous effects of multiple ARV interventions, as well as the public health impact of resistance, not just its prevalence.