Cognition and Memory after Covid-19 in a Large Community Sample.

BACKGROUND: Cognitive symptoms after coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are well-recognized. Whether objectively measurable cognitive deficits exist and how long they persist are unclear. METHODS: We invited 800,000 adults in a study in England to complete an online assessment of cognitive function. We estimated a global cognitive score across eight tasks. We hypothesized that participants with persistent symptoms (lasting ≥12 weeks) after infection onset would have objectively measurable global cognitive deficits and that impairments in executive functioning and memory would be observed in such participants, especially in those who reported recent poor memory or difficulty thinking or concentrating ("brain fog"). RESULTS: Of the 141,583 participants who started the online cognitive assessment, 112,964 completed it. In a multiple regression analysis, participants who had recovered from Covid-19 in whom symptoms had resolved in less than 4 weeks or at least 12 weeks had similar small deficits in global cognition as compared with those in the no-Covid-19 group, who had not been infected with SARS-CoV-2 or had unconfirmed infection (-0.23 SD [95% confidence interval {CI}, -0.33 to -0.13] and -0.24 SD [95% CI, -0.36 to -0.12], respectively); larger deficits as compared with the no-Covid-19 group were seen in participants with unresolved persistent symptoms (-0.42 SD; 95% CI, -0.53 to -0.31). Larger deficits were seen in participants who had SARS-CoV-2 infection during periods in which the original virus or the B.1.1.7 variant was predominant than in those infected with later variants (e.g., -0.17 SD for the B.1.1.7 variant vs. the B.1.1.529 variant; 95% CI, -0.20 to -0.13) and in participants who had been hospitalized than in those who had not been hospitalized (e.g., intensive care unit admission, -0.35 SD; 95% CI, -0.49 to -0.20). Results of the analyses were similar to those of propensity-score-matching analyses. In a comparison of the group that had unresolved persistent symptoms with the no-Covid-19 group, memory, reasoning, and executive function tasks were associated with the largest deficits (-0.33 to -0.20 SD); these tasks correlated weakly with recent symptoms, including poor memory and brain fog. No adverse events were reported. CONCLUSIONS: Participants with resolved persistent symptoms after Covid-19 had objectively measured cognitive function similar to that in participants with shorter-duration symptoms, although short-duration Covid-19 was still associated with small cognitive deficits after recovery. Longer-term persistence of cognitive deficits and any clinical implications remain uncertain. (Funded by the National Institute for Health and Care Research and others.).

Dynamics of SARS-CoV-2 infection hospitalisation and infection fatality ratios over 23 months in England.

The relationship between prevalence of infection and severe outcomes such as hospitalisation and death changed over the course of the COVID-19 pandemic. Reliable estimates of the infection fatality ratio (IFR) and infection hospitalisation ratio (IHR) along with the time-delay between infection and hospitalisation/death can inform forecasts of the numbers/timing of severe outcomes and allow healthcare services to better prepare for periods of increased demand. The REal-time Assessment of Community Transmission-1 (REACT-1) study estimated swab positivity for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in England approximately monthly from May 2020 to March 2022. Here, we analyse the changing relationship between prevalence of swab positivity and the IFR and IHR over this period in England, using publicly available data for the daily number of deaths and hospitalisations, REACT-1 swab positivity data, time-delay models, and Bayesian P-spline models. We analyse data for all age groups together, as well as in 2 subgroups: those aged 65 and over and those aged 64 and under. Additionally, we analysed the relationship between swab positivity and daily case numbers to estimate the case ascertainment rate of England's mass testing programme. During 2020, we estimated the IFR to be 0.67% and the IHR to be 2.6%. By late 2021/early 2022, the IFR and IHR had both decreased to 0.097% and 0.76%, respectively. The average case ascertainment rate over the entire duration of the study was estimated to be 36.1%, but there was some significant variation in continuous estimates of the case ascertainment rate. Continuous estimates of the IFR and IHR of the virus were observed to increase during the periods of Alpha and Delta's emergence. During periods of vaccination rollout, and the emergence of the Omicron variant, the IFR and IHR decreased. During 2020, we estimated a time-lag of 19 days between hospitalisation and swab positivity, and 26 days between deaths and swab positivity. By late 2021/early 2022, these time-lags had decreased to 7 days for hospitalisations and 18 days for deaths. Even though many populations have high levels of immunity to SARS-CoV-2 from vaccination and natural infection, waning of immunity and variant emergence will continue to be an upwards pressure on the IHR and IFR. As investments in community surveillance of SARS-CoV-2 infection are scaled back, alternative methods are required to accurately track the ever-changing relationship between infection, hospitalisation, and death and hence provide vital information for healthcare provision and utilisation.

Impact of national commissioning of pre-exposure prophylaxis (PrEP) on equity of access in England: a PrEP-to-need ratio investigation.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV acquisition. In England, NHS availability was limited to participants of the PrEP Impact Trial until late 2020. Some key populations at greater risk of HIV were under-represented in the trial suggesting inequities in trial PrEP access. We used the PrEP-to-need ratio (PnR; number of PrEP users divided by new HIV diagnoses) to investigate whether PrEP access improved following routine commissioning in October 2020 and identify populations most underserved by PrEP. METHODS: Aggregated numbers of people receiving ≥1 PrEP prescription and non-late new HIV diagnoses (epidemiological proxy for PrEP need) were taken from national surveillance data sets. We calculated the PnR across socio-demographics during Impact (October 2017 to February 2020; pre-COVID-19 pandemic) and post-commissioning PrEP era (2021) in England. RESULTS: PnR increased >11 fold, from 4.2 precommissioning to 48.9 in 2021, due to a fourfold reduction in non-late new HIV diagnoses and near threefold increase in PrEP users. PnR increased across genders, however, the men's PnR increased 12-fold (from 5.4 precommissioning to 63.9 postcommissioning) while the women's increased sevenfold (0.5 to 3.5). This increasing gender-based inequity was observed across age, ethnicity and region of residence: white men had the highest PnR, increasing >13 fold (7.1 to 96.0), while Black African women consistently had the lowest PnR, only increasing slightly (0.1 to 0.3) postcommissioning, suggesting they were the most underserved group. Precommissioning, the PnR was 78-fold higher among white men than Black women, increasing to 278-fold postcommissioning. CONCLUSIONS: Despite the overall increase in PrEP use, substantial PrEP Impact trial inequities widened postcommissioning in England, particularly across gender, ethnicity and region of residence. This study emphasises the need to guide HIV combination prevention based on equity metrics relative to the HIV epidemic. The PnR could support the optimisation of combination prevention to achieve zero new HIV infections in England by 2030.

Validity of Self-testing at Home With Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Detection by Lateral Flow Immunoassay.

BACKGROUND: We explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow immunoassay (LFIA) performance under field conditions compared to laboratory-based electrochemiluminescence immunoassay (ECLIA) and live virus neutralization. METHODS: In July 2021, 3758 participants performed, at home, a self-administered Fortress LFIA on finger-prick blood, reported and submitted a photograph of the result, and provided a self-collected capillary blood sample for assessment of immunoglobulin G (IgG) antibodies using the Roche Elecsys® Anti-SARS-CoV-2 ECLIA. We compared the self-reported LFIA result to the quantitative ECLIA and checked the reading of the LFIA result with an automated image analysis (ALFA). In a subsample of 250 participants, we compared the results to live virus neutralization. RESULTS: Almost all participants (3593/3758, 95.6%) had been vaccinated or reported prior infection. Overall, 2777/3758 (73.9%) were positive on self-reported LFIA, 2811/3457 (81.3%) positive by LFIA when ALFA-reported, and 3622/3758 (96.4%) positive on ECLIA (using the manufacturer reference standard threshold for positivity of 0.8 U mL-1). Live virus neutralization was detected in 169 of 250 randomly selected samples (67.6%); 133/169 were positive with self-reported LFIA (sensitivity 78.7%; 95% confidence interval [CI]: 71.8, 84.6), 142/155 (91.6%; 95% CI: 86.1, 95.5) with ALFA, and 169 (100%; 95% CI: 97.8, 100.0) with ECLIA. There were 81 samples with no detectable virus neutralization; 47/81 were negative with self-reported LFIA (specificity 58.0%; 95% CI: 46.5, 68.9), 34/75 (45.3%; 95% CI: 33.8, 57.3) with ALFA, and 0/81 (0%; 95% CI: 0, 4.5) with ECLIA. CONCLUSIONS: Self-administered LFIA is less sensitive than a quantitative antibody test, but the positivity in LFIA correlates better than the quantitative ECLIA with virus neutralization.

Barriers and facilitators to HIV Pre-Exposure Prophylaxis (PrEP) in Specialist Sexual Health Services in the United Kingdom: A systematic review using the PrEP Care Continuum.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) delivery in the UK is inequitable; over 95% of PrEP users were men who have sex with men (MSM) despite making up less than 50% of new HIV diagnoses. We conducted a systematic review to identify modifiable barriers and facilitators to PrEP delivery in the UK among underserved populations. METHODS: We searched bibliographic/conference databases using the terms HIV, PrEP, barriers, facilitators, underserved populations, and UK. Modifiable factors were mapped along the PrEP Care Continuum (PCC) to identify targets for interventions. RESULTS: In total, 44 studies were eligible: 29 quantitative, 12 qualitative and three mixed-methods studies. Over half (n = 24 [54.5%]) exclusively recruited MSM, whereas 11 were in mixed populations (all included MSM as a sub-population) and the other nine were in other underserved populations (gender and ethnicity minorities, women, and people who inject drugs). Of the 15 modifiable factors identified, two-thirds were at the PrEP contemplation and PrEParation steps of the PCC. The most reported barriers were lack of PrEP awareness (n = 16), knowledge (n = 19), willingness (n = 16), and access to a PrEP provider (n = 16), whereas the more reported facilitators were prior HIV testing (n = 8), agency and self-care (n = 8). All but three identified factors were at the patient rather than provider or structural level. CONCLUSIONS: This review highlights that the bulk of the scientific literature focuses on MSM and on patient-level factors. Future research needs to ensure underserved populations are included and prioritized (e.g. ethnicity and gender minorities, people who inject drugs) and provider and structural factors are investigated.

Design and Implementation of a National Program to Monitor the Prevalence of SARS-CoV-2 IgG Antibodies in England Using Self-Testing: The REACT-2 Study.

Data System. The UK Department of Health and Social Care funded the REal-time Assessment of Community Transmission-2 (REACT-2) study to estimate community prevalence of SARS-CoV-2 IgG (immunoglobulin G) antibodies in England. Data Collection/Processing. We obtained random cross-sectional samples of adults from the National Health Service (NHS) patient list (near-universal coverage). We sent participants a lateral flow immunoassay (LFIA) self-test, and they reported the result online. Overall, 905 991 tests were performed (28.9% response) over 6 rounds of data collection (June 2020-May 2021). Data Analysis/Dissemination. We produced weighted estimates of LFIA test positivity (validated against neutralizing antibodies), adjusted for test performance, at local, regional, and national levels and by age, sex, and ethnic group and area-level deprivation score. In each round, fieldwork occurred over 2 weeks, with results reported to policymakers the following week. We disseminated results as preprints and peer-reviewed journal publications. Public Health Implications. REACT-2 estimated the scale and variation in antibody prevalence over time. Community self-testing and -reporting produced rapid insights into the changing course of the pandemic and the impact of vaccine rollout, with implications for future surveillance. (Am J Public Health. 2023;113(11):1201-1209. https://doi.org/10.2105/AJPH.2023.307381).

Design and Implementation of a National SARS-CoV-2 Monitoring Program in England: REACT-1 Study.

Data System. The REal-time Assessment of Community Transmission-1 (REACT-1) Study was funded by the Department of Health and Social Care in England to provide reliable and timely estimates of prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection over time, by person and place. Data Collection/Processing. The study team (researchers from Imperial College London and its logistics partner Ipsos) wrote to named individuals aged 5 years and older in random cross-sections of the population of England, using the National Health Service list of patients registered with a general practitioner (near-universal coverage) as a sampling frame. We collected data over 2 to 3 weeks approximately every month across 19 rounds of data collection from May 1, 2020, to March 31, 2022. Data Analysis/Dissemination. We have disseminated the data and study materials widely via the study Web site, preprints, publications in peer-reviewed journals, and the media. We make available data tabulations, suitably anonymized to protect participant confidentiality, on request to the study's data access committee. Public Health Implications. The study provided inter alia real-time data on SARS-CoV-2 prevalence over time, by area, and by sociodemographic variables; estimates of vaccine effectiveness; and symptom profiles, and detected emergence of new variants based on viral genome sequencing. (Am J Public Health. 2023;113(5):545-554. https://doi.org/10.2105/AJPH.2023.307230).

Trends in SARS-CoV-2 infection prevalence during England's roadmap out of lockdown, January to July 2021.

BACKGROUND: Following rapidly rising COVID-19 case numbers, England entered a national lockdown on 6 January 2021, with staged relaxations of restrictions from 8 March 2021 onwards. AIM: We characterise how the lockdown and subsequent easing of restrictions affected trends in SARS-CoV-2 infection prevalence. METHODS: On average, risk of infection is proportional to infection prevalence. The REal-time Assessment of Community Transmission-1 (REACT-1) study is a repeat cross-sectional study of over 98,000 people every round (rounds approximately monthly) that estimates infection prevalence in England. We used Bayesian P-splines to estimate prevalence and the time-varying reproduction number (Rt) nationally, regionally and by age group from round 8 (beginning 6 January 2021) to round 13 (ending 12 July 2021) of REACT-1. As a comparator, a separate segmented-exponential model was used to quantify the impact on Rt of each relaxation of restrictions. RESULTS: Following an initial plateau of 1.54% until mid-January, infection prevalence decreased until 13 May when it reached a minimum of 0.09%, before increasing until the end of the study to 0.76%. Following the first easing of restrictions, which included schools reopening, the reproduction number Rt increased by 82% (55%, 108%), but then decreased by 61% (82%, 53%) at the second easing of restrictions, which was timed to match the Easter school holidays. Following further relaxations of restrictions, the observed Rt increased steadily, though the increase due to these restrictions being relaxed was offset by the effects of vaccination and also affected by the rapid rise of Delta. There was a high degree of synchrony in the temporal patterns of prevalence between regions and age groups. CONCLUSION: High-resolution prevalence data fitted to P-splines allowed us to show that the lockdown was effective at reducing risk of infection with school holidays/closures playing a significant part.

A SARS-CoV-2 outbreak in a plastics manufacturing plant.

BACKGROUND: A SARS-CoV-2 outbreak with an attack rate of 14.3% was reported at a plastics manufacturing plant in England. METHODS: Between 23rd March and 13th May 2021, the COVID-OUT team undertook a comprehensive outbreak investigation, including environmental assessment, surface sampling, molecular and serological testing, and detailed questionnaires, to identify potential SARS-CoV-2 transmission routes, and workplace- and worker-related risk factors. RESULTS: While ventilation, indicated using real-time CO2 proxy measures, was generally adequate on-site, the technical office with the highest localized attack rate (21.4%) frequently reached peaks in CO2 of 2100ppm. SARS-CoV-2 RNA was found in low levels (Ct ≥35) in surface samples collected across the site. High noise levels (79dB) were recorded in the main production area, and study participants reported having close work contacts (73.1%) and sharing tools (75.5%). Only 20.0% of participants reported using a surgical mask and/or FFP2/FFP3 respirator at least half the time and 71.0% expressed concerns regarding potential pay decreases and/or unemployment due to self-isolation or workplace closure. CONCLUSIONS: The findings reinforce the importance of enhanced infection control measures in manufacturing sectors, including improved ventilation with possible consideration of CO2 monitoring, utilising air cleaning interventions in enclosed environments, and provision of good-quality face masks (i.e., surgical masks or FFP2/FFP3 respirators) especially when social distancing cannot be maintained. Further research on the impacts of job security-related concerns is warranted.

SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2.

BACKGROUND: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. METHODS: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September-27 September 2021) and 15 (19 October-5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. RESULTS: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8-23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. CONCLUSIONS: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

Usability and Acceptability of Home-based Self-testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antibodies for Population Surveillance.

BACKGROUND: This study assesses acceptability and usability of home-based self-testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies using lateral flow immunoassays (LFIA). METHODS: We carried out public involvement and pilot testing in 315 volunteers to improve usability. Feedback was obtained through online discussions, questionnaires, observations, and interviews of people who tried the test at home. This informed the design of a nationally representative survey of adults in England using two LFIAs (LFIA1 and LFIA2) which were sent to 10 600 and 3800 participants, respectively, who provided further feedback. RESULTS: Public involvement and pilot testing showed high levels of acceptability, but limitations with the usability of kits. Most people reported completing the test; however, they identified difficulties with practical aspects of the kit, particularly the lancet and pipette, a need for clearer instructions and more guidance on interpretation of results. In the national study, 99.3% (8693/8754) of LFIA1 and 98.4% (2911/2957) of LFIA2 respondents attempted the test and 97.5% and 97.8% of respondents completed it, respectively. Most found the instructions easy to understand, but some reported difficulties using the pipette (LFIA1: 17.7%) and applying the blood drop to the cassette (LFIA2: 31.3%). Most respondents obtained a valid result (LFIA1: 91.5%; LFIA2: 94.4%). Overall there was substantial concordance between participant and clinician interpreted results (kappa: LFIA1 0.72; LFIA2 0.89). CONCLUSIONS: Impactful public involvement is feasible in a rapid response setting. Home self-testing with LFIAs can be used with a high degree of acceptability and usability by adults, making them a good option for use in seroprevalence surveys.

Modern contraceptive use among unmarried girls aged 15-19 years in South Western Nigeria: results from a cross-sectional baseline survey for the Adolescent 360 (A360) impact evaluation.

PURPOSE: Adolescents 360 (A360) is an initiative being rolled out across Nigeria with the aim of increasing voluntary modern contraception use among women aged 15 to 19 years. Using evaluation study baseline data, we identified sexuality, fertility and contraceptive use characteristics of young unmarried girls in South Western Nigeria. METHODS: A cross-sectional baseline survey of unmarried girls aged 15 to 19 years was conducted in Ogun state, Nigeria in August 2017. A clustered sampling design was used. We identified determinants of modern contraceptive use in this subpopulation using logistic regression. RESULTS: Of 12,024 women interviewed, 15.3% reported sexual intercourse in the past year. The majority of respondents (79.6%, 9525/11,967) had heard of contraception. 45.3% of sexually active respondents were using a modern contraceptive method. Of those using any method of contraception, male condoms (50.3%) were the most widely used modern method followed by the emergency contraceptive pill (16.7%). Following adjustment for socio-demographic characteristics, there was evidence that the use of modern contraception was positively associated with having never given birth, living in an urban area, current enrolment in education, high level of education, high socioeconomic status, exposure to information about contraception, perceived social support for contraception, and self-efficacy for contraception. CONCLUSIONS: In South Western Nigeria, unmarried sexually active adolescent girls have relatively low levels of modern contraceptive use. Programmes should aim to increase access to modern contraception and to increase social support and acceptability of contraceptive use.

Comparing Public Perceptions and Preventive Behaviors During the Early Phase of the COVID-19 Pandemic in Hong Kong and the United Kingdom: Cross-sectional Survey Study.

BACKGROUND: Given the public health responses to previous respiratory disease pandemics, and in the absence of treatments and vaccines, the mitigation of the COVID-19 pandemic relies on population engagement in nonpharmaceutical interventions. This engagement is largely driven by risk perception, anxiety levels, and knowledge, as well as by historical exposure to disease outbreaks, government responses, and cultural factors. OBJECTIVE: The aim of this study is to compare psychobehavioral responses in Hong Kong and the United Kingdom during the early phase of the COVID-19 pandemic. METHODS: Comparable cross-sectional surveys were administered to adults in Hong Kong and the United Kingdom during the early phase of the epidemic in each setting. Explanatory variables included demographics, risk perception, knowledge of COVID-19, anxiety level, and preventive behaviors. Responses were weighted according to census data. Logistic regression models, including effect modification to quantify setting differences, were used to assess the association between the explanatory variables and the adoption of social distancing measures. RESULTS: Data from 3431 complete responses (Hong Kong, 1663; United Kingdom, 1768) were analyzed. Perceived severity of symptoms differed by setting, with weighted percentages of 96.8% for Hong Kong (1621/1663) and 19.9% for the United Kingdom (366/1768). A large proportion of respondents were abnormally or borderline anxious (Hong Kong: 1077/1603, 60.0%; United Kingdom: 812/1768, 46.5%) and regarded direct contact with infected individuals as the transmission route of COVID-19 (Hong Kong: 94.0%-98.5%; United Kingdom: 69.2%-93.5%; all percentages weighted), with Hong Kong identifying additional routes. Hong Kong reported high levels of adoption of various social distancing measures (Hong Kong: 32.6%-93.7%; United Kingdom: 17.6%-59.0%) and mask-wearing (Hong Kong: 98.8% (1647/1663); United Kingdom: 3.1% (53/1768)). The impact of perceived severity of symptoms and perceived ease of transmission of COVID-19 on the adoption of social distancing measures varied by setting. In Hong Kong, these factors had no impact, whereas in the United Kingdom, those who perceived their symptom severity as "high" were more likely to adopt social distancing (adjusted odds ratios [aORs] 1.58-3.01), and those who perceived transmission as "easy" were prone to adopt both general social distancing (aOR 2.00, 95% CI 1.57-2.55) and contact avoidance (aOR 1.80, 95% CI 1.41-2.30). The impact of anxiety on adopting social distancing did not vary by setting. CONCLUSIONS: Our results suggest that health officials should ascertain baseline levels of risk perception and knowledge in populations, as well as prior sensitization to infectious disease outbreaks, during the development of mitigation strategies. Risk should be communicated through suitable media channels-and trust should be maintained-while early intervention remains the cornerstone of effective outbreak response.

Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 seroprevalence survey.

BACKGROUND: Accurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required. METHODS: Sensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by reverse transcription PCR and were ≥21 days from symptom onset. In phase I, we evaluated five LFIAs in clinic (with finger prick) and laboratory (with blood and sera) in comparison to (1) PCR-confirmed infection and (2) presence of SARS-CoV-2 antibodies on two 'in-house' ELISAs. Specificity analysis was performed on 500 prepandemic sera. In phase II, six additional LFIAs were assessed with serum. FINDINGS: 95% (95% CI 92.2% to 97.3%) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8 out of 11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21% to 92% versus PCR-confirmed cases and from 22% to 96% versus composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2%-99.8%). INTERPRETATION: LFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI 97.1% to 99.4%)), moderate sensitivity (84.4% with finger prick (95% CI 70.5% to 93.5%)) and moderate concordance, suitable for seroprevalence surveys.

New approaches to controlling an outbreak of chickenpox in a large immigration detention setting in England: the role of serological testing and mathematical modelling.

Chickenpox is caused by varicella-zoster-virus (VZV) and is highly contagious. Immigration detention settings are a high-risk environment for primary VZV transmission, with large, rapidly-changing populations in close quarters, and higher susceptibility among non-UK-born individuals. During outbreaks, operational challenges occur in detention settings because of high-turnover and the potential need to implement population movement restriction for prolonged periods. Between December 2017 and February 2018, four cases of chickenpox were notified amongst 799 detainees in an immigration removal centre (IRC). Microbiological investigations included case confirmation by vesicular fluid polymerase chain reaction, and VZV serology for susceptibility testing. Control measures involved movement restrictions, isolation of cases, quarantining and cohorting of non-immune contacts and extending VZV immunity testing to the wider detainee population to support outbreak management. Immunity was tested for 301/532 (57%) detainees, of whom 24 (8%) were non-immune. The level of non-immunity was lower than expected based on the existing literature on VZV seroprevalence in detained populations in England. Serology results identified non-immune contacts who could be cohorted and, due to the lack of isolation capacity, allowed the placement of cases with immune detainees. The widespread immunity testing of all detainees was proving challenging to sustain because it required significant resources and was having a severe impact on operational capacity and the ability to maintain core business activities at the IRC. Therefore, mathematical modelling was used to assess the impact of scaling back mass immunity testing. Modelling demonstrated that interrupting testing posed a risk of one additional case compared to continuing with testing. As such, the decision was made to stop testing, and the outbreak was successfully controlled without excessive strain on resources. Operational challenges generated learning for future outbreaks, with implications for a local and national policy on IRC staff occupational health requirements, and proposed reception screening of detainees for VZV immunity.

Sexuality, fertility and family planning characteristics of married women aged 15 to 19 years in Ethiopia, Nigeria and Tanzania: a comparative analysis of cross-sectional data.

BACKGROUND: Adolescents 360 (A360) is an initiative being rolled out across Ethiopia, Nigeria and Tanzania with the aim of increasing uptake of voluntary modern contraception among sexually active women aged 15 to 19 years. Using evaluation baseline survey data, we described key sexuality, fertility and contraceptive use characteristics of married women aged 15 to 19 years living in three sub-national settings. METHODS: Cross-sectional baseline surveys of married women aged 15 to 19 years were conducted in Oromia (Ethiopia), Nasarawa (Northern Nigeria), and Mwanza (Tanzania) between August 2017 and February 2018. We also interviewed the husbands of a sub-group of married respondents to measure spousal acceptance and support for adolescent women to use modern contraception. A clustered sampling design was used in all three countries. We produced descriptive statistics on the socio-demographic and sexual and reproductive health characteristics of married women aged 15 to 19 years by study setting. RESULTS: In Oromia, Nasarawa and Mwanza, 31.4% (327/1198), 27.4% (1321/4816) and 7.5% (15/201) of married women surveyed had no education, and 68.3, 81.3 and 83.1% had ever been pregnant, respectively. Unmet need for modern contraception was 20.5, 21.9 and 32.0% in married women in Oromia, Nasarawa and Mwanza, made up almost entirely of unmet need for spacing. The vast majority of married women surveyed in Oromia (89.1%) and Mwanza (90.1%) had seen or heard about contraception in the last 12 months, compared to 30.1% of those surveyed in Nasarawa. Modern contraceptive prevalence (mCPR) was highest in married women aged 15 to 19 years in Oromia (47.2%), followed by Mwanza (19.4%) and Nasarawa (8.7%). Of those using a modern method of contraception in Oromia, 93.4% were using injectables or long-acting methods, compared to 49.4% in Nasarawa and 69.6% in Mwanza. CONCLUSIONS: Overall, unmet need for modern contraception is high among married women aged 15 to 19 years across the three settings. mCPR for married women aged 15 to 19 years is low in Nasarawa and Mwanza. Ultimately, no single intervention will suit all situations, but improving the quality, analyses and utilisation of subnational data can help decision-makers design more context specific interventions.

Rapid Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis Among Vaccinated and Unvaccinated Individuals Within 1 Year of Rotavirus Vaccine Introduction in England and Wales.

BACKGROUND: The oral infant rotavirus vaccine, Rotarix, was introduced in England and Wales in July 2013. We estimated the impact on laboratory-confirmed rotavirus infections and hospitalizations for all-cause acute gastroenteritis (AGE) during the first year after introduction. METHODS: We extracted data on laboratory-confirmed rotavirus infections (July 2000 through June 2015) and all-cause AGE-associated hospitalizations (July 2007 through June 2014) for all age groups using national databases (LabBase2 and HES). We determined the ratio of the rate during the 2013-2014 rotavirus season to the rate during the prevaccination era. RESULTS: In infants, there was a 77% decline (rate ratio [RR], 0.23; 95% confidence interval [CI], .16-.32) in laboratory-confirmed rotavirus infections and a 26% decline (RR, 0.74; 95% CI, .65-.84) in all-cause AGE-associated hospitalizations in 2013-2014, compared with the prevaccination era. Large reductions were also observed in older children, adults, and older adults. We estimated that 10 884 laboratory-confirmed infections and 50 427 all-cause AGE-associated hospital admissions were averted in 2013-2014. Similar reductions have been observed for laboratory-confirmed rotavirus infections during the 2014-2015 season. CONCLUSIONS: The rapid declines in rotavirus infection and AGE in vaccinated and unvaccinated age groups within 1 year of introducing an infant rotavirus vaccination program are far greater than expected and than previously reported by other countries.

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.

A SARS-CoV-2 outbreak investigation at a storage and distribution centre in England: an assessment of worker- and workplace-related risk factors.

An outbreak of SARS-CoV-2 (1 March to 10 May 2021) with an attack rate of 26.5% among approximately 1150 workers at a storage and distribution centre in England prompted a multidisciplinary outbreak investigation (5 May to 6 August 2021), with the aim of better understanding worker- and workplace-related risk factors for viral transmission in the warehousing sector. Overall, environmental factors (e.g., ventilation, humidity and temperature) were assessed to be appropriate at the facility. Nevertheless, 39 (51.3%) surface samples from across the site tested positive for low/ very low levels of SARS-CoV-2 RNA (Ct value ≥ 32.0 for all). Among the study participants, of whom 35.6% were confirmed or suspected cases, 95.5% reported having received COVID-19 prevention training, 100.0% reported handwashing, and 80.0% reported use of face coverings at work. Notably, 43.9% and 19.0% reported working with a symptomatic and a positive contact respectively. Furthermore, 80.5% and 46.3% had concerns regarding reduction in their income and future unemployment, respectively, due to self-isolation. The findings of this study suggest that, in addition to targeted workplace infection control measures and tailored work area specific risk assessments, an enhanced and equitable sick leave policy may help limit presenteeism and viral transmission in large workplaces.