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.

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.

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.

Awareness and perceptions of Long COVID among people in the REACT programme: Early insights from a pilot interview study.

BACKGROUND: Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID. METHODS: People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis. RESULTS: We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID. CONCLUSION: This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.

Characteristics and predictors of persistent symptoms post-COVID-19 in children and young people: a large community cross-sectional study in England.

OBJECTIVE: To estimate the prevalence of, and associated risk factors for, persistent symptoms post-COVID-19 among children aged 5-17 years in England. DESIGN: Serial cross-sectional study. SETTING: Rounds 10-19 (March 2021 to March 2022) of the REal-time Assessment of Community Transmission-1 study (monthly cross-sectional surveys of random samples of the population in England). STUDY POPULATION: Children aged 5-17 years in the community. PREDICTORS: Age, sex, ethnicity, presence of a pre-existing health condition, index of multiple deprivation, COVID-19 vaccination status and dominant UK circulating SARS-CoV-2 variant at time of symptom onset. MAIN OUTCOME MEASURES: Prevalence of persistent symptoms, reported as those lasting ≥3 months post-COVID-19. RESULTS: Overall, 4.4% (95% CI 3.7 to 5.1) of 3173 5-11 year-olds and 13.3% (95% CI 12.5 to 14.1) of 6886 12-17 year-olds with prior symptomatic infection reported at least one symptom lasting ≥3 months post-COVID-19, of whom 13.5% (95% CI 8.4 to 20.9) and 10.9% (95% CI 9.0 to 13.2), respectively, reported their ability to carry out day-to-day activities was reduced 'a lot' due to their symptoms. The most common symptoms among participants with persistent symptoms were persistent coughing (27.4%) and headaches (25.4%) in children aged 5-11 years and loss or change of sense of smell (52.2%) and taste (40.7%) in participants aged 12-17 years. Higher age and having a pre-existing health condition were associated with higher odds of reporting persistent symptoms. CONCLUSIONS: One in 23 5-11 year-olds and one in eight 12-17 year-olds post-COVID-19 report persistent symptoms lasting ≥3 months, of which one in nine report a large impact on performing day-to-day activities.

Long-term health impacts of COVID-19 among 242,712 adults in England.

The COVID-19 pandemic is having a lasting impact on health and well-being. We compare current self-reported health, quality of life and symptom profiles for people with ongoing symptoms following COVID-19 to those who have never tested positive for SARS-CoV-2 infection and those who have recovered from COVID-19. Overall, 276,840/800,000 (34·6%) of invited participants took part. Mental health and health-related quality of life were worse among participants with ongoing persistent symptoms post-COVID compared with those who had never had COVID-19 or had recovered. In this study, median duration of COVID-related symptoms (N = 130,251) was 1·3 weeks (inter-quartile range 6 days to 2 weeks), with 7·5% and 5·2% reporting ongoing symptoms ≥12 weeks and ≥52 weeks respectively. Female sex, ≥1 comorbidity and being infected when Wild-type variant was dominant were associated with higher probability of symptoms lasting ≥12 weeks and longer recovery time in those with persistent symptoms. Although COVID-19 is usually of short duration, some adults experience persistent and burdensome illness.

Machine learning to support visual auditing of home-based lateral flow immunoassay self-test results for SARS-CoV-2 antibodies.

Background: Lateral flow immunoassays (LFIAs) are being used worldwide for COVID-19 mass testing and antibody prevalence studies. Relatively simple to use and low cost, these tests can be self-administered at home, but rely on subjective interpretation of a test line by eye, risking false positives and false negatives. Here, we report on the development of ALFA (Automated Lateral Flow Analysis) to improve reported sensitivity and specificity. Methods: Our computational pipeline uses machine learning, computer vision techniques and signal processing algorithms to analyse images of the Fortress LFIA SARS-CoV-2 antibody self-test, and subsequently classify results as invalid, IgG negative and IgG positive. A large image library of 595,339 participant-submitted test photographs was created as part of the REACT-2 community SARS-CoV-2 antibody prevalence study in England, UK. Alongside ALFA, we developed an analysis toolkit which could also detect device blood leakage issues. Results: Automated analysis showed substantial agreement with human experts (Cohen's kappa 0.90-0.97) and performed consistently better than study participants, particularly for weak positive IgG results. Specificity (98.7-99.4%) and sensitivity (90.1-97.1%) were high compared with visual interpretation by human experts (ranges due to the varying prevalence of weak positive IgG tests in datasets). Conclusions: Given the potential for LFIAs to be used at scale in the COVID-19 response (for both antibody and antigen testing), even a small improvement in the accuracy of the algorithms could impact the lives of millions of people by reducing the risk of false-positive and false-negative result read-outs by members of the public. Our findings support the use of machine learning-enabled automated reading of at-home antibody lateral flow tests as a tool for improved accuracy for population-level community surveillance.

Risk of thrombosis with thrombocytopenia syndrome after COVID-19 vaccination prior to the recognition of vaccine-induced thrombocytopenia and thrombosis: A self-controlled case series study in England.

Background: Several studies have found increased risks of thrombosis with thrombocytopenia syndrome (TTS) following the ChAdOx1 vaccination. However, case ascertainment is often incomplete in large electronic health record (EHR)-based studies. Objectives: To assess for an association between clinically validated TTS and COVID-19 vaccination. Methods: We used the self-controlled case series method to assess the risks of clinically validated acute TTS after a first COVID-19 vaccine dose (BNT162b2 or ChAdOx1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case ascertainment was performed uninformed of vaccination status via a retrospective clinical review of hospital EHR systems, including active ascertainment of thrombocytopenia. Results: One hundred seventy individuals were admitted to the hospital for a TTS event at the study sites between January 1 and March 31, 2021. A significant increased risk (relative incidence [RI], 5.67; 95% confidence interval [CI], 1.02-31.38) of TTS 4 to 27 days after ChAdOx1 was observed in the youngest age group (18- to 39-year-olds). No other period had a significant increase, although for ChAdOx1 for all ages combined the RI was >1 in the 4- to 27- and 28- to 41-day periods (RI, 1.52; 95% CI, 0.88-2.63; and (RI, 1.70; 95% CI, 0.73-3.8, respectively). There was no significant increased risk of TTS after BNT162b2 in any period. Increased risks of TTS following a positive SARS-CoV-2 test occurred across all age groups and exposure periods. Conclusions: We demonstrate an increased risk of TTS in the 4 to 27 days following COVID-19 vaccination, particularly for ChAdOx1. These risks were lower than following SARS-CoV-2 infection. An alternative vaccine may be preferable in younger age groups in whom the risk of postvaccine TTS is greatest.

Modern contraceptive use among sexually active women aged 15-19 years in North-Western Tanzania: results from the Adolescent 360 (A360) baseline survey.

OBJECTIVES: To describe differences in modern contraceptive use among adolescent women aged 15-19 years according to their marital status and to determine factors associated with modern contraceptive use among sexually active women in this population. DESIGN: Cross-sectional analysis of Adolescent 360 evaluation baseline survey. SETTING: The 15 urban and semiurban wards of Ilemela district, Mwanza region, North-Western Tanzania. PARTICIPANTS: Adolescent women aged 15-19 years who were living in the study site from August 2017 to February 2018 and who provided informed consent. Women were classified as married if they had a husband or were living as married. Unmarried women were classified as sexually active if they reported having sexual intercourse in the last 12 months. OUTCOME MEASURE: Prevalence of modern contraceptive among adolescent women aged 15-19 years. RESULTS: Data were available for 3511 women aged 15-19 years, of which 201 (5.7%) were married and 744 (22.5%) were unmarried-sexually active. We found strong evidence of differences in use of modern contraceptive methods according to marital status of adolescent women. Determinants of modern contraception use among unmarried-sexually active women were increasing age, increasing level of education, being in education, hearing of modern contraception from interpersonal sources or in the media in the last 12 months, perceiving partner and/or friends support for contraceptive use, as well as higher knowledge and self efficacy for contraception. CONCLUSIONS: Sexual and reproductive health programmes aiming to increase uptake of modern contraceptives in this population of adolescent women should consider the importance of girl's education and social support for contraceptive use particularly among unmarried-sexually active women.

Effectiveness of oral rotavirus vaccination in England against rotavirus-confirmed and all-cause acute gastroenteritis.

BACKGROUND: The monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. METHODS: We used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. RESULTS: VE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40-84%) for one dose and 77% (95%CI: 66-85%) for two doses. Two-dose VE in children aged <12 months and ≥12 months was 85% (95%CI: 74-91%) and 54% (95%CI: 15-75%), respectively. In contrast, we found no evidence that the vaccine was effective against all-cause AGE (VE = -20%, 95%CI: -36% to -5%), or against AGE hospitalisations (VE = 35%, 95% CI: -86% to 77%). CONCLUSIONS: In this first detailed assessment of VE of the Rotarix® vaccine in the English national programme, we show that Rotarix® was highly effective in preventing laboratory-confirmed rotavirus infection in young children. This provides reassurance about the vaccine's performance in real-life settings and gives key information for future cost-effectiveness analyses. The high VE against rotavirus-specific AGE, and the exceptionally successful implementation of the national rotavirus vaccine programme (with >90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios.

The UK immunisation schedule: changes to vaccine policy and practice in 2013/14.

Vaccination programmes are implemented either as new vaccines become available or evidence about them accumulates, or in response to specific situations. In the United Kingdom, development and implementation of the national immunisation programme is centrally coordinated and funded by the Department of Health on behalf of England, Wales, Scotland and Northern Ireland. A number of significant changes were made to the UK immunisation schedule for 2013/2014. Three new vaccines were introduced: intranasal influenza and oral rotavirus for children and subcutaneous shingles for older adults. To ensure protection against meningococcal C infection into adulthood, there has been a change to the schedule for meningitis C vaccination. The temporary pertussis vaccination programme for pregnant women, set up in response to an increase in the number of cases of pertussis particularly among young babies, has been extended until further notice. Furthermore, in response to large outbreaks of measles in south Wales and other parts of the UK, a national measles, mumps and rubella catch-up campaign specifically targeted at unvaccinated children aged 10-16 years was launched to ensure that all children and young people have received two doses of measles, mumps and rubella vaccine. This review describes the rationale behind these policy changes.

Direct and indirect effects of rotavirus vaccination: comparing predictions from transmission dynamic models.

Early observations from countries that have introduced rotavirus vaccination suggest that there may be indirect protection for unvaccinated individuals, but it is unclear whether these benefits will extend to the long term. Transmission dynamic models have attempted to quantify the indirect protection that might be expected from rotavirus vaccination in developed countries, but results have varied. To better understand the magnitude and sources of variability in model projections, we undertook a comparative analysis of transmission dynamic models for rotavirus. We fit five models to reported rotavirus gastroenteritis (RVGE) data from England and Wales, and evaluated outcomes for short- and long-term vaccination effects. All of our models reproduced the important features of rotavirus epidemics in England and Wales. Models predicted that during the initial year after vaccine introduction, incidence of severe RVGE would be reduced 1.8-2.9 times more than expected from the direct effects of the vaccine alone (28-50% at 90% coverage), but over a 5-year period following vaccine introduction severe RVGE would be reduced only by 1.1-1.7 times more than expected from the direct effects (54-90% at 90% coverage). Projections for the long-term reduction of severe RVGE ranged from a 55% reduction at full coverage to elimination with at least 80% coverage. Our models predicted short-term reductions in the incidence of RVGE that exceeded estimates of the direct effects, consistent with observations from the United States and other countries. Some of the models predicted that the short-term indirect benefits may be offset by a partial shifting of the burden of RVGE to older unvaccinated individuals. Nonetheless, even when such a shift occurs, the overall reduction in severe RVGE is considerable. Discrepancies among model predictions reflect uncertainties about age variation in the risk and reporting of RVGE, and the duration of natural and vaccine-induced immunity, highlighting important questions for future research.