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Antigen lateral flow devices (LFDs) have been widely used to control SARS-CoV-2. We aimed to improve understanding of LFD performance with changes in variant infections, vaccination, viral load, and LFD use, and in the detection of infectious individuals. In this diagnostic study, paired LFD and RT-PCR test results were prospectively collected from asymptomatic and symptomatic participants in the UK between Nov 4, 2020, and March 21, 2022, to support the National Health Service (NHS) England's Test and Trace programme. The LFDs evaluated were the Innova SARS-CoV-2 Antigen Rapid Qualitative Test, the Orient Gene Rapid Covid-19 (Antigen) Self-Test, and the Acon Flowflex SARS-CoV-2 Antigen Rapid Test (Self-Testing). Test results were collected across various community testing settings, including predeployment testing sites, routine testing centres, homes, schools, universities, workplaces, targeted community testing, and from health-care workers. We used multivariable logistic regression to analyse LFD sensitivity and specificity using RT-PCR as a reference standard, adjusting for viral load, LFD manufacturer, test setting, age, sex, test assistance, symptom status, vaccination status, and SARS-CoV-2 variant. National contact tracing data from NHS Test and Trace (Jan 1, 2021, to Jan 11, 2022) were used to estimate the proportion of transmitting index patients (with ≥1 RT-PCR-positive or LFD-positive contact) potentially detectable by LFDs (specifically Innova, as the most widely used LFD) with time, accounting for index viral load, variant, and symptom status. We assessed 75 382 pairs of LFD and RT-PCR tests. Of these, 4131 (5·5%) were RT-PCR-positive. LFD sensitivity versus RT-PCR was 63·2% (95% CI 61·7–64·6) and specificity was 99·71% (95% CI 99·66–99·74). Increased viral load was independently associated with being LFD positive (adjusted odds ratio [aOR] 2·85 [95% CI 2·66–3·06] per 1 log10 copies per mL increase; p<0·0001). There was no evidence that LFD sensitivity differed for delta (B.1.617.2) infections versus alpha (B.1.1.7) or pre-alpha (B.1.177) infections (aOR 1·00 [0·69–1·45]; p=0·99), whereas omicron (BA.1 or BA.2) infections appeared more likely to be LFD positive (aOR 1·63 [1·02–2·59]; p=0·042). Sensitivity was higher in symptomatic participants (68·7% [95% CI 66·9–70·4]) than in asymptomatic participants (52·8% [50·1–55·4]). Among 347 374 unique index patients with probable onward transmission, 78·3% (95% CI 75·3–81·2) were estimated to have been detectable with LFDs (Innova), and this proportion was mostly stable with time and for successive variants. Overall, the estimated proportion of infectious index patients detectable by the Innova LFD was lower in asymptomatic patients (57·6% [53·6–61·9]) versus symptomatic patients (79·7% [76·7–82·5]). LFDs remained able to detect most SARS-CoV-2 infections throughout vaccine roll-out and across different viral variants. LFDs can potentially detect most infections that transmit to others and reduce the risk of transmission. However, performance is lower in asymptomatic individuals than in symptomatic individuals. UK Health Security Agency, the UK Government Department of Health and Social Care, National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, and the University of Oxford NIHR Biomedical Research Centre.

BackgroundRapid identification of individuals with acute respiratory infections is crucial for preventing nosocomial infections. For rapid diagnosis, especially in EDs, lateral flow devices (LFDs) are a convenient, inexpensive option with a rapid turnaround. Several ‘multiplex’ LFDs (M-LFDs) now exist, testing for multiple pathogens from a single swab sample. We evaluated the real-world performance of M-LFD versus PCR testing in detecting influenza A, B and SARS-CoV-2) in the ED setting.MethodsAfter preliminary evaluation of an M-LFD (SureScreen) with laboratory-grown virus and PCR-negative clinical samples, it was evaluated in a real-world setting at the ED of St Thomas’ Hospital (London, UK) from 1 December 2022 to 21 April 2023. Eligible participants were ≥18 years of age, admitted with respiratory symptoms and received concurrent M-LFD and PCR tests. Main endpoints were sensitivity to detect influenza A/B (primary) and SARS-CoV-2 (secondary) versus PCR. The probability of a true positive in relation to viral concentration (expressed as PCR cycle threshold (Ct)) was analysed using logistic regression.ResultsIn total, 808 symptomatic participants were included (49.8% female; mean age 46.9 years). Test sensitivity (95% CI) was 67.0% (56.9% to 76.1%) for influenza A (n=100), 94.1% (71.3% to 99.9%) for influenza B (n=17) and 48.2% (39.7% to 56.8%) for SARS-CoV-2 (n=141). Sensitivity for SARS-CoV-2 was significantly lower than that for influenza A and B (p=0.0057 and p=0.00088, respectively). The probability of a true positive was 98% for Ct<25 for influenza A and SARS-CoV-2 (influenza B non-evaluable). No co-infections were identified by PCR or M-LFD.ConclusionThe real-world performance of SureScreen M-LFD was consistent with laboratory evaluation and achieved a high sensitivity for individuals with high viral concentration, most likely to be infectious. Given the representative UK population sample, results could be generalised for use in other settings.

This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood–brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF:serum albumin ratio indicative of impairment of the blood–CSF and blood–brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-α levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood–brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood–brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-α was associated with a good prognosis.

Human herpes virus 6 (HHV6) DNA was detected in two of eight fetuses with hydrops and none of ten non-hydropic dead fetuses. Both cases with HHV6 DNA had chromosomal abnormalities. Positive results were confirmed with a second PCR specific for an alternate region of the HHV6 genome. Restriction endonuclease analysis confirmed that the viral DNA was representative of HHV6 type A.

Objectives: To assess the feasibility and utility of sentinel laboratory surveillance of HIV testing as a tool for understanding patterns and trends in HIV testing in a range of healthcare services. Methods: Data on all anti-HIV antibody tests carried out by the Leeds General Infirmary laboratory over a twelve-month period were collated and analysed by demographic information and place of test. Individuals who tested positive were matched to the national database of HIV diagnoses to identify the proportion newly diagnosed with HIV. Results: 41,013 individuals over one year of age were tested at least once for HIV during the study period, of whom 0.8% (n=312) were positive. The majority of individuals (77%) were tested in a GUM clinic or as part of antenatal care, whilst routine testing of people undergoing haemodialysis, fertility treatment or occupational health screening accounted for a further 14% of testing. Few individuals (<4%) were tested in general practice. Of the 312 people testing positive, 286 could be matched to the HIV national database and 173 (60%) were identified as newly diagnosed. Conclusions: Little HIV testing is currently performed outside GUM and antenatal settings. Monitoring of HIV testing is essential given new guidelines recommending the expansion of testing in a wide range of settings. Sentinel laboratory surveillance can provide useful demographic data on persons tested for HIV and can assess trends in testing over time. Data on HIV testing could be incorporated into existing hepatitis sentinel surveillance, allowing rapid scale-up of this surveillance scheme with minimal effort.

AIMS/BACKGROUND: Herpes simplex virus (HSV) may establish latent infection in the cornea and therefore be transmissible by corneal transplantation. Monitoring of donor cornea culture medium was evaluated for HSV infection. METHODS: HSV was sought using virus isolation in cell culture, and its DNA was amplified to detectable levels using the polymerase chain reaction (PCR). RESULTS: Virus isolation in cell culture was negative on neat, cell pellet, and cell free supernatant prepared from the spent culture media of 80 corneas. Three cell pellets (3.8%) were positive for HSV DNA. The PCR positive culture negative results might have reflected latent rather than active HSV infection of the cornea. Post transplant follow up of the three recipients of corneas with HSV PCR positive organ culture media revealed no evidence of HSV induced eye disease or primary graft failure. CONCLUSION: Screening of corneal culture medium for HSV by virus culture or for HSV DNA by PCR could not be recommended.

A further item of value in detection of nucleic acid in ocular specimens is in the assessment of treatment failure. [...]recently, treatment failure was defined solely on the basis of positive culture. [...]nucleic acid amplification procedures are valuable modern techniques for the diagnosis of infectious ocular disease.

Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7–8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials. Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers. Genomic landscape of childhood cancers The genetic alterations that give rise to childhood cancer are less well studied than those that give rise to adult cancers. Two papers in this issue report some of the first pan-cancer analyses of childhood cancers. Stefan Pfister and colleagues studied germline and somatic genomes from 914 young cancer patients, including children, adolescents and young adults. The tumour samples comprised 24 distinct molecular cancer types, including the most frequent and clinically relevant childhood cancers. The team characterized somatic mutation frequencies, genomic alterations, including structural variations and copy-number analysis, and mutational signatures. They found signatures associated with deficiencies of double-stranded break repair across all cancer types. Additionally, 7.6% of patients carried a likely pathogenic germline variant in a candidate cancer predisposition gene. Jinghui Zhang and colleagues analysed the genomes, exomes and transcriptomes of 1,699 paediatric leukaemias and solid tumours. They identified 142 driver genes in paediatric cancers, over half of which were specific to a single histotype. They also characterized copy number alterations and structural variation and identified 11 mutational signatures. Together, these papers provide a comprehensive resource for genomic alterations across common paediatric tumours, and highlight differences compared with the genomic alterations seen in adult cancers.