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Inquilinus limosus is an uncommon, poorly understood bacterium capable of infecting the respiratory tracts of people with cystic fibrosis. The transmission, clinical relevance and changes in antimicrobial resistance of I. limosus over time are unclear due to the low frequency of identification. We report three co-habiting brothers with cystic fibrosis who developed chronic I. limosus infection and document the clinical and microbiological features of the infections. Clinical evolution after Inquilinus infection varied but was associated with an initial decline in lung function. Familial clustering of this rare pathogen raises the possibility of cross-infection as a potential mechanism of transmission of Inquilinus between CF patients.

Abstract Background The objective of this study is to analyze the spatial and temporal patterns of malaria incidence as to determine the means by which climatic factors such as temperature, rainfall and humidity affect its distribution in Maputo province, Mozambique. Methods This study presents a model of malaria that evolves in space and time in Maputo province-Mozambique, over a ten years period (1999-2008). The model incorporates malaria cases and their relation to environmental variables. Due to incompleteness of climatic data, a multiple imputation technique is employed. Additionally, the whole province is interpolated through a Gaussian process. This method overcomes the misalignment problem of environmental variables (available at meteorological stations - points) and malaria cases (available as aggregates for every district - area). Markov Chain Monte Carlo (MCMC) methods are used to obtain posterior inference and Deviance Information Criteria (DIC) to perform model comparison. Results A Bayesian model with interaction terms was found to be the best fitted model. Malaria incidence was associated to humidity and maximum temperature. Malaria risk increased with maximum temperature over 28°C (relative risk (RR) of 0.0060 and 95% Bayesian credible interval (CI) of 0.00033-0.0095) and humidity (relative risk (RR) of 0.00741 and 95% Bayesian CI 0.005141-0.0093). The results would suggest that additional non-climatic factors including socio-economic status, elevation, etc. also influence malaria transmission in Mozambique. Conclusions These results demonstrate the potential of climate predictors particularly, humidity and maximum temperature in explaining malaria incidence risk for the studied period in Maputo province. Smoothed maps obtained as monthly average of malaria incidence allowed to visualize months of initial and peak transmission. They also illustrate a variation on malaria incidence risk that might not be related to climatic factors. However, these factors are still determinant for malaria transmission and intensity in the region.

Abstract Background The objective was to study if an association exists between the incidence of malaria and some weather parameters in tropical Maputo province, Mozambique. Methods A Bayesian hierarchical model to malaria count data aggregated at district level over a two years period is formulated. This model made it possible to account for spatial area variations. The model was extended to include environmental covariates temperature and rainfall. Study period was then divided into two climate conditions: rainy and dry seasons. The incidences of malaria between the two seasons were compared. Parameter estimation and inference were carried out using MCMC simulation techniques based on Poisson variation. Model comparisons are made using DIC. Results For winter season, in 2001 the temperature covariate with estimated value of -8.88 shows no association to malaria incidence. In year 2002, the parameter estimation of the same covariate resulted in 5.498 of positive level of association. In both years rainfall covariate determines no dependency to malaria incidence. Malaria transmission is higher in wet season with both covariates positively related to malaria with posterior means 1.99 and 2.83 in year 2001. For 2002 only temperature is associated to malaria incidence with estimated value 2.23. Conclusions The incidence of malaria in year 2001, presents an independent spatial pattern for temperature in summer and for rainfall in winter seasons respectively. In year 2002 temperature determines the spatial pattern of malaria incidence in the region. Temperature influences the model in cases where both covariates are introduced in winter and summer season. Its influence is extended to the summer model with temperature covariate only. It is reasonable to state that with the occurrence of high temperatures, malaria incidence had certainly escalated in this year.

Abstract Background Asthma and COPD are major health problems and an extensive burden for the patient and the health care system. Patient education has been recommended, but the influence on knowledge and health outcomes is not fully examined. Our aims were to compare patient characteristics, education and knowledge in patients who had an emergency room (ER) visit, to explore factors related to disease knowledge, and to investigate patient characteristics, patient education and knowledge in relation to further ER visits over a 12 month period. Methods Eighty-four patients with asthma and 52 with COPD, who had had an ER visit, were included. They were interviewed by telephone 4 to 6 weeks after the ER visit and followed for a year. Results Patients with COPD were older, more sedentary, had had more ER visits the previous year, and had more co morbidity than patients with asthma. About 80% of the patients had received information from health professionals or participated in education/rehabilitation, but a minority (< 20%) reported that their knowledge about how to handle the disease was good. Patients with "good knowledge" were younger, were more likely to have asthma diagnose, and had a higher educational background (p < 0.05). Sixty-seven percent of the patients with COPD had repeated ER visits during the following year versus 42% in asthma (p < 0.05) (adjusted HRR: 1.73 (1.03-2.90)). Patients who had had ER visits the year before inclusion had a higher risk of ER visits the following year (adjusted HRR: 3.83 (1.99-7.38)). There were no significant differences regarding patient education and knowledge between the group with and without further ER visits after adjusting for sex, diagnose, age, and educational background. Conclusion Patients with asthma had a better self reported knowledge of disease management and were less likely to have new exacerbations than patients with COPD. Reported level of knowledge was, however, in it self not a predictor of exacerbations. This indicates that information is not sufficient to reduce the burden of disease. Patient education focused on self-management and behavioral change should be emphasized.

Introduction and Objectives: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). In African populations, HCC frequently presents at an advanced stage with poor outcomes. We applied whole genome sequencing (WGS) to compare HBV genomes in individuals with and without HCC., Materials and Methods: We identified adults with HBV infection, with and without complicating HCC, in Cape Town, South Africa. We generated HBV WGS using pan-genotypic probe-based enrichment followed by Illumina sequencing., Results: Compared to the non-HCC group, HCC patients were more likely to be male (p < 0.0001), older (p = 0.01), HIV-negative (p = 0.006), and have higher HBV viral loads (p < 0.0001). Among 19 HCC and 12 non-HCC patients for whom WGS was obtained, genotype A dominated (74 %), of which 96 % were subgenotype A1. PreS2 deletions (Δ38-55) were enriched in HBV sequences from HCC patients (n = 7). The sequence motif most strongly associated with HCC comprised either a deletion or polymorphism at site T53 in PreS2 - collectively coined 'non-T53' - together with a basal core promoter (BCP) mutation G1764A (AUROC = 0.79)., Conclusions: In this setting, HBV sequence polymorphisms and deletions are associated with HCC, and 'non-T53 + G1764A' represents a putative signature motif for HCC. Additional investigations are needed to disaggregate the impact of other demographic, clinical, and environmental influences, to ascertain the extent to which viral polymorphisms contribute to oncogenesis, and to determine whether HBV sequence is a useful biomarker for HCC risk stratification., Competing Interests: Declaration of competing interest PCM has participated in projects supported by GSK, outside the direct scope of the work presented here. MIA has participated in projects supported by Prenetics, J&J, and Pfizer outside the direct scope of this work. AK is an Associate Editor for the journal Annals of Hepatology. All other authors declare no conflicts of interest., (Copyright © 2025 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals., (© 2024 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Objectives: Chronic hepatitis B infection affects 65 million people in the WHO African Region, but only 4.2% of these are diagnosed and 0.2% on treatment. Here, we present a short report describing establishment of a hepatitis B virus (HBV) programme in Kenya. We share experiences, successes and challenges to support development of future programmes., Methods: From March 2023, we began the 'STRIKE-HBV' Study to identify people living with HBV (PLWHB) in Kilifi, Kenya. We employed local staff and provided education and training. Individuals were identified through three routes: (1) we offered free-of-charge HBV testing for all non-pregnant adults attending Kilifi Country Hospital (KCH) outpatient department; (2) we invited PLWHB to reattend for review; and (3) we invited close contacts of PLWHB for screening and vaccination if HBV was negative. All those seropositive for HBV were offered a comprehensive liver health assessment., Results: We have established a framework for HBV screening, assessment and linkage to care in Kilifi. Between March 2023 and March 2024, we collected data for 80 PLWHB, comprising (1) screening of 1862 people of whom 30 were seropositive, (2) enrolment of 38 people known to be living with HBV and (3) testing of 97 close contacts of PLWHB, of whom 12 were positive. Among a limited subset with elastography data, we identified 9 of 59 as having significant fibrosis, and a further 6 people had laboratory aspartate transaminase (AST) to platelet ratio index (APRI) scores in keeping with fibrosis. We encountered challenges including procurement delays for hepatitis B surface antigen testing kits and HBV vaccinations, and issues accessing liver elastography., Conclusions: HBV screening was well received by the Kilifi population, has identified people at risk of liver disease progression and is improving linkage to care and vaccination at KCH. Future HBV programmes in WHO Africa can build on this experience as we work to develop accessible, affordable and acceptable care pathways., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Hepatitis B virus (HBV) elimination requires expanding and decentralising HBV care services. However, peripheral health facilities lack access to diagnostic tools to assess eligibility for antiviral therapy. Through the Hepatitis B in Africa Collaborative Network (HEPSANET), we aimed to develop and evaluate a score using tests generally available at lower-level facilities, to simplify the evaluation of antiviral therapy eligibility in people living with HBV., Methods: We surveyed the availability of clinical and laboratory parameters across different health-care levels in sub-Saharan Africa. We used data from the HEPSANET dataset, the largest cross-sectional dataset of treatment-naive people living with HBV in sub-Saharan Africa, to derive and validate the score. Participants from this dataset were included in the analysis if they were aged 18 years or older and had liver fibrosis stages determined by a liver stiffness measurement or liver histopathology. Participants with co-infections or metabolic disorders were excluded. We allocated participants to the derivation and validation sets by geographical site. In the derivation set, we used stepwise logistic regression to identify the best performing parameters for identifying participants that met the 2017 European Association for the Study of the Liver (EASL) criteria. Regression coefficients were converted into integer points to construct simplified algorithms for different health-care levels. In the validation set, we estimated the area under the receiver operating characteristic, sensitivity, and specificity of the simplified algorithm for identifying antiviral therapy eligibility defined by the 2017 EASL criteria., Findings: At 11 sites from eight countries that returned surveys, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count were generally available at district hospital levels, and hepatitis B e antigen and point-of-care HBV DNA tests were available only at regional and provincial hospital levels or above. Among 2895 participants included from the HEPSANET database (1740 [60·1%] male, 1155 [39·9%] female), 409 (14·1%) met EASL antiviral therapy eligibility criteria. In the derivation set, the optimal district-level hospital score was: ALT (IU/L), less than 40 (0 points), 40-79 (+1), 80 or greater (+2); AST (IU/L), less than 40 (0), 40-79 (+1), 80 or greater (+2); and platelet counts (10 9 /L), less than 100 (+2), 100-149 (+1), 150 or greater (0). When combined with family history and clinical data for decompensated cirrhosis that do not require any biological tests, a cut-off of 2 points or more had a sensitivity and specificity of 82% (95% CI 76-86) and 95% (93-96) to identify treatment-eligible individuals in the derivation set, and 78% (71-85) and 87% (86-89) in the validation set, respectively., Interpretation: Using a score incorporating platelet counts, AST, and ALT, the majority of people living with HBV requiring antiviral therapy can be identified. Our findings suggest that clinical staging can be decentralised down to district hospital level in sub-Saharan Africa., Funding: European Association for the Study of the Liver Foundation, John C Martin Foundation., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests CWS has received speaker bureau honoraria from Gilead Sciences and Abbott, as well as travel support from Gilead Sciences. ES has received a research grant from Gilead Sciences. GW has received a research grant from Roche Diagnostics, Roche Molecular, and Gilead Sciences, and consulting fees from Gilead Sciences, Merck Sharp and Dohme, and ViiV. MA has received research grants from Prenetics, Pfizer, and Johnson & Johnson; consulting fees from Prenetics; honoraria from Pfizer; travel support from WHO; reports planned patents for Ramanomics and LAMP GC/CT/HSV/HBV; and is an unpaid board member of the Charity E3 initiative. MSo has received speaker bureau honoraria from Roche and Gilead Sciences, and travel support from Gilead Sciences. MV has received funding from the US National Institutes of Health (R01AI147727), and travel support from Africa Centres for Disease Control and Prevention. PCM has received funding from the Wellcome Trust (110110) and the Francis Crick Institute, and also reports sponsorship from GSK for a doctoral student, outside the scope of the current work. YS has received a research grant and honoraria for lectures from Gilead Sciences and research materials from Abbott Laboratories and Fujirebio. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Chronic hepatitis B infection (CHB) is a significant problem worldwide with around 300 million people infected. Ambitious goals have been set towards its elimination as a public health threat by 2030. However, accurate seroprevalence estimates in many countries are lacking or fail to provide representative population estimates, particularly in the WHO African Region (AFRO). This means the full extent of HBV infection is not well described, leading to a lack of investment in diagnostics, treatment and disease prevention. Clinical trials in the WHO AFRO region have been increasing over time and many test for infectious diseases including hepatitis B virus (HBV) to determine baseline eligibility for participants, however these screening data are not reported. Here we review data from six clinical trials completed at the KEMRI-Wellcome Trust Research Programme between 2016 and 2023 that screened for HBV using hepatitis B surface antigen (HBsAg) as part of the trial exclusion criteria. 1727 people had HBsAg results available, of which 60 tested positive. We generated a crude period HBV prevalence estimate of 3.5% (95% CI 2.6-4.5%), and after standardisation for sex and age to account for the population structure of the Kilifi Health Demographics Surveillance System (KHDSS), the prevalence estimate increased to 5.0% (95% CI 3.4-6.6%). The underrepresentation of women in these trials was striking with 1263/1641 (77%) of participants being male. Alanine aminotransferase (ALT) was significantly higher in the HBsAg positive group but was not outside the normal range. We argue that routine collation and publishing of data from clinical trials could increase precision and geographical representation of global HBV prevalence estimates, enabling evidence-based provision of clinical care pathways and public health interventions to support progress towards global elimination targets. We do acknowledge when using clinical trials data for seroprevalence estimates, that local population structure data is necessary to allow standardisation of results, and the point of care tests used here are limited in sensitivity and specificity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: To determine the impact of the COVID-19 pandemic on the population with chronic Hepatitis B virus (HBV) infection under hospital follow-up in the UK, we quantified the coverage and frequency of measurements of biomarkers used for routine surveillance (alanine transferase [ALT] and HBV viral load)., Methods: We used anonymized electronic health record data from the National Institute for Health Research (NIHR) Health Informatics Collaborative (HIC) pipeline representing five UK National Health Service (NHS) Trusts., Results: We report significant reductions in surveillance of both biomarkers during the pandemic compared to pre-COVID-19 years, both in terms of the proportion of patients who had ≥1 measurement annually, and the mean number of measurements per patient., Conclusions: These results demonstrate the real-time utility of HIC data in monitoring health-care provision, and support interventions to provide catch-up services to minimise the impact of the pandemic. Further investigation is required to determine whether these disruptions will be associated with increased rates of adverse chronic HBV outcomes., Competing Interests: Competing interests: GC reports personal fees from Gilead and Merck Sharp & Dohme outside the submitted work. BG reports other from Imperial National Institute for Health Research (NIHR) Biomedical Research Centres (BRC), during the conduct of the study. EN reports grants from ViiV healthcare, grants from GlaxoSmithKline (GSK), grants from Gilead, outside the submitted work. Other authors have no conflict of interest., (Copyright: © 2023 Campbell C et al.)

Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19., Methods and Analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid)., Eligibility Criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18-49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial., Ethics and Dissemination: Ethical approval granted by South Central-Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals., Trial Registration Number: ISRCTN30448031; EudraCT number: 2021-005748-31., Competing Interests: Competing interests: JN-V-T was seconded to the Department of Health and Social Care, England (DHSC) from October 2017 to March 2022. The views expressed in this paper are those of its authors and not necessarily those of DHSC. JN-V-T reports a lecture fee from Gilead Sciences Ltd (manufacturer of remdesivir) and a paid Influenza Advisory Board for F. Hoffmann-La Roche (manufacturer of tocilizumab), both after March 2022. KH is a member of the following NIHR committees: HTA General Committee, HTA Funding Strategy Group, Research Professors Funding Committee. KH is co-investigator on the grant provided by UKRI/NIHR, Grant number NIHR135366 (subcontract from University of Oxford to Cardiff University). KH received a grant from AstraZeneca to support a trial of Evusheld for the prevention of COVID in high-risk individuals (to Cardiff University). KH is an independent member of the IDMC for the OCTAVE-DUO trial of vaccines for COVID in high-risk individuals (unpaid). DML has received grants/contracts from LifeArc, Medical Research Council, Bristol Myers Squibb and Blood Cancer UK. DML received personal fees/honoraria for a lecture from Biotest UK, for an educational video from Gilead and for a ‘round table’ discussion with Merck. SP is co-investigator on the grant provided by UKRI/NIHR, Grant number NIHR135366. DR has received consulting fees from OMASS therapeutics. DR has a leadership/fiduciary role in the Heal-COVID trial TMG. BRS reports grant money paid to his employer (Berry Consultants, LLC) from The University of Oxford, from the Sponsor’s grant from the UKRI/NIHR, per the statistical design and analyses for the PANORAMIC trial. GH reports that the NIHR funded this study. ML reports funding directly from the PANORAMIC trial (NIHR). ML reports being a RAPIS-TEST (NIHR EME) DMC member. JM reports that this is part of his consulting work for Berry Consultants. SK reports research funding from GSK, ViiV Healthcare, Ridgeback Biotherapeutics, Vir and Merck unrelated to this work. SK reports speaker’s fees from ViiV Healthcare and participation on ViiV Healthcare, Pfizer advisory boards. SK reports receiving donation of drugs for clinical studies from ViiV Healthcare, Toyama and GSK. JFS reports receiving research grants from MRC (MR/X004724/1), Wellcome, NIHR, DNDi, Gates and MRC (MR/W015560/1) paid to his institution. JFS reports receiving Pharmacometric consultancy fees from Adrenomed Ltd paid to his institution. JFS reports participation on a Data Safety Monitoring board/Advisory Board for GSK Sotrovimab paediatric programme. MIA reports receiving grants from BTRU – GEMS, Janssen – Cartography, Pfizer – Myst, Prenetics, Dunhill Medical Trust, BMA Trust – Kathleen Harper Fund and Antibiotic Research UK – all paid to the institution. MIA reports receiving consultancy fees from Prenetics and OxDx. MIA reports a planned patent for Ramanomics. MIA reports participation on a Data Safety Monitoring board/Advisory Board for Prenetics. MIA has an unpaid leadership/fiduciary role in the E3 Initiative. NPBT reports his current affiliations with RCGP and NIHR TVSM. NPBT reports a payment for a single episode of participation on the MSD advisory board in July 2021, prior to any knowledge or planning of this trial. OvH reports receiving an NIHR Development and Skills Personal Award. OvH reports receiving consulting fees for MINDGAP BV, with the fees paid to Oxford University lnnovation Limited. OvH reports unpaid participation on a Data Safety Monitoring board/Advisory Board for The CHIldren with COugh Cluster Randomised Controlled Trial (CHICO). OvH has an unpaid leadership/fiduciary role in the British Society of Antimicrobial Chemotherapy. CB reports full employment with the Nuffield Department of Primary Care Health Sciences. AU reports receiving consulting fees and payment/honoraria from Merck/MSD and Gilead Sciences. RH reports receiving expenses reimbursed for talks on COVID monoclonal antibodies. PL reports support from the NIHR for the grant to do the PANORAMIC study. NF reports receiving consulting fees from Abbott Diagnostics and GSK, a presentation fee from Abbott Diagnostics, and has stocks in Synairgen PLC., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To present a systematic review and critical analysis of clinical studies for necrotising otitis externa (NOE), with the aim of informing best practice for diagnosis and management., Design: Medline, Embase, Cochrane Library and Web of Science were searched from database inception until 30 April 2021 for all clinical articles on NOE. The review was registered on PROSPERO (ID: CRD42020128957) and conducted in accordance with PRISMA guidelines., Results: Seventy articles, including 2274 patients were included in the final synthesis. Seventy-three percent were retrospective case series; the remainder were of low methodological quality. Case definitions varied widely. Median patient age was 69.2 years; 68% were male, 84% had diabetes and 10% had no reported immunosuppressive risk factor. Otalgia was almost universal (96%), with granulation (69%) and oedema (76%) the commonest signs reported. Pseudomonas aeruginosa was isolated in 62%, but a range of bacterial and fungal pathogens were reported and 14% grew no organism. Optimal imaging modality for diagnosis or follow-up was unclear. Median antimicrobial therapy duration was 7.2 weeks, with no definitive evidence for optimal regimens. Twenty-one percent had surgery with widely variable timing, indication, or procedure. One-year disease-specific mortality was 2%; treatment failure and relapse rates were 22% and 7%, respectively., Conclusion: There is a lack of robust, high-quality data to support best practice for diagnosis and management for this neglected condition. A minimum set of reporting requirements is proposed for future studies. A consensus case definition is urgently needed to facilitate high-quality research., (© 2023 The Authors. Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Objective: To establish consensus definitions for necrotising otitis externa (NOE) to facilitate the diagnosis and exclusion of NOE in clinical practice and expedite future high-quality study of this neglected condition., Design: The work comprised of a systematic review of the literature, five iterative rounds of consultation via a Delphi process and open discussion within the collaborative. An expert panel analysed the results to produce the final outputs which were shared with and endorsed by national specialty bodies., Setting: Secondary care in the UK., Participants: UK clinical specialists practising in infection, ear nose and throat (ENT) surgery or radiology., Main Outcome Measures: Definitions and statements meeting the following criteria were accepted: (a) minimum of 70% of respondents in agreement or strong agreement with a definition/statement AND (b) <15% of respondents in disagreement or strong disagreement with a definition/statement., Results: Seventy-four UK clinicians specialising in ENT, Infection and Radiology with a special interest in NOE took part in the work which was undertaken between 2019 and 2021. The minimum response rate for a Round was 76%. Consensus criteria for all proposed case definitions, outcome definitions and consensus statements were met in the fifth round., Conclusions: This work distills the clinical opinion of a large group of multidisciplinary specialists from across the UK to create practical definitions and statements to support clinical practice and research for NOE. This is the first step in an iterative process. Further work will seek to validate and test these definitions and inform their evolution., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There are 82 million people living with hepatitis B (PLWHB) in the World Health Organization Africa region, where it is the main cause of liver disease. Effective vaccines have been available for over 40 years, yet there are 990,000 new infections annually, due to limited implementation of hepatitis B birth dose vaccination and antenatal tenofovir prophylaxis for highly viraemic women, which could eliminate mother-to-child transmission. Despite effective and cheap antiviral treatment which can suppress hepatitis B virus replication and reduce the risk of hepatocellular carcinoma (HCC), < 2% of PLWHB are diagnosed, and only 0.1% are treated. As a result, PLWHB are frequently diagnosed only when they have already developed decompensated cirrhosis and late-stage HCC, and consequently 80,000 hepatitis B-associated deaths occur each year. Major barriers include complex treatment guidelines which were derived from high-income settings, lack of affordable diagnostics, lack or insufficient domestic funding for hepatitis care, and limited healthcare infrastructure. Current treatment criteria may overlook patients at risk of cirrhosis and HCC. Therefore, expanded and simplified treatment criteria are needed. We advocate for decentralized community treatment programmes, adapted for low-resource and rural settings with limited laboratory infrastructure. We propose a strategy of treat-all except patients fulfilling criteria that suggest low risk of disease progression. Expanded treatment represents a financial challenge requiring concerted action from policy makers, industry, and international donor agencies. It is crucial to accelerate hepatitis B elimination plans, integrate hepatitis B care into existing healthcare programmes, and prioritize longitudinal and implementation research to improve care for PLWHB., Competing Interests: Competing interestsML has received consultancy fees from Abbott and GILEAD Sciences. CWS has received Speaker Bureau Fees for educational purposes from GILEAD Sciences and Abbott. MWS has received Speaker Bureau Fees for educational purposes from GILEAD Sciences. GW has received fees for advisory boards and lectures from MSD, Gilead Sciences and ViiV; all these fees were paid to his institution. The remaining authors declare that they have no competing interests., (© The Author(s) 2023.)

Reverse transcription (RT) - loop-mediated isothermal amplification (LAMP) assay is a rapid and one-step method to detect SARS-CoV-2 in the pandemic. Quantitative estimation of the viral load of SARS-CoV-2 in patient samples could help physicians make decisions on clinical treatment and patient management. Here, we propose to use a quantitative LAMP (qLAMP) method to evaluate the viral load of SARS-CoV-2 in samples. We used threshold time (TT) values of qLAMP, the isothermal incubation time required for the fluorescent or colorimetric signal to reach the threshold, to indicate the viral load of clinical samples. Similar to the cycle threshold (C t ) values in conventional qPCR, TT values of qLAMP show a linear relationship to the copy numbers of SARS-CoV-2. The higher the viral loadings, the lower qLAMP TT values are. The RT-qLAMP assay was demonstrated to quantify the viral loads of synthesized full-length RNA, inactivated viral particles (BBIBP-CorV), and clinical samples within 15 min by fluorescent reading and 25 min by colorimetric reading. The RT-qLAMP has been applied to detect Alpha, Beta, Kappa, Delta, and Omicron variants of SARS-CoV-2, as well as the human beta-actin gene, and their TT values showed the linear patterns. The RT-qLAMP assays were evaluated by 64 clinical samples (25 positives and 39 negatives) for the assessment of viral loads, and it was also used to quantify the human beta-actin gene, which was used as a control and an indicator of sampling quality in clinical swab samples. The result of RT-qLAMP was in good agreement with the result of RT-qPCR. The RT-qLAMP assay detected all clinical samples, including those with C t  = 35, within 10 min using fluorescent reading., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

High rates of azole-resistance and limited availability of pharmacological agents within the UK can make recurrent vulvovaginal candidiasis (RVVC) with Candida glabrata a challenging infection to treat. In this report, we describe our experience in managing C. glabrata RVVC and present the case of a patient with poor response to therapy and a protracted treatment course, spanning almost 4 years. We also highlight the need for evidence-based management protocols that consider the national availability of alternative treatments.

Background: Necrotising otitis externa is a severe ear infection for which there are no established diagnostic or treatment guidelines., Method: This study described clinical characteristics, management and outcomes for patients managed as necrotising otitis externa cases at a UK tertiary referral centre., Results: A total of 58 (63 per cent) patients were classified as definite necrotising otitis externa cases, 31 (34 per cent) as probable cases and 3 (3 per cent) as possible cases. Median duration of intravenous and oral antimicrobial therapy was 6.0 weeks (0.49-44.9 weeks). Six per cent of patients relapsed a median of 16.4 weeks (interquartile range, 23-121) after stopping antimicrobials. Twenty-eight per cent of cases had complex disease. These patients were older ( p = 0.042), had a longer duration of symptoms prior to imaging ( p < 0.0001) and higher C-reactive protein at diagnosis ( p = 0.005). Despite longer courses of intravenous antimicrobials (23 vs 14 days ; p = 0.032), complex cases were more likely to relapse ( p = 0.016)., Conclusion: A standardised case-definition of necrotising otitis externa is needed to optimise diagnosis, management and research.

Background: Colchicine has been proposed as a COVID-19 treatment., Aim: To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community., Design and Setting: Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE)., Method: Adults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models., Results: The trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine ( n = 156), usual care ( n = 1145), and other treatments ( n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of -0.4% (95% CrI = -2.7 to 2.4)., Conclusion: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community., (© The Authors.)

Introduction: Current UK guidelines for cervical cancer screening are based on the assumption that most women living with HIV (WLWH) are also high-risk (HR) human papillomavirus (HPV)-positive. We aimed to provide data on prevalence of HR-HPV in WLWH in the UK and to assess feasibility and acceptability of HR-HPV self-sampling in this group., Methods: Women living with HIV attending six HIV services in London/south of England, with no history of cervical cancer, were enrolled. Participants self-collected a vaginal swab for the detection of HR-HPV, completed a survey about sexual/gynaecological history, attitudes towards annual screening and perception of HR-HPV self-sampling, and were asked to have their annual cervical smear., Results: In all, 67 women were included: 86.5% were of black ethnicity, the median (range) age was 47 (24-60) years, median CD4 T-cell count was 683 cells/µL [interquartile range (IQR): 527-910], and 95.4% had viral load ≤ 50 copies/mL. All performed the vaginal swab. Eighteen (27%) had no cervical smear results; none of these women attended HIV services where this was routinely offered. No cervical samples were positive for HR-HPV. Three-quarters (75.8%) of participants reported adherence to annual screening, with only one woman (1.5%) attending irregularly. On visual analogue scales (from 0 to 100), median (IQR) acceptability and necessity of smear tests were 100 (75-100) and 100 (85-100), respectively., Conclusions: Our results suggest that the prevalence of HR-HPV in WLWH in the UK may be low. Self-sampling seems to be acceptable, suggesting, if validated, its potential role in supporting less frequent smear testing and improving screening uptake in WLWH., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Stenotrophomonas maltophilia causes opportunistic respiratory infections and is associated with declining lung function in patients with cystic fibrosis (CF). Risk factors for carrying S. maltophilia remain unclear., Methods: We conducted a retrospective study of patients yielding ⩾1 respiratory S. maltophilia isolate at the Oxford University Hospitals Trust between 2014 and 2019 and a cohort study of S. maltophilia carriage in CF patients attending annual review in 2018., Results: Seven hundred and forty isolates were identified from 238 patients (median 1.0 isolate/patient). Predisposing conditions included invasive ventilation (29.8%), CF (25.6%) and non-CF bronchiectasis (24.4%). The rates of Stenotrophomonas isolates and co-trimoxazole resistance were stable over time. About 10.8% of isolates were co-trimoxazole-resistant, with resistance more common in CF than in other diagnoses (29.5% vs 5.8%, p  < 0.001). No clinical features were significantly associated with S. maltophilia carriage in the CF population., Discussion: We present new insight into the epidemiology of Stenotrophomonas colonisation/infection and identify increased co-trimoxazole resistance in CF isolates.

Rationale: Chronic fatigue syndrome (CFS) is a common and burdensome illness with a poorly understood pathophysiology, though many of the characteristic symptoms are likely to be of brain origin. The use of high-field proton magnetic resonance spectroscopy (MRS) enables the detection of a range of brain neurochemicals relevant to aetiological processes that have been linked to CFS, for example, oxidative stress and mitochondrial dysfunction., Methods: We studied 22 CFS patients and 13 healthy controls who underwent MRS scanning at 7 T with a voxel placed in the anterior cingulate cortex. Neurometabolite concentrations were calculated using the unsuppressed water signal as a reference., Results: Compared to controls, CFS patients had lowered levels of glutathione, total creatine and myo-inositol in anterior cingulate cortex. However, when using N-acetylaspartate as a reference metabolite, only myo-inositol levels continued to be significantly lower in CFS participants., Conclusions: The changes in glutathione and creatine are consistent with the presence of oxidative and energetic stress in CFS patients and are potentially remediable by nutritional intervention. A reduction in myo-inositol would be consistent with glial dysfunction. However, the relationship of the neurochemical abnormalities to the causation of CFS remains to be established, and the current findings require prospective replication in a larger sample., (© 2021. The Author(s).)

Background: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community., Methods: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing., Findings: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19)., Interpretation: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications., Funding: National Institute of Health Research and United Kingdom Research Innovation., Competing Interests: Declaration of interests MB reports grants from AstraZeneca, personal fees from AstraZeneca, Chiesi, and GlaxoSmithKline; and is a member of advisory boards for Albus Health and ProAxsis, outside the submitted work. DR reports being a former employee of GlaxoSmithKline, outside the submitted work. BRS, NB, MAD, MF, and CS report grants from The University of Oxford, for the University of Oxford's grant from the UK National Institute for Health Research (NIHR) and for statistical design and analyses for the PRINCIPLE trial during the conduct of the study. SdL is Director of the Oxford–Royal College of General Practitioners (RCGP) Research and Surveillance Centre and reports that through his university he has had grants outside the submitted work from AstraZeneca, GlaxoSmithKline, Sanofi, Seqirus, and Takeda for vaccine-related research, and membership of advisory boards for AstraZeneca, Sanofi, and Seqirus. MIA reports grants and personal fees from Prenetics outside the submitted work. PJB reports grants and personal fees from AstraZeneca and Boehringer Ingelheim; and personal fees from Teva and Covis, during the conduct of the study. REKR reports grants from AstraZeneca and personal fees from Boehringer Ingelheim, Chiesi UK, and GlaxoSmithKline, during the conduct of the study. SR reports grants and non-financial support from Oxford respiratory NIHR Biomedical Research Centre (BRC), during the conduct of the study; and non-financial support from AstraZeneca and personal fees from the Australian Government Research Training Program, outside the submitted work. FDRH and CCB report grants from UK Research and Innovation, during the conduct of the study. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Tocilizumab (TCZ), an IL-6 receptor antagonist, is used in the treatment of severe COVID-19 caused by infection with SARS-CoV-2. However, unintended consequences of TCZ therapy include reactivation of tuberculosis (TB) or hepatitis B virus (HBV), and worsening of hepatitis C virus (HCV). We set out to assimilate existing data for these complications, in order to help inform evidence-based risk assessments for the use of TCZ, and thus to reduce the risk of serious but preventable complications. Methods: We searched the global WHO database of Individual Case Safety Reports (ICSRs) and adverse drug reactions (ADRs) ("VigiBase") and undertook a systematic literature review, in accordance with PRISMA guidelines. We generated mean cumulative incidence estimates for infection complications. Results: Mean cumulative incidence of HBV and TB were 3.3 and 4.3%, respectively, in patients receiving TCZ. Insufficient data were available to generate estimates for HCV. These estimates derive from heterogeneous studies pre-dating SARS-CoV-2, with differing epidemiology and varied approaches to screening and prophylaxis, so formal meta-analysis was not possible. Conclusions: We underline the need for careful individual risk assessment prior to TCZ prescription, and present an algorithm to guide clinical stratification. There is an urgent need for ongoing collation of safety data as TCZ therapy is used in COVID., Competing Interests: CC receives PhD fellowship funding from GSK. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Campbell, Andersson, Ansari, Moswela, Misbah, Klenerman and Matthews.)

We have optimised a reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the detection of SARS-CoV-2 from extracted RNA for clinical application. We improved the stability and reliability of the RT-LAMP assay by the addition of a temperature-dependent switch oligonucleotide to reduce self- or off-target amplification. We then developed freeze-dried master mix for single step RT-LAMP reaction, simplifying the operation for end users and improving long-term storage and transportation. The assay can detect as low as 13 copies of SARS-CoV2 RNA per reaction (25-μL). Cross reactivity with other human coronaviruses was not observed. We have applied the new RT-LAMP assay for testing clinical extracted RNA samples extracted from swabs of 72 patients in the UK and 126 samples from Greece and demonstrated the overall sensitivity of 90.2% (95% CI 83.8-94.7%) and specificity of 92.4% (95% CI 83.2-97.5%). Among 115 positive samples which Ct values were less than 34, the RT-LAMP assay was able to detect 110 of them with 95.6% sensitivity. The specificity was 100% when RNA elution used RNase-free water. The outcome of RT-LAMP can be reported by both colorimetric detection and quantifiable fluorescent reading. Objective measures with a digitized reading data flow would allow for the sharing of results for local or national surveillance., (© 2021. The Author(s).)

Bangladesh is one of the top-ten most heavily burdened countries for viral hepatitis, with hepatitis B (HBV) infections responsible for the majority of cases. Recombinant and occult HBV infections (OBI) have been reported previously in the region. We investigated an adult fever cohort ( n =201) recruited in Dhaka, to determine the prevalence of HBV and OBI. A target-enrichment deep sequencing pipeline was applied to samples with HBV DNA >3.0 log 10 IU ml -1 . HBV infection was present in 16/201 (8 %), among whom 3/16 (19 %) were defined as OBI (HBsAg-negative but detectable HBV DNA). Whole genome deep sequences (WGS) were obtained for four cases, identifying genotypes A, C and D. One OBI case had sufficient DNA for sequencing, revealing multiple polymorphisms in the surface gene that may contribute to the occult phenotype. We identified mutations associated with nucleos(t)ide analogue resistance in 3/4 samples sequenced, although the clinical significance in this cohort is unknown. The high prevalence of HBV in this setting illustrates the importance of opportunistic clinical screening and DNA testing of transfusion products to minimise OBI transmission. WGS can inform understanding of diverse disease phenotypes, supporting progress towards international targets for HBV elimination.

Introduction: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications., Methods and Analysis: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes., Ethics and Dissemination: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals., Trial Registration Number: ISRCTN86534580., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model's outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa., Methods: Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing., Results: Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive., Conclusions: This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.

Background: Transfusion-transmitted hepatitis E virus (HEV) infection is a potential risk to recipients of blood transfusions. Infection with HEV poses a high risk to immunocompromised recipients with an increased likelihood of developing chronic infection. The aims of this study were to determine the prevalence of past and active HEV infections in donors from the Western Cape and to identify the risk factors associated with infection., Materials and Methods: We prospectively tested 10 250 blood donors for HEV infection. A risk factor sub-study investigated 250 donors who completed a questionnaire, and plasma samples were tested for HEV IgG antibodies and pooled for HEV RNA detection. The demographic and risk factors associated with HEV infection were assessed. The molecular study tested 10 000 individual donations using a commercial assay to detect viraemia. HEV viral load and genotype were also determined., Results: The overall anti-HEV IgG seroprevalence was 42·8% (107/250) among donors participating in the risk factor sub-study. The likelihood of past HEV infection was higher with an increase in age. Of the 10 000 donor samples individually tested for HEV RNA, one sample was positive with a viral load of 7·9 x 10 4 IU/ml and belonged to HEV genotype 3., Conclusion: We found a high seroprevalence of anti-HEV IgG but a low HEV RNA prevalence among donors in the Western Cape, South Africa. The study provides evidence for a potential risk of HEV contamination in the blood supply in South Africa. A cost-benefit analysis is needed before considering the introduction of routine donor screening in our setting., (© 2020 International Society of Blood Transfusion.)

Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19., Competing Interests: Competing interests: DWE has received personal fees from Gilead, outside the submitted work., (Copyright: © 2020 Andersson MI et al.)

SARS-CoV-2 IgG screening of 1,000 antenatal serum samples in the Oxford area, United Kingdom, between 14 April and 15 June 2020, yielded a 5.3% seroprevalence, mirroring contemporaneous regional data. Among the 53 positive samples, 39 showed in vitro neutralisation activity, correlating with IgG titre (Pearson's correlation p<0.0001). While SARS-CoV-2 seroprevalence in pregnancy cohorts could potentially inform population surveillance, clinical correlates of infection and immunity in pregnancy, and antenatal epidemiology evolution over time need further study.

In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients co-infected with hepatitis B virus (HBV) and the human immunodeficiency virus (HIV) are at risk of developing hepatocellular carcinoma (HCC). In sub-Saharan Africa, the overlap between high HIV and HBV prevalence may increase the incidence of HCC. This study investigated the impact of HBV/HIV co-infection on age at presentation and survival of HCC., Methods: Ethical approval was obtained to recruit, following informed written consent, patients diagnosed with HCC at oncology units at four South African hospitals. Between December 2012 and August 2015, patients newly diagnosed with HCC were recruited and provided demographic and clinical data and blood specimens. Patients were tested for HBV, hepatitis C virus (HCV) and HIV. Survival data was available for a subset of patients., Results: Of 107 HCC cases, 83 (78%) were male. Median age was 46 years (range 18 to 90 years), 68/106 (64%) were HBsAg-positive, and 22/100 (22%) were HIV infected. Among HBV surface antigen (HBsAg)-positive HCC cases, 18/66 (27%) were HIV-infected compared to 3/34 (9%) among those that were HBsAg-negative (p = 0.04). A greater proportion of HBV/HIV co-infected cases were female than HBV mono-infected (6/18, 33% vs 6/47, 13%; p = 0.005). In addition, HBV/HIV co-infected females presented at a younger mean age (36.8 years) than HBV mono-infected women (50.5 years) (p = 0.09). Median survival was 82 days among the HIV-infected HCC patients compared to 181 days among those without HIV (p = 0.15)., Conclusions: HCC is an important complication in the HIV/HBV infected patient. HIV-positive patients presented with HCC at a younger age than HIV-negative patients, this effect appears to be greater in women. These data provide more evidence supporting the call to address. HCC as a cause of morbidity and mortality in the HBV/HIV co-infected patient population. (281 words).

Background: Hepatitis B causes more than 800 000 deaths globally each year. Perinatal infections are a major driver of this burden but can be prevented by vaccination within 24 h of birth. Currently, only 44% of newborn babies in low-income and middle-income countries (LMICs) receive a timely birth dose. We investigated the effects and cost-effectiveness of implementing ambient storage of hepatitis B vaccines under a controlled temperature chain (CTC) protocol and the use of compact prefilled auto-disable (CPAD) devices for community births., Methods: In this mathematical modelling study of perinatal hepatitis B transmission and disease progression, we estimated the coverage impact and cost-effectiveness of implementing CTC and CPAD interventions in the six Global Burden of Disease (GBD) regions containing LMICs. Combinations of four different scenarios of birth dose delivery strategies (cold chain, CTC) and interventions (needle and syringe, CPAD) were modelled across facility or community birth locations. We also estimated the minimum cost and most cost-effective strategy to achieve the WHO 90% hepatitis B birth dose coverage target in GBD regions and in 46 LMICs with a reported coverage of less than 90%., Findings: Current delivery protocols achieved a maximum coverage of 65% (IQR 64-65) across GBD regions. Reaching 90% hepatitis B birth dose coverage across all GBD regions was estimated to cost a minimum of US$687·5 million per annum ($494·0 million more than the estimated current expenditure), of which $516·5 million (75%) was required for CTC and CPAD interventions. Reaching 90% coverage in this way was estimated to be cost saving in five of the six regions (and in 40 of 46 LMICs individually assessed) due to the disease costs averted, with the cost per disability-adjusted life-years averted being less than $83·27 otherwise., Interpretation: Hepatitis B birth dose coverage of 90% is unlikely to be reached under current protocols. CTC and CPAD vaccine strategies present cost-effective solutions to overcome coverage barriers., Funding: The Burnet Institute., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)