Convalescent plasma therapy for persistent hepatitis E virus infection

No abstract available

Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020.

Healthcare workers (HCW) are potentially at increased risk of infection with coronavirus disease (COVID-19) and may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to vulnerable patients. We present results from staff testing at Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom. Between 16 and 29 March 2020, 1,533 symptomatic HCW were tested, of whom 282 (18%) were positive for SARS-CoV-2. Testing HCW is a crucial strategy to optimise staffing levels during this outbreak

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial

Background Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. Methods In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Findings Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). Interpretation Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia

Identification, diagnosis and management of persistent Hepatitis E virus infection

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the UK and leads to persistent HEV infection in immunosuppressed individuals. The prevalence and clinical outcomes of persistent HEV are unknown in the UK. It is hypothesized that persistent HEV is an under-recognised disease in the UK, that screening of high-risk immunocompromised patients will be cost-effective and enhanced surveillance of persistent HEV cases will identify pragmatic parameters for clinical monitoring. Within this study, the prevalence of HEV infection was investigated in three distinct immunocompromised cohorts. A commercial assay for detecting HEV antigen (HEV-Ag) was explored for use as a screening assay and monitoring tool. A cost-effectiveness analysis modelled the impact of annual HEV screening in solid organ transplant (SOT) recipients. The diagnostic findings and clinical outcomes were reported on a case series of persistent HEV infections across England and Wales and whole genome sequencing (WGS) was utilized to explore viral mutations with and without antiviral pressure. This work demonstrates that persistent HEV infections are under-recognised in transplant recipients, with biochemical abnormalities often attributed to other causes by clinicians. Viraemia rates were similar to other European studies among SOT recipients. HEV-Ag had both high sensitivity and specificity as a screening assay for persistent HEV infections. The annual screening of SOT recipients either by RNA or HEV-Ag testing is projected to be cost-effective for the NHS. The case series showed that a broad range of immunosuppressed patients are at risk of persistent infection, however the magnitude of risk in antibody-deficient patients and those with a haematological malignancy were lower than in SOT. Finally, WGS revealed the emergence of mutations in the RNA-dependent RNA polymerase region associated with clinical phenotypic resistance to ribavirin. However, further optimization of HEV sequencing is required to investigate samples with lower HEV viral loads.Open Acces

Roll-out of SARS-CoV-2 testing for healthcare workers at a large NHS Foundation Trust in the United Kingdom, March 2020

Healthcare workers (HCW) are potentially at increased risk of infection with coronavirus disease (COVID-19) and may transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to vulnerable patients. We present results from staff testing at Sheffield Teaching Hospitals NHS Foundation Trust, United Kingdom. Between 16 and 29 March 2020, 1,533 symptomatic HCW were tested, of whom 282 (18%) were positive for SARS-CoV-2. Testing HCW is a crucial strategy to optimise staffing levels during this outbreak.</jats:p