Cases of high-consequence infectious diseases identified in the UK, 1962-2023.

The management of patients with acute infectious diseases can present significant challenges, especially if the causative agent has a propensity for person-to-person transmission. In such cases, effective patient management is dependent on both rapid identification of disease and the provision of necessary medical care while adhering to suitable infection prevention and control measures to reduce the potential for onwards transmission. The UK has operated a defined system for managing patients with high-consequence infectious diseases (HCIDs) since the 1970s, when protocols were first implemented following the first descriptions of several viral haemorrhagic fever diseases, including Marburg virus disease, Lassa fever and Ebola virus disease (EVD). While more than 200 people with HCIDs have been treated in UK hospitals since the 1970s, most of these patients had COVID-19 or mpox during the early phases of new public health emergencies of international concern (PHEICs), prior to their removal from the UK HCID list in March 2020 and June 2022, respectively. Excluding PHEICs, 26 patients have been treated in HCID treatment centres between 1962 and 2023: 10 patients with Lassa fever, 7 with mpox prior to the 2022 PHEIC, 4 with Middle East respiratory syndrome (MERS), 4 with EVD and 1 with Crimean-Congo haemorrhagic fever (CCHF). In total, 15 additional HCID patients were identified where treatment in a specialist centre did not occur due to retrospective diagnosis (4 patients with Lassa fever), mild or moderate illness [5 patients with avian influenza A(H5N1), 1 with MERS and 1 with CCHF] or death prior to transfer (2 patients with Lassa fever, 1 with CCHF and 1 with pneumonic plague). Here we summarize the UK HCID experience, including details about their detection, patient management and outcomes

Regulatory and operational complexities of conducting a clinical treatment trial during an Ebola Virus Disease epidemic

The first Phase II and III clinical trials for treatments for Ebola Virus Disease were conducted during the west Africa (2013-16) outbreak. We report the operational practicalities of conducting a phase II clinical trial of TKM-130803 to international standards during this outbreak

Vaccine-derived rotavirus strains in infants in England.

OBJECTIVE: To describe infants with acute gastroenteritis symptoms in primary and secondary care who have the Rotarix vaccine-derived G1P[8] rotavirus strain identified in their stools. DESIGN: This is a prospective national surveillance conducted by Public Health England (PHE). Rotavirus-positive samples from vaccine-eligible children are routinely submitted to PHE for confirmation, and general practitioners are requested to complete a surveillance questionnaire for all cases. The modified Vesikari Score was used to assess severity of gastroenteritis. SETTING: England, July 2013-September 2016. RESULTS: 2637 rotavirus strains were genotyped and 215 (8%) identified as the Rotarix vaccine-derived G1P[8] strain. There were no Rotarix vaccine-derived G1P[8] strains detected in unimmunised infants. Rotarix vaccine-derived G1P[8] strains clustered around the time of rotavirus vaccination and were responsible for 82% (107 of 130) of rotavirus-positive samples in 2-month-old infants and 68% (36 of 53) in 3-month-old infants. However, 13 samples were obtained more than 7 weeks after the last vaccination date; 10 of these specimens were from six children who were subsequently diagnosed with severe combined immunodeficiency (SCID). Diarrhoea was the single most common presenting symptom (83.0%) in infants with Rotarix vaccine-derived G1P[8] strains, who were less likely to present with fever, vomiting, dehydration or severe gastroenteritis than infants with wild-type rotavirus infection. CONCLUSIONS: Rotavirus identified in stools of infants around the time of their routine immunisations is most likely the Rotarix vaccine-derived G1P[8] strain. Infants with undiagnosed SCID at the time of rotavirus immunisation may experience prolonged gastroenteritis symptoms. Most infants with vaccine strains in their stools more than 7 weeks after immunisation had SCID

Patterns of systemic and local inflammation in patients with asthma hospitalised with influenza.

BACKGROUND: Patients with asthma are at risk of hospitalisation with influenza, but the reasons for this predisposition are unknown. STUDY SETTING: A prospective observational study of adults with PCR-confirmed influenza in 11 UK hospitals, measuring nasal, nasopharyngeal and systemic immune mediators and whole-blood gene expression. RESULTS: Of 133 admissions, 40 (30%) had previous asthma; these were more often female (70% versus 38.7%, OR 3.69, 95% CI 1.67 to 8.18, p=0.0012), required less mechanical ventilation (15% versus 37.6%, χ2 6.78, p=0.0338) and had shorter hospital stays (mean 8.3 versus 15.3 d, p=0.0333) than those without. In patients without asthma, severe outcomes were more frequent in those given corticosteroids (OR=2.63, 95% CI=1.02-6.96, p=0.0466) or presenting >4 days after disease onset (OR 5.49, 95% CI 2.28-14.03, p=0.0002). Influenza vaccination in at-risk groups (including asthma) were lower than intended by national policy and the early use of antiviral medications were less than optimal. Mucosal immune responses were equivalent between groups. Those with asthma had higher serum IFN-α but lower serum TNF, IL-5, IL-6, CXCL8, CXCL9, IL-10, IL-17 and CCL2 levels (all p<0.05); both groups had similar serum IL-13, total IgE, periostin and blood eosinophil gene expression levels. Asthma diagnosis was unrelated to viral load, IFN-α, IFN-γ, IL-5 or IL-13 levels. CONCLUSIONS: Asthma is common in those hospitalised with influenza, but may not represent classical Type 2-driven disease. Those admitted with influenza tend to be female with mild serum inflammatory responses, increased serum IFN-α levels and good clinical outcomes.MOSAIC (Mechanisms of Severe Influenza Consortium) was supported by the MRC (UK) and Wellcome Trust (090382/Z/09/Z). The study was also supported by the National Institute of Healthcare Research (NIHR) Biomedical Research Centres (BRCs) in London and Liverpool and by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Respiratory Infections at Imperial College London in partnership with Public Health England (PHE). P.J.O. was supported by EU FP7 PREPARE project 602525

Symptom-based case definitions for COVID-19: time and geographical variations for detection at hospital admission among 260,000 patients

Introduction: Case definitions are used to guide clinical practice, surveillance, and research protocols. However, how they identify COVID-19-hospitalised patients is not fully understood. We analysed the proportion of hospitalised patients with laboratory-confirmed COVID-19, in the ISARIC prospective cohort study database, meeting widely used case definitions. Methods: Patients were assessed using the CDC, ECDC, WHO, and UKHSA case definitions by age, region, and time. Case fatality ratios (CFR) and symptoms of those who did and who did not meet the case definitions were evaluated. Patients with incomplete data and non-laboratory-confirmed test-result were excluded. Results: 263,218 of the patients (42%) in the ISARIC database were included. Most patients (90.4%) were from Europe and Central Asia. The proportions of patients meeting the case definitions were 56.8% (WHO), 74.4% (UKHSA), 81.6% (ECDC), and 82.3% (CDC). For each case definition, patients at the extremes of age distribution met the criteria less frequently than those aged 30 to 70 years; geographical and time variations were also observed. Estimated CFRs were similar for the patients that met the case definitions. However, when more patients did not meet the case definition, the CFR increased. Conclusions: The performance of case definitions might be different in different regions and may change over time. Similarly concerning is the fact that older patients often did not meet case definitions. While epidemiologists must balance their analytics with field applicability, ongoing revision of case definitions is necessary to improve patient care through early diagnosis and limit potential nosocomial spread

Air and surface sampling for monkeypox virus in a UK hospital: an observational study

Background An outbreak of monkeypox virus infections in non-endemic countries was recognised on May 12, 2022. As of September 29, more than 67 000 infections have been reported globally, with more than 3400 confirmed cases in the UK by September 26. Monkeypox virus is believed to be predominantly transmitted through direct contact with lesions or infected body fluids, with possible involvement of fomites and large respiratory droplets. A case of monkeypox in a health-care worker in the UK in 2018 was suspected to be due to virus exposure while changing bedding. We aimed to measure the extent of environmental contamination in the isolation rooms of patients with symptomatic monkeypox. Methods We investigated environmental contamination with monkeypox virus from infected patients admitted to isolation rooms at the Royal Free Hospital (London, UK) between May 24 and June 17, 2022. Surface swabs of high-touch areas in five isolation rooms, of the personal protective equipment (PPE) of health-care workers in doffing areas in three rooms, and from air samples collected before and during bedding changes in five rooms were analysed using quantitative PCR to assess monkeypox virus contamination levels. Virus isolation was performed to confirm presence of infectious virus in selected positive samples. Findings We identified widespread surface contamination (56 [93%] of 60 samples were positive) in occupied patient rooms (monkeypox DNA cycle threshold [Ct] values 24·7–37·4), on health-care worker PPE after use (Ct 26·1–35·6), and in PPE doffing areas (Ct 26·3–36·8). Of 20 air samples taken, five (25%) were positive. Three (75%) of four air samples collected before and during a bedding change in one patient's room were positive (Ct 32·7–36·2). Replication-competent virus was identified in two (50%) of four samples selected for viral isolation, including from air samples collected during bedding change. Interpretation These data show contamination in isolation facilities and potential for suspension of monkeypox virus into the air during specific activities. PPE contamination was observed after clinical contact and changing of bedding. Contamination of hard surfaces in doffing areas supports the importance of cleaning protocols, PPE use, and doffing procedures. Fundin

Long-term Randomized Controlled Trial

Funding Information: The authors thank Sarah E Scott for her valuable contributions as the trial manager and in the user experience evaluation, and Susana Cunha for her contribution in conducting and reporting the focus groups. This project has received funding from the European Union?s Horizon 2020 research and innovation program under grant agreement number 643309. The material presented and views expressed here are the responsibility of the authors only. The European Union Commission does not take responsibility for any use made of the information set out.Background: Digital behavior change interventions (DBCIs) offer a promising channel for providing health promotion services. However, user experience largely determines whether they are used, which is a precondition for effectiveness. Objective: The primary aim of this study is to evaluate user experiences with the NoHoW Toolkit (TK)—a DBCI that targets weight loss maintenance—over a 12-month period by using a mixed methods approach and to identify the main strengths and weaknesses of the TK and the external factors affecting its adoption. The secondary aim is to objectively describe the measured use of the TK and its association with user experience. Methods: An 18-month, 2×2 factorial randomized controlled trial was conducted. The trial included 3 intervention arms receiving an 18-week active intervention and a control arm. The user experience of the TK was assessed quantitatively through electronic questionnaires after 1, 3, 6, and 12 months of use. The questionnaires also included open-ended items that were thematically analyzed. Focus group interviews were conducted after 6 months of use and thematically analyzed to gain deeper insight into the user experience. Log files of the TK were used to evaluate the number of visits to the TK, the total duration of time spent in the TK, and information on intervention completion. Results: The usability level of the TK was rated as satisfactory. User acceptance was rated as modest; this declined during the trial in all the arms, as did the objectively measured use of the TK. The most appreciated features were weekly emails, graphs, goal setting, and interactive exercises. The following 4 themes were identified in the qualitative data: engagement with features, decline in use, external factors affecting user experience, and suggestions for improvements. Conclusions: The long-term user experience of the TK highlighted the need to optimize the technical functioning, appearance, and content of the DBCI before and during the trial, similar to how a commercial app would be optimized. In a trial setting, the users should be made aware of how to use the intervention and what its requirements are, especially when there is more intensive intervention content.publishersversionpublishe