Diagnostic Pathways as Social and Participatory Practices: The Case of Herpes Simplex Encephalitis

Herpes simplex virus (HSV) encephalitis is a potentially devastating disease, with significant rates of mortality and co-morbidities. Although the prognosis for people with HSV encephalitis can be improved by prompt treatment with aciclovir, there are often delays involved in the diagnosis and treatment of the disease. In response, National Clinical Guidelines have been produced for the UK which make recommendations for improving the management of suspected viral encephalitis. However, little is currently known about the everyday experiences and processes involved in the diagnosis and care of HSV encephalitis. The reported study aimed to provide an account of the diagnosis and treatment of HSV encephalitis from the perspective of people who had been affected by the condition. Thirty narrative interviews were conducted with people who had been diagnosed with HSV encephalitis and their significant others. The narrative accounts reveal problems with gaining access to a diagnosis of encephalitis and shortfalls in care for the condition once in hospital. In response, individuals and their families work hard to obtain medical recognition for the problem and shape the processes of acute care. As a consequence, we argue that the diagnosis and management of HSV encephalitis needs to be considered as a participatory process, which is co-produced by health professionals, patients, and their families. The paper concludes by making recommendations for developing the current management guidelines by formalising the critical role of patients and their significant others in the identification, and treatment of, HSV encephalitis

Care beyond the hospital ward: understanding the socio-medical trajectory of herpes simplex virus encephalitis

Background Herpes simplex virus (HSV) encephalitis is a life-threatening infection of the brain, which has significant physical, cognitive and social consequences for survivors. Despite increasing recognition of the long-term effects of encephalitis, research and policy remains largely focused on its acute management, meaning there is little understanding of the difficulties people face after discharge from acute care. This paper aims to chart the problems and challenges which people encounter when they return home after treatment for HSV encephalitis. Methods The paper reports on data from 30 narrative interviews with 45 people affected by HSV encephalitis and their significant others. The study was conducted as part of the ENCEPH-UK programme grant on Understanding and Improving the Outcome of Encephalitis. Results The findings show the diverse challenges which are experienced by people after treatment for HSV encephalitis. We first chart how peoples’ everyday lives are fragmented following their discharge from hospital. Second, we document the social consequences which result from the longer-term effects of encephalitis. Finally, we show how the above struggles are exacerbated by the lack of support systems for the post-acute effects of encephalitis, and describe how people are consequently forced to devise their own care routines and strategies for managing their problems. Conclusion The paper argues that in order to improve long-term outcomes in encephalitis, it is vital that we develop pathways of support for the condition beyond the acute hospital setting. We conclude by making recommendations to enhance communication and care for the post-acute consequences of encephalitis, to ensure those affected are fully supported through the chronic effects of this devastating disease

A pragmatic cluster randomised controlled trial of a tailored intervention to improve the initial management of suspected encephalitis

Objective To determine whether a tailored multifaceted implementation strategy improves the initial management of patients with suspected encephalitis. Design Pragmatic two arm cluster randomised controlled trial. Setting Hospitals within the United Kingdom. Participants Twenty-four hospitals nested within 12 postgraduate deaneries. Patients were identified retrospectively by searching discharge, microbiology, radiology and pharmacy records and included if they met clinical criteria or had a recorded suspicion of encephalitis. Intervention An implementation strategy designed to overcome barriers to change, comprising local action planning, education and training, feedback on performance, a lumbar puncture pack and a range of optional components. Outcomes The primary outcome was the proportion of patients with suspected encephalitis undergoing diagnostic lumbar puncture within 12 hours of admission and starting aciclovir treatment within six hours. Secondary outcomes included the proportions of adults and children who had a lumbar puncture, who had appropriate cerebrospinal fluid investigations, and who had appropriate radiological imaging within 24 hours of admission. Data were collected from patient records for 12 months before and 12 months during the intervention period, and analysed blind to allocation. Results 13 hospitals were randomised to intervention and 11 to control (no intervention), with 266 and 223 patients with suspected encephalitis identified respectively. There was no significant difference in primary outcome between intervention and control hospitals (13.5% and 14.8% respectively, p = 0.619; treatment effect -0.188, 95% confidence interval -0.927 to 0.552), but both had improved compared to pre-intervention (8.5%). Conclusion The improvement in both intervention and control arms may reflect overall progress in management of encephalitis through wider awareness and educatio

Acute seizure risk in patients with encephalitis: development and validation of clinical prediction models from two independent prospective multicentre cohorts

\ua9 2022 Author(s) (or their employer(s)). Objective: In patients with encephalitis, the development of acute symptomatic seizures is highly variable, but when present is associated with a worse outcome. We aimed to determine the factors associated with seizures in encephalitis and develop a clinical prediction model. Methods: We analysed 203 patients from 24 English hospitals (2005-2008) (Cohort 1). Outcome measures were seizures prior to and during admission, inpatient seizures and status epilepticus. A binary logistic regression risk model was converted to a clinical score and independently validated on an additional 233 patients from 31 UK hospitals (2013-2016) (Cohort 2). Results: In Cohort 1, 121 (60%) patients had a seizure including 103 (51%) with inpatient seizures. Admission Glasgow Coma Scale (GCS) ≤8/15 was predictive of subsequent inpatient seizures (OR (95% CI) 5.55 (2.10 to 14.64), p<0.001), including in those without a history of prior seizures at presentation (OR 6.57 (95% CI 1.37 to 31.5), p=0.025). A clinical model of overall seizure risk identified admission GCS along with aetiology (autoantibody-associated OR 11.99 (95% CI 2.09 to 68.86) and Herpes simplex virus 3.58 (95% CI 1.06 to 12.12)) (area under receiver operating characteristics curve (AUROC) =0.75 (95% CI 0.701 to 0.848), p<0.001). The same model was externally validated in Cohort 2 (AUROC=0.744 (95% CI 0.677 to 0.811), p<0.001). A clinical scoring system for stratifying inpatient seizure risk by decile demonstrated good discrimination using variables available on admission; age, GCS and fever (AUROC=0.716 (95% CI 0.634 to 0.798), p<0.001) and once probable aetiology established (AUROC=0.761 (95% CI 0.6840.839), p<0.001). Conclusion: Age, GCS, fever and aetiology can effectively stratify acute seizure risk in patients with encephalitis. These findings can support the development of targeted interventions and aid clinical trial design for antiseizure medication prophylaxis

Proceedings from the Third International Post-Tuberculosis Symposium: expanding the circle

In light of the recent growth in interest and knowledge of post-TB sequelae, there were high levels of engagement during the 3rd International Post-Tuberculosis Symposium held in Stellenbosch, South Africa. This multi-disciplinary symposium aimed to: 1) Advocate for greater global awareness of post-TB sequelae and empower TB-affected communities; 2) Advance knowledge by sharing current evidence and identifying key priorities; 3) Foster collaborations by strengthening research networks and developing concrete plans for research driven advocacy; and 4) Advance the field by establishing areas of consensus around diagnosis, care, and management. Guided by a 14-member Steering Committee, 9 academic working groups came together to develop key content for plenary sessions and facilitated workshops related to: Patient Engagement, Epidemiology and Modelling, Pathogenesis, Post-TB Lung Disease; Cardiovascular and Pulmonary Vascular Disease; Central Nervous System and Musculoskeletal Disease; Paediatrics Economic; Social and Psychological Sequelae; and Advocacy, Policy, and Stakeholder Engagement. Each group outlined progress within their respective fields and defined key priorities to focus discussion. The Symposium further catalysed coordinated action for the post-TB community of patients, advocates, clinicians, and researchers to define a clear path towards improving outcomes, reducing inequities, and ensuring TB survivors receive the care and support they deserve

Understanding parental perspectives on outcomes following paediatric encephalitis: A qualitative study

Background Encephalitis, characterised as inflammation of the brain tissue, is an important cause of acquired brain injury in children. Objective clinical outcomes vary significantly between affected patients, however they do not always correlate with quality of life as reported by parents. The aim of this study was to explore how parents experience and interpret outcomes in relation to their child who has been affected by encephalitis. Methods Data were derived from in-depth, semi-structured interviews, with 15 parents of 12 children and young people affected by encephalitis. Paediatric cases were identified from the retrospective arm of the research programme ‘ENCEPH-UK-Understanding and Improving the Outcome of Encephalitis’, and from the prospective UK childhood meningitis and encephalitis cohort study (UK-ChiMES, 2012 to 2016). Data were analysed thematically. Results Parents’ perspectives on important outcomes for their child and family changed during the different stages of the encephalitis illness trajectory: from acute illness, recovery and rehabilitation, then reintegration into everyday life. Parents’ understanding of their children’s overall outcome was informed by their own experiences, involving comparisons with other children and reflections on their child’s problems before, during and after the acute illness. Conclusion Outcomes in paediatric encephalitis need to be understood in terms of the context of the patient and family experience as well as the timeframe of recovery. The research highlights the need to include more patient, parent and/or carer reported outcome measures during patient assessment, and that assessment should be repeated during recovery as family concerns change. In the longer term, these parameters could be included in clinical and rehabilitation practice to further support child recovery

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study

\ua9 2025. The Author(s). It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases). Among the 651 patients, [362 (55%) cases and 289 (45%) controls], a higher proportion of cases had impairment in ADLs (199 [68.9%] vs 101 [51.8%], OR 2.06, p < 0.0002) and reported symptoms impacting employment (159 [58.2%] vs 69 [35.6%] OR 2.53, p < 0.0001). There was no significant difference in the proportion with depression or anxiety between case and control groups overall. For cases, impairment of ADLs was associated with increased risk in female sex, age > 50 years and hypertension (OR 5.43, p < 0.003, 3.11, p = 0.02, 3.66, p = 0.04). Those receiving either statins or angiotensin converting enzyme (ACE) inhibitors had a lower risk of impairment in ADLs (OR 0.09, p = 0.0006, 0.17, p = 0.03). Patients with neurological or psychiatric complications of COVID-19 had worse functional outcomes than those with respiratory COVID-19 alone in terms of ADLs and employment. Female sex, age > 50 years, and hypertension were associated with worse outcomes, and statins or ACE inhibitors with better outcomes

Staphylococcal Panton-Valentine Leucocidin as a Major Virulence Factor Associated to Furuncles

Panton-Valentine Leucocidin (PVL), one of the β-barrel pore-forming staphylococcal leucotoxins, is known to be associated to furuncles and some severe community pneumonia. However, it is still uncertain how many other virulence factors are also associated to furuncles and what the risk factors of furuncles are in immuno-compromised status of patients, especially the HIV (+) patients. In this paper, we use antigen immunoprecipitation and multiplex PCR approach to determine the presence of 19 toxins, 8 adhesion factors and the PFGE profiles associated to furuncles in three independent patient study groups of S. aureus (SA) isolates collected from the Cayenne General Hospital (French Guiana). The patient groups were made of: 16 isolates from HIV (−) patients, 9 from HIV (+) patients suffering from furuncles, and 30 control isolates from patients with diverse secondary infected dermatitis. Our data reveals that the majority (96%) of SA strains isolated from HIV patient-derived furuncles significantly produced PVL (p<10−7), whereas only 10% of SA strains produced this toxin in secondary infected dermatosis. A high prevalence of LukE-LukD-producing isolates (56 to 78%) was recorded in patient groups. Genes encoding clumping factor B, collagen- and laminin-binding proteins (clfB, cna, lbp, respectively) were markedly frequent (30 to 55%), without being associated to a specific group. Pulse field gel electrophoresis evidenced 24 overall pulsotypes, whereas the 25 PVL-producing isolates were distributed into 15 non clonal fingerprints. These pulsotypes were not specific PVL-producing isolates. PVL appears to be the major virulence factor associated to furuncles in Europe and in South America regardless of the immune status of the HIV patients

Paediatric meningitis in the conjugate vaccine era and a novel clinical decision model to predict bacterial aetiology.

OBJECTIVES: The aims of this study were to assess aetiology and clinical characteristics in childhood meningitis, and develop clinical decision rules to distinguish bacterial meningitis from other similar clinical syndromes. METHODS: Children aged <16 years hospitalised with suspected meningitis/encephalitis were included, and prospectively recruited at 31 UK hospitals. Meningitis was defined as identification of bacteria/viruses from cerebrospinal fluid (CSF) and/or a raised CSF white blood cell count. New clinical decision rules were developed to distinguish bacterial from viral meningitis and those of alternative aetiology. RESULTS: The cohort included 3002 children (median age 2·4 months); 1101/3002 (36·7%) had meningitis, including 180 bacterial, 423 viral and 280 with no pathogen identified. Enterovirus was the most common pathogen in those aged <6 months and 10-16 years, with Neisseria meningitidis and/or Streptococcus pneumoniae commonest at age 6 months to 9 years. The Bacterial Meningitis Score had a negative predictive value of 95·3%. We developed two clinical decision rules, that could be used either before (sensitivity 82%, specificity 71%) or after lumbar puncture (sensitivity 84%, specificity 93%), to determine risk of bacterial meningitis. CONCLUSIONS: Bacterial meningitis comprised 6% of children with suspected meningitis/encephalitis. Our clinical decision rules provide potential novel approaches to assist with identifying children with bacterial meningitis. FUNDING: This study was funded by the Meningitis Research Foundation, Pfizer and the NIHR Programme Grants for Applied Research