Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary ...team meeting (MDT). We describe the experience and outcomes of the MDT over three years.
A retrospective analysis was performed to summarise patient demographics, MDT outcomes and final diagnoses.
Over the three-year period, 324 discussions of 238 patients took place. Cases were diverse; approximately 40% related to COVID-19 or brain infection, 40% autoimmune or other inflammatory disorders and 20% encephalitis mimics or uncertain aetiologies. Feedback from an online survey sent to referring teams and attendees highlighted the value of the MDT; 94% reported the discussion was useful and 69% reported resulting change in patient management.
Multidisciplinary input is crucial in this challenging area, ensuring that all diagnostic avenues are explored and opening doors to novel diagnostics and therapeutics. It also supports clinicians dealing with unwell patients, including in centres where less specialist input is available, and when decisions have to be made where there is little or no evidence base.
•Suspected encephalitis cases are frequently challenging to diagnose and treat, often in evidence-free zones.•A regular MDT in a tertiary care centre enabled multidisciplinary input with open dialogue and formulation of management plans.•We urge closer working relationships between centres, and incorporation of referral to these centres in national guidelines for special cases.•There is also a need for robust collection of observational data from treatment decisions made by the MDT to inform future decision making.
Encephalitis causes high morbidity and mortality. An incidence of 4.3 cases of encephalitis/100 000 population has been reported in the UK. We performed a retrospective evaluation of the diagnosis ...and management of adults admitted to hospital with a clinical diagnosis of encephalitis/meningoencephalitis. Clinical, laboratory and radiological data were collated from electronic records. Thirty-six patients, median age 55 years and 24 (67%) male were included. The aetiology was confirmed over nine months in 25 (69%) of whom 16 were infections (six viral, seven bacterial, two parasitic and one viral and parasitic co-infection); 7 autoimmune; 1 metabolic and 1 neoplastic. Of 24 patients with fever, 15 (63%) had an infection. The median time to computed topography, magnetic resonance imaging and electroencephalography (EEG) was 1, 8 and 3 days respectively. Neuroimaging was abnormal in 25 (69%) and 17 (89%) had abnormal EEGs. Only 19 (53%) received aciclovir treatment. Six (17%) made good recoveries, 16 (44%) had moderate disability, 8 (22%) severe disability and 6 (17%) died. Outcomes were worse for those with an infectious cause. In summary, a diagnosis was made in 69.4% of patients admitted with encephalitis/meningoencephalitis. Autoimmune causes are important to consider at an early stage due to a successful response to treatment. Only 53% of patients received aciclovir on admission. Neuroimaging and EEG studies were delayed. The results of this work resulted in further developing the clinical algorithm for managing these patients.
Hepatitis E Virus (HEV) is a common cause of acute viral hepatitis worldwide. Typically associated with a self-limiting illness, infection may persist in immunosuppressed populations with significant ...morbidity and mortality. Based on clinical data published world-wide, UK blood safety guidance recommends the universal screening for HEV RNA of blood donors and donors of tissue, organs and stem cells.
This cross-sectional study aimed to determine the point prevalence of HEV viraemia and clinical course of viraemic patients in the peri-transplant period in solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) recipients transplanted over a 3-year period (2013-2015).
Nucleic acid extracts of whole blood from patients undergoing SOT or HSCT were tested by an in-house real-time reverse-transcriptase polymerase chain reaction assay for HEV RNA. Samples were tested at baseline (time of transplant), 30, 60 and 90 days post-transplant.
870 patients (259 HSCT, 262 liver and 349 kidney transplant) were included with 2554 samples meeting the inclusion criteria. No kidney transplant patients had HEV viraemia at time of testing. One HSCT and three liver transplant patients were found to be HEV RNA positive. Overall this represented 0.46% of the patients testing positive for HEV viraemia.
Prevalence of HEV viraemia in SOT and HSCT patients in U.K. although higher than in the general population is low at baseline and remains low throughout the early post-transplant phase. Clearance of viraemia can be maintained despite ongoing immunosuppression. Prospective U.K. studies are necessary to inform screening policies in this population.
•We performed a systematic review of MS-based peptide sequencing to identify cerebrospinal fluid biomarkers to diagnose neurological infections.•Eleven studies were identified, with results ...demonstrating feasibility and potential for diagnosis of a range of aetiologies, including tuberculosis, West Nile virus infection and trypanosomiasis.•Six studies performed further work termed verification or validation. In two of these studies, it was possible to extract data on sensitivity and specificity of the biomarkers detected by ELISA, ranging from 89–94% and 58–92% respectively.•We highlight the need for strong interdisciplinary collaboration and investment in these studies, to ensure appropriate study design, and see biomarkers progress through to validation.•Successful CSF protein biomarkers could potentially be detected by MALDI-ToF, ELISA and point-of-care immunochromatographic tests.
Central nervous system (CNS) infections account for considerable death and disability every year. An urgent research priority is scaling up diagnostic capacity, and introduction of point-of-care tests. We set out to assess current evidence for the application of mass spectrometry (MS) peptide sequencing in identification of diagnostic biomarkers for CNS infections.
We performed a systematic review (PROSPEROCRD42018104257) using PRISMA guidelines on use of MS to identify cerebrospinal fluid (CSF) biomarkers for diagnosing CNS infections. We searched PubMed, Embase, Web of Science, and Cochrane for articles published from 1 January 2000 to 1 February 2019, and contacted experts. Inclusion criteria involved primary research except case reports, on the diagnosis of infectious diseases except HIV, applying MS to human CSF samples, and English language.
4,620 papers were identified, of which 11 were included, largely confined to pre-clinical biomarker discovery, and eight (73%) published in the last five years. 6 studies performed further work termed verification or validation. In 2 of these studies, it was possible to extract data on sensitivity and specificity of the biomarkers detected by ELISA, ranging from 89–94% and 58–92% respectively.
The findings demonstrate feasibility and potential of the methods in a variety of infectious diseases, but emphasise the need for strong interdisciplinary collaborations to ensure appropriate study design and biomarker validation.
Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and ...widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global ‘Prevent, Detect and Respond’ strategy.
The term metagenomics refers to the use of sequencing methods to simultaneously identify genomic material from all organisms present in a sample, with the advantage of greater taxonomic resolution ...than culture or other methods. Applications include pathogen detection and discovery, species characterisation, antimicrobial resistance detection, virulence profiling, and study of the microbiome and microecological factors affecting health. However, metagenomics involves complex and multistep processes and there are important technical and methodological challenges that require careful consideration to support valid inference. We co-ordinated a multidisciplinary, international expert group to establish reporting guidelines that address specimen processing, nucleic acid extraction, sequencing platforms, bioinformatics considerations, quality assurance, limits of detection, power and sample size, confirmatory testing, causality criteria, cost, and ethical issues. The guidance recognises that metagenomics research requires pragmatism and caution in interpretation, and that this field is rapidly evolving.
The Lancet's Editor-in-Chief, Richard Horton, criticised National Health Service (NHS) front-liners in his Offline Comment1 (May 6, p 1783) after attending a seminar at the London School of Hygiene & ...Tropical Medicine. We were disappointed by his interpretation of an “extraordinary inability of health leaders to reflect critically on their own failings, preferring instead to blame others.” 1
Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance ...in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication.
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