Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study

McGill, Fiona; Griffiths, Michael J.; Bonnett, Laura; Geretti, Anna María; Michael, Benedict; Beeching, Nicholas; McKee, David; Scarlett, Paula; Hart, Ian; Mutton, Kenneth J.; Jung, Agam; Adan, Guleed; Gummery, Alison; Sulaiman, Wan Aliaa Wan; Ennis, Kate; Martin, Antony; Haycox, Alan; Miller, Alastair; Solomon, Tom; Adedeji, Adekola; Katharine, Ajdukiewicz; David, Birkenhead; Thomas, Blanchard; Antony, Cadwgan; David, Chadwick; John, Cheesbrough; Richard, C.; John, Croall; Crossingham, Iain; James, Dunbar; Simon, Ellis; Camelia, Faris; Peter, Flegg; Clive, Graham; Katherine, Gray; Shirley, Hammersley; Jao, Kevin; Matthew, Jones; Ildiko, Kustos; Larkin, Susan; Karim, Mahawish; Sarah, Maxwell; Jane, Minton; Kavya, Mohandas; Martin, Mostert; Moran, Ed; Christopher, Murphy; Monika, Pasztor; Paraiso, Hassan; Premchand, Nikhil; Rathur, Haris; Mark, Roberts; Amy, Robinson; Rosser, Andrew; Stefan, Schumacher; Monty, Silverdale; Philip, Stanley; Neil, T. C. H.; Alastair, Watt; Martin, Wiselka

doi:10.1016/s1473-3099(18)30245-7

Cited by 125 publications

(173 citation statements)

References 33 publications

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“…In addition to being time consuming, this approach is often ineffective; no etiology is identified in 60% of patients with encephalitis 92-94 and meningitis. 95 Moreover, the cost of such a workup has been estimated to be up to $10,000 per patient. 96 Therefore, there is considerable interest in broadrange assays that offer the potential to identify multiple pathogens with a single test.…”

Section: Broad-range Diagnostic Testing Approachesmentioning

confidence: 99%

Diagnostic Testing in Central Nervous System Infection

2019

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Several key points should guide providers managing a patient with suspected CNS infection. The first is the importance of developing a plan for the diagnostic workup. Clinicians are recommended to first test for the most likely and Keywords ► meningitis ► encephalitis ► diagnostic ► metagenomic sequencing AbstractPatients with central nervous system (CNS) infection experience very high levels of morbidity and mortality, in part because of the many challenges inherent to the diagnosis of CNS infection and identification of a causative pathogen. The clinical presentation of CNS infection is nonspecific, so clinicians must often order and interpret many diagnostic tests in parallel. This can be a daunting task given the large number of potential pathogens and the availability of different testing modalities. Here, we review traditional diagnostic techniques including Gram stain and culture, serology, and polymerase chain reaction (PCR). We highlight which of these are recommended for the pathogens most commonly tested among U.S. patients with suspected CNS infection. Finally, we describe the newer broadrange diagnostic approaches, multiplex PCR and metagenomic sequencing, which are increasingly used in clinical practice.This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.• What pathogen is being interrogated;• How to test for it (e.g., serology vs. PCR);• Where to look (e.g., CSF vs. blood);• When to test (e.g., need for paired acute/convalescent sera).Another important consideration is the turnaround time between ordering a test and receiving its results, since clinical decisions often need to be made empirically while awaiting test results. In general, PCR tests are rapid and often available in-house, while specialized serology tests may only be available at reference laboratories. However, there is substantial variation between clinical microbiology laboratories, so close communication with laboratory personnel is essential. Detection of Immune Response by SerologySerological tests are widely used in the diagnosis of CNS infections, particularly for pathogens present at low levels or for brief periods of time, and for diseases whose manifestations are primarily mediated by the host antibody response.

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Section: Broad-range Diagnostic Testing Approachesmentioning

confidence: 99%

Diagnostic Testing in Central Nervous System Infection

2019

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“…As a perspective for future research, it would be useful to assess the characteristics of each diagnostic physical examination test after classifying the patients based on the detected meningitis‐causing microorganisms, that is, viruses or bacteria. Because bacterial meningitis is usually more urgent and fatal than viral meningitis, knowing the sensitivity and specificity of each physical examination for each type of the causative microorganism may help clinicians to estimate the risk for bacterial meningitis in the primary care setting. Likewise, subgroup analyses for the characteristics of each physical examination test with variables other than the microorganism, such as disease severity or the level of CSF pleocytosis, would be also important.…”

Section: Discussionmentioning

confidence: 99%

Sensitivity and specificity of meningeal signs in patients with meningitis

Akaishi

Kobayashi

Abe

et al. 2019

J of Gen and Family Med

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Background Several types of physical examinations are used in the diagnosis of meningitis, including nuchal rigidity, jolt accentuation, Kernig's sign, and Brudzinski's sign. Jolt accentuation was reported to have sensitivity of nearly 100% and to be highly efficient for excluding meningitis, but more recent studies showed that a number of patients with meningitis may present negative in this test. Methods We systematically reviewed studies on the above‐mentioned physical examination tests and performed meta‐analysis of their diagnostic characteristics to evaluate the clinical usefulness. Nine studies, comprising a total of 599 patients with pleocytosis in the cerebrospinal fluid (CSF) and 1216 patients without CSF pleocytosis, were enrolled in the analysis. Results Jolt accentuation showed a decent level of odds ratio (3.62; 99% confidence interval (CI): 1.13‐11.60, P = 0.004) comparable to that in nuchal rigidity (2.52; 1.21‐5.27, P = 0.001) for the correct prediction of CSF pleocytosis among subjects with suspected meningitis. The estimated sensitivity was relatively high (40%‐60%) in nuchal rigidity or jolt accentuation tests. On the other hand, Kernig's and Brudzinski's signs exhibited relatively low sensitivity (20%‐30%). The estimated specificity was higher in Kernig's and Brudzinski's signs (85%‐95%) than in nuchal rigidity or jolt accentuation tests (65%‐75%). Conclusion Approximately half of the patients with meningitis may not present typical meningeal signs upon physical examination. Combining several examinations for the detection of meningeal signs may decrease the risk of misdiagnosis.

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“…8 Some, but not all studies, have shown an increased risk of neurological morbidity after HSV-2 meningitis, [8][9][10] and a recent UK-study found that patients with HSV-2 meningitis had a lower quality of life than healthy controls at one-year follow-up. 2 Studies on long-term outcomes of HSV CNS infections are scarce and often hampered by small or selected study populations restricted to patients with severe HSV encephalitis, patients admitted to referral centers, or patients from a single center, and by lack of adequate comparison cohorts. 5,6,10,11 Follow-up rarely exceeds one year, 12 and no studies have included complete national data on all HSV-1 and HSV-2 CNS infections.…”

Section: Introductionmentioning

confidence: 99%

<p>Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000–2016</p>

Hansen¹,

Vestergaard²,

Dessau³

et al. 2020

CLEP

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Background: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated. Patients and Methods: We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830). Results: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (−0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference −19.8%; 95% CI: −34.7% to −4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: −0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/ year; 95% CI: 7.9 to 10.4). Conclusion: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.

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Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study

Cited by 125 publications

References 33 publications

Diagnostic Testing in Central Nervous System Infection

Diagnostic Testing in Central Nervous System Infection

Sensitivity and specificity of meningeal signs in patients with meningitis

<p>Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000–2016</p>

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