Infectious meningitis and encephalitis in adults in Denmark: a prospective nationwide observational cohort study (DASGIB)

ObjectivesTo monitor epidemiological trends of infectious meningitis (bacterial and viral) and encephalitis in Denmark.MethodsNationwide prospective observational study of all cases of proven community-acquired infectious meningitis and encephalitis in adults treated in all infectious diseases departments in Denmark from 1 January 2015 to 30 June 2016. We included data on symptoms, aetiology, treatment and outcome assessed by the Glasgow Outcome Scale (GOS) 30 days after discharge. GOS 1–4 was categorized as unfavourable outcome.ResultsDuring 18 months of observation, we identified 252 cases of viral meningitis (3.6/100 000/year), 214 cases of bacterial meningitis (3.1/100 000/year) and 96 cases of infectious encephalitis (1.4/100 000/year). In bacterial meningitis, Streptococcus pneumoniae was the most frequent infectious agent (n = 101) followed by Staphylococcus aureus (n = 24) and β-haemolytic streptococci (n = 14). Meningococcal meningitis was rare (n = 11). In encephalitis, herpes simplex virus type 1 was most common (n = 37) followed by varicella zoster virus (n = 20), whereas varicella zoster virus (n = 61) was most common in viral meningitis followed by enterovirus (n = 50) and herpes simplex virus type 2 (n = 46). Case fatality and unfavourable outcome occurred in 31/214 (15%) and 96/214 (45%) with bacterial meningitis and in 5/96 (5%) and 55/89 (62%) with encephalitis. For viral meningitis, unfavourable outcome occurred in 41/252 (17%).ConclusionsThe epidemiology and clinical presentation of the examined central nervous system infections differed considerably and bacterial meningitis was more frequent than previously estimated. Overall prognosis remains poor for bacterial meningitis and encephalitis. Prospective nationwide clinical databases of central nervous system infections may be superior to epidemiological monitoring based on notifications or laboratory systems.     

Aseptic meningitis in adults and children: Diagnostic and management challenges

BackgroundAseptic meningitis represents a common diagnostic and management dilemma to clinicians.ObjectivesTo compare the clinical epidemiology, diagnostic evaluations, management, and outcomes between adults and children with aseptic meningitis.Study designWe conducted a retrospective study from January 2005 through September 2010 at 9 Memorial Hermann Hospitals in Houston, TX. Patients age ≥ 2 months who presented with community-acquired aseptic meningitis with a CSF white blood cell count >5 cells/mm³ and a negative Gram stain and cultures were enrolled. Patients with a positive cryptococcal antigen, positive blood cultures, intracranial masses, brain abscesses, or encephalitis were excluded.ResultsA total of 509 patients were included; 404 were adults and 105 were children. Adults were most likely to be female, Caucasian, immunosuppressed, have meningeal symptoms (headache, nausea, stiff neck, photophobia) and have a higher CSF protein (P < 0.05). In contrast, children were more likely to have respiratory symptoms, fever, and leukocytosis (P < 0.05). In 410 (81%) patients, the etiologies remained unknown. Adults were more likely to be tested for and to have Herpes simplex virus and West Nile virus while children were more likely to be tested for and to have Enterovirus (P < 0.001). The majority of patients were admitted (96.5%) with children receiving antibiotic therapy more frequently (P < 0.001) and adults receiving more antiviral therapy (P = 0.001). A total of 384 patients (75%) underwent head CT scans and 125 (25%) MRI scans; all were normal except for meningeal enhancement. All patients had a good clinical outcome at discharge.DiscussionAseptic meningitis in adults and children represent a management challenge as etiologies remained unknown for the majority of patients due to underutilization of currently available diagnostic techniques.     

Blood-CSF-barrier dysfunction is a marker for encephalitic involvement in patients with aseptic meningitis/meningoencephalitis

BackgroundThe term “aseptic meningitis” encompasses cases of meningitis with negative bacterial CSF culture, which predominantly are of viral etiology. While the clinical course is usually benign, complications such as encephalitic involvement resulting in a more severe clinical course may occur. Dysfunction of the blood-brain-barrier (BBB), which is a prerequisite for viral entry into the brain parenchyma, can be approximated using the CSF/serum albumin ratio, readily obtainable in routine CSF analysis.ObjecitvesAnalysis of CSF patterns in patients with aseptic meningitis/meningoencephalitis with a focus on BBB dysfunction as a marker for encephalitic involvement.Study designRetrospective chart review of patients admitted to our hospital between 2004 and 2016 with a diagnosis of aseptic meningitis/meningoencephalitis.ResultsPatients with aseptic meningitis displaying clinical, MR-tomographic or electroencephalographic signs of encephalitic involvement were significantly older than patients without these features (47.4 vs. 35.5 yrs., p = 0.002). In patients with meningoencephalitis, CSF analysis revealed a more severe disruption of BBB, approximated by the CSF/serum albumin ratio (p = 0.002). Compromised BBB function correlated positively with length of hospitalization (p = 0.007), indicative of a more severe clinical course. The number of CSF lymphocytes was found to predict the severity of the BBB disruption, which additionally was more frequently observed when herpesviridae were identified as infectious agents.ConclusionsWe suggest that the CSF/serum albumin ratio as an estimate for BBB function should be attended to in the evaluation of patients with aseptic meningitis. Severe BBB dysfunction, older age and infection with herpesviridae appear to raise the risk for encephalitic involvement.     

Reactivation of herpes simplex type 1 in pneumococcal meningitis

BackgroundAcute bacterial meningitis (ABM) and herpes simplex type 1 (HSV-1) encephalitis are two rare but serious infections affecting the central nervous system (CNS). Concurrent bacterial and viral CNS infection has occasionally been reported.ObjectivesTo illustrate the possibility of intrathecal infection with both Streptococcus pneumonia and HSV-1 by presenting a case and to examine whether herpesvirus reactivation is common in ABM.Study designWe report a case diagnosed with HSV-1 reactivation in the cerebrospinal fluid (CSF) during treatment for pneumococcal ABM. A retrospective analysis of CSF samples from 21 patients with ABM was performed, with analysis of DNA from HSV-1 and four other neurotropic herpesviruses.ResultsAll 21CSF samples were negative for HSV-1, HSV-2, varicella zoster-virus, Epstein–Barr virus and human herpesvirus 6 DNA by PCR.ConclusionsAlthough herpesvirus infection does not seem to be a common phenomenon in ABM we suggest that HSV-1 reactivation could be kept in mind if patients with ABM show symptoms or signs compatible with encephalitis.     

Impact of dexamethasone on SARS-CoV-2 concentration kinetics and antibody response in hospitalized COVID-19 patients: results from a prospective observational study

ObjectivesDexamethasone has become the standard of care for severe coronavirus disease 2019 (COVID-19), but its virological impact is poorly understood. The objectives of this work were to characterize the kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) concentration in the upper respiratory tract (URT) and the antibody response in patients with (D⁺) and without (D^–) dexamethasone treatment.MethodsData and biosamples from hospitalized patients with severe COVID-19, enrolled between 4th March and 11th December 2020 in a prospective observational study, were analysed. SARS-CoV-2 virus concentration in serial URT samples was measured using RT-PCR. SARS-CoV-2-specific immunoglobulins A and G (IgA and IgG) were measured in serum samples using S1-ELISA.ResultsWe compared 101 immunocompetent patients who received dexamethasone (according to the inclusion criteria and dosage determined in the RECOVERY trial) to 93 immunocompetent patients with comparable disease severity from the first months of the pandemic, who had not been treated with dexamethasone or other glucocorticoids. We found no inter-group differences in virus concentration kinetics, duration of presence of viral loads >10⁶ viral copies/mL (D⁺ median 17 days (IQR 13–24), D^– 19 days (IQR 13–29)), or time from symptom onset until seroconversion (IgA: D⁺ median 11.5 days (IQR 11–12), D^– 14 days (IQR 11.5–15.75); IgG: D⁺ 13 days (IQR 12–14.5), D^– 12 days (IQR 11–15)).ConclusionDexamethasone does not appear to lead to a change in virus clearance or a delay in antibody response in immunocompetent patients hospitalized with severe COVID-19.     

The diagnostic value of cytokine and nitric oxide concentrations in cerebrospinal fluid for the differential diagnosis of meningitis

PurposeIn several cases of meningitis routinely used diagnostic procedures are unable to identify the cause of this disease. The objective of the present study was to determine whether proinflammatory cytokine (tumour necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8)) and nitric oxide (NO) concentrations in the CSF are useful markers for the differential diagnosis of meningitis.Material and MethodsSixty-seven patients (42 patients with bacterial meningitis and 25 patients with viral meningitis) were included in the present study. In the investigated group, the TNF-α, IL-1β and IL-8 concentrations in the CSF samples collected on the day of admission were assessed. Furthermore, the NO concentrations were assessed in 23 patients.ResultsThe results revealed that the measurement of proinflammatory cytokines in CSF can aid in a differential diagnosis. In particular, a high concentration of TNF-α may be a sensitive and specific marker of a bacterial aetiology of the neuroinfection. In the present study, TNF-α concentrations greater than 75.8 pg/ml differentiated between bacterial and viral meningitis with 100% sensitivity and specificity. The NO concentration in the CSF was also significantly greater in patients with bacterial meningitis than in those with viral meningitis.ConclusionsThe assessment of TNF-α, IL-1β and IL-8 concentrations in the CSF is useful in the differential diagnosis of neuroinfection. Because many factors may influence NO production in the central nervous system (CNS), it is not clear whether NO values can be used for the differential diagnosis of meningitis, and further studies are required     

The use of dried cerebrospinal fluid filter paper spots as a substrate for PCR diagnosis of the aetiology of bacterial meningitis in the Lao PDR

We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro CardTM (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/μL (interquartile range 5.5 GE/μL) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 10⁴ GE/μL (1.2 × 10⁵; 1 to ×.1 × 10⁶ DNA GE/μL). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies.     

Lyme neuroborreliosis with encephalitis; a systematic literature review and a Scandinavian cohort study

BackgroundLyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described.ObjectivesTo describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study.Data sourcesMedline, Embase, Scopus, Cochrane library.Study eligibility criteriaThere was no discrimination on study type, time of publication or language.ParticipantsReview: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990–2019 were screened for patients with encephalitis.MethodsReview: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered.ResultsReview: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2–90 days). Of 38 patients with available follow-up after median 12 months (IQR 5–13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48–76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2–4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7–34), with further 7 days (IQR 3–34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113–389), 65.6% had residual symptoms. None had died.ConclusionsThis study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.     

High Prevalence of Cryptococcal Antigenaemia amongst Asymptomatic Advanced HIV Patients in Pune,India

Background: The World Health Organization recommends routine cryptococcal antigen (CrAg) screening in advanced AIDS patients initiating antiretroviral treatment (ART). India has yet to adopt this strategy as the burden of cryptococcal antigenaemia is unknown. Methods: A prospective study was conducted in a large public sector ART centre and the inpatient wards of Sassoon Hospital, Pune, India. All consenting patients >18 years of age with CD4 count <100 cells/mm³ were screened for CrAg by latex agglutination assay. Those with positive CrAg underwent cerebrospinal fluid analysis, chest radiograph and abdominal ultrasound to rule out cryptococcal disease. The impact of CrAg positivity on all-cause mortality was assessed by logistic regression analysis. Results: Amongst 208 AIDS patients with CD4 cells <100 cells/mm³ who underwent CrAg testing, median age was 40 (interquartile range [IQR], 35–49) years, 134 (64%) were male and median CD4 count was 64.5 cells/mm³ (IQR, 37–82). Overall, 16 (8%, 95% confidence interval [CI], 4–12) patients were positive for CrAg, of which 8 (50%) had CD4 cells <50 cells/mm³ and 3 (19%) CrAg-positive patients had incidental cryptococcal meningitis. At 6-month follow-up, the case fatality rate was higher amongst CrAg-positive patients (38%) compared with CrAg-negative patients (18%) (P = 0.06). After adjusting for age, sex, CD4 count and ART, there was a trend towards increased all-cause mortality (adjusted OR, 3.18, 95% CI, 0.60–16.88, P = 0.17). Conclusions: We found an 8% prevalence of cryptococcaemia amongst adult AIDS patients with CD4 cells <100 cells/mm³. Given the high fatality rates observed, routine screening for CrAg should be considered for all Indian persons with advanced HIV disease.     

HIV-associated DLBCL: Clinicopathological factors including dual-colour chromogenic in situ hybridisation to assess MYC gene copies

IntroductionDiffuse large B-cell lymphoma (DLBCL) comprises up to 43% of non-Hodgkin lymphomas in South Africa due to the high seroprevalence of human immunodeficiency virus (HIV) infection in the southern African region. We explored the prognostic influence of an array of clinicopathological factors, including MYC gene copy numbers, within HIV-associated DLBCL.MethodsThe retrospective inclusion of 123 tumours was followed by c-MYC immunohistochemistry and dual-colour MYC and centromere 8 (CEN8) chromogenic in situ hybridisation on formalin-fixed paraffin-embedded sections. Clinicopathological data were collected, interpreted and analysed.ResultsHIV seropositive patients comprised 81% (93/115), mean age 42 (SD 10.8) years, with 55% males, HIV negative patients comprised 19% (22/115), mean age 57 (SD 16.7) years (p = 0.001), with 59% males and the HIV status was unknown for 8 patients. The median CD4 count was 162 (IQR 215) cells/mm³, 33% of patients presented with CD4 counts <100 cells/mm³ and the median viral load was 217 (IQR 182 981) copies/mL. There was advanced stage at presentation (i.e., III-IV, 87%), with Ki-67 proliferation indices ≥90% in 85%- and c-MYC expression (i.e., ≥40%) in 58% of tumours. Double expression of c-MYC and BCL2 was associated with a non-germinal center immunophenotype (p < 0.01). Low-level increase of MYC gene copy numbers and MYC rearrangements occurred in 57% and 12%, respectively. C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/increased MYC gene copies were also detected. Inferior median overall survival (OS) occurred when the CD4 counts were <100 cells/mm³ (149 days 95% CI 44-254, p 0,04) and when IPI scores were 3–5 [155 days (95% CI 37–273), p = 0.01]. Concomitant infections negatively impacted the survival outcome, multivariate regression analysis (HR 4.01, 95% CI 1.86–12.20, p = 0.02).Conclusionc-MYC protein expression, low-level increase in MYC gene copy numbers, rearrangement, C8 polysomy, MYC gene clusters and concurrent MYC rearrangement/low-level gains are present in HIV+ DLBCL. CD4 counts < 100 cells/mm³, IPI scores 3-5 and concomitant infections negatively impact the survival outcome.     

Community-acquired pneumonia in patients with bacterial meningitis: a prospective nationwide cohort study

ObjectivePneumonia is considered a focus of infection in patients presenting with community-acquired bacterial meningitis but the impact on disease course is unclear. The aim was to study presenting characteristics, clinical course and outcome of meningitis patients with co-existing pneumonia on admission.MethodsWe evaluated adult patients with community-acquired bacterial meningitis with pneumonia on admission in a nationwide, prospective cohort performed from March 2006 to June 2017. We performed logistic regression analysis to identify clinical characteristics predictive of pneumonia on admission, and to quantify the effect of pneumonia on outcome.ResultsPneumonia was diagnosed on admission in 315 of 1852 (17%) bacterial meningitis episodes and confirmed by chest X-ray in 256 of 308 (83%) episodes. Streptococcus pneumoniae was the causative organism in 256 of 315 episodes (81%). Pneumonia on admission was associated with advanced age (OR 1.03 per year increase, 95% CI 1.02–1.04, p < 0.001), alcoholism (OR 1.96, 95% CI 1.23–3.14, p 0.004), cancer (OR 1.54, 95% CI 1.12–2.13, p 0.008), absence of otitis or sinusitis (OR 0.44, 95% CI 0.32–0.59, p < 0.001) and S. pneumoniae (OR 2.14, 95% CI 1.55–2.95, p < 0.001) in the multivariate analysis. An unfavourable outcome defined as a score of 1–4 on the Glasgow Outcome Scale was observed in 172 (55%) episodes and 87 patients (28%) died. Pneumonia on admission was independently associated with unfavourable outcome and mortality in the multivariate analysis (OR 1.48, 95% CI 1.12–1.96; p 0.005).ConclusionPneumonia on admission in bacterial meningitis is a frequent coexisting infection and is independently associated with unfavourable outcome and mortality.     

Use of an antiviral mouthwash as a barrier measure in the SARS-CoV-2 transmission in adults with asymptomatic to mild COVID-19: a multicentre,randomized, double-blind controlled trial

ObjectivesTo determine if commercially available mouthwash with β-cyclodextrin and citrox (bioflavonoids) (CDCM) could decrease the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) salivary viral load.MethodsIn this randomized controlled trial, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive patients aged 18–85 years with asymptomatic to mild coronavirus disease 2019 (COVID-19) symptoms for <8 days were recruited. A total of 176 eligible patients were randomly assigned (1:1) to CDCM or placebo. Three rinses daily were performed for 7 days. Saliva sampling was performed on day 1 at 09.00 (T1), 13.00 (T2) and 18.00 (T3). On the following 6 days, one sample was taken at 15.00. Quantitative RT-PCR was used to detect SARS-CoV-2.ResultsThe intention-to-treat analysis demonstrated that, over the course of 1 day, CDCM was significantly more effective than placebo 4 hours after the first dose (p 0.036), with a median percentage (log₁₀ copies/mL) decrease T1–T2 of –12.58% (IQR –29.55% to –0.16%). The second dose maintained the low median value for the CDCM (3.08 log₁₀ copies/mL; IQR 0–4.19), compared with placebo (3.31 log₁₀ copies/mL; IQR 1.18–4.75). At day 7, there was still a greater median percentage (log₁₀ copies/mL) decrease in salivary viral load over time in the CDCM group (–58.62%; IQR –100% to –34.36%) compared with the placebo group (–50.62%; IQR –100% to –27.66%). These results were confirmed by the per-protocol analysis.ConclusionsThis trial supports the relevance of using CDCM on day 1 (4 hours after the initial dose) to reduce the SARS-CoV-2 viral load in saliva. For long-term effect (7 days), CDMC appears to provide a modest benefit compared with placebo in reducing viral load in saliva.     

Bacteriological profile of community acquired acute bacterial meningitis: a ten-year retrospective study in a tertiary neurocare centre in South India

Purpose: Ten years retrospective study to evaluate the bacteriological spectrum of community acquired acute bacterial meningitis (CAABM). Methods: Cerebrospinal fluid (CSF) samples from 385 clinically suspected cases of pyogenic meningitis were processed for cell counts, cytospin Gram stain, culture, antigen detection by latex agglutination (LAT) and antibiotic susceptibility test. Eighteen of these CSF samples were also subjected to a polymerase chain reaction (PCR) assay for detection of pneumococcal DNA. Results: The etiological agent could be identified in 284 (73.8%) of the total 385 cases by culture and/or smear and /or LAT. Streptococcus pneumoniae was the predominant pathogen accounting for 238 (61.8%) cases. Haemophilus influenzae and Neisseria meningitidis accounted for 7 (1.8%) and 4 (1%) cases respectively. Other gram negative bacilli, Streptococcus spp. and Staphylococcus aureus were isolated from 19 (4.9%), 9 (2.3%) and 7 (1.8%) cases respectively. Conclusions: Streptococcus pneumoniae remains the major aetiological agent of CAABM both in adults and children in our set-up. No penicillin resistance was detected among the isolates. Further research should focus on preventable aspects of CAABM, especially pneumococcal vaccines, to help reduce the disease burden.     

Diagnostic accuracy of rapid antigen tests in cerebrospinal fluid for pneumococcal meningitis: a systematic review and meta-analysis

BackgroundStreptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately.ObjectivesTo elucidate whether rapid antigen tests in CSF are useful in the triage of pneumococcal meningitis.MethodsData sourcesCochrane CENTRAL, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases were searched.Study eligibility criteriaAll types of cohort studies except multiple-group studies, where the sensitivity and specificity of rapid antigen tests in CSF compared with CSF culture can be extracted.ParticipantsPatients with suspected meningitis.TestsRapid antigen tests in CSF.Reference standardsOne or more of the following: blood culture, CSF culture, and polymerase chain reaction in CSF.Assessment of risk of biasThe methodological quality of the included studies was assessed using QUADAS-2.Methods of data synthesisWe used a random-effects bivariate model for the meta-analysis. We conducted a subgroup analysis by dividing studies into types of antigen tests, adults and children, low-income and high-income countries, and with or without exposure to antibiotics before lumbar puncture.ResultsForty-four studies involving 14 791 participants were included. Most studies had a moderate-to-low methodological quality. Summary sensitivity and specificity were 99.5% (95% confidence interval (CI), 92.4–100%) and 98.2% (95% CI, 96.9–98.9%), respectively. Positive predictive values and negative predictive values at the median prevalence (4.2%) in the included studies were 70.8% (95% CI, 56.6–79.9%) and 100% (95% CI, 99.7–100%), respectively. The diagnostic accuracy was consistent across the various subgroups, except for slightly reduced sensitivity in high-income countries.ConclusionsRapid antigen tests in CSF would be useful in triaging pneumococcal meningitis. Further studies are warranted to investigate the clinical benefit of ruling out pneumococcal meningitis based on the results of rapid antigen tests.     

CMV plasma DNAemia and risk of cancer among HIV-infected patients: A case–control study nested in the ANRS CO3 Aquitaine Cohort,France, 2002–2007

BackgroundCMV reactivation, which enhances immune senescence, could be associated with a higher risk of cancer.ObjectivesWe compared the prevalence of positive CMV DNAemia in HIV-infected patients with and without cancer.Study designThis case–control study, nested in the ANRS-CO3 Aquitaine Cohort, included patients with a first diagnosis of cancer (2002–2007) as cases. Two controls were matched per case.Cancer risk was estimated using conditional logistic regression models, an Odds Ratio (OR) of 2 could be detected with 80% power. The variables considered were: ≥1 positive CMV DNAemia, CD4+ and CD8+ counts, HIV plasma load. Plasma CMV DNA was retrospectively quantified within the 3-year period preceding the endpoint.ResultsThe 143 cases (93 non-AIDS-related and 50 AIDS-related cancers) and 284 controls had a median age of 47 years (IQR: 41–56). At the time of diagnosis or censorship, for cases and controls, median values were respectively, for CD4+ count: 327 cells/mm³ (IQR: 164–514) and 416 (IQR: 275–582), and for HIV plasma load: 2.6 log₁₀ copies/mL (IQR: 1.7–4.7) and 1.7 log₁₀ copies/mL (IQR: 1.7–3.3). We performed 2056 CMV PCR; 14 cases (9.8% [95% CI: 4.9–14.7]) and 19 controls (6.7% [CI: 3.8–9.6]) presented ≥1 positive PCR. CMV DNAemia was not associated with the risk of cancer (unadjusted and adjusted p-values = 0.19 and 0.54, respectively). HIV load >500 copies/mL was independently associated with a higher risk of cancer (OR = 2.02; p = 0.002; 95% CI: 1.29–3.17).ConclusionThis large case–control study did not show any differential exposure to positive CMV plasma DNAemia between cancer cases and controls.     

Clinical features of acute human immunodeficiency virus infection in Taiwan: A multicenter study

Background/purposeAcute HIV infection is characterized by a high concentration of HIV RNA in the plasma and rapid depletion of the CD4 cell count. This multicenter, retrospective observational study aimed to characterize the manifestations of acuteHIV infection in Taiwan.MethodsBetween 1 January 2012 and 31 December 2016, all patients aged 20 years or greater who presented with acute HIV infection were included. Demographic and clinical characteristics of the patients at diagnosis were collected. Baseline laboratory assessment included hemogram, CD4 count, plasma HIV RNA load (PVL), serologic markers of syphilis and hepatitis A, B, and C viruses, and serum biochemistry.ResultsThe proportion of acute HIV infection was 6.9% among the patients with newly diagnosed HIV infection during the study period. The most common presenting symptoms of acute HIV infection were fever, fatigue, and myalgia. The median PVL at diagnosis was 5.9 log₁₀ copies/ml, and median CD4 count was 307 cells/mm³. A total of 68 patients (27%) had baseline CD4 count less than 200 cells/mm³. Multiple logistic regression analysis, showed that the baseline CD4 count (OR, 4.02; p = 0.013) and aspartate aminotransaminase levels (OR, 3.49; p = 0.002) were associated with high PVL (>5 log₁₀ copies/ml); and high baseline PVL (OR, 2.64; p = 0.002) was associated with symptomatic acute HIV infection.ConclusionsManifestations of acute HIV infection are nonspecific and of wide spectrum ranging from fever to severe illness. A higher proportion of patients with initial CD4 counts of 200 cells/mm³ or less during acute HIV infection warrants early, timely diagnosis and treatment to prevent rapid disease progression.     

Predominance of enterovirus B and echovirus 30 as cause of viral meningitis in a UK population

Background/ObjectivesEnteroviruses are the most common cause of aseptic or lymphocytic meningitis, particularly in children. With reports of unusually severe neurological disease in some patients infected with enterovirus D68 in North America, and a recent increase in the number of paediatric enterovirus meningitis cases presenting in this UK Midlands population, a retrospective regional surveillance study was performed.Study designCerebrospinal fluid (CSF) samples received were tested using the polymerase chain reaction (PCR) for HSV-1/2, VZV, enteroviruses and parechoviruses. Enterovirus PCR positive CSF samples were sent for further serotyping. A phylogenetic tree was constructed of the echovirus 30 VP1 sequences, where sufficient sample remained for sequencing.ResultsThe number of enterovirus positive CSFs from each year were: 21 (2008), 7 (2011), 53 (2012), 58 (2013) and 31 (2014). Overall, 163 of the 170 serotyped enteroviruses belonged to the species B (echovirus 5, 6, 7, 9, 11, 13, 16, 17, 18, 21, 25, 30; coxsackie B1, B2, B3, B4, B5, A9), with only 7 belonging to species A (coxsackie A2, A6, A16 and enterovirus 71). Echovirus 30 was the predominant serotype overall, identified in 43 (25.3%) of samples, with a significantly higher proportion in the adult age group (37.3%) compared to the infant age group (12.3%). Phylogenetic analysis showed that these UK Midlands echovirus 30 VP1 sequences clustered most closely with those from Europe and China.ConclusionThis study showed a continued predominance of echovirus 30 as a cause of viral meningitis, particularly in adults, though more surveillance is needed.     

Bacterial counts in cerebrospinal fluid of children with meningitis

Eighty-five cerebrospinal fluid (CSF) specimens from the same number of pediatric patients with meningitis were examined to determine the bacterial count and the relationship of this count to the microscopy results, the ages of the patients and the bacterial species isolated. Bacterial counts ranged from 2 × 10 to 4 × 10⁹ CFU/ml CSF. Twenty-five percent of the 85 CSF specimens positive forHaemophilus influenzae type b,Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli K1 and group B streptococci had counts of 10⁷ CFU/ml or higher. Children between 1 and 6 months of age had significantly higher counts (p < 0.05) than the other age groups. The three patients who had positive CSF cultures 24 h after the start of therapy all had initial bacterial counts of 10⁷ CFU/ml or higher. The detection limit for Gram stain/microscopy was 10⁵ CFU/ml. No correlation was found between bacterial count and the number of polymorphonuclear leukocytes.