Ability of Procalcitonin and C-Reactive Protein for Discriminating between Bacterial and Enteroviral Meningitis in Children Using Decision Tree.

Bacterial meningitis (BM) is a public health burden in developing countries, including Central Asia. This disease is characterized by a high mortality rate and serious neurological complications. Delay with the start of adequate therapy is associated with an increase in mortality for patients with acute bacterial meningitis. Cerebrospinal fluid culture, as a gold standard in bacterial meningitis diagnosis, is time-consuming with modest sensitivity, and this is unsuitable for timely decision-making. It has been shown that bacterial meningitis differentiation from viral meningitis could be done through different parameters such as clinical signs and symptoms, laboratory values, such as PCR, including blood and cerebrospinal fluid (CSF) analysis. In this study, we proposed the method for distinguishing the bacterial form of meningitis from enteroviral one. The method is based on the machine learning process deriving making decision rules. The proposed fast-and-frugal trees (FFTree) decision tree approach showed an ability to determine procalcitonin and C-reactive protein (CRP) with cut-off values for distinguishing between bacterial and enteroviral meningitis (EVM) in children. Such a method demonstrated 100% sensitivity, 96% specificity, and 98% accuracy in the differentiation of all cases of bacterial meningitis in this study. These findings and proposed method may be useful for clinicians to facilitate the decision-making process and optimize the diagnostics of meningitis.

The association between serum sodium level and tuberculous meningitis compared with viral and bacterial meningitis.

We evaluated the association between hyponatremia and tuberculous meningitis (TBM) with the aim of providing additional information for differential diagnosis from other types of infectious meningitis, especially viral meningitis (VM). Cross-sectional and longitudinal data involving 5026 participants older than 18 years were analyzed in the total population and a propensity-matched population. The initial and lowest sodium levels and longitudinal changes in TBM, bacterial meningitis (BM), and VM patients were compared. Participants in the TBM group were enrolled when they were diagnosed as possible, probable, or definite TBM according to the Marais' criteria. The initial serum sodium level was significantly lower in TBM patients than in BM and VM patients (136.9 ± 5.9 vs. 138.3 ± 4.7 mmol/L, p < 0.001 for TBM vs. BM, and 139.0 ± 3.1, p < 0.001 for TBM vs. VM), and it decreased significantly more steeply to lower levels in both the TBM and BM patients compared with VM patients. The lowest serum sodium level was in the order of TBM < BM < VM patients, and the change was statistically significant in all subgroups (131.8 ± 6.4, 133.1 ± 5.1, 137.4 ± 3.7, respectively, p < 0.001). Participants with lower serum sodium level were more likely to have a diagnosis of TBM rather than VM, and this association was more pronounced for the lowest sodium level than the initial sodium level [OR 4.6 (95% CI 2.4-8.8, p < 0.001)]. These findings indicate that baseline and longitudinal evaluation of serum sodium level can provide information for differential diagnosis of TBM from BM or VM.

Serum and cerebrospinal fluid neurofilament light chain in patients with central nervous system infections caused by varicella-zoster virus.

Varicella-zoster virus (VZV) is a common cause of viral central nervous system (CNS) infection, and patients may suffer from severe neurological sequelae. The biomarker neurofilament light chain (NFL) is used for assessment of neuronal damage and is normally measured in cerebrospinal fluid (CSF). Novel methods have given the possibility to measure NFL in serum instead, which could be a convenient tool to estimate severity of disease and prognosis in VZV CNS infections. Here, we investigate the correlation of serum and CSF NFL in patients with VZV CNS infection and the association of NFL levels in serum and CSF with different VZV CNS entities. NFL in serum and CSF was measured in 61 patients who were retrospectively identified with neurological symptoms and VZV DNA in CSF detected by PCR. Thirty-three herpes zoster patients and 40 healthy blood donors served as control groups. NFL levels in serum and CSF correlated strongly in the patients with VZV CNS infection. Encephalitis was associated with significantly higher levels of NFL in both serum and CSF compared with meningitis and Ramsay Hunt syndrome. Surprisingly, herpes zoster controls had very high serum NFL levels, comparable with those shown in encephalitis patients. We show that analysis of serum NFL can be used instead of CSF NFL for estimation of neuronal injury in patients with VZV CNS infection. However, high levels of serum NFL also in patients with herpes zoster, without signs of CNS involvement, may complicate the interpretation.

Diagnosing enterovirus meningitis via blood transcriptomics: an alternative for lumbar puncture?

BACKGROUND: Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. METHODS: In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3' mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. RESULTS: Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. CONCLUSIONS: Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis.

Identification of Cerebrospinal Fluid Metabolites as Biomarkers for Enterovirus Meningitis.

Enteroviruses are among the most common causes of viral meningitis. Enteroviral meningitis continues to represent diagnostic challenges, as cerebrospinal fluid (CSF) cell numbers (a well validated diagnostic screening tool) may be normal in up to 15% of patients. We aimed to identify potential CSF biomarkers for enteroviral meningitis, particularly for cases with normal CSF cell count. Using targeted liquid chromatography-mass spectrometry, we determined metabolite profiles from patients with enteroviral meningitis (n = 10), and subdivided them into those with elevated (n = 5) and normal (n = 5) CSF leukocyte counts. Non-inflamed CSF samples from patients with Bell's palsy and normal pressure hydrocephalus (n = 19) were used as controls. Analysis of 91 metabolites revealed considerable metabolic reprogramming in the meningitis samples. It identified phosphatidylcholine PC.ae.C36.3, asparagine, and glycine as an accurate (AUC, 0.92) combined classifier for enterovirus meningitis overall, and kynurenine as a perfect biomarker for enteroviral meningitis with an increased CSF cell count (AUC, 1.0). Remarkably, PC.ae.C36.3 alone emerged as a single accurate (AUC, 0.87) biomarker for enteroviral meningitis with normal cell count, and a combined classifier comprising PC.ae.C36.3, PC.ae.C36.5, and PC.ae.C38.5 achieved nearly perfect classification (AUC, 0.99). Taken together, this analysis reveals the potential of CSF metabolites as additional diagnostic tools for enteroviral meningitis, and likely other Central nervous system (CNS) infections.

T3 level may be a helpful marker to predict disease prognosis of acute central nervous system viral infections.

AIM OF THE STUDY: Acute central nervous system viral infections are progressive and inflammatory diseases with inflammatory cells infiltrating into the central nervous system (CNS), and thyroid hormone (TH) level is associated with the oxidative and antioxidant status. Variations in oxidative stress and antioxidant status are related to the pathogenesis of inflammatory diseases. Our study aimed to investigate the possible correlation between viral infections in CNS and TH levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3). MATERIALS AND METHODS: We measured serum concentrations of TSH, fT4, and fT3 in 206 individuals, including 59 viral meningitis (VM) patients, 60 viral encephalitis (VE) patients, and 87 healthy controls. RESULTS: Our findings showed that VE and VM patients had lower levels of fT3 and higher levels of fT4 compared with healthy controls, whether male or female. Moreover, levels of TSH and fT3 in patients with viral infections in CNS were inversely correlated with disease prognosis measured by the Glasgow Outcome Scale. CONCLUSIONS: Variations in TH level may represent the oxidative status and are surrogate biomarkers for disease prognosis of acute central nervous system viral infections.

Usefulness of blood and cerebrospinal fluid laboratory testing to predict bacterial meningitis in the emergency department. / Utilidad de las determinaciones analíticas en sangre y líquido cefalorraquídeo para predecir meningitis bacterianas en el servicio de urgencias.

INTRODUCTION: The classic clinical presentation of bacterial meningitis (BM) is observed in less than half of the cases in adults, and symptoms are less specific in children, the elderly or immunocompromised, and other chronic patients. The usual signs and symptoms do not provide optimal sensitivity and specificity for distinguishing possible BM from viral meningitis (VM), which may lead to a delay in the appropriate antimicrobial therapy. Society therefore stands to benefit from the development of effective, objective, and rapid tools able to predict and identify patients with BM. These tools include laboratory tests for blood and cerebrospinal fluid (CSF). The aim of this review is to summarise recently published scientific evidence in order to clarify existing controversies and compare the usefulness and diagnostic ability of the different parameters used to predict BM. DEVELOPMENT: Systematic search of the main bibliographic databases and platforms to identify articles published between January 2000 and January 2016. We selected 59 articles that meet the objectives of this review. CONCLUSIONS: CSF lactate, proportion of polymorphonuclear leukocytes, and CSF glucose, as well as serum procalcitonin (PCT), are the independent factors most predictive of bacterial aetiology. The model that combines serum PCT and CSF lactate achieves the highest predictive power for BM, with a sensitivity and specificity exceeding 99%. We should consider BM when CSF lactate >33 md/dL and/or PCT>0.25ng/mL.

Comparison of C Reactive Protein and Procalcitonin Levels in Cerebrospinal Fluid and Serum to Differentiate Bacterial from Viral Meningitis.

GOALS: It is unclear whether C reactive protein (CRP) and procalcitonin (PCT) levels in cerebrospinal fluid (CSF) improve the accuracy compared to their serum levels for the differential diagnosis of infectious meningitis. The aim of this study was to compare the accuracy of CRP and PCT levels in CSF and serum in order to differentiate between bacterial and viral meningitis. PROCEDURES: CRP and PCT levels were measured in CSF and serum from patients with bacterial or viral meningitis. The diagnostic accuracy was determined using receiver operating characteristic curves (ROC), calculating the area under the ROC curve (AUC). RESULTS: Thirty patients were included in this study, 18 of whom had bacterial meningitis and 12 viral meningitis. The AUCs to differentiate bacterial from viral meningitis using serum CRP, CSF CRP, serum PCT and CSF PCT were 0.926; 0.898; 0.963; and 0.694 respectively. Serum CRP and PCT exhibited 100% and 88.9% sensitivity, 83.3% and 100% specificity with a cut-off =14.0 mg/L and 0.18 µg/L respectively. CONCLUSIONS: Levels of CRP and PCT in CSF did not present greater accuracy in differentiating bacterial from viral meningitis compared to serum levels. Serum CRP and PCT showed a high diagnostic accuracy, therefore its quantification is recommended in all patients with suspected infectious meningitis.

A study on correlations of procalcitonin and interleukin-6 with viral meningitis.

OBJECTIVE: To study the change rules of inflammatory factors in cerebrospinal fluid (CSF) and serum of patients with viral meningitis. PATIENTS AND METHODS: 742 patients with suspected viral meningitis admitted to Department of Neurosurgery in our hospital from August 2012 to May 2016 were selected as research objects and retrospectively analyzed. 536 patients were diagnosed with viral meningitis by CSF with the lumbar puncture and brain computed tomography (CT), while the other 206 patients were diagnosed with non-infectious nervous system disease, as the control group. The levels of inflammatory factors interleukin-6 (IL-6) in peripheral blood and procalcitonin (PCT) in cerebrospinal fluid were detected and compared between two groups of patients. RESULTS: Compared with those in control group, the white blood cell (WBC) count, and levels of serum IL-6 and PCT in cerebrospinal fluid of patients with viral meningitis were all increased (p<0.01). PCT and IL-6 were positively correlated with viral meningitis (r=0.8267, 0.9234). The sensitivity of the two items was 77.81% and 81.32%, respectively, and the specificity was 90.53% and 88.64%, respectively. CONCLUSIONS: The levels of inflammatory factors IL-6 and PCT in serum and CSF of patients with viral meningitis are slightly increased. The detection of the expression levels of IL-6 and PCT in patients with viral meningitis is of great significance for the preliminary diagnosis and rehabilitation of viral meningitis.

Blood-Brain Barrier and Intrathecal Immune Response in patients with neuroinfections.

Cerebrospinal fluid/serum albumin ratio is one of the most informative parameters for blood-brain barrier (BBB) integrity in cases of central nervous system (CNS) infectious diseases. Normally, CNS albumin concentration is a function of diffusion processes along with CSF drainage and resorption. In pathological processes CSF albumin levels are dependent only on the rate of CSF drainage resulting in non-linear reciprocal changes of albumin quotient (Qalb). IgG, IgA and IgM concentrations both in CSF and serum can be compared to Qalb, thus determining the intrathecal immune response. The aim of the study was to detect BBB permeability impairment and the intrathecal immune response in patients with CNS infections with various etiologies. CSF/serum ratios were calculated and related to IgG IgA and IgM concentrations in CSF and blood serum. The results were integrated and presented by Reibergrams. The results demonstrated typical patterns which prove albumin to be the main modulator of protein dynamics and at the same time explicates the complex pathophysiological mechanisms involved in BBB disruption and intrathecal immune response in CNS infections. The diagnostic model presented in our study seeks to explain the observations of meningitis and meningoencephalitis pathophysiology and points out the mandatory cooperation between clinicians and laboratory for accurate diagnosis and proper treatment.

Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis: A cross-sectional study.

There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children.All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated.Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%).The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis.

With a little help from a computer: discriminating between bacterial and viral meningitis based on dominance-based rough set approach analysis.

Differential Diagnosis of bacterial and viral meningitis remains an important clinical problem. A number of methods to assist in the diagnoses of meningitis have been developed, but none of them have been found to have high specificity with 100% sensitivity.We conducted a retrospective analysis of the medical records of 148 children hospitalized in St. Joseph Children's Hospital in Poznan. In this study, we applied for the first time the original methodology of dominance-based rough set approach (DRSA) to diagnostic patterns of meningitis data and represented them by decision rules useful in discriminating between bacterial and viral meningitis. The induction algorithm is called VC-DomLEM; it has been implemented as software package called jMAF (http://www.cs.put.poznan.pl/jblaszczynski/Site/jRS.html), based on java Rough Set (jRS) library.In the studied group, there were 148 patients (78 boys and 70 girls), and the mean age was 85 months. We analyzed 14 attributes, of which only 4 were used to generate the 6 rules, with C-reactive protein (CRP) being the most valuable.Factors associated with bacterial meningitis were: CRP level ≥86 mg/L, number of leukocytes in cerebrospinal fluid (CSF) ≥4481 µL, symptoms duration no longer than 2 days, or age less than 1 month. Factors associated with viral meningitis were CRP level not higher than 19 mg/L, or CRP level not higher than 84 mg/L in a patient older than 11 months with no more than 1100 µL leukocytes in CSF.We established the minimum set of attributes significant for classification of patients with meningitis. This is new set of rules, which, although intuitively anticipated by some clinicians, has not been formally demonstrated until now.

Age-specific application of neutrophil-to-lymphocyte ratio in meningitis: a nationwide study.

Cerebrospinal fluid (CSF) neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) are useful in distinguishing bacterial and viral meningitis. Given that meningitis is clinically heterogeneous with regard to age, here we investigated the validity of the CSF NLR and neutrophil assay according to age group. Data from the nationwide referral of >4,000 meningitis cases to the Hellenic Meningitis Reference Laboratory between 2006 and 2013 were examined. CSF NLR and neutrophil counts were stratified according to age, and assay performance was determined using previous cut-off values of 2 and 287 cells/µl for CSF NLR and neutrophils respectively. The distribution of bacterial versus viral meningitis was heterogenous across age groups, with a low proportion of bacterial meningitis in patients aged 5-14. CSF neutrophil count and NLR were significantly more discriminatory for bacterial meningitis in patients aged over 14 years than those aged 0-14. The odds ratio (OR), sensitivity, specificity and positive predictive value (PPV) were significantly higher in older patients for both biomarkers. When combined, the false-positive and false-negative detection of bacterial meningitis was 3.9 and 8.5% respectively, and the OR of 262.2 was 2.5-fold greater than expected from a multiplicative effect alone in patients aged >14 years. Care is required when applying diagnostic tests for meningitis in different age groups because of patient heterogeneity. This is the first description of the age distribution of meningitis cases in Greece, and knowledge of the age-related distribution of neutrophils and NLR in meningitis cases could help towards developing age-specific meningitis diagnostic assays.

Procalcitonin as a potential predicting factor for prognosis in bacterial meningitis.

We investigated the potential role of serum procalcitonin in differentiating bacterial meningitis from viral meningitis, and in predicting the prognosis in patients with bacterial meningitis. This was a retrospective study of 80 patients with bacterial meningitis (13 patients died). In addition, 58 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed between the groups. We used the mortality rate during hospitalization as a marker of prognosis in patients with bacterial meningitis. Multiple logistic regression analysis showed that high serum levels of procalcitonin (>0.12ng/mL) were an independently significant variable for differentiating bacterial meningitis from viral meningitis. The risk of having bacterial meningitis with high serum levels of procalcitonin was at least 6 times higher than the risk of having viral meningitis (OR=6.76, 95% CI: 1.84-24.90, p=0.004). In addition, we found that high levels of procalcitonin (>7.26ng/mL) in the blood were an independently significant predictor for death in patients with bacterial meningitis. The risk of death in patients with bacterial meningitis with high serum levels of procalcitonin may be at least 9 times higher than those without death (OR=9.09, 95% CI: 1.74-47.12, p=0.016). We found that serum procalcitonin is a useful marker for differentiating bacterial meningitis from viral meningitis, and it is also a potential predicting factor for prognosis in patients with bacterial meningitis.

Procalcitonin in cerebrospinal fluid in meningitis: a prospective diagnostic study.

OBJECTIVES: Bacterial meningitis is a severe but treatable condition. Clinical symptoms may be ambiguous and current diagnostics lack sensitivity and specificity, complicating diagnosis. Procalcitonin (PCT) is a protein that is elevated in serum in bacterial infection. We aimed to assess the value of PCT in cerebrospinal fluid (CSF) in the diagnosis of bacterial meningitis. METHODS: We included patients with bacterial meningitis, both community acquired and post neurosurgery. We included two comparison groups: patients with viral meningitis and patients who underwent lumbar punctures for noninfectious indications. We calculated mean differences and 95% confidence intervals of procalcitonin in CSF and plasma in patients with and without bacterial meningitis. RESULTS: Average PCT concentrations in CSF were 0.60 ng mL-1 (95% CI: 0.29-0.92) in the bacterial meningitis group (n = 26), 0.81 (95% CI: 0.33-1.28) in community-acquired meningitis (n = 16) and 0.28 (95% CI: 0.10-0.45) in postneurosurgical meningitis (n = 10), 0.10 ng mL-1 (95% CI: 0.08-0.12) in the viral meningitis group (n = 14) and 0.08 ng mL-1 (95% CI: 0.06-0.09) in the noninfectious group (n = 14). Mean difference of PCT-CSF between patients with community-acquired bacterial meningitis and with viral meningitis was 0.71 ng mL-1 (95% CI: 0.17-1.25) and 0.73 ng mL-1 (95% CI: 0.19-1.27) for community-acquired bacterial meningitis versus the noninfectious group. The median PCT CSF: plasma ratio was 5.18 in postneurosurgical and 0.18 in community-acquired meningitis (IQR 4.69 vs. 0.28). CONCLUSION: Procalcitonin in CSF was significantly higher in patients with bacterial meningitis when compared with patients with viral or no meningitis. PCT in CSF may be a valuable marker in diagnosing bacterial meningitis, and could become especially useful in patients after neurosurgery.

Abnormal galactosylation of immunoglobulin G in cerebrospinal fluid of multiple sclerosis patients.

BACKGROUND: Glycosylation alterations have been associated with the development of several human diseases and their animal models, including multiple sclerosis. OBJECTIVES: We aimed to determine whether immunoglobulin G galactosylation might be changed in multiple sclerosis. METHODS: Immunoglobulin G was isolated from serum and cerebrospinal fluid of patients with multiple sclerosis or viral meningitis and control patients without history of inflammatory or autoimmune disease. A lectin-based assay was used to investigate potential galactosylation modifications of immunoglobulin G. RESULTS AND CONCLUSION: Galactosylation of immunoglobulin G isolated from cerebrospinal fluid of control patients was found to be age- and gender-dependent. In addition, immunoglobulin G galactosylation was significantly altered in cerebrospinal fluid but not in serum of multiple sclerosis patients. Furthermore, this modification was correlated with an active progression of multiple sclerosis. Finally, the loss of galactosyl moieties was not simply associated with inflammation as no such change was detected in viral meningitis patients characterized by brain inflammation.

Comparison of hyponatremia and SIADH frequency in patients with tick borne encephalitis and meningitis of other origin.

AIM: The aim of the study was the evaluation of frequency and origin of hyponatremia in tick borne encephalitis (TBE) in comparison to non-TBE viral meningitis and bacterial meningitis. METHODS: A total of 124 patients aged 18-80 years, with TBE were included to the study. The mild form of TBE was diagnosed in 59 patients, while the severe form was diagnosed in 65 patients. The first control group (VMG) consisted of 72 patients with viral meningitis, but excluded TBE. The second control group (BMG) consisted of 16 patients diagnosed with bacterial meningitis. RESULTS: Hyponatremia was diagnosed in 55 (44.4%) patients with TBE. In 12 (9.7%) patients (mean age 56.6 ± 19.9 years; 9 men, 3 women) syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was diagnosed. In VMG hyponatremia was diagnosed in 7 (9.7%) patients. In the age group <35 years and in the age group of 50-64 years the frequency of hyponatremia and SIADH was higher in TBE than in VMG (p < 0.05). In BMG hyponatremia was diagnosed in 6 (37.5%) patients. No statistically significant differences in frequency of hyponatremia between BMG and TBE groups were observed. CONCLUSIONS: (1) Hyponatremia is a common disorder in TBE and is more frequent than in other viral types of meningitis, especially in young patients (< 35 years). (2) The most common cause of hyponatremia in TBE patients is dehydration and fluid supplementation should be a treatment of choice. (3) Overall, 16.9% of the patients with the severe form of TBE develop SIADH syndrome and they required treatment based on fluid restriction and hypertonic saline infusion.

Procalcitonin as a Serum Biomarker for Differentiation of Bacterial Meningitis From Viral Meningitis in Children: Evidence From a Meta-Analysis.

Several studies have explored the use of serum procalcitonin (PCT) in differentiating between bacterial and viral etiologies in children with suspected meningitis. We pooled these studies into a meta-analysis to determine the PCT diagnostic accuracy. All major databases were searched through March 2015. No date or language restrictions were applied. Eight studies (n = 616 pediatric patients) were included. Serum PCT assay was found to be very accurate for differentiating the etiology of pediatric meningitis with pooled sensitivity and specificity of 0.96 (95% CI = 0.92-0.98) and 0.89 (95% CI = 0.86-0.92), respectively. The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and area under the curve (AUC) for PCT were 7.5 (95% CI = 5.6-10.1), 0.08(95% CI = 0.04-0.14), 142.3 (95% CI = 59.5-340.4), and 0.97 (SE = 0.01), respectively. In 6 studies, PCT was found to be superior than CRP, whose DOR was only 16.7 (95%CI = 8.8-31.7). Our meta-analysis demonstrates that serum PCT assay is a highly accurate and powerful test for rapidly differentiating between bacterial and viral meningitis in children.

CSF lactate for accurate diagnosis of community-acquired bacterial meningitis.

CSF lactate measurement is recommended when nosocomial meningitis is suspected, but its value in community-acquired bacterial meningitis is controversial. We evaluated the diagnostic performance of lactate and other CSF parameters in a prospective cohort of adult patients with acute meningitis. Diagnostic accuracy of lactate and other CSF parameters in patients with microbiologically documented episodes was assessed by receiver operating characteristic (ROC) curves. The cut-offs with the best diagnostic performance were determined. Forty-five of 61 patients (74%) had a documented bacterial (n = 18; S. pneumoniae, 11; N. meningitidis, 5; other, 2) or viral (n = 27 enterovirus, 21; VZV, 3; other, 3) etiology. CSF parameters were significantly different in bacterial vs. viral meningitis, respectively (p < 0.001 for all comparisons): white cell count (median 1333 vs. 143/mm(3)), proteins (median 4115 vs. 829 mg/l), CSF/blood glucose ratio (median 0.1 vs. 0.52), lactate (median 13 vs. 2.3 mmol/l). ROC curve analysis showed that CSF lactate had the highest accuracy for discriminating bacterial from viral meningitis, with a cutoff set at 3.5 mmol/l providing 100% sensitivity, specificity, PPV, NPV, and efficiency. CSF lactate had the best accuracy for discriminating bacterial from viral meningitis and should be included in the initial diagnostic workup of this condition.