scholarly journals Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Anahita Bakochi ◽  
Tirthankar Mohanty ◽  
Paul Theodor Pyl ◽  
Carlos Alberto Gueto-Tettay ◽  
Lars Malmström ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Host Response ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Tissue Cell ◽  
Response Patterns ◽  
Lasso Regression ◽  
Specific Host

Meningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.

scholarly journals Cerebrospinal fluid proteome maps detect pathogen-specific host response patterns in meningitis

2020 ◽  
Author(s):  
Anahita Bakochi ◽  
Tirthankar Mohanty ◽  
Paul Theodor Pyl ◽  
Lars Malmström ◽  
Adam Linder ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Host Response ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Tissue Cell ◽  
Response Patterns ◽  
Lasso Regression ◽  
Specific Host

AbstractMeningitis is a potentially life-threatening infection characterized by the inflammation of the leptomeningeal membranes. Many different viral and bacterial pathogens can cause meningitis, with differences in mortality rates, risk of developing neurological sequelae and treatment options. Here we constructed a compendium of digital cerebrospinal fluid (CSF) proteome maps to define pathogen-specific host response patterns in meningitis. The results revealed a drastic and pathogen-type specific influx of tissue-, cell- and plasma proteins in the CSF, where in particular a large increase of neutrophil derived proteins in the CSF correlated with acute bacterial meningitis. Additionally, both acute bacterial and viral meningitis result in marked reduction of brain-enriched proteins. Generation of a multi-protein LASSO regression model resulted in an 18-protein panel of cell and tissue associated proteins capable of classifying acute bacterial meningitis and viral meningitis. The same protein panel also enabled classification of tick-borne encephalitis, a subgroup of viral meningitis, with high sensitivity and specificity. The work provides insights into pathogen specific host response patterns in CSF from different disease etiologies to support future classification of pathogen-type based on host response patterns in meningitis.

scholarly journals Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Leonardo Silva de Araujo ◽  
Kevin Pessler ◽  
Kurt-Wolfram Sühs ◽  
Natalia Novoselova ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Cell Count ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Characteristic Curve ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Membrane Phospholipids ◽  
Cns Disorders

Abstract Background The timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis. Methods We used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell’s palsy, Tourette syndrome, normal pressure hydrocephalus). Results PC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman’s ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis. Conclusions Increased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.

The Use of Cytokine and C-Reactive Protein Measurements in Cerebrospinal Fluid during Acute Infective Meningitis

1994 ◽  
Vol 31 (3) ◽  
pp. 255-261 ◽  
Author(s):  
M Stearman ◽  
H J Southgate
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
White Cell Count ◽  
Correct Diagnosis ◽  
Viral Meningitis ◽  
Acute Bacterial Meningitis ◽  
Control Group ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Factor Α

Cerebrospinal fluid (CSF) concentrations of C-reactive protein (CRP), tumour necrosis factor α (TNF), interleukin-6 (IL-6), total protein (TP) and white cell count with differential (WCC) have been measured in 24 patients presenting with acute bacterial or viral meningitis and also in a non-infected, non-inflammed control group ( n = 24). In acute viral meningitis, CRP levels were not raised when compared to controls and there was a discordance between high levels of the primary inflammatory mediators (IL-6 and TNF) and the low measured CRP levels. CRP levels were raised in cases of bacterial meningitis. A concentration of 100 ng/mL CRP had a sensitivity of 87% for bacterial meningitis. TNF concentrations in the CSF were significantly raised in cases of acute bacterial meningitis ( P < 0·001). Smaller but variable elevations were seen in the patients with acute viral meningitis. One patient, who succumbed to bacterial infection, showed low CSF levels of CRP, TNF and WCC but an elevated IL-6 concentration. Another, presenting with low CSF WCC, had raised concentrations of CRP, TNF and IL-6 which pointed to the correct diagnosis of acute bacterial meningitis. The development of methods yielding rapid analysis for these cytokines together with a sensitive assay for CRP in CSF would be a useful adjunct to conventional investigation.

Neurotrophin-3 Levels in Cerebrospinal Fluid From Children With Bacterial Meningitis, Viral Meningitis, or Encephalitis

2000 ◽  
Vol 15 (1) ◽  
pp. 19-21 ◽  
Author(s):  
Yumi Mizuno ◽  
Hidetoshi Takada ◽  
Kyoko Urakami ◽  
Kenji Ihara ◽  
Ryutaro Kira ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Viral Meningitis ◽  
Neurotrophin 3

scholarly journals Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

2003 ◽  
Vol 47 (10) ◽  
pp. 3104-3108 ◽  
Author(s):  
Federico Pea ◽  
Federica Pavan ◽  
Ennio Nascimben ◽  
Claudio Benetton ◽  
Pier Giorgio Scotton ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Bacterial Meningitis ◽  
Acute Bacterial Meningitis ◽  
Terminal Phase ◽  
Communicating Hydrocephalus ◽  
Synergistic Activity ◽  
Dosing Interval ◽  
Concentration Time ◽  
Meningeal Inflammation

ABSTRACT In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams. Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections. Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state. Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography. The peak concentration of levofloxacin at steady state (C max ss)was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of the C max ss in CSF to the C max ss in plasma being 0.47. The areas under the concentration-time curves during the 12-h dosing interval (AUC0-τs) were 47.69 mg · h/liter for plasma and 33.42 mg · h/liter for CSF, with the ratio of the AUC0-τ for CSF to the AUC0-τ for plasma being 0.71. The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 ± 1.57 and 5.51 ± 1.36 h, respectively; P = 0.034). The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval. In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma. The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults. This cotreatment could be useful both for overcoming Streptococcus pneumoniae resistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.

Cerebrospinal Fluid Leucine-Rich Alpha-2 Glycoprotein (LRG) Levels in Children with Acute Bacterial Meningitis

2021 ◽  
Author(s):  
Kushal Talukder ◽  
Rajniti Prasad ◽  
Abhisek Abhinay ◽  
Ankur Singh ◽  
Ragini Srivastava ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Acute Bacterial Meningitis

scholarly journals Cerebrospinal fluid Lipocalin 2 as a marker for the detection of acute bacterial meningitis

2019 ◽  
Vol 16 ◽  
pp. 157-158
Author(s):  
Eman M. Barakat ◽  
Doaa Z. Zaky ◽  
Mohamed S. Abdelhamid ◽  
Mentallah A. Shaaban ◽  
Hegazy A. Haddad
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Acute Bacterial Meningitis ◽  
Lipocalin 2

scholarly journals Effect of Antibiotic Pretreatment on Cerebrospinal Fluid Profiles of Children with Acute Bacterial Meningitis

2013 ◽  
Vol 2 (2) ◽  
pp. 135-139 ◽  
Author(s):  
S Adhikari ◽  
E Gauchan ◽  
G BK ◽  
KS Rao
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Antibiotic Therapy ◽  
Lumbar Puncture ◽  
Laboratory Finding ◽  
Clinical Findings ◽  
Acute Bacterial Meningitis ◽  
Antibiotic Administration ◽  
Intravenous Antibiotic ◽  
Considerable Difficulty

Background: Analysis of cerebrospinal fluid is gold standard for diagnosis of meningitis. There is considerable difficulty in interpreting laboratory finding after prior antibiotic therapy. This study was conducted to evaluate the effect of intravenous antibiotic administration before lumbar puncture on cerebrospinal fluid profiles in children with bacterial meningitis. Methods: A hospital based retrospective study carried out using the data retrieved from the medical record department of Manipal Teaching Hospital Pokhara, Nepal; from 1st July 2006 to 31st July 2011. Clinical findings and relevant investigations were entered in a predesigned proforma. Patients were divided in two different groups as bacterial meningitis with and without prior intravenous antibiotic therapy. Various laboratory parameters including CSF were compared between these two groups using the statistical software, SPSS version 18.0. Results: A total of 114 children were included in this study among which 49(43%) children had received intravenous antibiotics before lumbar puncture. Mean CSF WBC count was(267.6± 211 vs. 208.1±125.3.3) and protein level (114.1±65.9 vs. 98.3±37.7mg/dl) in untreated vs. pretreated groups respectively. Neutrophil percentage was decreased (57.1±28.1vs.72.9±18.9) with higher CSF sugar level (43.3±11.8 vs. 51.2±13.2) after prior antibiotics therapy (p<0.001). Conclusion: Antibiotic pretreatment was associated with higher cerebrospinal fluid glucose levels with decreased neutrophils and increased lymphocytes. Pretreatment did not modify total cerebrospinal fluid white blood cell count and cerebrospinal fluid protein levels. Nepal Journal of Medical Sciences | Volume 02 | Number 02 | July-December 2013 | Page 135-139 DOI: http://dx.doi.org/10.3126/njms.v2i2.8963

scholarly journals Culture Proven Bacterial Meningitis in Children: Agents, Clinical Profile and Outcome

2012 ◽  
Vol 9 (1) ◽  
pp. 36-40 ◽  
Author(s):  
I Ansari ◽  
Y Pokhrel
Keyword(s):  
Cerebrospinal Fluid ◽  
Bacterial Meningitis ◽  
Clinical Profile ◽  
Cortical Atrophy ◽  
Acute Bacterial Meningitis ◽  
Influenza B ◽  
Haemophilus Influenza ◽  
Hemolytic Streptococcus ◽  
Young Infants ◽  
Nepalese Children

Background Meningitis is a serious infection. Little is known about the bacterial agents and their antibacterial sensitivity in Nepalese children. Objectives To study bacteriological agents, clinical profile and immediate outcome in patients admitted to children’s ward of Patan Hospital with meningitis. Methods Prospective observational study conducted in paediatric ward of Patan Hospital. All the children admitted to the ward, with the diagnosis of culture proven bacterial meningitis’ on discharge were eligible. Results Out of 7,751 children, 296 (3.8%) had meningitis. This was a group ranging from neonates to adolescents aged 18 years. Only 13 (4.4%) of cerebrospinal fluid samples taken from them yielded positive culture reports. The organisms were pneumococcus (6), Haemophilus influenza ‘b’ (3), ?-hemolytic Streptococcus (1), ?-hemolytic Streptococcus (1), N. meningitides (1) and Pseudomonas (1). Whereas Haemophilus influenza ‘b’ was isolated from young infants, pneumococci were found in the young as well as the old. Fever, vomiting, high leukocyte count with left shift were all commonly present. All but one had cerebrospinal fluid pleocytosis. Low sugar and high protein was found in most specimens. Neuroimaging was done in six children of which three were abnormal (all young infants and pneumococci cases). Ceftriaxone was given to all but one child. Everybody recovered but three had complications – profound hearing loss and cortical atrophy with subdural collection in pneumococcal and septic arthritis with persistence of fever in Haemophilus influenzae ‘b’ meningitis. Conclusion The present study corroborates most of the epidemiological and clinical features of acute bacterial meningitis and sheds light on the causative agents of bacterial meningitis in Nepalese children. http://dx.doi.org/10.3126/kumj.v9i1.6260 Kathmandu Univ Med J 2011;9(1):36-40

Sign in / Sign up

Export Citation Format

Share Document