Investigating the role of T helper related cytokines in cerebrospinal fluid for the differential diagnosis of bacterial meningitis in pre-treated paediatric patients

Jafari, Maedeh; Jahani, Peyman Mohammadzadeh; Choopanizadeh, Maral; Jamalidoost, Marzieh; Pourabbas, Bahman; Pouladfar, Gholamreza; Kalani, Mehdi

doi:10.1080/1354750x.2020.1714737

Cited by 6 publications

(7 citation statements)

References 29 publications

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“…other studies have mainly explored the expression dynamics of specific CKs in different forms of meningitis (1,4,16,31), as well as how they correlate with parameters such as CSF glucose, protein and WBC count (13,30). Attempts have been made to combine such results for early diagnostic purposes with promising results (15,34,46). In the present study, the RF state-of-the-art machine learning algorithm was employ for this purpose.…”

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confidence: 99%

“…In recent years, increasing importance has been ascribed to the cytokine/chemokine (CT/CK) levels of patients with meningitis to identify particularities of the host immune response that could represent a 'host signature' of infection (13)(14)(15)(16)(17)(18). CTs/CKs released during the host immune response have an important role in the recruitment of innate and adaptive immune cells, but they also promote inflammation, thus playing an essential role in the pathogenesis of meningitis.…”

Section: Introductionmentioning

confidence: 99%

“…In one study, higher levels of IL-6, interferon-γ (IFN-γ) and IL-10 were detected in the CSF of children with BM compared with those without BM (15). In another study, it was found that epithelial-neutrophil activating peptide-78 (ENA-78) was undetectable in patients with aseptic meningitis or control subjects but was present at high concentrations in patients with BM (27).…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid cytokines and chemokines exhibit distinct profiles in bacterial meningitis and viral meningitis

Caragheorgheopol

Țucureanu²,

Lazăr

et al. 2023

Exp Ther Med

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Differential diagnosis of bacterial meningitis (BM) and viral meningitis (VM) is a critical clinical challenge, as the early and accurate identification of the causative agent determines the appropriate treatment regimen and markedly improves patient outcomes. Clinical and experimental studies have demonstrated that the pathogen and the host immune response contribute to mortality and neurological sequelae. As BM is associated with the activation of an inflammatory cascade, the patterns of pro-and anti-inflammatory cytokines/chemokines (CTs/CKs) present in the cerebrospinal fluid (CSF) in response to the immune assault may be useful as sensitive markers for differentiating BM from VM. In the present study, the ability of CTs/CKs in the CSF to differentiate between BM and VM was investigated. For this, biochemical markers and CT/CK profiles were analysed in 145 CSF samples, divided into three groups: BM (n=61), VM (n=58) and the control group (C; n=26) comprising patients with meningism. The CSF concentrations of monocyte chemoattractant protein-1, interleukin (IL)-8, IL-1β, IL-6, macrophage inflammatory protein-1α (MIP-1α), epithelial-neutrophil activating peptide, IL-10, tumour necrosis factor-α (TNF-α), proteins and white blood cells were significantly higher and the CSF glucose level was significantly lower in the BM group compared with the VM and C groups (P<0.01). Correlation analysis identified 28 significant correlations between various CTs/CKs in the BM group (P<0.01), with the strongest positive correlations being for TNF-α/IL-6 (r= 0.75), TNF-α/MIP-1α (r= 0.69), TNF-α/IL-1β (r=0.64) and IL-1β/MIP-1α (r=0.64). To identify the optimum CT/CK patterns for predicting and classifying BM and VM, a dataset of 119 BM and VM samples was divided into training (n=90) and testing (n=29) subsets for use as input for a Random Forest (RF) machine learning algorithm. For the 29 test samples (15 BM and 14 VM), the RF algorithm correctly classified 28 samples, with 92% sensitivity and 93% specificity. The results show that the patterns of CT/CK levels in the CSF can be used to aid discrimination of BM and VM.

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confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal fluid cytokines and chemokines exhibit distinct profiles in bacterial meningitis and viral meningitis

Caragheorgheopol

Țucureanu²,

Lazăr

et al. 2023

Exp Ther Med

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“…As inflammation has a crucial role in meningitis, inflammatory biomarkers are studied for discriminating BM from other forms of the disease. Among them, CSF cytokine and chemokine levels proved helpful in the differential diagnosis of bacterial meningitis [9][10][11][12][13]. These studies were based on biomarkers measured in the CSF, collected through an invasive procedure that is not al-ways feasible, particularly in the case of infants [14].…”

Section: Introductionmentioning

confidence: 99%

Serum cytokine and chemokine profiles of patients with confirmed bacterial and viral meningitis

Caragheorgheopol,

Țucureanu,

Lazăr

et al. 2023

Revista Romana De Medicina De Laborator

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Introduction: Cerebrospinal fluid (CSF) cytokines and chemokines have been reported by several studies as useful markers to discriminate bacterial and viral meningitis (BM and VM). This study aimed to investigate if serum cytokine and chemokine profiles could also differentiate BM from VM, thus circumventing the need for an invasive lumbar puncture. Methods: Serum cytokines and chemokines were measured in 153 samples from patients with BM (n=58), VM (n=69), and controls (C, n=26) using multiplex assays. Cytokine and chemokine concentrations were compared among groups, correlation analyses were performed, and BM and VM cases classification based on cytokine and chemokine patterns was tested using a Machine Learning algorithm. Results: IL-8, IL-1β, IL-6, IL-10, TNF-α, MCP-1, and ENA-78 showed a pronounced increase in the BM group compared to C (P<0.01). Comparison of cytokines and chemokines in BM vs. VM showed significantly higher levels of MCP-1, IL-8, IL-1β, IL-6 and IL-10 (P<0.01). Serum cytokine and chemokine concentrations were highly correlated in BM, being strongest for: MCP-1/IL-8, MCP-1/IL-1β, and IL-8/IL-1β (r=0.83; r=0.72; r=0.78, respectively). In VM, cytokine and chemokine correlations were weaker. The best predictors in the cytokine and chemokine pattern identified with a Random Forest algorithm for classifying BM vs VM were IL-8 and IL-10, and IL-6, but the specificity and sensitivity were low (85% and 69%, respectively). Conclusion: Our results suggest significant changes in serum IL-6, IL-8, IL-10, and IL-1β in BM, but these mediators may have limited value in differentiating BM from VM.

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“…Bacterial meningitis (BM) is one of the most severe infectious diseases that affect children, with a high mortality and morbidity rate. The most prevalent causes of community-acquired BM in children are Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b (Hib) (1)(2)(3)(4). Other bacterial etiologies such as Salmonella enterica are uncommon causes of BM in children beyond the neonatal period (5,6).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Multiplex Real-time PCR and WHO Criteria for Diagnosing Childhood Bacterial Meningitis in a Tertiary Referral Hospital in Iran

Pouladfar

Dashti

Kadivar

et al. 2022

Arch Pediatr Infect Dis

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Background: Childhood bacterial meningitis (BM) requires prompt and precise diagnosis to provide proper treatment and decline mortality and morbidity. Objectives: We aimed to evaluate the World Health Organization (WHO) criteria and polymerase chain reaction (PCR) for diagnosing BM in children admitted to a tertiary referral hospital in Shiraz, southern Iran. Materials: We included all 492 children aged one month to 17 years suspected of meningitis who had cerebrospinal fluid (CSF) leukocytosis admitted to Nemazi Hospital from August 2016 to September 2017. The CSF specimens were examined for routine analysis, Gram staining, and culture. A multiplex real-time PCR was used to identify Streptococcus pneumoniae, Haemophilus influenzae type b (Hib), and Neisseria meningitidis in the CSF samples. Seven viruses were also investigated using real-time PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the WHO criteria and the multiplex real-time PCR results. Results: Seventy-four CSF samples had leukocytosis. Nineteen (22.9%) patients had BM caused by S. pneumoniae (n = 14), Hib (n = 2), Salmonella enterica (n = 2), and N. meningitidis (n = 1). The PCR test detected all cases, except for two with Salmonella meningitis (sensitivity 89.4%, specificity 100%, PPV 100%, and NPV 96%). The WHO criteria detected all cases, except three who received antibiotics at least four days before performing lumbar puncture (sensitivity 84.2%, specificity 98.2%, PPV 94.1%, and NPV 94.7%). Enterovirus was the most common viral etiology (6.75%). Conclusions: The WHO criteria and the multiplex real-time PCR had high accuracy in our setting, and their use could decrease the antibiotic over-prescription in febrile children suspected of meningitis.

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Investigating the role of T helper related cytokines in cerebrospinal fluid for the differential diagnosis of bacterial meningitis in pre-treated paediatric patients

Cited by 6 publications

References 29 publications

Cerebrospinal fluid cytokines and chemokines exhibit distinct profiles in bacterial meningitis and viral meningitis

Cerebrospinal fluid cytokines and chemokines exhibit distinct profiles in bacterial meningitis and viral meningitis

Serum cytokine and chemokine profiles of patients with confirmed bacterial and viral meningitis

Evaluation of Multiplex Real-time PCR and WHO Criteria for Diagnosing Childhood Bacterial Meningitis in a Tertiary Referral Hospital in Iran

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