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Year : 2013  |  Volume : 1  |  Issue : 1  |  Page : 35-42

Study of different diagnostic markers used to differentiate septic from aseptic meningitis

1 Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, University of Tanta, Egypt; Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia
2 Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, University of Tanta, Saudi Arabia
3 Department of Medical Microbiology & Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
4 Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, University of Tanta, Egypt; Department of Medical Microbiology & Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
5 Department of Medical Biochemistry, Faculty of Medicine, University of Tanta, Egypt; Department of Clinical Biochemistry and Medical Education, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
6 Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Tanta, Egypt
7 Department of Pediatric, Faculty of Medicine, University of Tanta, Egypt

Date of Web Publication24-Jan-2018

Correspondence Address:
Sahar El-Yamany
Department of Medical Microbiology & Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.1016/j.jmau.2013.06.007

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Aim: The aim of this study was to evaluate the diagnostic accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in comparison to procalcitonin (PCT) and C-reactive protein (CRP) in early diagnosis of septic meningitis and its usefulness to distinguish between septic and aseptic meningitis.
Patients and methods: This study included 26 patients with septic meningitis, 32 patients with aseptic meningitis and 15 controls. Besides Gram staining, cultures of blood and CSF and latex agglutination test of CSF, CRP, serum PCT and sTREM-1 measurement were done on admission and after 48–72 h of treatment.
Results: Septic meningitis was diagnosed in 26 (44.82%) of the studied cases. Patients with septic meningitis had a significant increase in serum sTREM-1 and PCT levels at the time of admission (mean 32.99 ± 19.7 ng/ml and 97.9 ± 86.35 ng/ml, respectively), while patients with aseptic meningitis showed (6.8 ± 5.67 ng/ml and 1.88 ± 1.6 ng/ml, respectively). Control group showed sTREM-1 and PCT levels (6.6 ± 4.6 ng/ml and 0.58 ± 0.36 ng/ml, respectively) (P < 0.05). sTREM-1 demonstrated significantly higher sensitivity (93.7%) and specificity (94.3%) in the early prediction of sepsis with an area under the receiver operator characteristic (ROC) curve (95% CI) of 0.94 (0.84–0.99) at a cut off value of 12.4 ng/ml. Moreover, sTREM-1 but not PCT or CRP concentration was significantly lower (P < 0.001) at admission in patients with poor outcome than in those with good prognosis.
Conclusions: Both serum PCT and sTREM-1 are valuable in the early distinguishing of septic from aseptic meningitis in children but with markedly higher diagnostic discriminatory power for sTREM-1. Moreover, sTREM-1 has a significant value in determining the prognosis of cases with septic meningitis.

Keywords: sTREM-1, Procalcitonin, CRP, Septic meningitis

How to cite this article:
Mayah WW, El-Yamany S, Jiman-Fatani A, El Saadany S, Hassanien M, Hasan A, Abo-Hagar H. Study of different diagnostic markers used to differentiate septic from aseptic meningitis. J Microsc Ultrastruct 2013;1:35-42

How to cite this URL:
Mayah WW, El-Yamany S, Jiman-Fatani A, El Saadany S, Hassanien M, Hasan A, Abo-Hagar H. Study of different diagnostic markers used to differentiate septic from aseptic meningitis. J Microsc Ultrastruct [serial online] 2013 [cited 2020 Apr 6];1:35-42. Available from: http://www.jmau.org/text.asp?2013/1/1/35/223896

  1. Introduction Top

Acute meningitis in children is mainly aseptic and does not require antibiotic treatment [1]. On the other hand, the mortality and disabling neurological sequelae from septic meningitis among children are significant making early differentiation between aseptic and septic meningitis cases a must [2],[3], as early warning signs and symptoms are often non-specific, and the routine examination of cerebrospinal fluid (CSF) and blood is sometimes misleading [4],[5]. A rapid and reliable test that predicts sepsis, and identify children at highest risk with poor ability to start antibiotic treatment early improve the outcome [4],[6].

These markers include the routine C-reactive protein (CRP) [7], the powerful and massively studied procalcitonin (PCT) [2],[8],[9],[10] as well as the newly proposed, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) markers [11],[12]. CRP, having a molecular mass of 120 kDa with a gene location between 1q21 and 1q23, is an important component of innate defense system against infections [13]. It recognizes the phosphocholine on the surface of many bacteria activates the classical complement pathway and facilitates phagocytosis by neutrophils. Due to the lack of its specificity, it is used as an additional marker with more conventional parameters such as number of leukocytes in CSF, blood count and protein level to help the clinician to make a differential diagnosis [14],[15],[16].

PCT, the calcitonin precursor propeptide, is a 13 kDa protein that is synthesized in C cells of the thyroid gland and secreted from leukocytes of the peripheral blood [17]. Its gene is located on the short arm of chromosome 11 (11p15.4) [16]. The secretion of PCT was found to increase up to several thousand-fold in the presence of bacterial sepsis but remains normal or slightly increases in viral infections and inflammatory reactions that are not infectious [18],[19]. In contrast to CRP levels that rise between 12 and 18 h after bacterial challenge [20], serum PCT level rises within 2–3 h after infection with a peak value at 6–12 h, and normalizes within 2 days [21]. PCT is stable in plasma with plasma half-life of approximately 22 h. It is also extremely stable in vitro, unlike most cytokines, which makes it not only a promising new marker for early and sensitive identification of infected patients, but also for titration of response to the treatment [10],[19],[22],[23],[24],[25]. Still, PCT is not considered as a good marker as it can be elevated in conditions other than infection, and may remain low in infections [26]. Additionally, interpretation of the studies dealing with PCT is complicated by variation in the choice of the abnormal cut off value, and by the diverse age range and nature of the study populations [22].

On the other hand, TREM-1 is a trans-membrane glycoprotein cell-surface receptor of the immunoglobulin superfamily which acts in cooperation with toll-like receptors (TLRs) under the control of nuclear factor-κβ (NF-κβ) [27]. The expression of TREM-1 is up-regulated on phagocytic cells in the presence of bacteria and fungi, triggering the secretion of the pro-inflammatory cytokines that amplify the host response to these microbial agents [28],[29]. As data demonstrated that expression of membrane-bound TREM-1 on neutrophils and monocytes/macrophages is strongly altered during sepsis, as is the release of its soluble form with 6 h peaking, it was highlighted that this protein may be useful in the diagnosis of sepsis [27],[30].

The aim of this study was to evaluate the diagnostic and prognostic utility of these markers in septic meningitis and their usefulness in early differentiation between septic and aseptic meningitis in Egyptian children presenting with signs and symptoms suggestive of meningitis.

  2. Patients and methods Top

Children identified as possible cases of meningitis who were admitted to Pediatric Department in Tanta University Hospital, Tanta, Egypt were included in this case control prospective study. Patients were excluded if they had received antibiotics in the past seven days or had co-existing morbidities. Informed signed consent was obtained from parents for their children to participate in the study.

All patients were divided into the following groups:

  • Bacterial meningitis (no = 26): Meningitis was defined as septic according to WHO case definition criteria [31] “children presenting with clinical symptoms of meningitis; fever, headache, stiff neck, bulging fontanelle or mental status changes, CSF with an elevated protein (>100 mg/dl), decreased glucose (<40 mg/dl) or leukocytosis (WBC > 100/mm3) with at least 80% neutrophils, Identification of bacteria directly by Gram stain smears or cultures from blood or CSF or indirectly by latex agglutination test of CSF” were done.
  • Aseptic meningitis (no = 32): Aseptic meningitis was defined as the presence of acute onset of meningitis symptoms, WBC of > 5/mm3 of which >50% were mononuclear/lymphocyte cells with the absence of an bacterial meningitis laboratory criteria.
  • Control group (no = 15): The control group was defined by absence of inflammatory cells in CSF (WBC < 5/mm3 and sterile bacteriologic findings in afebrile children with positive meningeal signs.

2.1. Protocol

Upon admission, the following items were recorded for each enrolled patient: age, sex, vital signs as well as clinical symptoms and signs. Additionally, blood and CSF samples were withdrawn. Blood samples were used forroutine laboratory investigations including CRP, leukocyte count and blood culture, in addition to PCT and sTREM-1 measurement. CSF samples were examined for protei, glucose, total and differential WBC. After centrifugation, the deposits were subjected to Gram stain examinatioin and microbiological culture. Latex agglutination tests using the Wellcogen bacterial antigen kit (Abbott Murex Biotech, UK) were performed on CSF samples suggestive of meningitis. After 48–72 h of treatment, CRP and serum PCT an sTREM-1 levels were re-estimated for patients with meningitis only. Prognosis of cases was followed over a period of 7 days.

2.2. Methods

All patients were subjected to the following investigations:

1. Microbiological cultures: Blood and CSF samples were collected under complete aseptic conditions according to the standardized techniques [32]. Microbiological cultivation and identification with detection of antibiogram of the isolated organisms were carried out in Microbiology and Immunology Department, Tanta Faculty of Medicine, Egypt. After aspiration of blood samples (3–5 ml) they were subjected to blood cultures (Egyptian diagnostic media [EDM], Egypt). Blood culture bottles were incubated at 37°C and examined each 24 h for turbidity. Subculture from blood culture flasks and culture of CSF deposits were made on sheep blood agar, incubated both aerobically and anarobically at 37 °C for 48–72 h and any growth was identified by colony morphology, Gram staining and appropriate biochemical reactions were performed according to the standard microbiological protocol. The performance of antibiotic sensitivity test and the choice of disks for each isolated organism and the interpretation of zone diameters results were guided by the Clinical and Laboratory Standards Institute (CLSI) guidelines [33].

2. Serum analysis: Serum was separated from blood samples collected on admission from all patients and after 2–3 days in patients with meningitis, stored at −20°C, and used subsequently for assaying CRP, PCT and sTREM-1.

2.1. C-reactive protein measurement: CRP was measured using a nephelometric assay (Dade-Behring, France) with a detection limit of 0.2 mg/l and intra-assay coefficients of variation at low and high concentrations of 3.3% and 2%, respectively. The normal value is 6 mg/l.

2.2. Procalcitonin assay: PCT was measured in duplicate by a specific immunoluminometric assay (LUMItest®, Brahms Diagnostica GmbH, Germany), requiring 20 μl of serum and 2 h to complete. Luminescence was measured automatically on a Berilux Analyzer 250 (Behring Diagnostics, Germany). The detection limit was 0.08 ng/ml, and the intra-assay coefficients of variation at low and high concentrations were 12% and 5%, respectively. The normal serum procalitonin with this is <0.5 ng/ml.

2.3. Soluble triggering receptor expressed on myeloid cells-1 ELISA: TREM-1 was measured by commercially available human ELISA kit according to the manufacturer's instructions (Quantikine Human TREM-1 Immunoassay, R&D Systems, USA), using mouse monoclonal antibody specific for human TREM-1 coated on a 96-well plate, 50 μl recombinant human TREM-1 standards and/or samples, 200 μl polyclonal antibody against TREM-1 conjugated to horseradish peroxidase and 200 μl TMB solution containing tetramethylbenzidine as a substrate. The color was developed in proportion to the amount of TREM-1 bound, changed from blue to yellow by the stop solution and the intensity was measured at 450 nm. The concentration of sTREM-1 was then obtained from the standard curve. The mean minimum detectable dose was 13.8 pg/ml with intra-assay variability of 3–7% and inter-assay variability of 6–8% when measuring in duplicates.

2.3. Statistical analysis

It was performed by using SPSS for Windows, version 9. Data were expressed as range and mean ± standard deviation (SD) or numbers and percentages. Receiver operator characteristic (ROC) plots were performed using MedCalc software to determine the areas under the curve (AUCs) with 95% confidence intervals for the three markers to predict septic meningitis. Differences between groups in continuous variables were tested for significance with the one way ANOVA and Mann–Whitney tests while univariate analysis was done by Fisher's exact test. For all statistical tests done, P value < 0.05 was considered significant.

  3. Results Top

Out of 73 children enrolled in this study, 58 (79.4%) had a final diagnosis of meningitis. They were 34 (58.6%) males, and 24 (41.3%) females, aged 3 to 156 months (mean ± SD, 69.3 ± 49.9). Septic meningitis was diagnosed in 26 (44.85%, mean age ± SD: 63.6 ± 57.36, males vs females 15:11) and aseptic meningitis in 32 (55.15%, mean age ± SD: 69 ± 44, males vs females 19:13). Fifteen children (7 males and 8 females) with age range of 7–154 months (mean ± SD 72.6 ± 51.4) were proven to be nonmeningitis cases and served as controls. All children of control group were diagnosed with epilepsy. There was no difference between the studied groups in respect to age or sex (P > 0.05).

The common manifestations at the time of diagnosis in the meningitis groups were fever, headache, nausea or vomiting and convulsion while in control group were convulsion and nausea or vomiting [Figure 1]. In the 26 (44.85%) infected cases of bacteriological origin, 12 (46.15%) were found to be  Neisseria More Details meningitidis, 8 (30.77%) Haemophilus influenza type b and 6 (23%) Streptococcus pneumoniae. The CSF Gram staining, CSF culture, CSF soluble antigens and blood culture results showed sensitivity of 69.1%, 81.6%, 31.3% and 26.2%, respectively.
Figure 1: Clinical manifestation of the different studied groups.

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Routine blood parameters differed significantly between patients with bacterial and aseptic meningitis [Table 1]. WBC count and ESR level were significantly higher in patients with septic meningitis than patients with aseptic meningitis and controls at the time of diagnosis (P < 0.05). On the other hand, patients with aseptic meningitis had significantly higher WBC count (P < 0.05) than in control group, but with no significant difference regarding ESR (P > 0.05).
Table 1: Comparison of the routine blood and CSF laboratory findings in the studied groups.

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CSF laboratory findings are shown in [Table 2]. Patients with septic meningitis had significantly increased CSF protein, WBC count and neutrophil percentage in comparison with both aseptic meningitis and control groups (P < 0.05), while CSF glucose level was significantly lower in patients with septic meningitis than in patients with aseptic meningitis (P < 0.05) and controls (P < 0.05).
Table 2: Cerebrospinal fluid (CSF laboratory findings in the studied groups.

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To determine the role of CRP, PCT and sTREM-1 as diagnostic tools in septic meningitis, their levels were evaluated on admission. Baseline CRP, PCT and sTREM-1 levels were significantly higher in patients with septic meningitis than in patients with aseptic meningitis and control groups (P < 0.05). On the other hand, patients with aseptic meningitis had significantly higher CRP value (P < 0.05) than in control group, but with no significant difference regarding serum PCT and sTREM-1 levels (P > 0.05) [Table 3]. Although their levels were significantly decreased (P < 0.05) after 48–72 h of treatment in patients with septic meningitis, CRP, PCT and sTREM-1 values were still significantly higher (P < 0.05) than in patients with aseptic meningitis.
Table 3: Comparison of CRP, PCT and sTREM serum levels on admission between the different studied groups.

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Plasma sTREM-1 levels at admission were 32.99 ± 19.79 ng/ml in septic meningitis cases and 6.8 ± 5.67 ng/ml in aseptic meningitis cases. As shown in [Figure 2], plasma sTREM-1 levels yielded the highest discriminative value with area under the ROC curve being 0.94 (95% CI, 0.84–0.99). Although this value did not show statistical significance when compared with 0.92 of PCT (95% CI, 0.81–0.98; P > 0.05), the difference became significantly evident for 0.87 of CRP (95% CI, 0.75–0.95; P =0.03).
Figure 2: Receiver operating characteristic (ROC) curves comparing admission, CRP, PCT and sTREM-1 for prediction of septic meningitis.

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The sensitivity, specificity, and positive and negative predictive values of CRP, PCT and sTREM-1 are shown in [Table 4]. At a cutoff of 12.4 ng/ml, sTREM-1 yielded a sensitivity of 93.7% and a specificity of 94.3% in differentiating patients with septic from those with aseptic meningitis. Of notice, the use of combination of sTREM-1 and PCT did not affect the sensitivity but increased the specificity to 97.1% with no improvement when CRP values were added.
Table 4: Sensitivity, specificity, positive and negative predictive values (%) of admission CRP, PCT and sTREM values for septic meningitis.

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Comparison of CRP, PCT and sTREM-1 serum levels at admission and after 48–72 h in and between patients with aseptic and bacterial meningitis is shown in [Table 5]. After 48 h, there was no significant difference in CRP (P= 0.058), PCT (P =0.16) and sTREM-1 (P =0.09) levels compared to their levels at admission in aseptic group. In contrary, CRP (P < 0.001), PCT (P =0.01) and sTREM-1 (P =0.002) values were significantly reduced 48–72 h after admission compared to their baseline values in septic group. The level of these markers were significantly higher in septic than nonseptic group after 48–72 h (CRP: P =0.016, PCT: P < 0.001 and sTREM-1: P < 0.001).
Table 5: Comparison of CRP, PCT and sTREM-1 serum levels at admission and after 48–72 h in and among patients with aseptic and bacterial meningitis.

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[Figure 2] shows the receiver operating characteristic (ROC) curves comparing admission, C-reactive protein (CRP), procalcitonin (PCT) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) for prediction of septic meningitis. The area under the curve (95% CI) was 0.87 (0.75–0.95) for CRP, 0.92 (0.81–0.98) for PCT and 0.94 (0.84–0.99) for sTREM-1.

The use of the current parameters as prognostic markers was also evaluated. Seven (26.9%) of 26 patients with septic meningitis showed poor outcome and died. Serum sTREM-1 level [10 ± 7.4 ng/ml vs 41.4 ± 15.6 ng/ml, Z = 2.7; P < 0.001) but not PCT [120.97 ± 81.64 ng/ml vs 99.97 ± 88 ng/ml, Z = 1.13, P = 0.58) or CRP levels [114 ± 48.84 ng/ml vs 130 ± 102.49 ng/ml, Z = 0.17, P = 0.69). Noticeably, the AUCs of ROC for CRP, PCT and sTREM-1 in predicting septic meningitis poor outcome were 0.53 (95% CI 0.42–0.61), 0.62 (95% CI 0.58–0.71) and 0.87 (95% CI 0.78–0.92), respectively.

  4. Discussion Top

Diagnosis of septic meningitis is the milestone in preventing unnecessary antibiotic and hospital admission in one hand and serious neurological damage or even death in the other. Management strategies have oriented toward the use of combination of clinical and laboratory information such as CBC, neutrophil count, and CRP concentration with up to 40% possibility of overlap between septic and aseptic cases [34]. Intensive researches have been carried out to find new accurate, rapid, and reliable diagnostic methods to differentiate between bacterial and viral meningitis with a varying degree of success and only few of them reported in children [35]. Therefore, this work aimed to evaluate the use of sTREM in comparison to PCT and CRP in early diagnosis and differentiation between septic and aseptic meningitis cases in Egyptian children with evaluation of their role as prognostic markers.

Procalcitonin was initially described as a potential marker of bacterial diseases by Assicot et al. [36] and assumed to be a protein of the acute phase of inflammation with kinetics faster than that of CRP [21]. Indeed, the current hypothesis on this marker in sepsis has gained a solid scientific basis as many researches demonstrated that quantitative evaluation of PCT is superior to the other used biomarkers, can markedly reduce antibiotic usage and as being a hormokine mediator, immunoneutralisation of it might offer new hope for more effective treatment options [12],[24],[25],[26].

However, on reviewing the results of different studies carried out all over the world to evaluate PCT discriminative ability in detecting septic meningitis, controversial was clear. Prasad et al. [37] found that, serum PCT level was significantly higher in children with septic meningitis than in those with aseptic meningitis or in controls and it may be used to differentiate between septic and aseptic meningitis. Another Egyptian study by Ibrahim et al. [38] who reported that, serum PCT levels were significantly higher in bacterial meningitis (BM) compared with non bacterial meningitis. There is a positive correlation between serum PCT, TLC and CRP in bacterial and non-bacterial meningitis cases but this relation becomes highly significant with bacterial meningitis positive group. After 3–6 days of treatment serum PCT was significantly lower than on admission levels. Therefore, serum procalcitonin has a better diagnostic and prognostic value to differentiate between bacterial and aseptic meningitis. It is also a good indicator of the efficacy of treatment of bacterial meningitis [39].

This was supported by the British study of Hatherill et al. [22] who revealed high discriminative power of serum PCT with AUC of 0.93. In the Slovenia study by Jereb et al. [40] a sensitivity of 90% and a specificity of 100% for the diagnosis of bacterial meningitis or encephalitis, using a decision threshold of 0.5 ng/ml for serum PCT was obtained. On contrary, Hoffmann et al. [41] reported normal PCT serum concentrations in 12 adults suffering from bacterial meningitis, where PCT on admission was ≤0.5 ng/ml. In another German study of Schwarz et al. [8] neither the sensitivity nor the specificity of the test using the PCT were significantly better than those using the CRP test. On the regional level, an African study led by Carrol et al. [12] concluded that PCT is the best diagnostic and prognostic marker of sever bacterial sepsis in Malawian children, including those with septic meningitis.

This work supported the role of serum PCT measurement in early distinguishing of septic from aseptic meningitis with 87.5% sensitivity and 88.6% specificity at admission PCT cut off value of 3.3 ng/ml. Although the performance of PCT was nearly similar to that of CRP in predicting sepsis, the rapid kinetics and the more specificity of PCT made it superior to CRP in that aspect. It is important to notify that the increase of PCT and CRP in bacterial meningitis is due to extracellular multiplication in the bloodstream which induce a strong systemic inflammatory response [42]. This is supported by the study of Jereb et al. [40] where two cases of bacterial meningitis with low serum PCT occurred due to non-encapsulated bacteria that multiply intracellularly, these were proved to be caused by borreliosis and tuberculosis.

The specific involvement of TREM-1 solely in cases of infection has led researchers to investigate the diagnostic value of plasma sTREM-1 assay in distinguishing sepsis from severe systemic non-infectious inflammation among newly admitted critically ill patients with suspected infection [30]. Although baseline plasma levels of CRP, PCT and sTREM-1 were higher among septic patients than in patients with systemic inflammatory response syndrome, only serum sTREM-1 levels appeared to be the most helpful parameter in differentiating between them. Unfortunately, little is known about the role of sTREM in meningitis [43]. Carrol et al. [12] in their comparative study of accuracy of five markers in the diagnosis of serious bacterial infections (SBI) including meningitis concluded that PCT not sTREM-1, was the best diagnostic and prognostic marker in SBI while PCT and CD163 was superior to the other markers in predicting fatal outcome. On attempting to evaluate the diagnostic role of measuring sTREM-1 in CSF, unlike PCT, sTREM-1 was concluded to be unregulated in the CSF of patients with bacterial meningitis [44],[45].

So, one of our main goals in this work was to evaluate the role of measuring serum sTREM-1 levels as an easy and non invasive procedure in early differentiating of septic from aseptic meningitis. Similar to PCT but with markedly higher diagnostic discriminatory power, serum sTREM-1 showed significantly higher concentrations early in septic meningitis compared to patients with aseptic meningitis and controls which was not the case in patients with aseptic meningitis when compared with the control group. After 48-72 h of treatment, patients with septic meningitis still had high serum PCT but significantly decreased in comparison with the admission levels.

With agreement to our study, Su et al. [46] reported that, on ICU day 1, the sepsis group had higher serum sTREM-1, PCT, and CRP levels compared with non-infectious systemic inflammatory response syndrome (SIRS) group. The previous report was also supported by the recent Japanese study of Oku et al. [47].

Unlike PCT and CRP, soluble TREM-1 concentration was significantly low at admission in patients with poor outcome with neatly stationary value after 48–72 h. Additionally, the low baseline sTREM-1 level was found to be the best prognostic factor of the poor outcome with the highest AUC value denoting in other word that elevated baseline sTREM-1 level could be a valuable protective marker. Interestingly, the mechanism by which sTREM modulate the immune response is still unclear however in a mouse model, blockade sTREM-1 signaling reduced but did not abolish NF-κB activation and cytokine production through competing with the natural ligand of TREM-1 and/or impairing TREM-1 dimerization, thus protecting septic animals from hyper-responsiveness and death [11],[48].

In conclusion, both serum PCT and sTREM are valuable in early distinguishing of septic from aseptic meningitis in children but with markedly higher diagnostic discriminatory power for sTREM-1. Moreover, this study pointed to the significant value of sTREM-1 in determining septic meningitis prognosis. However, it remains to be confirmed in larger populations.

Conflict of interest


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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

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