Tuesday, August 16, 2011

Biomarkers for Diagnosis of meningitis

The supernatant part of centrifuged CSF tested for glucose , protein , lactate , C-Reactive protein , adenosine deaminase (ADA) content , estimation of the level of cytokines ,

lysozyme tests,total and differential leucocytic count ( Salmaso et al ., 1997).

(a)- Glucose content :

Simultaneous estimation of blood and CSF glucose levels is the most discriminatory test of the nonspecific CSF parameters to differentiate between bacterial and viral meningitis. CSF contain 2.2-4 mmol glucose/liter .Normal CSF glucose is about 60% of serum glucose value. If CSF glucose is <50% of serum glucose this will raise the possibility of bacterial meningitis. Glucose level is usually reduced in bacterial meningitis but may be normal or slight decreased in viral meningitis (Cinque et al ; 1996) . (b)- Protein content : Protein concentration which is below 0.4 g/L in normal CSF is usually more elevated in bacterial meningitis but may be normal or mild elevated in viral meningitis. In purulent (septic) meningitis , the glucose concentration is reduced and the protein concentration increased but in AM , the glucose concentration is normal and the protein concentration either normal or raised a little ( Cinque et al ; 1996). (c)- CSF lactate : The best test to differentiate bacterial from viral meningitis is the measurement of CSF lactate . Lactate levels are particularly important when CSF Gram staining is negative and there is a predominance of PMNs with low glucose in the CSF. CSF lactate concentrations greater than 3.5 mmol/L are characteristic of acute bacterial meningitis. As the lactate concentration in the CSF is independent of that of serum, there is no necessity to test the serum level (Cunha,2004). (d)- Acute phase reactants : Hansson et al.( 1993) found that determination of concentrations of alpha-¬1-acid glycoprotein (AAG) and C-reactive protein (CRP) in serum and alpha-2-ceruloplasmin (CER) in CSF are useful in differentiation between bacterial and viral meningitis. In children younger than 6 years of age , a discriminatory level of serum CRP of 20 mg/L can be used to distinguish between bacterial and viral meningitis but for older patients, a discriminatory level of 50 mg/L is more appropriate. Determination of AAG, CRP in serum are good markers for treatment efficacy and infectious complications in case of bacterial meningitis (Kwaik et al; 1995 and Paradowski et al; 1995) . (e)-Estimation of cytokines : Interleukin 6 (IL6) in CSF was reported to be as a diagnostic marker in the differential diagnosis of meningitis.It can be measured using monoclonal antibody enzyme immunoassay or Radioimmunoassay(RIA). CSF IL6 concentrations were found to be elevated in pyogenic meningitis in 100% of cases and in >50% of viral and other subarachnoid space infections and rarely in patients without CNS infections. Though, patients affected by pyogenic meningitis show the highest levels of CSF IL6 (Lopez-Cortes et al;1997).

(f)- Lysozyme test :

The principle of this test is to add polymexin M sulfate into
the gel bacterial medium. Rapid differential diagnosis of bacterial and viral meningitis with the use of this test is based on different time of the appearance of the lyses areas in bacterial meningitis. The CSF lysozyme activity is detectable within 15-120 min whereas in viral meningitis it manifests 40-50 min later or does not manifest at all. The results are dependant on the time of the CSF collection as more positive results are obtained when CSF samples are early collected (Babich et al ;1992).

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