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   Infections involving the central nervous
    system, particularly meningitis and
    encephalitis are likely to arouse tremendous
    anxiety in both the physician and patients.
   Reliable, cost effective,rapid screening tests
    which can be performed in any standard
    pathology laboratory could be of help in the
    differentiation of various types of meningitis
    in adults.
   In this regard, CRP level and ADA activity can
    be used .


   Used as rapid tests in the differential
    diagnosis of meningitis.
 Adenosine deaminase (also known as ADA) is an
  enzyme involved in purine metabolism.
 It is needed for the breakdown of adenosine
  from food and for the turnover of nucleic acids in
  tissues.
 ADA irreversibly deaminates
  adenosine, converting it to the related
  nucleoside inosine by the substitution of the
  amino group for a hydroxyl group.
 ADA can also be used in the workup,specimens
  with low ADA levels essentially excludes
  tuberculosis from consideration.
   There are 2 isoforms of ADA: ADA1 and
    ADA2.

   ADA1 is found in most body cells, particularly
    lymphocytes and macrophages.

   ADA2 was first identified in human spleen.It
    was subsequently found in other tissues
    including the macrophage where it co-exists
    with ADA1.
   C-reactive protein (CRP) is a protein, the
    levels of which rise in response to
    inflammation.
   The acute phase response develops in a wide
    range of acute and chronic inflammatory
    conditions like bacterial, viral, or fungal
    infections; These conditions cause release of
    interleukin-6 and other cytokines that trigger
    the synthesis of CRP and fibrinogen by the
    liver.
   CRP is used mainly as a marker of
    inflammation. Apart from liver failure, there
    are few known factors that interfere with CRP
    production.
   There is currently no single test to diagnose
    the etiology of meningitis promptly and
    accurately. Given its high sensitivity and easy
    measurability, CRP may be a useful
    supplement for rapid diagnosis and
    categorization of bacterial meningitis.
   A total of 50 patients of suspected meningitis
    admitted to Sri Siddhartha Medical Hospital
    between August 2006 and September 2008
    were included in the study.

   All patients were above 18 years of age with
    clinical features suggestive of meningitis.
 Those excluded from the study were patients
  with acute infections at sites other than
-the central nervous system,
-those in whom lumbar puncture was
  contraindicated and
-those with severe hepatic dysfunction and
  those with fungal meningitis.
   Depending on the clinical and laboratory
    findings, patients were assigned to one of the
    following groups:
    (1) 5 cases of gram stain and culture positive
    cases of pyogenic meningitis. These patients
    had CSF analysis showing pleocytosis of
    >250cells/mm3, protein>45mg/dl, sugar
    <40mg/dl or <40% of blood glucose
    concentration
    (2) Patients with TBM. Clinical features being the
    insidious onset of symptoms of meningitis, signs of
    meningeal irritation and presence of focal
    neurological deficits.

   The CSF analysis showing pleocytosis of >25
    cells/mm3 predominantly lymphocytes, protein
    >45mg/dl, sugar<40mg/dl or <40% of blood glucose
    concentration.
   Neuroimaging showing evidence of meningeal
    enhancement, basal exudates or tuberculoma were
    supportive. These cases numbered 24.
    (3) 21 patients with viral meningitis based on
    clinical and CSF laboratory findings of
    lymphocytic pleocytosis of >25
    cells/mm3, protein >45mg/dl and normal
    sugar.
   The increase in ADA in tuberculosis is due to
    increase in ADA2. It is required to determine the
    isoenzyme 1 and 2 of ADA if there is suspicion of
    malignancy, lymphoma or collagen vascular
    disease where ADA may be falsely elevated.
   The above were not in our differential when we
    were considering meningitis.
    Moreover, to estimate the precise quantity of
    ADA1 and ADA2 in a specimen, one should
    separate the two isoenzymes.
    This is complicated and expensive and hence
    was not done.
   ADA activity was found to be the highest in
    TBM. With the cut-off value of ADA of 10IU/L,
    the mean value was 14.14±7.44IU/l.
    Patients with pyogenic meningitis had a
    mean ADA of 3.80±1.92 IU/l. The higher cut-
    off of ADA chosen helped overcome the
    overlap between tubercular and pyogenic
    meningitis. In addition, a low CRP favored the
    diagnosis of TBM .
   CRP levels were elevated in pyogenic
    meningitis. The mean CRP level was 33±5.0
    mg/dl.

   The patients with TBM and viral meningitis
    had a mean CRP level of 1.09±0.3 and
    1.12±0.48 respectively.
Type of            Number   Number CRP   ADA (IU/L)
meningitis                  (mg/dl)
Number
TBM                24       1.09         14.14



Pyogenic           5        27.00        9.80
meningitis


Viral meningitis   21       1.12         1.85
   There is a need for a rapid test that could be
    supportive in the diagnosis of TBM.
   Since early diagnosis and treatment can alter
    the outcome of these patients, ADA seems to
    be the appropriate test for this purpose.
   C reactive protein can help differentiate
    pyogenic from non-pyogenic meningitis and
    hence aid in the differential diagnosis and
    management of meningitis.
   This study emphasizes the need to raise the
    awareness about using the 2 rapid tests like
    CRP and ADA for diagnosing meningitis .




   -----------------------------THANK   YOU.

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Journal club

  • 1.
  • 2.
  • 3. Infections involving the central nervous system, particularly meningitis and encephalitis are likely to arouse tremendous anxiety in both the physician and patients.  Reliable, cost effective,rapid screening tests which can be performed in any standard pathology laboratory could be of help in the differentiation of various types of meningitis in adults.
  • 4. In this regard, CRP level and ADA activity can be used .  Used as rapid tests in the differential diagnosis of meningitis.
  • 5.  Adenosine deaminase (also known as ADA) is an enzyme involved in purine metabolism.  It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.  ADA irreversibly deaminates adenosine, converting it to the related nucleoside inosine by the substitution of the amino group for a hydroxyl group.  ADA can also be used in the workup,specimens with low ADA levels essentially excludes tuberculosis from consideration.
  • 6. There are 2 isoforms of ADA: ADA1 and ADA2.  ADA1 is found in most body cells, particularly lymphocytes and macrophages.  ADA2 was first identified in human spleen.It was subsequently found in other tissues including the macrophage where it co-exists with ADA1.
  • 7. C-reactive protein (CRP) is a protein, the levels of which rise in response to inflammation.  The acute phase response develops in a wide range of acute and chronic inflammatory conditions like bacterial, viral, or fungal infections; These conditions cause release of interleukin-6 and other cytokines that trigger the synthesis of CRP and fibrinogen by the liver.
  • 8. CRP is used mainly as a marker of inflammation. Apart from liver failure, there are few known factors that interfere with CRP production.  There is currently no single test to diagnose the etiology of meningitis promptly and accurately. Given its high sensitivity and easy measurability, CRP may be a useful supplement for rapid diagnosis and categorization of bacterial meningitis.
  • 9. A total of 50 patients of suspected meningitis admitted to Sri Siddhartha Medical Hospital between August 2006 and September 2008 were included in the study.  All patients were above 18 years of age with clinical features suggestive of meningitis.
  • 10.  Those excluded from the study were patients with acute infections at sites other than -the central nervous system, -those in whom lumbar puncture was contraindicated and -those with severe hepatic dysfunction and those with fungal meningitis.
  • 11. Depending on the clinical and laboratory findings, patients were assigned to one of the following groups:  (1) 5 cases of gram stain and culture positive cases of pyogenic meningitis. These patients had CSF analysis showing pleocytosis of >250cells/mm3, protein>45mg/dl, sugar <40mg/dl or <40% of blood glucose concentration
  • 12. (2) Patients with TBM. Clinical features being the insidious onset of symptoms of meningitis, signs of meningeal irritation and presence of focal neurological deficits.   The CSF analysis showing pleocytosis of >25 cells/mm3 predominantly lymphocytes, protein >45mg/dl, sugar<40mg/dl or <40% of blood glucose concentration.  Neuroimaging showing evidence of meningeal enhancement, basal exudates or tuberculoma were supportive. These cases numbered 24.
  • 13. (3) 21 patients with viral meningitis based on clinical and CSF laboratory findings of lymphocytic pleocytosis of >25 cells/mm3, protein >45mg/dl and normal sugar.
  • 14. The increase in ADA in tuberculosis is due to increase in ADA2. It is required to determine the isoenzyme 1 and 2 of ADA if there is suspicion of malignancy, lymphoma or collagen vascular disease where ADA may be falsely elevated.  The above were not in our differential when we were considering meningitis.  Moreover, to estimate the precise quantity of ADA1 and ADA2 in a specimen, one should separate the two isoenzymes.  This is complicated and expensive and hence was not done.
  • 15. ADA activity was found to be the highest in TBM. With the cut-off value of ADA of 10IU/L, the mean value was 14.14±7.44IU/l.  Patients with pyogenic meningitis had a mean ADA of 3.80±1.92 IU/l. The higher cut- off of ADA chosen helped overcome the overlap between tubercular and pyogenic meningitis. In addition, a low CRP favored the diagnosis of TBM .
  • 16. CRP levels were elevated in pyogenic meningitis. The mean CRP level was 33±5.0 mg/dl.  The patients with TBM and viral meningitis had a mean CRP level of 1.09±0.3 and 1.12±0.48 respectively.
  • 17. Type of Number Number CRP ADA (IU/L) meningitis (mg/dl) Number TBM 24 1.09 14.14 Pyogenic 5 27.00 9.80 meningitis Viral meningitis 21 1.12 1.85
  • 18. There is a need for a rapid test that could be supportive in the diagnosis of TBM.  Since early diagnosis and treatment can alter the outcome of these patients, ADA seems to be the appropriate test for this purpose.  C reactive protein can help differentiate pyogenic from non-pyogenic meningitis and hence aid in the differential diagnosis and management of meningitis.
  • 19. This study emphasizes the need to raise the awareness about using the 2 rapid tests like CRP and ADA for diagnosing meningitis .  -----------------------------THANK YOU.