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TBM, introduction
The most severe extrapulmonary TB Diagnosis remains difficult Early recognition is crucial for better outcome High mortality rate; sequalae in survivors Optimal treatment has not been established HIV increases, TBM increases
Diagnostic categories
Thwaites (2005)
Diagnostic categories
Ogawa (1987)
Thwaites (2005)
Definite TBM:
Clinical meningitis and Abnormal CSF parameters and Acid-fast bacilli in CSF (microscopy) and/or culture positive for M. tuberculosis
Diagnostic categories
Ogawa (1987)
Thwaites (2005)
Probable TBM:
Clinical meningitis and Abnormal CSF parameters and At least 1 of the following: Suspected active pulmonary tuberculosis (chest radiography) AFB found in any sample other than from the CSF
Diagnostic categories
Thwaites (2005)
Possible TBM:
Clinical meningitis and Abnormal CSF parameters and At least 4 of the following: History of tuberculosis MN predominance in the CSF Illness of > 5 days in duration CSF:blood glucose ratio < 0.5 Altered consciousness Yellow (xanthochromic) CSF Focal neurological signs
Grade II
GCS 10 14 + focal neurological deficit OR GCS 15 with focal neurological deficit
Grade III
GCS < 10 with or without focal neurological deficit
TBM, diagnostics
What is expected
Reliable Easy access Easy to be done
TBM, treatment
Optimal TBM treatment has not been established in clinical trials
Same drug Different pharmacokinetics
Various guidelines
Intensive phase of 4 drugs (RHZ+S or E or ethionamide) Continuation phase of 2 drugs (RH) Treatment duration 9 12 months
HIV-associated TBM
Thwaites et al (JID, 2005)
96 HIV-infected and 432 HIV-uninfected patients No difference in clinical presentation HIV ~ more EPTB No differences in relapses or adverse events HIV reduces survival rates
Meningitis, HIV+ vs HIVDiagnosis HIV-positive (n=41) 27 (65.9%) 7 HIV-negative (n=111) 96 (86.5%) 59 Total population (n=152) 123 (80.9%) 66
Probable TBM
Cryptococcal meningitis Probable bacterial meningitis Unknown cause
20
12 (29.3%) 2 (4.8%)
37
1 (0.9%) 10 (9%) 4 (3.6%)
57
13 (8.6%) 10 (6.6%) 6 (3.9%)
Fever on presentation*
Focal neurological sign* CSF leukocyte count > 70/mm3 Peripheral leukocyte > 10,000/ mm3 Abnormal Chest X-ray
27/56 (48.2)
35 (57.4) 30 (49.2) 32/56 (57.1) 41/57 (71.9)
25/86 (29.1)
37 (40.7) 45 (49.4) 39/88 (44.3) 61/89 (68.5)
30/49 (61.2)
64/87 (73.6)
HIV positive Altered consciousness (GCS < 14) Fever on presentation Focal neurological sign CSF leukocyte count > 70/mm3 Peripheral leukocyte > 10,000/ mm3 Abnormal Chest X-ray Plasma sodium < 136 mEq/L
Percent survival
HI HI
HIV-negative
50
HIV-positive
0 0 100 200
daysdays
300
Conclusion
Clinical meningitis with abnormal CSF pattern, and supporting evidence of extraneural TB significant for diagnosis Diagnostics: Lab! volume is important for positive CSF result Treatment ~ other EPTB: different PK Give adjunctive corticosteroid
Conclusion
Influence of HIV in the development of TBM anticipated burden to health system HIV dramatically decreases the survival rate of TBM patients High prevalence of HIV HIV screening to any meningitis case High mortality rate warrants further studies