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Abstract
Headline!
Introduction
Pathogenesis of Tuberculous Meningitis (TBM)
Host and Pathogen Genetics in TBM
Laboratory diagnosis of TBM
Treatment of TBM
HIV-associated TBM
Adjunctive anti-inflammatory therapies
Conclusion
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ABSTRACT
+ Tuberculous meningitis (TBM) is the most severe form of infection caused by
Mycobacterium tuberculosis in the central nervous system, causing death or
disability in more than half of those infected.
+ The diagnosis of TBM remain difficult as its presentation is non-specific and
may mimic other causes of chronic meningoencephalitis. Rapid recognition of
TBM is crucial, as delays in initiating treatment are associated with poor
outcome.
+ The optimal therapy of TBM has not been established in clinical trials.
+ Laboratory methods to improve the rapid diagnosis of TBM are urgently
required.
+ The use of biomarkers to improve the rapid diagnosis of TBM warrants further
investigation.
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INTRODUCTION
+ TBM is the most frequent form of central nervous system tuberculosis.
+ CNS disease accounts for only 5% of all cases of extra-pulmonary
tuberculosis and peak incidence is children under 4 years of age.
+ TBM is classified into three grades of severity according to the British
Medical Research Council TBM grade.
+ Grade 1 TBM (GCS 15 + no focal neurology)
+ Grade 2 TBM (GCS 15 + focal neurology or GCS 11-14)
+ Grade 3 TBM (GCS ≤ 10)
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Clinical features of tuberculous meningitis
Pathogenesis of Tuberculous Meningitis
SNP 558T
Increase the possibility of
dissemination and TBM.
TLR 2
Laboratory Diagnosis of TBM
Laboratory Diagnosis of TBM
Treatment of TBM
Drug Dose in Children Dose in Adults Duration Common Side Effects
Rifampicin (R) 10–20 mg/kg/day 450 mg (weight <50 12 months Orange discolouration of
(maximum 600 kg) bodily fluids, hepatoxocity,
mg/day) 600 mg (weight <50 gastrointestinal symptoms,
kg) headache, drowsiness
Isoniazid (H) 10–20 mg/kg/day 300 mg 12 months Hepatotoxicity, peripheral
(maximum 500 neuropathy (with high
mg/day) doses), optic neuropathy,
gastrointestinal symptoms
Pyrazinamid (Z) 15–30 mg/kg/day 1.5 g (weight <50 kg) 2 months Hepatoxicity
(maximum 2 g/day) 2 g (weight <50 kg)
Ethambutol (E) 15–20 mg/kg/day 15 mg/kg 2 months Optic neuritis, red/green
(maximum 1 g/day) colour blindness,
peripheral neuritis
Treatment of TBM
+ 2 months of RHZE (initiation phase) and 10 months of RH (continuation
phase). (NICE Guidelines)
+ Two recent studies have investigated the role of intensified therapy for TBM
(adding fluoroquinolones–levofloxacin, gatifloxacin, ciprofloxacin)
+ Study in Vietnam shows that worse outcome with low or high exposure of
fluoroquinolones than with intermediate exposure.
+ Study in Indonesia shows that high-dose rifampicin (600 mg) and high (800
mg) or standard (400 mg) dose of moxifloxacin resulted in an increase in
plasma and CSF levels and was associated with reduced mortality.
HIV Associated TBM
+ The treatment of TBM with HIV is complicated by the need to treat
both conditions simultaneously, with the attendant drug interactions
and toxicities, and the risk of immune reconstitution inflammatory
syndrome (IRIS), a potentially fatal condition.
+ There is still controversial whether it is better to initiate the ART
earlier.
Adjunctive Anti-Inflammatory Therapies
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