What is the sensitivity of cerebrospinal fluid (CSF) Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) and CSF Adenosine Deaminase (ADA) in diagnosing tuberculous meningitis?

Sensitivity of CSF CBNAAT and CSF ADA in Tuberculous Meningitis

CSF CBNAAT (Nucleic Acid Amplification Test/PCR)

The sensitivity of CSF CBNAAT for tuberculous meningitis is poor, ranging from 25-70% depending on the volume tested, making it insufficient as a standalone diagnostic test. 1

• The IDSA/ASM guidelines explicitly state that nucleic acid amplification tests (NAAT) for M. tuberculosis in non-respiratory specimens like CSF may have poor sensitivity 1
• Culture remains the gold standard with reported sensitivity of 25-70% for diagnosing tuberculous meningitis 1
• The highest yields for AFB smear and culture occur when large volumes (≥5 mL) of CSF are used 1
• Despite advances in molecular technology, CBNAAT/PCR should always be accompanied by culture requests due to suboptimal sensitivity 1

Key Pitfall

The major limitation is that a negative CBNAAT does not rule out tuberculous meningitis—you must still send culture and consider empiric treatment based on clinical presentation and CSF parameters 1

CSF Adenosine Deaminase (ADA)

CSF ADA demonstrates sensitivity of 82-95% and specificity of 83-92% for tuberculous meningitis when using appropriate cutoff values (10-11.39 IU/L), making it a more reliable rapid diagnostic tool than CBNAAT. 2, 3

Sensitivity and Specificity Data

• Using a cutoff of 11.39 IU/L: sensitivity 82%, specificity 83% 2
• Using a cutoff of ≥10 IU/L: sensitivity 84%, specificity 92% 3
• Using a cutoff of >5 IU/L in children: sensitivity 89%, specificity 92% 4
• Using a cutoff of ≤5 IU/L: sensitivity 62.5%, specificity 88.9% for differentiating TBM from partially treated bacterial meningitis 5

Predictive Values

• Positive predictive value: 90% 6
• Negative predictive value: 95% 6
• When combining CSF ADA (≥10 IU/L) with serum ADA (≥15 IU/L), specificity increases from 92% to 97% 3

Clinical Utility

• Mean CSF ADA in tuberculous meningitis: 11.80-14.31 IU/L 2, 3
• Mean CSF ADA in bacterial meningitis: 8.52-9.25 IU/L 2, 3
• Mean CSF ADA in viral/aseptic meningitis: 5.26 IU/L 3
• Mean CSF ADA in non-infectious neurological disorders: 2.71 IU/L 2

Advantages of CSF ADA

• Simple, rapid, cost-effective test that can be performed in any standard pathology laboratory 6, 2, 4
• Results available much faster than culture (which takes weeks) 6
• Particularly valuable when differentiating tuberculous from partially treated bacterial meningitis, where traditional markers overlap 5
• CSF ADA correlates significantly with CSF cell count, lymphocyte percentage, and protein concentration 4

Critical Distinction

CSF ADA levels do not differ significantly among different stages of tuberculous meningitis, but confirmed TBM cases have significantly higher levels than clinical TBM 4. This means ADA remains elevated regardless of disease stage, making it useful even in advanced presentations.

Practical Algorithm

1. Collect ≥5 mL CSF for optimal testing 1
2. Send simultaneously: AFB smear, culture, CBNAAT, and ADA 1, 2
3. If CSF ADA ≥10 IU/L with lymphocytic pleocytosis, low glucose, and high protein: strongly consider TBM and initiate empiric treatment 2, 3
4. If serum ADA also ≥15 IU/L, specificity increases to 97% 3
5. Do not wait for culture or CBNAAT results to start treatment if clinical suspicion is high and ADA is elevated 1, 6
6. A CSF ADA <5 IU/L has 95% negative predictive value—makes TBM unlikely 6