What is the role of Cartridge-Based Nucleic Acid Amplification Test (CBNAAT) in diagnosing Tuberculosis (TB) meningitis?

Role of CBNAAT in Diagnosing TB Meningitis

CBNAAT (Cartridge-Based Nucleic Acid Amplification Test) has moderate sensitivity (approximately 62%) but excellent specificity (98%) for diagnosing TB meningitis, making it a valuable diagnostic tool when positive, though a negative result cannot rule out TB meningitis due to its paucibacillary nature. CBNAAT should be performed on cerebrospinal fluid specimens from patients with suspected TB meningitis as it can provide rapid results within 24-48 hours and reliably detect Mycobacterium tuberculosis weeks earlier than culture when positive.

Diagnostic Performance of CBNAAT in TB Meningitis

• CBNAAT has approximately 62% sensitivity for detecting TB in cerebrospinal fluid, meaning it misses about 38% of true TB meningitis cases 1
• Specificity is excellent at approximately 98%, indicating that false-positive results are rare (only about 2%) 1
• A positive CBNAAT result can be used as evidence of TB meningitis and guide decision-making because false-positive results are unlikely 1
• However, a negative CBNAAT result cannot be used to exclude TB meningitis because false-negative results are exceedingly common due to the paucibacillary nature of the disease 1, 2

Advantages of CBNAAT in TB Meningitis Diagnosis

• Provides results within 24-48 hours compared to culture which takes 2-6 weeks 1, 3
• Can detect the presence of M. tuberculosis bacteria weeks earlier than culture for 80-90% of patients whose TB is ultimately confirmed by culture 1
• Simultaneously detects rifampicin resistance by targeting the rpoB gene, which is critical for treatment planning 3, 4
• Earlier laboratory confirmation of TB can lead to earlier treatment initiation, improved patient outcomes, and increased opportunities to interrupt transmission 1

Limitations of CBNAAT in TB Meningitis

• TB meningitis is a paucibacillary disease, meaning it has low bacterial loads in CSF, which often evades definitive diagnosis 3, 2
• Even the best current testing may miss up to 30% of TB meningitis cases 2
• Conventional tests for TB meningitis that focus on detection of TB bacilli (including CBNAAT) are inadequate as standalone tests 2
• Smear microscopy is rapid but only ~10-15% sensitive, while culture has 50-60% sensitivity but is slow 2

Diagnostic Algorithm for TB Meningitis

1. Collect cerebrospinal fluid (CSF) specimens from patients with suspected TB meningitis 1
2. Perform CBNAAT on CSF as a first-line rapid diagnostic test 1, 3
3. Simultaneously send CSF for conventional testing including:
   • AFB smear microscopy (though sensitivity is only 10-15%) 2
   • Mycobacterial culture (gold standard but takes 2-6 weeks) 1, 2
   • CSF analysis for cell count, protein, and glucose levels 5
4. Interpret results:
   • If CBNAAT is positive: Diagnose as TB meningitis and initiate appropriate treatment immediately 1, 3
   • If CBNAAT is negative: Cannot exclude TB meningitis; consider empiric treatment based on clinical features and other laboratory findings 1, 2

Clinical Considerations and Pitfalls

• Early diagnosis and treatment initiation is the single most important determinant of outcome in TB meningitis 3
• Empirical treatment for a minimum of 9 months is warranted based on clinical judgment when TB meningitis is strongly suspected, even with negative diagnostic tests 3
• All TB meningitis patients should receive adjunctive corticosteroids, even those with HIV infection 3, 6
• Five features predictive of TB meningitis diagnosis include: age, length of history, white blood cell count, total CSF white cell count, and CSF neutrophil proportion 5
• Consider testing for biomarkers of host response as an adjunctive approach to improve diagnosis of TB meningitis 2

Special Populations

• Young children and people living with HIV are at highest risk for TB meningitis 6
• In HIV co-infected patients, early initiation of antiretroviral therapy in TB meningitis is associated with higher rates of adverse reactions without improved survival 6
• Drug resistance is strongly associated with previous TB treatment, and bedaquiline and delamanid have received approvals for multidrug-resistant (MDR) TB 3