GeneXpert and CBNAAT Are the Same Technology
GeneXpert and CBNAAT (Cartridge-Based Nucleic Acid Amplification Test) refer to the identical diagnostic platform—the Xpert MTB/RIF assay—which is the WHO-endorsed standard for rapid tuberculosis diagnosis and rifampicin resistance detection. 1, 2
Understanding the Terminology
- CBNAAT is simply the generic technical term describing the cartridge-based nucleic acid amplification methodology, while GeneXpert is the commercial brand name manufactured by Cepheid for this technology 3, 4
- Both terms describe the same automated molecular diagnostic system that integrates sample processing, nucleic acid amplification, and real-time PCR detection in a single-use disposable cartridge 3
- The official assay name is Xpert MTB/RIF, which simultaneously detects Mycobacterium tuberculosis complex DNA and rifampicin resistance-associated mutations in the rpoB gene within 2 hours 3, 4
Clinical Performance Characteristics
For Pulmonary Tuberculosis Diagnosis:
- In AFB smear-positive specimens: Sensitivity 96-100%, specificity 85-93% 1, 5, 4
- In AFB smear-negative specimens: Sensitivity 66-69%, specificity 98% 1, 6, 4
- Overall diagnostic accuracy: 92.6% across all specimen types 7
For Rifampicin Resistance Detection:
- Sensitivity >92% on single specimen, increasing to >97% when performed on 3 specimens 1
- Specificity >99% for rifampicin resistance detection 1
- Rifampicin resistance serves as a surrogate marker for MDR-TB in approximately 82-90% of cases 1, 8
Recommended Clinical Algorithm
Initial Diagnostic Testing:
- Collect at least 2 sputum specimens for AFB microscopy and 1 specimen for GeneXpert/CBNAAT testing 2
- Simultaneously send specimens for liquid culture regardless of GeneXpert results, as culture remains the gold standard 1, 2, 6
- GeneXpert results should be available within 48 hours of specimen collection 6
Result Interpretation:
- AFB smear-positive + GeneXpert positive: Presume tuberculosis and initiate treatment immediately (PPV >95%) 6
- AFB smear-negative + GeneXpert positive: Use as presumptive evidence of TB when clinical suspicion is intermediate-to-high 1
- AFB smear-positive + GeneXpert negative: Evaluate for PCR inhibitors and collect new specimen; may indicate nontuberculous mycobacteria 6, 7
- GeneXpert negative with high clinical suspicion: Cannot exclude TB—false-negative rate is 34% in smear-negative cases; proceed with empiric treatment if indicated 1, 6
Critical Limitations and Pitfalls
- GeneXpert sensitivity drops dramatically in extrapulmonary TB (56-79%) and miliary TB (50-60%), with false-negative rates of 40-50% 6, 5
- All molecular resistance results must be confirmed by phenotypic culture-based drug susceptibility testing—this is mandatory per ATS/IDSA/CDC guidelines 1, 2, 9
- PCR inhibitors can cause false-negative results; if AFB smear is positive but GeneXpert is negative, test for inhibitors and repeat with fresh specimen 6
- Low positive predictive value for rifampicin resistance in low-prevalence populations—restrict testing to high-risk groups: previous TB treatment, birth/residence ≥1 year in countries with MDR-TB prevalence ≥2%, MDR-TB contacts, or HIV-infected patients 1, 2
When to Perform Rifampicin Resistance Testing
Perform GeneXpert/CBNAAT with rifampicin resistance detection on initial respiratory specimens only for patients meeting these criteria: 1
- Previous tuberculosis treatment history
- Born in or lived ≥1 year in country with TB incidence ≥20 per 100,000 or MDR-TB prevalence ≥2%
- Known contact of MDR-TB patient
- HIV-infected status
Management of Indeterminate Rifampicin Results
- Immediately repeat GeneXpert on new specimen and simultaneously send for phenotypic DST via liquid culture 2
- Initiate standard four-drug first-line therapy (rifampicin, isoniazid, pyrazinamide, ethambutol) while awaiting confirmatory results 2
- Do not start MDR-TB treatment without phenotypic confirmation—unnecessary toxicity outweighs benefits 2
- Perform monthly sputum smear and culture while awaiting final DST results 2