A New Era: Molecular Tuberculosis Diagnosis

Shahin Lockman, MD, MS

Disclosures

June 24, 2011

In This Article

The GeneXpert MTB/RIF Test

The GeneXpert MTB/RIF test, which is based on nucleic acid amplification and detection of an MTB-specific region of the rpoB gene, uses real-time polymerase chain reaction with molecular beacons. The test also detects mutations associated with rifampin resistance, which serves as a proxy for MDR-TB. This fully automated system integrates sputum processing, DNA extraction, and amplification to diagnose TB. Technicians can be trained in 1-2 days; just 2 steps (addition of buffer and sputum sample) are manual; and results are available within 90 minutes. Each tabletop-sized module can process 4 samples daily (larger modules can run 200 tests in an 8-hour day), and because it is a closed system, biosafety and contamination concerns are minimized.

Xpert MTB/RIF Test Performance

The Xpert MTB/RIF test exhibits high sensitivity and specificity for detecting pulmonary TB disease. An in vitro study demonstrated a limit of detection of as few as 131 colony-forming units/mL of MTB, compared with approximately 10,000 colony-forming units/mL with conventional smear microscopy.[4] In a clinical study conducted in 1462 patients with suspected pulmonary TB in Peru, Azerbaijan, South Africa, and India, the sensitivity of the MTB/RIF test on just 1 sputum sample was 92.2% for culture-positive TB; 98.2% for smear- and culture-positive cases; and 72.5% for smear-negative, culture-positive cases, with a specificity of 99.2%. Sensitivity and higher specificity were slightly higher when 3 samples were tested[5] (Table).

Table. Performance of the Xpert® MTB/RIF Test on Sputum Samples

  Sensitivity Specificity
Culture/Smear
Results
All Culture
Positive
Smear
Positive,
Culture
Positive
Smear
Negative,
Culture
Positive
 
1 sputum
sample
675/732
(92.2%)
551/561
(98.2%)
124/171
(72.5%)
604/609
(99.2%)
3 sputum
samples
723/741
(97.6%)
566/567
(99.8%)
157/174
(90.2%)
604/616
(98.1%)

 

In this same study, the MTB/RIF test correctly detected rifampin resistance in 209 of 211 patients (99.1% sensitivity) and rifampin susceptibility in all 506 patients with rifampin-susceptible strains (100% specificity).[5] Similar levels of sensitivity and specificity for detecting TB and rifampin resistance were observed in a program-implementation study conducted in 6648 patients.[6] Modeling studies have estimated that use of this test (replacing or adding to microscopy) would increase TB case finding by 30% and would increase MDR-TB case finding approximately 3-fold, replacing culture and conventional drug-susceptibility testing.

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