Rapid TB test shows high sensitivity, specificity

Boehme CC. N Engl J Med. 2010;363:1005-1015.

An automated molecular test for Mycobacterium tuberculosis and rifampin resistance identified 98.2% of patients with smear-positive tuberculosis and 72.5% of patients with smear-negative tuberculosis. The test was 99.2% specific in patients without tuberculosis, according to the study.

Catharina C. Boehme, MD, of the Foundation for Innovative New Diagnostics in Geneva, and colleagues evaluated the Mycobacterium tuberculosis/resistance to rifampin (MTB/RIF) test (Xpert, Cepheid), which integrates sample processing and real-time polymerase chain reaction into a single disposable plastic cartridge that contains all of the necessary reagents. The cartridge is inserted into an MTB/RIF test platform (GeneXpert, Cepheid) and results are provided within 2 hours.

The test was developed in response to a global need for a quick, accurate, easy-to-use TB test that can be employed outside of reference laboratories. The Xpert MTB/RIF test’s “features of simplicity and safety of use could allow for cost-effective and highly sensitive detection of tuberculosis and drug resistance outside reference centers, which would increase access to testing and decrease delays in diagnosis, without the need to build large numbers of laboratories equipped for advanced biosafety,” the researchers wrote. The test could help efforts to reach the estimated 500,000 worldwide patients who have multidrug-resistant TB and 1.37 million patients who have TB with HIV coinfection.

For the multicenter, prospective study, the test was performed on 1,462 patients across eight sites in areas known for prevalence of TB, HIV and multidrug-resistance. Each patient provided sputum samples, and the presence of TB was confirmed with smears and cultures. A total of 567 (38.8%) patients had culture- and smear-positive TB; 174 (11.9%) had culture-positive but smear-negative TB; 105 (7.2%) had smear- and culture-negative TB but were treated for the diseases on the basis of clinical and radiological findings; and 616 (42.1%) had no clinical evidence of TB.

Overall sensitivity of the MTB/RIF test was 97.6% among patients with culture-positive TB. Sensitivity was 90.2% for smear-negative, culture-positive cases and 99.8% for smear- and culture-positive. Among patients with pulmonary TB and HIV coinfections, sensitivity was 93.9% compared with 98.4% in HIV-negative patients (P=.02).

Specificity was 99.2% if a single MTB/RIF test was performed, 98.6% for two tests and 98.1% for three tests. Overall, the test compared favorably in sensitivity and specificity to the Cobas Amplicor MTB (Roche) and ProbeTec ET MTB (BD) tests.

The MTB/RIF test was able to detect rifampin resistance in 209 of 211 patients (99.1% sensitivity) and in all 506 patients with rifampin susceptibility (100% specificity).

The researchers said there were several limitations of their study, including the test’s high cost and the fact that all of the eight sites in the study were reference facilities. “It is not certain that our findings would be replicated in microscopy centers, health posts, and other point-of-treatment settings where temperature and electricity supply will be more variable and training issues will be more relevant,” they wrote.