Meta-analysis bolsters strength of tuberculosis assay



The sensitivity and specificity of a diagnostic test that rapidly detects tuberculosis support its use as an initial diagnostic test in adults suspected of having TB, including multidrug- resistant or HIV-associated disease, based on a meta-analysis of studies evaluating the test, researchers say.

In addition, the meta-analysis results suggest that the test, the Xpert assay, "may also be valuable as an add-on test following a negative smear microscopy result in patients suspected of having TB," said Karen Steingart, of the University of Washington School of Public Health, Seattle, and her associates. The researchers were from the Cochrane Infectious Diseases Group; McGill University, Montreal; and the Foundation for Innovative New Diagnostics (FIND), Geneva. The study was published in the Cochrane Database of Systematic Reviews (doi:10.1002/14651858.CD009593.pub2).

Photo Credit: Janice Carr, Centers for Disease Control and Prevention

The World Health Organization reported that there were 8.8 million new cases of TB worldwide in 2010.

Xpert, manufactured by Cepheid Inc., is an automated polymerase chain reaction test that detects Mycobacterium tuberculosis complex and rifampin resistance within two hours using a sputum sample, used outside of a reference lab "with minimal hands-on technical time," as opposed to conventional sputum smear microscopy, which is cheaper, but requires a microscope in a lab and does not detect drug resistance.

In 2010, Xpert was endorsed by the World Health Organization for use as the initial diagnostic test on people suspected of having MDR-TB or HIV-associated TB. That year, WHO reported that there were 8.8 million new cases of TB worldwide; and that 1.1 million people who did not have HIV and 350,000 people with HIV died of TB.

The study reviewed 18 studies of more than 7,500 adults, mostly in low and middle-income countries, with a high burden of TB, which evaluated the test as an initial test used as a replacement for microscopy, and as an add-on test when a microscopy smear was negative, in adults suspected of having in pulmonary TB, or multidrug-resistant TB, with or without HIV infection.

The main results of the test are as follows:

• A "modest" sensitivity of 88% and a "high" specificity of 98% for detecting TB when used it as an initial test that replaced smear microscopy.

• A sensitivity of 67% and a specificity of 98% when used as an add-on follow-up test to detect TB, after a negative smear microscopy.

• A sensitivity of 80% for detecting TB in people with HIV and 89% in people without HIV.

•A sensitivity of 94% and a specificity of 98% for detecting rifampin resistance (an indicator of multidrug resistances) when used as a replacement for culture based-drug susceptibility testing

The rate of indeterminate results was a "very low" 1%, they said.

The results "lend support to the WHO recommendation on the use of Xpert as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having MDR-TB or HIV-associated TB," the authors concluded. Future studies should include those that evaluate the results of the test in children, as those data are starting to accumulate, and result of the test in different settings, such as TB screening centers and antiretroviral clinics, they added.

The review "provides high quality evidence that reinforces WHO’s endorsement of this test," Dr. Karin Weyer, the coordinator of Diagnostics and Drug Resistance Laboratories at WHO, said in a written statement. "Recent price reductions have greatly facilitated roll-out of this technology," with 1.4 million test cartridges and the instruments needed to perform the test to be distributed in 21 countries with a high TB burden, she added.

In the United States, TB has been declining, since a peak in 1992, with 10,528 TB cases reported in 2011, almost a 6% drop from the number of reports in 2010, according to the Centers for Disease Control and Prevention. In 2009, the last year mortality data are available, there were 529 TB deaths, a 10% drop from 2008, when there were 590 deaths.

The editorial base of the Cochrane Infectious Diseases Group (CIDG), which provided part of the funding for the review, is funded by the U.K. Department for International Development "for the benefit of developing countries." One study author disclosed having conducted studies and published on the Xpert test in a project with FIND, Cepheid, and academic partners. Others reported having no relevant financial conflicts.

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