Two-Hour Test for TB Reported to be Clinically Effective

Research assessing the effectiveness of a new diagnostic test for the detection of tuberculosis (TB) is featured in the Sept. 1 edition of the New England Journal of Medicine. A rapid automated molecular test, which was developed as a result of a public-private partnership between scientists at the UMDNJ-New Jersey Medical School, Cepheid and the Foundation for Innovative New Diagnostics (FIND), showed excellent performance in the first large-scale field trial.

Dr. David Alland, chief of infectious diseases at the UMDNJ-New Jersey Medical School, who led the development of the test in collaboration with Cepheid and FIND, was one of the co-authors of the article, "Rapid Molecular Detection of Tuberculosis and Rifampin Resistance." The study focused on the dual detection of TB and drug-resistant forms of TB, in individuals with and without human immunodeficiency virus infection (HIV). The test is known as the "Xpert MTB/RIF" test for Mycobacterium tuberculosis and resistance to rifampin (RIF).

Individuals from Lima, Peru; Baku, Azerbaijan; Cape Town and Durban, South Africa; and Mumbai, India participated in the study. Each of 1,730 individuals, suspected of having drug-sensitive or multidrug resistant pulmonary TB, provided three sputum specimens. The sputum samples were assessed with the Xpert MTB/RIF test, and these results were compared to conventional tests including sputum microscopy and bacterial culture. Researchers found that the Xpert MTB/RIF test diagnosed TB in less than two hours in 99.2 percent of the patients. Importantly, a single Xpert MTB/RIF test detected TB in 72.5 percent of individuals with TB who did not appear to have TB on conventional microscopic examination, but who were later found to have positive TB cultures.

TB cultures can take as long as six weeks to become positive, which can lead to long delays in starting treatment. The addition of a second and third Xpert MTB/RIF test permitted TB to be detected in 90.2 percent of sputum microscopy-negative individuals. The new test also detected the presence of rifampin-resistance in 97.6 percent of individuals who were later found to be rifampin-resistant on TB culture. Rifampin-resistance is a good predictor of infection with multi drug-resistant TB, which requires different treatment compared to drug-susceptible TB.

According to Alland, who is also the interim director of the UMDNJ Center for Emerging Pathogens, "The test that we developed with Cepheid and FIND finally makes it possible to detect TB in a single clinic visit. The test also indicates rapidly whether difficult-to-treat drug-resistant forms are present. This is a major advance over other rapid TB detection methods which are complex, labor-intensive, and technically challenging. The Xpert MTB/RIF test is also much simpler than sputum microscopy and is days to weeks faster than bacterial culture." Based in California, Cepheid is a molecular diagnostic company.

Currently, only a small fraction of the estimated 500,000 patients who have multidrug resistant TB and 1.37 million patients who have co-infection with tuberculosis and HIV worldwide each year have access to sufficiently sensitive case detection or drug-susceptibility testing.

The study was designed and supervised by the sponsor, FIND. The development of the Xpert MTB/RIF test was funded by grants from the National Institutes of Health and FIND.