Breakthrough in TB Diagnostics

A rapid DNA-based diagnostic test for tuberculosis could help health workers in poor countries detect drug-resistant forms of the infection much earlier, making it easier to treat. The World Health Organization, the U.S. government, and donor groups such as the Gates Foundation are now helping these countries acquire the technology, which was developed by a team of academic, industry, and nonprofit researchers. “It’s completely changing the way people think about how to diagnose TB,” says Madhukar Pai a tuberculosis researcher at McGill University in Montreal.

TB remains a major global health problem, killing nearly 2 million people each year, according to the WHO. While the disease is typically treatable with antibiotics, drug- resistant forms, which are much more difficult to cure, are increasingly common. Last spring, the WHO reported 440,000 cases of drug-resistant TB—the highest number yet recorded.

The diagnostic method that’s standard for TB in poor countries—looking at sputum samples under a microscope—cannot detect drug-resistant forms. Instead, clinic workers must turn to cell culture tests, which are expensive and take several weeks. By that point, the infected person may have passed the disease on to countless others in the community. However, the new test can detect drug-resistant tuberculosis in the clinic in less than two hours, according to research published in the New England Journal of Medicine.

The test directly detects genetic sequences associated with TB and drug-resistant TB. Although researchers have known about these sequences since the mid-1990s, incorporating the molecular technologies needed to detect them into tests for the developing world has been impractical until recently, says David Persing, the chief medical and technology officer at Cepheid, the California-based company that manufactures the test.

The test starts by adding a simple chemical mixture—sodium hydroxide and alcohol—to the patient sample to kill off any TB, eliminating the need for expensive biosafety equipment. Then the sample is transferred to a closed cartridge that uses microfluidics to purify the patient’s DNA and detect the target sequence. All the clinic staff has to do is wait for a printout that tells them whether a patient has TB and if it is drug-resistant.

The Foundation for Innovative New Diagnostics, the Switzerland-based organization that spearheaded the project, has already tested the device in clinics around the world. “Users have uniformly said that the test was simpler than microscopy,” says Mark Perkins, FIND’s chief scientific officer. “It’s a huge leap forward,” says Karen Steingart, a tuberculosis researcher at the University of California, San Francisco, who compares the test to cell phones in terms of potential impact.

As with cell phones, cost will be a key factor in determining how widespread the test becomes. FIND and Cepheid have managed to bring down the cost to about $17 per test (the machine itself costs $17,000) for developing countries, which is cheaper than cell culture. But there’s still room for improvement. “The main thing that will drive the cost down is volume,” says Perkins, “so we’re hoping that the uptake will be strong so that everyone can benefit from lower pricing.” Several hundred thousand tests have already been ordered for next year.