WHO Endorses 'Revolutionary' New Diagnostic Test for TB

LONDON—A new rapid test for tuberculosis (TB) has received an important thumbs-up from the World Health Organization (WHO), a move expected to lead to its worldwide rollout over the next few years. The new test, in which a device the size of a carry-on suitcase looks for bacterial DNA in a person's sputum, is cheaper, faster, and more accurate than standard TB tests used in both developed and developing countries, WHO representatives said yesterday at a press conference here.

"This system allows doctors to test the patient while the patient sits there [in the waiting room]", says Marieke van der Werf, head of research at the KNCV Tuberculosis Foundation in the Netherlands, who was a member of a group that reviewed the evidence for the test's accuracy. The panel published its report in The New England Journal of Medicine in September.

The difference with existing tests is huge, says Van der Werf. Most current TB testing methods rely on a century-old technique in which sputum samples are cultured for 4 to 6 weeks, then examined under a microscope to check for the presence of the disease-causing Mycobacterium tuberculosis. This long delay is especially problematic for people who are immunosuppressed and who can't wait 2 months before going on treatment.

In 2009, 9.4 million new TB cases were recorded worldwide. TB can be treated with a 6- to 12-month course of four different drugs, but many patients in developing countries don't have access to the drugs or get medical attention too late. Untreated, the disease can be fatal. WHO estimates that there are about 1.7 million TB-related deaths each year worldwide.

The new TB test was developed by Cepheid, a company in Sunnyvale, California, in partnership with the Foundation for Innovation New Diagnostics (FIND) and the University of Medicine and Dentistry of New Jersey. It's a "fully automated" system, which even health workers in developing countries can operate after a minimum of training, says FIND Chief Executive Officer Giorgio Roscigno.

At yesterday's press conference, FIND staff members demonstrated the machine using a water sample. They placed the liquid in a beaker and added a reagent, which would neutralize any TB microbes in infected sputum by breaking apart their cell walls; then the sample was injected into an enclosed cartridge and popped into the machine. The test, which takes just 90 minutes, would detect TB bacteria by looking for characteristic genetic signatures, amplified in a process called PCR.

The test can also detect whether the microbes carry a gene that confers resistance to Rifampicin, a drug commonly used to treat TB. That's an important piece of information for doctors; if the patient is also resistant to a second drug called Isoniazid—it takes a separate test to find out—the strain is considered multi-drug resistant (MDR), and it requires a different cocktail of drugs to treat. WHO estimates that there were 440,000 new cases of MDR TB in 2008. The new test is also expected to lead to twice as many TB diagnoses among HIV-infected people; roughly 12% of those with the disease are also HIV-positive.

For nongovernmental organizations and low- and middle-income countries, the cost per test is $16, a price that is expected to fall to $14 within a year and to $10 within 2 years. The machine costs $17,000; that's after a 75% cut in Cepheid's original price negotiated by FIND. The price is a fraction of what it would cost to set up and staff a lab that conducts standard sputum smear microscopy test, says Roscigno.

WHO organized a global meeting last week in Geneva to lay out plans for how the new PCR-based test can be made available in as many countries worldwide as quickly as possible. The agency has produced a road map that places 116 low- to middle-income countries first in line to receive the low-priced machines.

South Africa, India, Uganda, and several other countries plan to roll out the test immediately. A crucial question is how well it performs in the field, where tropical temperatures and lack of electricity and Internet access--which the machine needs to signal that it needs maintenance--could pose problems. A trial of a version of the machine running on batteries is already under way in India and Pakistan, among other countries, and results are expected next year.

The new diagnostic tool does raise new questions, however. Even if countries can detect MDR patients, most aren't ready to treat large numbers of them, says Van der Werf. A WHO-led effort will have to be put in place to get treatment to those who need it, she says.