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A new diagnostic test for active TB may someday replace the sputum smear, and perhaps even the sputum culture, according to Sequella, Inc., the Rockville, MD-based biotech company developing the new technology. The test will begin enrolling for a late-stage prospective trial this summer, says Katherine Sacksteder, PhD, director of communications for Sequella.
The new device looks like a Band-Aid, with a gauze patch in the middle, and is used much like a tuberculin skin test. The gauze patch is impregnated with a protein that elicits an immune reaction — a reddening of the skin — in those with smear-positive TB. Although it measures something quite different from latency, the patch is placed on a subject’s forearm and read 48 to 72 hours later.
So far, the patch has been tested only on those with smear-positive TB. It’s proven adept at distinguishing them from healthy controls who are tuberculin skin-test positive. In addition, a small amount of data suggest the patch can also signal when a TB patient is cured, because erythema is evidently no longer elicited within a month or so after treatment is over. That, in turn, suggests the patch may also be able to sort out actively replicating TB from old disease.
Some important questions still need answering, however. How well will the test work on smear-negatives? And how will it perform on TB patients co-infected with HIV? There’s a third question, too. So far, the patch has been tried out only on moderately pigmented subjects; because it produces no palpable swelling, no one knows for sure how well it will work in very dark-skinned subjects, Sacksteder says. Sequella hopes to sort out the remaining issues in a late-stage, prospective trial due to start enrollment in June in Capetown, South Africa.
If the patch works well with sputum-smear-negative patients — and Sequella is betting it will, Sacksteder says — that alone would give it a big advantage over sputum smears, which become difficult to perform once bacterial levels dip below about 10,000 mycobacteria per milliliter. "I think we’ll be able to pick up most people who are smear-negative," Sacksteder says. "We may be able to pick even those who are both smear- and culture-negative." Sequella is also banking that the test will react in at least some HIV-infected TB patients, she adds. "My bet is that it will probably depend on how high their T-cell count is," Sacksteder says.
So far, the patch has been tested on about 250 people, about 150 of whom participated in two trials Sequella conducted in the Philippines. In the larger trial, the patch showed 88% sensitivity and 100% specificity, picking out 43 of 48 subjects with smear-positive TB and producing no false-positives among healthy tuberculin-reactive controls.
As soon as six months’ worth of data have been collected from this summer’s upcoming trial, Sequella plans to begin talks with the U.S. Food and Drug Administration, Sacksteder says. If all works out as the company hopes, there should be several ready-made markets for the new product, she says.
For example, the patch could serve as an inexpensive, accurate screening test for prospective immigrants, and presumably could foil would-be cheaters who are now simply substituting someone else’s chest X-ray for their own, Sacksteder notes. At home, the patch could be useful in contact investigations, where it could quickly spot someone with infectious TB, she adds.
The protein in the patch, MPB-64, was discovered by a Japanese researcher working for the Japan BCG Laboratory. MPB-64 is not present in most strains of BCG or in ambient environmental mycobacteria.
It was during the second of the two Philippines trials that researchers began putting the patch on patients who’d completed a six-month round of chemotherapy to see whether the erythema would disappear. According to tests on about a dozen subjects (tested at various points after their treatment had ended), the test read consistently negative starting at seven months, says Sacksteder. The Capetown trial will follow patients to see whether those early results can be replicated on a larger scale.
Sequella plans to market the test worldwide but may use a tiered pricing structure to make sure it is affordable to poor countries, Sacksteder says. Although she says it’s too soon to hazard a guess as to the price, "it won’t be expensive," she says.
The Capetown trial will be conducted by Sequella’s nonprofit arm, Sequella Global Tuberculosis Foundation. If Sequella, Inc., decides not to market the test in developing countries, the foundation will be able to pick it up, Sacksteder says.