The World Health Organization (Geneva, Switzerland) estimates that as many as 60% of tuberculosis (TB) cases are seen only at the peripheral health clinic, where current diagnosis is impossible. A new test for TB could improve the speed and accuracy of diagnosis of the disease and therefore enable healthcare providers to report results to patients within minutes. The TB REaD POC is being developed by GBDbio (Temple, Texas) and is said to identify a new chemical compound to spot the bacteria that cause TB with a level of sensitivity that currently takes months to produce.
Recently Jeffrey Cirillo, PhD, professor at the Texas A&M Health Science Center College of Medicine (Bryan, Texas), in collaboration with GBDbio, and investigators at Stanford University (Stanford, California) identified a new chemical compound to spot the bacteria that cause TB. The findings are the foundation of the TB REaD technology.
Results from the first human clinical trial data show the test can determine that a patient has TB with 86% sensitivity and 73% specificity and were published this week in the journal Angewandte Chemie. Smear microscopy, the most widely used test in the world, has a significantly lower ability to detect TB, ranging between 50% to 60% sensitivity.
Using a fluorescent substrate, the device targets BlaC – an enzyme produced by the bacteria that cause TB – as an indicator of the bacteria's presence. Once sputum samples are combined with the reactive substance, a battery-powered, portable tabletop device, the TB REaD, is then used to detect any fluorescence and deliver the diagnosis in as little as 10 minutes.
"The basic technology is keying off a specific enzyme that the TB bacteria produces," Michael Norman, CEO of GBDbio, told Medical Device Daily. "What the researchers created was a biochemical that is cleaved by this enzyme. When that occurs this chemical is cleaved and light is released. It's a fluorescent light that is quenched until the enzyme acts on the chemical. The test is based on this concept – no light if you don't have TB, and light if you do have TB. The reaction is very rapid and very sensitive."
To date, one of the most prominent ways TB is tested is by a method called GeneXpert, by Cepheid (Sunnyvale, California). The GeneXpert method can detect M. Tuberculosis DNA within a couple of hours, but it needs specialized equipment and trained personnel – which make it difficult to use in isolated areas or developing countries, Norman said.
"It's very good test and it's very sensitive and specific," Norman said of GeneXpert. "The main problem is that it's a fairly sophisticated piece of equipment that's expensive and it's a fairly sophisticated cartridge that's fairly expensive for endemic markets for TB. Thirty minutes is our target for [TB REaD's] response and we want to have it in a format that's usable and portable. The other major goal we have is to have a test that can be used outside of a laboratory or a well equipped healthcare center, and actually have something that can be in a clinic or a doctor's office or be taken by a group that's going to a more remote location."
He added, "we wanted to have a model where the [clinician] is able to take the diagnostic to the patient, rather than a more passive model where the patient has to come in for the test."
The firm has been working on the product for nearly five years.
"The technology was developed out of Texas A&M Medical School and Stanford University," he said. "That work was funded by the Bill and Melinda Gates foundation. Our company was created [in 2009] as a spin-out of Texas A&M to commercialize this technology and we have been in development of the technology since then. We've been through multiple iterations of the chemical development and are now into full kit and reader development for an actual product."
Norman noted that the company has not yet settled on a final design for the test, but hoped to do a third party validation of the prototype of the technology by the fall of this year and then move next year to finalization of the product.
"We hope to have a product through developed and CE marked by the end of next year," he said. "Certainly, eventually we would want to have the product in the U.S., but we're designing it for low-cost high-burden countries and so the best regulatory path to be available in multiple countries around the world is CE mark."
GBDBio noted that funding hasn't come from traditional sources and that support has come mostly from grants. The firm did say that attitudes toward funding the test have changed in recent years.
"It's been challenging to raise money from more traditional sources, who have less interest in a target that's a developing country or third world country," Norman said. "Although I think that's changed in the last few years. Five years ago, there was very little interest. But I think that Cepheid's success with GeneXpert has helped me to paint a picture that says 'hey you can do this and make money and have a return on investment'."