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GMU Investigators Create Highly Sensitive Diagnostic Tool for TB in HIV-Negative Patients

DEC 14, 2017 | KRISTI ROSA
In 2016, a staggering 10.4 million individuals contracted tuberculosis (TB)—only 6.3 million of those individuals received a diagnosis.

Current diagnostic methods for TB require sputum collection and analysis using bacteria staining, culture, and polymerase chain reaction (PCR) in hospital laboratories, which makes accessibility to diagnostic testing harder for those living in underserved rural communities and outpatient clinics. However, investigators from George Mason University (GMU) have developed a new diagnostic tool for TB, a sensitive, noninvasive urine test.

Reportedly, the test can detect TB in all individuals, even those without HIV. Attempts to develop such a test have been made in the past; however, past tests have lacked sufficient sensitivity; they were only able to detect TB in patients who were severely immunocompromised by advanced HIV infection.

The surface of TB bacteria is “coated” with several sugar molecules, all attached to a protein; the coating of the bacteria is thought to be a defense mechanism against immune system response. Lipoarabinomannan (LAM), a sugar molecule which has previously been identified to be a key player in TB infection, is one of the sugar molecules that coats the bacteria. The investigators involved in this research “reasoned that LAM would be shed by tuberculosis bacteria in patients with active disease,” according to a fact sheet provided to the press. “The TB LAM molecule shed from living or dead bacteria enters the bloodstream, is filtered through the kidneys, and accumulates in the urine of the patient.”

The results of past research showed that the concentration of LAM in patients with active TB disease was low enough that it was “difficult or impossible” for investigators to detect. Therefore, for this study, GMU investigators turned to a new chemistry combined with nanotechnology. A key aspect of the study was the discovery of a dye molecule that was able to bind and capture the LAM molecule. The investigators then introduced the dye into nanoparticles, which served as “open mesh cages” that when mixed with urine, could “trap” LAM molecules in the patient’s urine. After inserting the dye, the investigators probed the content of the nanoparticles for captured LAM molecules, which allowed them to not only detect LAM, but also measure its concentration.

By applying this special dye chemistry with this new nanotechnology, the investigators developed a highly sensitive urine test at least 100 times more sensitive than previous tests have shown.

After verifying the test’s sensitivity and specificity, the investigators applied the test to urine samples collected from hospitalized patients in Peru who had culture-positive as well as sputum-stain positive active TB infection. Their findings? The test demonstrated high sensitivity and specificity for this patient population.

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