Knowledge of Latest Diagnostic Tests for TB Lacking in Low-Prevalence Settings

As the incidence of tuberculosis (TB) continues to decline in low-prevalence settings such as the United States, there is some concern within the infectious disease/public health field that clinicians may not be aware of the latest diagnostic technologies available to screen for the disease.

A “learning unit” published online in March via Open Forum Infectious Diseases (OFID), sought to review these platforms within the context of the latest diagnostic guidelines for TB. According to the Centers for Disease Control and Prevention (CDC), there were fewer than 10,000 reported cases of the disease in the United States in 2014, the last year for which data are available. Although this represents a roughly 2% decline in reported cases from 2013, it should be noted that this amounts to the smallest decline in incidence within the United States in more than a decade.

Incidence of TB has also declined dramatically, globally, with 9.6 million total cases in 2014, down 18% since 2000, but it remains a leading cause of death in women between 18 and 44 years of age. TB is also still the top cause of death worldwide for those with HIV.

“General practitioners probably don’t consider [TB] in their differential [diagnoses] in some settings, partially because they don’t see it as often,” Maunank Shah, MD, PhD, assistant professor, Center for TB Research, Johns Hopkins University and OFID paper co-author told Contagion. “As a result, there can be diagnostic and treatment delays in starting the evaluation process or getting ID consultations.”

In attempt to remedy these potential delays, Dr. Shah and his co-author, Natasha Chida, MD, MSPH, reviewed current data on established diagnostic platforms such as nucleic acid amplification tests (NAATs), which, they note, are “highly specific and allow for rapid detection of Mycobacterium tuberculosis” (MTB). Examples of available NAATs approved by the US Food and Drug Administration include the Amplified Mycobacterium tuberculosis Direct Test (MTD; Gen-Probe), the Amplicor Mycobacterium tuberculosis Test (Roche Diagnostics) and the Xpert MTB/RIF assay (Cepheid), the newest platform available.

In general, according to Drs. Shah and Chida, a positive NAAT “indicates a diagnosis of active… disease in patients presenting with signs or symptoms consistent with TB.” NAATs “also have a lower limit of detection than smear microscopy.” Despite the fact these tests were incorporated into the CDC guidelines for TB diagnosis in 2000, their use in the United States has been low, Drs. Shah and Chida note, “due to lack of provider awareness, costs, and availability.” The World Health Organization (WHO) recommends Xpert as the initial diagnostic test in all suspected cases of TB, including multi-drug-resistant TB and HIV-related TB.

“NAATs such as the GeneXpert are rapid, more sensitive than smear, and provide information on both TB and drug resistance,” Dr. Shah said. “Their usage can allow much more rapid diagnosis of drug-resistant disease. [However, they] are still imperfect. Mycobacterial culture still remains the reference standard and a negative NAAT test doesn’t exclude TB diagnosis.”

It’s hoped, though, that emerging diagnostic technologies such as the lateral-flow detection of lipoarabinomannan (LAM), which offers a point-of-care approach using urine specimens but is not currently available in the U.S., as well as newer molecular assays with improved limits of active TB detection, can improve upon the accuracy of NAATs. Lateral-flow detection of LAM is already recommended by WHO for use in immunosuppressed HIV-infected patients as an adjunctive method for quickly diagnosing active TB.

“There is a pipeline of new tests that are trying to reduce the limit of detection even further, which may truly revolutionize diagnostic testing,” Dr. Shah noted. “The point of care lateral flow LAM assay provides test results in 20 minutes. More research is still needed for implementation but this shows proof of concept of new approaches for TB detection.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.