Updated Guidelines Emphasize Newer Tests for TB Diagnosis

Patients at risk for tuberculosis (TB) infection should be assessed with newer tests, including interferon-gamma release assays (IGRAs) and molecular diagnostics, according to new guidelines developed by the American Thoracic Society, Infectious Diseases Society of America, and the U.S. Centers for Disease Control and Prevention (CDC). The guidelines, published in the December issue of Clinical Infectious Diseases, are the first updates in 17 years and were prompted by advances in testing.

"These guidelines develop a structured approach to testing, recommending that doctors test for latent TB in patients who are at risk for infection and who would benefit from treatment, and for TB disease in patients who have signs and symptoms of the disease," said David Lewinsohn, M.D., Ph.D., lead author of the guidelines in a statement. "Even though TB disease is not common in this country, it's important that doctors remember it's still around, and that they should test patients when appropriate."

"These guidelines develop a structured approach to testing, recommending that doctors test for latent TB in patients who are at risk for infection and who would benefit from treatment, and for TB disease in patients who have signs and symptoms of the disease."

—David Lewinsohn,
M.D., Ph.D.

In 2015 there were just over 9,500 cases of TB reported in the United States, a 1.6 percent increase over the previous year, according to the CDC. Additionally, the CDC says that up to 13 million Americans have latent TB, meaning they are infected with Mycobacterium tuberculosis (Mtb), but are asymptomatic. Eradication of TB in the United States, experts say will require expanding testing and treatment of latent TB.

The new guidelines recommend health care providers consider testing for latent TB in patients who live with a person who has TB disease, immigrated to the United States from a country where TB disease is common, or who are in high-risk settings, such as prison. The guidelines, though, now recommend IGRAs, instead of tuberculin skin tests, for testing for latent TB.

Data shows IGRAs blood tests are more effective at detecting TB disease than a TST, although neither can distinguish active TB from latent infection. IGRAs have the added benefit that they can be performed in one patient visit. Currently, there are two approved and commercially available IGRA platforms. They measure interferon-γ released by sensitized T cells in response to Mtb-specific antigens.

If a patient has active signs of TB disease, the guidelines recommend doctors should order smear (acid-fast bacilli smear microscopy on three samples), cultures (both liquid and solid), and molecular diagnostic testing (diagnostic nucleic acid amplification test on the initial respiratory specimen, as well as rapid molecular drug susceptibility testing), particularly in patients at higher risk, such as those who have HIV or live with a patient with TB disease.

"The ability to rapidly and accurately identify Mtb as well as drug resistance (e.g., through NAAT, line probe, molecular beacon, and Xpert MTB/RIF assays) reflects substantial advances," the authors write. "While rapid tests for TB diagnosis still have a sensitivity of 70 percent to 90 percent, they … also remain relatively expensive, making them difficult to implement in high-burden, low-resource settings. Ideally, what is needed is a simple, inexpensive, rapid (i.e., hours) test that is highly accurate (>95 percent sensitivity and specificity)."

The authors also note that future diagnostic development should focus around accurately identifying those with latent TB at risk for disease progression.

Takeaway: Substantial advances have been made in testing for TB prompting revised guidelines favoring newer tests, including IGRAs and molecular testing.