New Generation of Tuberculosis Diagnostic Tests Recommended in Updated IDSA Guidelines

As more antibiotic-resistant forms of the Mycobacterium tuberculosis bacterium (Mtb) are evolving, so too, should new ways to diagnose and treat tuberculosis (TB). Now, new guidelines from an international panel of doctors recommend that people who are at risk for TB undergo infection screening with a new generation of diagnostic tests.

In 2015, more than 10 million people around the world became ill with TB and 1.8 million died from the disease, making it one of the top 10 causes of death globally. A recent report from the World Health Organization (WHO) found that nearly one in four of the world’s human population have latent TB, meaning they carry the bacteria that cause the disease without showing any signs or symptoms of infection. An estimated 5% to 10% of people with latent TB will go on to develop TB disease, typically marked by severe lung infection, unless they receive the proper course of treatment, typically within the first two years of Mtb infection.

Though people cannot spread TB while the infection is not active, without an accurate diagnosis, an individual may not know that they are at risk of developing the disease. For years, the public health community has relied on traditional TB skin tests and blood tests to detect Mtb, but those tests can only confirm the presence of the bacteria; they are not able to differentiate between latent TB and active TB disease. Other tests use samples of respiratory tract mucus or chest x-rays to make a diagnosis of TB. In recent years, researchers around the world have worked to develop new TB diagnostic tools offering faster and more accurate results, including a test that can detect both TB infections along with bacterial resistance to rifampicin, an antibiotic used as a first-line treatment for the disease.

With the advent of better diagnostic tools, a team of researchers and scientists with the Infectious Diseases Society of America recently released a new set of guidelines on the best test for diagnosing latent TB infections, along with a set of recommendations for patients showing signs of active TB. The new recommendations were developed by doctors and researchers with the American Thoracic Society, Infectious Diseases Society of America, and the Centers for Disease Control and Prevention. Their report appears in the journal Clinical Infectious Diseases. In the new guidelines, the report’s authors support replacing traditional tuberculin skin tests (TST) with newer tests called interferon-gamma release assays (IGRAs), blood tests used to diagnose infection with TB that measures interferon gamma (IFN-γ) released by sensitized T-cells in response to highly-specific Mtb antigens. The tests can be given in a single visit with results available within 24 hours, though results cannot differentiate between latent TB and TB disease. In addition, there’s limited data on the test’s use in children under 5 years of age, in people recently exposed to Mtb, and in immunocompromised individuals. The new recommendations call for the use of IGRA tests in those aged 5 and older and for individuals likely to be infected with Mtb with a low or intermediate risk of disease progression. The TST remains an acceptable alternative when an IGRA is either unavailable or too costly.

In their report, the authors noted that while only 9,412 cases of TB disease were reported in the United States in 2014, the rate of TB was 13.4 times higher in foreign-born persons than in US-born individuals. In addition, they also found that the United States has a large reservoir of individuals who are infected with Mtb. “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 lead author David M. Lewinsohn, MD, PhD, in a recent press release. “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.” As such, the authors support testing for latent TB for anyone who lives with someone who has TB disease, has immigrated to the United States from a country where TB is common, or those who are in a high-risk setting.

The report also included recommendations on updated protocols for active TB disease testing, while emphasizing that the guidelines are not intended to impose a standard of care but provide a framework for diagnostic evaluation of patients who may have latent TB or TB disease. “Guidelines cannot take into account all of the often compelling unique individual clinical circumstances,” the authors pointed out. “Therefore, no one charged with evaluating clinicians’ actions should attempt to apply the recommendations from these guidelines by rote or in a blanket fashion. Qualifying remarks accompanying each recommendation are its integral parts and serve to facilitate more accurate interpretation.”