Tests for Tuberculosis

micrograph of Myobacterium tuberculosisOutdoor adventurers and persons who participate in global humanitarian relief efforts sometimes travel to locations where tuberculosis (TB) is prevalent. As noted in the article “Latent Tuberculosis Infection in the United States,” authored by C. Robert Horsburgh, Jr., MD and Eric J. Rubin, MD, PhD in The New England Journal of Medicine (N Engl J Med 2011;364:1441-8), most cases of tuberculosis in the United States result from reactivation of latent TB infection, and nearly all of these cases could be prevented by administration of proper antibiotic treatment. So, testing for latent TB infection is sometimes more than prudent—it can be very important. For instance, because I am a health care provider at Stanford, I am obligated to be tested on an annual basis, to determine if I am carrying TB, even though I do not have any signs or symptoms.

Testing for latent TB relies upon measuring the human immune response, since there is no test to directly measure the presence of the germ Mycobacterium tuberculosis in a person. Until recently, the only test to detect latent TB was the tuberculin skin test (TST), with which we are so familiar. That is the purified protein derivative (“PPD”) test in which a very small amount of test material is injected into the skin using a tiny needle and then the measured amount of reaction (swelling and hardening = “induration”; blistering is independently considered to represent a positive result) is observed and measured. A positive test is seen if someone has active TB, had a prior TB exposure, or at some point received the Bacille Calmette Guerin (BCG) vaccine. A “subdued” (interpreted as negative) test does not always mean that TB is not present, because an altered immune response can lessen or completely eliminate the reaction. The tuberculin skin test clearly has limitations.

There are two new diagnostic tests for latent TB infection. These are the QuantiFERON-TB Gold (QFT) and the T-SPOT.TB tests. These tests measure the stimulated (by TB) release of interferon-gamma from lymphocytes (a type of cell) in the blood sample drawn from the person being tested. These tests are reasonably accurate and have the added benefit of appearing to eliminate the positive reactions in persons who have been vaccinated with BCG. It is not yet determined if they are significantly better in terms of true positive tests and true negative tests. So, there is still a role for both the new tests and the TST. The authors of the paper cited above recommend the following for screening for latent TB:

1. Screening is recommended for persons with a high prevalence of latent TB infection or with a high likelihood of progression from latent to active TB infection (e.g., foreign-born persons, close contacts of persons with infectious TB, persons with HIV infection, persons with immunosuppression, etc.).
2. The new tests are preferred when the prevalence of recent infection is likely to be high (close contacts of persons with infectious TB, recently-arrived foreign persons, illicit drug users, persons in prison, and homeless persons). The new tests are also useful for screening persons who have received BCG vaccine.
3. The TST is preferred for persons in whom the prevalence of TB is expected to be low. Some authorities recommend following up a positive TST with one of the new blood tests for confirmation. If the person being tested is in a high-risk (for latent TB) group and has a negative TST, some authorizes recommend following up with one of the new blood tests.
4. Screening with either test is not recommended for persons at low risk, to avoid a plethora of false positive results.