LAS VEGAS (FRONTLINE MEDICAL NEWS) – In the clinical opinion of Dr. Andi L. Shane, tuberculin skin testing and interferon gamma release assay diagnostics and surveillance for Mycobacterium tuberculosis infection are game-changers in the ongoing effort to reduce the rates of TB infection nationwide.

“From 1982 to 2013, we’ve had a very nice decline in the number of TB cases. However, we still have quite a bit of work to do,” Dr. Shane said at a pediatric update sponsored by the American Academy of Pediatrics California District 9.

Reported case rates are especially high in California, Nevada, Texas, Florida, New York, Washington, New Jersey, and the District of Columbia. By age group, those under 5 years old and those aged 15-24 years are more likely to be affected.

“It’s really important to identify TB as soon as possible, especially in children,” said Dr. Shane of the department of pediatrics, division of infectious diseases, Emory University, Atlanta. “An interferon gamma release assay (IGRA) or a tuberculin skin test (TST) may be used in situation where assessment for MTB [M. tuberculosis] exposure is indicated. IGRA is preferred in persons who received BCG vaccine and who have low rates of test completion, while TST is preferred for testing of children younger than age 5.”

TB disease in people younger than age 15 years is a marker for transmission of TB, usually from an adult. “So when we identify a case of TB in children, that requires a contact investigation,” she said. “We’re more concerned with children under the age of 5 with TB because they are more likely to have disseminated disease.”

Latent TB means that the patient has been exposed to the disease but that his or her body has been able to control the infection; no systemic manifestations of infection are present. “It’s very important to identify the difference between latent tuberculosis infection (LTBI) and actual tuberculosis disease,” she said. “This is one of the most challenging aspects to explain to families when you’re giving your diagnosis. The reason this is important is that children or adults who have LTBI are not infectious to other people, whereas someone who has pulmonary or laryngeal TB is considered to be an infectious risk to other individuals.”

Dr. Shane went on to discuss limitations of the TST in diagnosing TB. For one, the test may be placed incorrectly, resulting in an inflammatory response or no response, “and there is reader variability,” she said. “The other issue is that the reading needs to occur 48-72 hours after placement of the test. So, if you place it on a Thursday, that means you really are not going to read it at the optimal time unless the child comes to you on a weekend or the test is read by somebody else.”

As an alternative, two IGRAs have been developed that measure how the immune system reacts to MTB. One is QuantiFERON, which is widely used in the United States; the other is the T-SPOT.TB test, which is widely used in Europe. A positive result on either test indicates that there has been interaction with MTB bacteria but it does not differentiate between LTBI and active TB disease.

“A negative IGRA tells you there is no reaction to the test and MTB is not likely, while an indeterminate result is when you’re unable to interpret the result due to low positive [mitogen] or increased negative control [nil] compared to TB response,” Dr. Shane said. “This usually indicates that there’s some problem with the assay itself. It can also indicate that the individual may not have an immune system that can respond to and produce the interferon gamma that’s needed.”

Assessment of IGRA accuracy is challenged by a lack of a standard for the diagnosis of LTBI and active TB, especially in children. “The reason is, we just don’t have a lot of good data from resource-endowed settings,” Dr. Shane explained. “We have good data from areas where TB is prevalent.” According to the Centers for Disease Control and Prevention and the AAP, IGRAs are probably reliable in children over the age of 5 years, but a TST is still recommended in children under the age of 5.

“The nice thing about the IGRAs is that their specificity is much higher” than TSTs, Dr. Shane said. “However, in some cases a TST might be more sensitive for detecting more remote MTB infections than an IGRA, but IGRAs may be better at detecting a recent infection. Like the TST, an IGRA also shows that if you’re infected with TB you have 5-10% chance of developing active TB in your lifetime.”

She also pointed out that a significant amount of blood is required to perform an IGRA. “That might not always be optimal, especially in a young child,” Dr. Shane said. “Low CD4 counts and other immunodeficiencies have also been associated with false-negative TST and indeterminate/false-negative IGRA results.”

For contact investigations, IGRAs offer increased specificity, are completed during a single visit, and their response is not boosted if an additional evaluation is needed 8-10 weeks after exposure. For periodic screening of health care workers, IGRA offers “technical and logistical advantages, and two-step testing is not required,” she said.

If the TST or IGRA is positive, additional diagnostic efforts are needed “to differentiate between LTBI and active MTB,” said Dr. Shane, who recommended the Curry International Tuberculosis Center as a resource for clinicians. “Your clinical history, chest radiography, [and results of] sputum/gastric aspirates will help,” she added.

If the TST or IGRA is negative, “it’s not sufficient to exclude MTB infection. If you have a discordant TST and IGRA result, consider history and epidemiologic risk factors. Treat with clinical suspicion or risk of a poor outcome (those younger than age 5 and those infected with HIV).”

Dr. Shane reported having no relevant financial disclosures.

On Twitter @dougbrunk


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