Atrium Health Levine Children’s Leads Study to Guide National Approach to Tuberculosis Testing for Young Children

Amina Ahmed, MD, professor of pediatric infectious disease and immunology at Levine Children’s Hospital, is the lead author of a recently published 4-year study to evaluate the effectiveness of blood tests to test for tuberculosis infection in children of all ages, including those under the age of 2 years.

Tuberculosis (TB) is caused by bacteria that usually attack the lungs, but TB bacteria can attack any part of the body such as the kidney, spine and brain, according to the CDC. Over 80% of tuberculosis in the United States is a consequence of reactivation of latent tuberculosis infection meaning an individual is infected with the tuberculosis (TB bacteria but does not have symptoms and cannot transmit the infection. Treatment of latent TB infection can prevent progression to TB disease. While the United States has reduced the incidence of TB disease to an all-time low of less than 3 per 100,000 population, up to an estimated 13 million people in the United States have latent TB infection.

“For over 100 years, physicians and experts have relied on the tuberculin skin test (TST) to screen for TB infection. However, it’s important to remember we get a lot of false positive results with TSTs, especially in the BCG-vaccinated population” said Dr. Ahmed. 

BCG, or Bacille Calmette-Guerin, is a vaccine for TB disease, given to children born in countries with a high prevalence of TB to prevent meningitis and miliary disease, according to the CDC. Dr. Ahmed explains BCG-vaccinated children are more likely to receive a false positive TST result due to cross reaction between the vaccine and proteins in the TST. This can lead to treating children unnecessarily who don’t need to be treated. 

The American Academy of Pediatrics has recommended the skin test rather than a blood test for children under 2 years of age due to lack of data on the performance of the blood tests in this younger population.

Dr. Ahmed and a team of researchers, with the support of the CDC Tuberculosis Epidemiologic Studies Consortium (TBESC), tested thousands of children with the skin test and blood tests and followed them to see who developed disease.

“We enrolled almost 3,600 children under 15 years of age, most of whom were born outside of the United States,” said Dr. Ahmed. “We followed the children tested for a median of 4 years, and, of 533 children whose skin test read positive and blood test negative who were not treated for infection, none of them went on to develop disease.”

“Ultimately what we learned was both types of these tests poorly predict progression to TB disease in most cases,” Dr. Ahmed continues. “The negative-predictive value of the blood tests, however, is high, meaning we are not likely to miss infection with negative results. Furthermore, by using the blood tests, we’re less likely to receive false positive results as with the TST, with a consequent reduction in over-diagnosis and over-treatment of latent tuberculosis infection in the non-U.S.-born population. 

The study concludes blood tests can be used on children of all ages, including those under the age of 2 years, especially in children born outside the U.S.