Article Review:
(Written by Scott Cohen, MD; John Belko, MD; Tara Greenhow, MD)
For over 100 years, the Purified Protein Derivative (PPD) has been utilized for diagnosing latent Mycobacterium tuberculosis (TB) infection. While highly sensitive, this test is also fraught with false-positive results in children who have received the BacilleCalmette-Guerin (BCG) vaccination or in children with infections with non-tuberculous strains of mycobacteria. It should be noted that PPD reactivity to BCG immunization classically wanes over time for the majority of immunized patients. Thus, a positive PPD in the setting of a past history of BCG immunization does NOT exclude the possibility of TB infection. BCG is very good at preventing CNS or disseminated TB in children but has not been shown to be of benefit in protecting against development of pulmonary TB.
Historically in the United States, the majority of cases of TB were identified in individuals from TB endemic countries who had a positive PPD. This observation led to the recommendations in 2001 to treat all children with a positive PPD irrespective of underlying BCG status. However, new data has shown that the Quantiferon Gold (TB-IGRA) blood test is more reliable in determining which children have had a true exposure to TB.
This report from the Center for Disease Control represents a departure from current practice in managing children who have received the BCG vaccination. One of the most important advantages of the TB-IGRA test is that previous vaccination with BCG vaccination will not result in a false-positive blood test.
Highlights of this report include:
TB Screening for Asymptomatic Children Under Age 5 Years:
· If the PPD is negative, no further workup is needed, regardless of BCG status.
· If the PPD is positive, and there is no history of BCG, begin 9 months of Isoniazid (INH) and vitamin B6 (pyridoxine) therapy if the chest x-ray (CXR) is negative. [Call pediatric ID if the CXR is positive]. Please do not start therapy until the CXR has been read as negative by radiology.
· If the child with a history of receiving BCG, has a positive PPD and a negative CXR, order a TB-IGRA blood test.
o If TB-IGRA is negative, INH therapy may be delayed.
o If the TB-IGRA is positive, begin 9 months of INH and vitamin B6 (pyridoxine) therapy.
o Please call your local Pedi ID doctor before ordering the TB-IGRA in a child 2 years of age or younger.
TB Screening for Asymptomatic children Age 5-18 Years :
· If a PPD is negative, regardless of BCG vaccination, no further workup is needed.
· If a PPD is positive and no history of BCG vaccination, order a CXR. Start 9 months of INH and vitamin B6 (pyridoxine) therapy if CXR is negative.
· If a child with a history of BCG vaccination has a positive PPD, order TB-IGRA. NB: TB-IGRA is preferred over PPD in all children who received BCG vaccination.
· If the BCG status is unknown, a PPD may be given, and if positive, a TB-IGRA should be ordered.
· If TB-IGRA is negative, no further workup is needed.
· If TB-IGRA is positive, a CXR should be ordered. Nine months of Isoniazid and vitamin B6 (pyridoxine) should be prescribed if the CXR is negative. A Pediatric Infectious Disease specialist should be consulted if the CXR is positive.
Editor’s Commentary:
BCG vaccination is given to newborns in developing countries where TB disease is endemic. While the BCG vaccine is not effective in preventing pulmonary tuberculosis, it is effective in preventing disseminated tuberculosis (miliary TB) including Tuberculosis meningitis. Immigrant children who have received this vaccine have posed difficulties in interpreting their PPD results. Many of these children have thus been subjected to nine months of INH therapy for a (+) PPD test. These new guidelines, which liberalize the use of the Quantiferon Gold blood test (TB-IGRA), offer a precise diagnosis of M. Tuberculosis exposure resulting in latent TB.
TB-IGRA is useful in children under age 5 years, who have had a history of BCG vaccination and a recent (+) PPD. The result of the TB-IGRA is the final determinant to decide if the child has latent TB or not. However, in this younger age group, the PPD is the recommended first-line test for TB screening. A discussion with your local Pediatric ID doctor is recommended before ordering the TB-IGRA in a child younger than 2 years of age.
For children over age 5 years who have received the BCG vaccination and require TB screening, a TB-IGRA blood test should be ordered instead of placing a PPD.
Commentary From Pediatric ID Specialists: John Belko, M.D. and Tara Greenhow, M.D.
There is a clear advantage to the use of TB IGRAs in the diagnosis of latent TB infections in patients with a history of BCG vaccination. Despite this, there are some important pitfalls to remember:
· For patients who have suspected active TB, a negative quantiferon test does NOT exclude the diagnosis of active TB. Similarly, a negative PPD does not exclude the diagnosis of active TB. This is because it can take up to 8 weeks for the body to develop its T-cell specific responses. Therefore, in this setting TB-IGRA is not more sensitive, though more specific than a PPD test. If there is a concern about possible active TB, based on clinical or radiographic grounds, a Pediatric ID doctor should be consulted.
· For patients who are on immunosuppressant medications (Prednisone, Remicade, Methotrexate, Tacrolimus, etc.) or who are immunosuppressed due to medical disease (Rheumatologic conditions, oncologic conditions, congenital or acquired immunodeficiencies, severe malnutrition etc…) there is little data on whether a TB-IGRA is preferred over a PPD. Any condition that affects the function of T cells will affect either of these tests negatively. In these patients, the use of either the PPD or the TB-IGRA should be discussed with a Pediatric ID specialist.
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