Options for diagnosing asymptomatic (latent) tuberculosis infection | AAP News - AAP News

Most infections caused by Mycobacterium tuberculosis in children and adolescents are asymptomatic. After exposure to a source case (a person with active tuberculosis), some people will become infected and others will not. Initially, the two groups cannot be distinguished. By 10 weeks after exposure, people who become infected will demonstrate a positive tuberculin skin test (TST) or a positive interferon gamma release assay (IGRA). Among exposed people who are not infected, the TST or IGRA will remain negative.

Tuberculosis infection (in contrast to tuberculosis disease) is defined as infection in a person with a positive IGRA or TST but no physical findings of disease and a chest radiograph that is normal or reveals evidence of an old, healed infection.

Which of the following statements are correct?

a) A TST or IGRA should be performed before initiation of a prolonged course of systemic corticosteroid or use of tumor necrosis factor (TNF)-alpha antagonists or blockers.

b) A positive IGRA result differentiates infection from tuberculosis disease.

c) Bacille Calmette-Guerin (BCG) is a live attenuated vaccine strain (Mycobacterium bovis).

d) Hilar adenopathy generally is interpreted as evidence of tuberculosis disease, but children without other symptoms of tuberculosis may respond to isoniazid as monotherapy.

e) The lifetime risk of developing tuberculosis disease in an adult who undergoes TST conversion is 5%-10% and is highest six to 24 months after infection. In a young child who undergoes purified protein derivative conversion, the risk of developing tuberculosis disease is greater than 40%.

Answer: a, c, d and e are correct

The Food and Drug Administration has licensed two IGRAs to assist in diagnosing M. tuberculosis infection. An IGRA measures interferon release from lymphocytes exposed to specific antigens found on M. tuberculosis. The antigens used in the IGRA do not cross react with antigens in BCG vaccine. White blood cells (WBCs) from most people who have been infected with M. tuberculosis will release gamma interferon when mixed in vitro with antigens derived from M. tuberculosis. The amount of gamma interferon released or the number of cells that release gamma interferon can be measured to determine the likelihood of infection. WBCs from a person who has not been infected will not release gamma interferon when exposed to these antigens.

The sensitivity of IGRA and TST are similar, but the specificity of the IGRA generally is greater than that of the TST because the antigens used in the IGRA are not found in BCG or most nontuberculous mycobacteria. Neither IGRA nor TST differentiates between latent tuberculosis infection and active disease.

Data suggest IGRA results are reliable in children 2 years of age or older. If the IGRA result is negative but the TST result is positive in an asymptomatic, unexposed child, infection by M. tuberculosis is unlikely.

The advantages of an IGRA include the need for only one visit (useful for people from groups that historically have poor rates of return for TST reading) and the fact that prior BCG vaccination does not cause a false-positive result. The limitations of the assay include higher cost than TST, limited experience in children younger than 2 years and limited usefulness in immunocompromised children.

IGRAs can be used in place of the TST in all situations where testing for tuberculosis is recommended. Because of possible interference from live virus vaccines, TST or IGRA testing should be performed on the same day as live vaccine administration or four to six weeks later.

Lack of reaction to a TST or a negative IGRA result does not exclude infection by M. tuberculosis. Young age, poor nutrition, immunosuppression, certain viral infections, disseminated tuberculosis and infection beginning less than three months previously may influence either test result.

For children younger than 2 years of age, the TST (Mantoux) generally is preferred for testing for diagnosis of latent or active M. tuberculosis infection. In a child 2 years or older who was BCG vaccinated and has a positive tuberculin skin test, an IGRA can help differentiate tuberculosis infection from positivity attributable to BCG vaccine. A positive IGRA result should be interpreted as evidence that a child has tuberculosis infection. However, a negative IGRA alone cannot be interpreted as a reason to exclude tuberculosis infection. Indeterminate/invalid IGRA results should not be used to determine the need for anti-tuberculosis therapy.

Universal testing with the TST or IGRA among populations at low risk of tuberculosis generally is not recommended because either test may result in a large number of false-positive results. A risk assessment for tuberculosis should be conducted when a new patient is first examined and on an annual basis. Having a household member who converts (result changes from negative to positive with serial testing) on a TST or IGRA is an indication for testing a child.

Dr. Meissner is professor of pediatrics at Floating Hospital for Children, Tufts Medical Center. He also is an ex officio member of the AAP Committee on Infectious Diseases and associate editor of the AAP Visual Red Book. Jeffrey R. Stark, M.D., FAAP, a member of the AAP Section on Infectious Diseases, provided helpful comments regarding this discussion. 

Coming in January: Options for management of a child who converts with TST or IGRA.

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