Latent TB Infection: Special Considerations for Testing

Latent TB Infection: Guide for Diagnosis and Treatment

Diagnosis

Special Considerations for Testing

BCG Vaccine

In many parts of the world where TB is common, BCG vaccine is used to protect infants and young children from serious, life-threatening disease, specifically miliary TB and TB meningitis. The World Health Organization (WHO) recommends that BCG vaccine be administered during infancy in TB endemic countries. BCG vaccination is not generally recommended in the United States. The effect of BCG vaccine on TST results often causes confusion. TST reactivity caused by BCG vaccine generally wanes with the passage of time, but periodic skin testing may prolong (boost) reactivity in vaccinated persons. A person with a history of BCG vaccination can be tested and treated for LTBI if they react to the TST. TST reactions should be interpreted based on risk stratification regardless of BCG vaccination history.

IGRAs use M. tuberculosis specific antigens that do not cross react with BCG, and therefore, do not cause false positive reactions in BCG recipients.

HIV Infection

The risk of progression from LTBI to TB disease is 7% to 10% each year for those with both LTBI and untreated HIV infection. Those with LTBI who are not HIV-infected have a 10% risk over their lifetime. Thus the risk of progression to TB disease is 10 times greater for those who are HIV infected. This risk is reduced with antiretroviral therapy for HIV, but is still higher than that in HIV-negative persons with LTBI.

HIV-infected persons should be tested for LTBI as soon as their HIV status becomes known. A negative TST or IGRA result does not exclude LTBI, as they may have a compromised ability to react to tests for TB infection. Annual testing should be considered for HIV-infected persons who are TST or IGRA negative on initial evaluation, and who have a risk for exposure to M. tuberculosis. The usefulness of anergy testing in HIV-infected individuals or others has not been demonstrated; therefore, it is not recommended.

After the initiation of antiretroviral therapy (ART), repeat testing for LTBI is recommended for HIV-infected persons previously known to have negative TST or IGRA results. This is because the immune response may be restored by ART.

Booster Phenomenon

Some people infected with M. tuberculosis may have a negative reaction to the TST if many years have passed since they became infected. They may have a positive reaction to a subsequent TST because the initial test stimulates their ability to react to the test. This is commonly referred to as the “booster phenomenon” and may incorrectly be interpreted as a skin test conversion (going from negative to positive). For this reason, the “two-step method” is recommended at the time of initial testing for individuals who may be tested periodically (e.g., health care workers). If the first TST result in the two-step baseline testing is positive, consider the person infected and evaluate and treat the person accordingly. If the first test result is negative, the TST should be repeated in 1–3 weeks. If the second test result is positive, consider the person infected and evaluate and treat the person accordingly; if both steps are negative, consider the person uninfected and classify the TST as negative at baseline testing).

When IGRAs are used for serial testing, there is no need for a second test because boosting does not occur.

Two-Step TST Testing

Contacts

For contacts of a person with infectious TB disease, retesting in 8–10 weeks after exposure has ended is indicated when the initial TST or IGRA result is negative. In contact investigations, retesting is not called two-step testing. The second test is needed to determine if infection occurred, but was too recent to be detected at the time of the first test.

• Children under the age of 5 years and immunosuppressed persons (e.g., HIV infected) who have negative TST or IGRA results should have a chest radiograph. If chest radiograph is normal, treatment should be started for LTBI and another TST or IGRA performed 8–10 weeks after contact has ended.
• If a repeat TST or IGRA result is positive, treatment should be continued. If it is negative, treatment can usually be discontinued.
• If testing is repeated, the same type of test (TST or IGRA) should be used.

Pregnancy

• TST is both safe and reliable throughout the course of pregnancy.
• Test only if specific risk factors are present for acquiring LTBI or for progression of LTBI to TB disease.
• If a TST or IGRA reaction is positive, obtain a chest radiograph using proper shielding.