TB Manual

Sequential testing refers to the use of both a TST and an IGRA to help support a decision to proceed with TPT in someone with evidence of TB infection. There are two main situations to consider sequential testing: (1) to improve sensitivity; and (2) to improve specificity.

Improved test sensitivity may be desired in persons with a high suspicion of TB infection and/or who are at increased risk of developing TB disease. In this situation, if the initial test is negative (either TST or IGRA), using another test may improve overall sensitivity (while lowering specificity). In a meta-analysis, among contacts with an initial negative TST (<10 mm), the risk of incident tuberculosis was 5.1 times (95% CI: 2.4 to 10.8) higher among persons with a subsequent positive IGRA versus negative IGRA. In the opposite situation, among contacts with an initial negative IGRA, the risk of incident tuberculosis was 3.6 times (95% CI: 1.8 to 7.2) higher among persons with a subsequent TST ≥10 mm versus TST <10 mm.²

Improved test specificity may be desired in persons with a low suspicion of TB infection and/or who received BCG vaccination post-infancy or at an unknown age and/or may be at increased risk of serious adverse events with TPT. In this situation, if the initial test is positive, using another test may improve overall specificity (while lowering sensitivity).⁸⁷ Current data suggest that sequential testing to enhance specificity should only be considered if the initial positive test is a TST. In a low-risk individual, such as a healthy adult receiving pre-employment screening, if the initial TST was positive (≥10 mm), the risk of incident tuberculosis is approximately 7.6 times (95% CI: 1.6 to 36.7) higher if the subsequent IGRA is positive. In an opposite scenario, if their initial test was a positive IGRA, the risk of incident tuberculosis is approximately 3.0 times higher (non-significant, with 95% CI: 0.2 to 40.7) if the subsequent TST is ≥10 mm.²

Recommendation

• We conditionally recommend sequential testing if:

• Either the initial tuberculin skin test or interferon-gamma release assay is NEGATIVE (in which case the other test may be used to increase sensitivity), when:

  • the risk for infection is high;

  • the risk for progression to TB disease is elevated;

  • the risk for a poor outcome from TB disease is high; and/or

  • a person has conditions or habits that may reduce the sensitivity of the test.

or

1. The initial tuberculin skin test is POSITIVE (in which case an interferon-gamma release assay may be used to increase specificity), when:

   • the likelihood of TB infection is low; and/or

   • the risk of a false positive result due to Bacille Calmette-Guérin is high. (poor evidence).

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