When can the second Tuberculin (TB) skin test be placed after reading the first in a 2-step TB skin test for an adult or adolescent with no known history of TB infection or recent exposure?

Timing of Second TB Skin Test in Two-Step Testing

The second tuberculin skin test should be placed 1-3 weeks after reading the first test. 1, 2, 3

Standard Two-Step Testing Protocol

Timing Between Tests

• Place the second test 1-3 weeks after the first test is read (not after placement, but after the 48-72 hour reading of the first test). 1, 2, 3
• The FDA drug label specifically states: "If the first test showed either no reaction or a small reaction, the second test should be performed one to four weeks later." 3
• Both tests must be read at 48-72 hours after placement to ensure accurate measurement of induration. 1, 3

Purpose of This Timing

• This 1-3 week interval allows detection of the "booster phenomenon" - where waned tuberculin sensitivity from remote infection is restored by the first test, preventing misinterpretation of a boosted reaction as a new infection during future serial testing. 1, 2
• A boosted response (≥10 mm on the second test) indicates past TB infection, not recent conversion. 2, 3
• Without proper two-step testing at baseline, subsequent positive tests in serial screening programs could be incorrectly classified as new infections, triggering unnecessary contact investigations and preventive therapy. 1, 2

Critical Distinction: Two-Step Testing vs. Post-Exposure Testing

Do NOT confuse these two different scenarios:

Two-Step Baseline Testing (1-3 weeks):

• Used for establishing baseline TB status in healthcare workers, nursing home residents, and others requiring serial testing. 1, 2
• Second test placed 1-3 weeks after first test reading. 1, 2, 3
• Purpose: Detect booster phenomenon to prevent future misclassification. 1, 2

Post-Exposure Contact Testing (8-10 weeks):

• Used for contacts of infectious TB patients with initially negative tests. 4, 2
• Second test placed 8-10 weeks after last exposure to infectious patient (NOT after first test). 4, 2
• Purpose: Allow time for immune system to develop detectable response to new infection. 4
• The window period for tuberculin sensitivity to develop after M. tuberculosis infection is 8-10 weeks, and testing before this period is unreliable for excluding infection. 4, 2, 3

Who Needs Two-Step Testing

High-Priority Populations

• All newly employed healthcare workers with initial negative PPD and no documented negative test within the preceding 12 months. 1, 2
• Residents of correctional institutions, nursing homes, and other congregate settings where periodic TB screening occurs. 1, 2
• Individuals with high rates of prior TB exposure or BCG vaccination history. 1

Special Considerations

• The booster phenomenon is more common in older adults, foreign-born persons from high TB prevalence countries, and individuals with previous BCG vaccination. 1, 2
• Boosted reactions can occur years after initial infection or BCG vaccination. 1

Common Pitfalls to Avoid

• Do not wait 8-10 weeks between tests for baseline two-step testing - this prolonged interval is only for post-exposure testing in contacts of infectious TB cases. 4, 2
• Do not perform the second test sooner than 1 week - insufficient time may fail to detect the booster phenomenon. 1, 2, 3
• Do not perform the second test later than 3-4 weeks - this timing is optimal for detecting boosting while maintaining practical screening efficiency. 1, 2, 3
• Do not use two-step testing for contact investigations - a contact whose second test is positive after initial negative result should be classified as recently infected, not boosted. 4
• Do not administer TB skin tests 1-4 weeks after live virus vaccination (measles, mumps, rubella) as this causes immunosuppression and false-negative results; either test same day as vaccine or wait 4-6 weeks. 5