What is the purpose and timing of the two-step Purified Protein Derivative (PPD) test?

From the Guidelines

The two-step PPD test is essential for healthcare workers and individuals with potential previous TB exposure to accurately diagnose latent tuberculosis infection and prevent misclassification of boosted reactions as new infections. The purpose of the two-step test is to identify the "booster phenomenon," where individuals with remote TB infection may have a false-negative initial test but a positive reaction on subsequent testing due to immune memory stimulation 1.

Key Points

• The first PPD is placed and read at 48-72 hours, and if negative, a second PPD is placed 1-3 weeks later and also read at 48-72 hours 1.
• This approach prevents misclassifying a boosted reaction as a new infection in future tests, which is crucial for individuals who will undergo periodic TB screening, such as healthcare workers 1.
• Two-step testing is particularly important for individuals who may have had TB exposure in the past but have waning immunity, such as older adults or those from TB-endemic regions 1.
• The test involves intradermal injection of 0.1 mL of 5 tuberculin units of PPD into the forearm, with induration (not just erythema) measured in millimeters to determine positivity based on risk factors.

Timing and Procedure

• The second test should be performed 1-3 weeks after the first test, and the results from the second test should be considered the "correct" result 1.
• If the second test result is positive, the individual should be classified as previously infected, and if the second test result remains negative, the individual is classified as uninfected 1.

From the Research

Two-Step PPD Purpose and Timing

• The purpose of a two-step PPD (purified protein derivative) test is to detect latent tuberculosis infection (LTBI) in individuals who may have been exposed to tuberculosis 2.
• The two-step test is used to avoid false-negative results, which can occur if an individual has not been recently exposed to tuberculosis or has a weakened immune system 3.
• The timing of the two-step PPD test is typically as follows:
  • The first step involves administering the PPD test and reading the results after 48-72 hours.
  • If the results are negative, a second test is administered 1-4 weeks later to confirm the absence of LTBI 4.
• The use of a two-step PPD test can help identify individuals with LTBI who may benefit from preventive therapy, such as isoniazid or rifapentine [(5,6)].

Preventive Therapy for Latent Tuberculosis Infection

• Preventive therapy for LTBI typically involves the use of isoniazid or rifapentine, either alone or in combination [(2,5)].
• The duration of preventive therapy can vary, but common regimens include:
  • 3 months of weekly rifapentine and isoniazid (3HP) [(2,6)].
  • 6-9 months of daily isoniazid 3.
• The choice of preventive therapy regimen depends on various factors, including the individual's medical history, potential drug interactions, and the presence of any underlying health conditions 4.

Cost-Effectiveness of Preventive Therapy

• The cost-effectiveness of preventive therapy for LTBI can vary depending on the regimen used and the individual's risk factors 6.
• A study found that 3HP may be a cost-effective alternative to isoniazid preventive therapy (IPT) in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay 6.