A.3.1. TST booster effect
A single TST may elicit little response yet stimulate an anamnestic immune response, such that a second TST at any time from 1 week to one year later will elicit a much greater response.89 This phenomenon is important to detect, as it represents a false positive, not a new TB infection. The booster effect was first described in older persons in whom it was felt to show TB infection acquired many years before (remotely) with subsequent waning of immunity.95 It has also been described in persons with prior BCG vaccination or sensitivity to nontuberculous mycobacterial antigens.94,116
A two-step TST should be performed if subsequent TSTs will be conducted at regular intervals (eg, among health care or correctional workers).89 This is to reduce the chance of a false-positive TST conversion when the TST is repeated. Please refer to Chapter 13: Tuberculosis Surveillance and Tuberculosis Infection Testing and Treatment in Migrants for recommendations on use of two-step TST in specific travelers.
The two-step protocol needs to be performed and documented ONCE. Any subsequent TST should be 1 step, regardless of how long it has been since the last TST.7
The same material and techniques of administration and reading should be used as with any other TST. The second test should be performed one to 4 weeks later. Less than one week does not allow enough time to elicit the booster phenomenon, while more than 4 weeks increases the possibility of a true TST conversion. Both tests should be read and recorded at 48 to 72 hours after administration. Expanding the interval to read the first TST after 1 week (and therefore immediately before a second TST) is less accurate and is not recommended.
Longitudinal studies of the risk of TB following a booster reaction defined the reaction simply as a second TST result of 10 mm or more induration.85,117–119 Therefore, a second TST result of 10 mm or more should be considered significant and the patient referred for medical evaluation and chest radiography. 7,89
All subjects with a reaction of 10 mm or more on the second TST of a two-step TST do not need a TST in the future. There is no clinical utility.7 They should be referred for medical evaluation, as performed for those with a positive first TST. In longitudinal studies of the elderly, subjects with a second TST response of 10 mm or more had a risk of TB that was approximately half that of subjects whose first TST response was 10 mm or more. Similar findings were shown in a small cohort of hemodialysis patients. Since the risk of TB is about half that of patients from the same population group whose initial TST result is positive, the decision to provide TPT should be individualized.
A common question is how to manage a person whose first TST measured 5-9 mm and the second test measured 10 + mm but increased by less than 6 mm from the first test. As previously mentioned, this should be managed as a “positive TST,” meaning referral for medical evaluation and no further TSTs. While appropriate epidemiologic data are lacking, it seems reasonable to suggest that the risk of TB disease would be lower than in persons whose second TST increased by at least 6 mm. The decision to provide TPT should be individualized.
A.3.2. TST conversions
If there has been recent exposure, such as close contact with a person with TB disease or occupational TB disease exposure, then TST conversion will be more likely than when there has been no exposure. Conversion is defined as a TST of 10 mm or greater when an earlier test resulted in a reaction of less than 5 mm. If the earlier result was between 5 and 9 mm, the definition of conversion is more controversial. Increases of 6 or 10 mm have been proposed, but there is weak evidence supporting both.89 In general, the larger the increase, the more likely it is due to a true conversion. However, like consideration of a “booster,” any second TST result of 10 mm or greater should be considered a “positive” and the patient evaluated for possible TPT.
All available experimental and epidemiologic evidence consistently shows that TST conversion occurs within 3-8 weeks of exposure.89 Therefore, to identify a true conversion (ie, new infection), a single TST should be performed as soon as possible after an exposure to tuberculosis is recognized and the contact is identified. If the first TST is negative and performed less than 8 weeks after contact with the index patient, then a second TST should be scheduled no sooner than 8 weeks after the contact was broken. This also means for contacts that are identified more than 8 weeks after contact with an index patient is broken (eg, casual contacts), a single TST can be performed, and the result acted upon.7
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