Perspectives: Tuberculin Skin Testing of Travelers

Perspectives: Tuberculin Skin Testing of Travelers is a topic covered in the CDC Yellow Book.

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Screening for asymptomatic tuberculosis (TB) infections should only be carried out for travelers at risk of acquiring TB at their destinations (see the preceding section on Tuberculosis). Screening with a tuberculin skin test (TST) or interferon-γ release assay (IGRA) in very low-risk travelers may result in false-positive test results, leading to unnecessary additional screening or unnecessary treatment. IGRAs, which require a blood draw, are approximately as specific as TST in people who have not been vaccinated with bacillus Calmette-Guérin (BCG) and are more specific in BCG-vaccinated populations. Using screening tests in very low-prevalence populations will likely produce more false positives than true positives.

Travelers at risk for TB infection include those going to live in a country with a high risk of TB or anyone intending to spend any length of time in routine contact with patients in health care facilities or populations living in congregate settings (such as homeless shelters, prisons, and refugee camps). The general recommendation is that people at low risk for exposure to TB, which includes most travelers, do not need to be screened before or after travel.

For travelers who anticipate a long stay or contact with a high-risk population, careful pretravel screening should be carried out with use of an IGRA or, when an IGRA is not available, 2-step pretravel TST screening. Guidelines recommend testing with an IGRA (over TST) for people aged ≥5 years in low-risk populations.

If an IGRA is used for pretravel testing and there is concern for a false positive in an otherwise low-risk traveler, a second test may be used, which confirms TB infection only if both tests are positive. If the IGRA result is negative, the traveler should have a repeat test 8–10 weeks after returning from the trip, but data are limited in supporting a recommendation for regular serial testing for a long-term traveler.

If the TST is used for pretravel testing, the 2-step TST should be used for any traveler undergoing TST testing for the first time. People whose baseline TSTs yield a negative result are retested 1–3 weeks after the initial test; if the second test result is negative, they are considered not infected. If the second test result is positive, they are classified as having had previous TB infection. The 2-step TST is recommended over single TST in this population for the following reasons:

  • The use of 2-step testing can reduce the number of positive TSTs that would otherwise be misclassified as recent skin test conversions during future periodic screenings.
  • Certain people who were infected with Mycobacterium tuberculosis years earlier exhibit waning delayed-type hypersensitivity to tuberculin. When they are skin tested years after infection, they might have a false-negative TST result (even though they are truly infected). However, the first TST might stimulate the ability to react to subsequent tests, resulting in a “booster” reaction. When the test is repeated, the reaction might be misinterpreted as a new infection (recent conversion) rather than a boosted reaction.

Two-step testing is important for travelers who will have potential prolonged or substantial TB exposure. Two-step testing before travel will detect boosting and potentially prevent “false conversions”—positive TST results that appear to indicate infection acquired during travel, but which are really the result of previous TB infection. This distinction is particularly important if the traveler is going to a country where multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are present: it would be critical to know whether the person’s skin test had been positive before travel.

If the 2-step pretravel TST result is negative, the traveler should have a repeat TST 8–10 weeks after returning from the trip. During extended (>6 months) stays in or repeated travel to high-risk settings, a TST should be performed every 6–12 months, depending on the risk of exposure while traveling outside the United States, and 8–10 weeks after final return. Two-step testing should be considered for the baseline testing of people who report no history of a recent TST and who will receive repeated TSTs as part of ongoing monitoring.

People who have repeat TSTs must be tested with the same commercial antigen, since switching antigens can also lead to false TST conversions. Two commercial TST antigens are approved by the Food and Drug Administration (FDA) and are commercially available in the United States: Aplisol (JHP Pharmaceuticals) and Tubersol (Sanofi Pasteur). For a traveler whose time before departure is short, a single-step TST would be an acceptable alternative if time is insufficient for the 2-step TST or the IGRAs are not available.

In general, it is best not to mix tests. There is up to 15% discordance between TST and IGRA, usually with the TST positive and the IGRA negative. There are multiple reasons for the discordance, and in any single person, it is often difficult to be confident about the reason for discordance. However, if the clinician decides to mix tests, it is better to go from TST to IGRA than the other way around, because the likelihood of having a discordant result with the TST negative and the IGRA positive is much lower. Such discordant results may become unavoidable as more medical establishments switch from TSTs to IGRAs.

The use of TSTs among travelers who are visiting friends and relatives in TB-endemic areas should take into account that the rate of TST positivity in people visiting their country of birth is often high. In a study among 53,000 adults in Tennessee, the prevalence of a positive TST among the foreign born was 11 times that among the US born (34% vs 3%). Confirming TST status before travel would prevent the conclusion that a positive TST after travel was due to recent infection.

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Screening for asymptomatic tuberculosis (TB) infections should only be carried out for travelers at risk of acquiring TB at their destinations (see the preceding section on Tuberculosis). Screening with a tuberculin skin test (TST) or interferon-γ release assay (IGRA) in very low-risk travelers may result in false-positive test results, leading to unnecessary additional screening or unnecessary treatment. IGRAs, which require a blood draw, are approximately as specific as TST in people who have not been vaccinated with bacillus Calmette-Guérin (BCG) and are more specific in BCG-vaccinated populations. Using screening tests in very low-prevalence populations will likely produce more false positives than true positives.

Travelers at risk for TB infection include those going to live in a country with a high risk of TB or anyone intending to spend any length of time in routine contact with patients in health care facilities or populations living in congregate settings (such as homeless shelters, prisons, and refugee camps). The general recommendation is that people at low risk for exposure to TB, which includes most travelers, do not need to be screened before or after travel.

For travelers who anticipate a long stay or contact with a high-risk population, careful pretravel screening should be carried out with use of an IGRA or, when an IGRA is not available, 2-step pretravel TST screening. Guidelines recommend testing with an IGRA (over TST) for people aged ≥5 years in low-risk populations.

If an IGRA is used for pretravel testing and there is concern for a false positive in an otherwise low-risk traveler, a second test may be used, which confirms TB infection only if both tests are positive. If the IGRA result is negative, the traveler should have a repeat test 8–10 weeks after returning from the trip, but data are limited in supporting a recommendation for regular serial testing for a long-term traveler.

If the TST is used for pretravel testing, the 2-step TST should be used for any traveler undergoing TST testing for the first time. People whose baseline TSTs yield a negative result are retested 1–3 weeks after the initial test; if the second test result is negative, they are considered not infected. If the second test result is positive, they are classified as having had previous TB infection. The 2-step TST is recommended over single TST in this population for the following reasons:

  • The use of 2-step testing can reduce the number of positive TSTs that would otherwise be misclassified as recent skin test conversions during future periodic screenings.
  • Certain people who were infected with Mycobacterium tuberculosis years earlier exhibit waning delayed-type hypersensitivity to tuberculin. When they are skin tested years after infection, they might have a false-negative TST result (even though they are truly infected). However, the first TST might stimulate the ability to react to subsequent tests, resulting in a “booster” reaction. When the test is repeated, the reaction might be misinterpreted as a new infection (recent conversion) rather than a boosted reaction.

Two-step testing is important for travelers who will have potential prolonged or substantial TB exposure. Two-step testing before travel will detect boosting and potentially prevent “false conversions”—positive TST results that appear to indicate infection acquired during travel, but which are really the result of previous TB infection. This distinction is particularly important if the traveler is going to a country where multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are present: it would be critical to know whether the person’s skin test had been positive before travel.

If the 2-step pretravel TST result is negative, the traveler should have a repeat TST 8–10 weeks after returning from the trip. During extended (>6 months) stays in or repeated travel to high-risk settings, a TST should be performed every 6–12 months, depending on the risk of exposure while traveling outside the United States, and 8–10 weeks after final return. Two-step testing should be considered for the baseline testing of people who report no history of a recent TST and who will receive repeated TSTs as part of ongoing monitoring.

People who have repeat TSTs must be tested with the same commercial antigen, since switching antigens can also lead to false TST conversions. Two commercial TST antigens are approved by the Food and Drug Administration (FDA) and are commercially available in the United States: Aplisol (JHP Pharmaceuticals) and Tubersol (Sanofi Pasteur). For a traveler whose time before departure is short, a single-step TST would be an acceptable alternative if time is insufficient for the 2-step TST or the IGRAs are not available.

In general, it is best not to mix tests. There is up to 15% discordance between TST and IGRA, usually with the TST positive and the IGRA negative. There are multiple reasons for the discordance, and in any single person, it is often difficult to be confident about the reason for discordance. However, if the clinician decides to mix tests, it is better to go from TST to IGRA than the other way around, because the likelihood of having a discordant result with the TST negative and the IGRA positive is much lower. Such discordant results may become unavoidable as more medical establishments switch from TSTs to IGRAs.

The use of TSTs among travelers who are visiting friends and relatives in TB-endemic areas should take into account that the rate of TST positivity in people visiting their country of birth is often high. In a study among 53,000 adults in Tennessee, the prevalence of a positive TST among the foreign born was 11 times that among the US born (34% vs 3%). Confirming TST status before travel would prevent the conclusion that a positive TST after travel was due to recent infection.

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