Perspectives: Tuberculin Skin Testing of Travelers
Screening for asymptomatic tuberculosis (TB) infections should only be carried out among travelers who will be at risk of acquiring TB if they are exposed at their destinations (see the preceding section on Tuberculosis). Screening with a tuberculin skin test (TST) in a very low-risk population of travelers may result in a false-positive test, leading to unnecessary additional screening or unnecessary treatment. Using screening tests in very low-prevalence populations will produce more false positives than true positives.
Therefore, the TST should be considered only for travelers who are spending years in a country with a high risk of TB or for those travelers who will spend any length of time in routine contact with hospital, prison, or homeless shelter populations. 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 pre-travel screening should be carried out, with use of 2-step pre-travel TST screening. For 2-step TSTs, 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 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 extensively drug-resistant TB (XDR TB) is present: it would be critical to know whether the person’s skin test had been positive before travel.
If the 2-step pre-travel TST result is negative, the traveler should have a repeat TST 8–10 weeks after returning from the trip or as part of a periodic screening examination for those who remain at high risk. 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 had repeat TSTs must be tested with the same commercial antigen, since switching antigens can also lead to false TST conversions. Two commercial tuberculin skin test 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).
An alternative to 2-step TST is a single FDA-approved interferon-γ release assay (IGRA), either the QuantiFERON TB test (Gold In-Tube versions) or T-SPOT.TB test. 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 much more specific in BCG-vaccinated populations. 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 and the IGRAs are not available.
In general, it is best not to mix tests. There is approximately 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 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 the high rate of TST positivity in people visiting their country of birth. 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 conversion.
Al-Jahdali H, Memish ZA, Menzies D. Tuberculosis in association with travel. Int J Antimicrob Agents. 2003 Feb;21(2):125–30.
Cobelens FG, van Deutekom H, Draayer-Jansen IW, Schepp-Beelen AC, van Gerven PJ, van Kessel RP, et al. Risk of infection with Mycobacterium tuberculosis in travellers to areas of high tuberculosis endemicity. Lancet. 2000 Aug 5;356(9228):461–5.
Haley CA, Cain KP, Yu C, Garman KF, Wells CD, Laserson KF. Risk-based screening for latent tuberculosis infection. South Med J. 2008 Feb;101(2):142–9.
Johnston VJ, Grant AD. Tuberculosis in travellers. Travel Med Infect Dis. 2003 Nov;1(4):205–12.
Jung P, Banks RH. Tuberculosis risk in US Peace Corps volunteers, 1996 to 2005. J Travel Med. 2008 Mar–Apr;15(2):87–94.
Leder K, Tong S, Weld L, Kain KC, Wilder-Smith A, von Sonnenburg F, et al. Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. Clin Infect Dis. 2006 Nov 1;43(9):1185–93.
Mancuso JD, Tobler SK, Keep LW. Pseudoepidemics of tuberculin skin test conversions in the US Army after recent deployments. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1285–9.
Mazurek M, Jereb J, Vernon A, LoBue P, Goldberg S, Castro K. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWR Recomm Rep. 2010 Jun 25;59 (RR-5):1–25.
Villarino ME, Burman W, Wang YC, Lundergan L, Catanzaro A, Bock N, et al. Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection. JAMA. 1999 Jan 13;281(2):169–71.