Perspectives: Testing Travelers for Mycobacterium Tuberculosis Infection

CDC Yellow Book 2024

Travel-Associated Infections & Diseases

Author(s): John Jereb

Screening for asymptomatic Mycobacterium tuberculosis infections should only be carried out for travelers at risk of acquiring tuberculosis (TB) at their destinations (see Sec. 5, Part 1, Ch. 22, Tuberculosis). Screening with a tuberculin skin test (TST) or interferon-γ release assay (IGRA) in very-low-risk travelers might produce false-positive test results, leading to unnecessary additional screening or treatment. IGRAs, which require a single 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. Moreover, TST is prone to boosting sensitivity in serial testing, necessitating a 2-step initial test for establishing a baseline, which is unneeded with IGRAs. Using screening tests in very-low-prevalence populations will probably produce more false positives than true positives.

Travelers at risk for TB infection include those going to live in a TB-endemic country or anyone intending to spend any length of time in routine contact with patients in health care facilities or populations living in congregate settings (e.g., homeless shelters, prisons, refugee camps). 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, perform pretravel screening by using an IGRA or, when IGRA is not available, 2-step TST screening. CDC guidelines recommend testing with an IGRA (as opposed to TST) for people aged ≥5 years in low-risk populations. The American Academy of Pediatrics guidelines recommend an IGRA for children ≥2 years old; some pediatric TB experts use IGRAs for all children. 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 can be used, which confirms TB infection only if both tests are positive. If the IGRA result is negative, repeat the traveler’s test 8–10 weeks after they return from their trip; however, data supporting a recommendation for regular serial testing for a long-term traveler are limited.

If TST is used for pretravel testing, use the 2-step TST for any traveler undergoing TST testing for the first time. The 2-step method is not needed for travelers who have already been tested and found to have a negative result within the previous 2 years. For the 2-step method, anyone whose baseline TST yields a negative result should be retested 1–3 weeks after the initial test; if the second test result is negative, the patient can be considered not infected. If the second test result is positive, the patient is classified as having skin test boosting, possibly because of previous M. tuberculosis infection.

The 2-step TST is recommended over single TST in this population because some people infected with M. tuberculosis years earlier (or who were sensitized by BCG or nontuberculous mycobacteria) exhibit waning delayed-type hypersensitivity to tuberculin. When skin tested years after infection, these people might have a negative initial TST result even though they had been sensitized previously. The first TST might stimulate the ability to react to subsequent tests, however, resulting in a “booster” reaction. When the test gets repeated at some future date, a positive result could be misinterpreted as a new M. tuberculosis infection (recent conversion) rather than a boosted reaction. For travelers who do not have enough time to complete a 2-step TST before departure, a single-step TST is an acceptable alternative, but an IGRA is preferred.

If the result of a pretravel test (either IGRA or 2-step TST) for M. tuberculosis infection is negative, a traveler should have a posttravel test with the same type of test used pretravel, 8–10 weeks after returning from their trip. People who have repeat TSTs should be tested with the same tuberculin purified protein derivative solution, because switching products can lead to different test results. The US Food and Drug Administration has approved 2 commercially available tuberculin solutions for skin testing: Aplisol (JHP Pharmaceuticals) and Tubersol (Sanofi Pasteur). During extended (>6 months) stays in, or repeated travel to, high-risk settings, travelers should have repeat testing every 6–12 months while traveling outside the United States and then 8–10 weeks after final return, all with the same type of test used pretravel.

In general, do not mix the types of tests used for a person. The discordance between TST and IGRA results is ≤15%; in most instances of discordance, the TST result is positive and the IGRA is negative. Multiple reasons for the discordance exist, and clinicians cannot be confident about the reason for discordance in any single person. If a clinician does decide to mix tests, going from TST to IGRA is better than the other way around, because the likelihood of a discordant result with the TST negative and the IGRA positive is much lower. Such discordant results might become unavoidable as more medical establishments switch from TSTs to IGRAs.

When testing travelers who were born or took up residence in TB-endemic areas, consider the greater background prevalence of infection in these places. In a study among 53,000 adults in Tennessee, the prevalence of a positive TST results among foreign-born participants was >11× that of US-born participants (34% vs. 3%). Confirming M. tuberculosis test status before travel would prevent the conclusion that a positive result after travel was due to recent infection.

The following authors contributed to the previous version of this chapter: Neela D. Goswami, Philip A. LoBue

Hagmann SH, Han PV, Stauffer WM, Miller AO, Connor BA, Hale DC. Travel-associated disease among US residents visiting US GeoSentinel clinics after return from international travel. Fam Pract. 2014;31(6):678–87.

Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL, Daley CL, Desmond E, et al. American Thoracic Society/Infectious Diseases Society/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clin Infect Dis. 2017;64(2):111–5.

US Preventive Services Task Force. Screening for latent TB infection in adults: US Preventive Services Task Force recommendation statement. JAMA. 2016:316(9):962–9.

. . . perspectives chapters supplement the clinical guidance in this book with additional content, context, and expert opinion. The views expressed do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).