TB in Travelers: U.S. Reports and IGRA for Screening
TB in Travelers: U.S. Reports and IGRA for Screening
Abstract & Commentary
By Lin H. Chen, MD
Dr. Chen is Assistant Clinical Professor, Harvard Medical School Director, Travel Medicine Center, Mt. Auburn Hospital, Cambridge, MA.
Dr. Chen reports no financial relationships relevant to this field of study.
Synopsis: Reports of tuberculosis to the US Quarantine Activity Reporting System increased dramatically in the year following a publicized case of tuberculosis in a traveler. Most of the cases reported were men and were identified after travel involving flights, raising concern for rapid spread during airline flights.
Sources: Modi S, et al. Reporting patterns and characteristics of tuberculosis among international travelers, United States, June 2006 to May 2008. Clin Infect Dis 2009;49:885-891.
Ingrams P, et al. Latent tuberculosis infection in travelers: Is there a role for screening using interferon-gamma release assays? J Travel Med 2009;16:352-356.
Modi et al. and colleagues from the Centers for Disease Control and Prevention examined reports of tuberculosis in the Quarantine Activity Reporting System (QARS) from June 1, 2007, through May 31, 2008 (year 2) and compared the data to those of the previous year, June 1, 2006, through May 31, 2007 (year 1). Cases of tuberculosis (TB) were classified according to the CDC and American Thoracic Society guidelines, which include 6 classes: no TB exposure (class 0), TB exposure (class 1), latent TB infection (class 2), clinically active TB disease (class 3), clinically inactive TB (class 4), and TB suspect (class 5).
A total of 415 QARS reports of possible TB disease from the 2-year period could be analyzed. Among 402 reports that could be classified, 294 (73.1%) fulfilled CDC-ATS criteria for active TB disease (class 3) and 108 (26.9%) were classified in the other classes (0, 1, 2, 4, 5). There were 73 active TB cases in year 1 (2.5% of total year 1 QARS reports) and 221 in year 2 (6.4% of total year 2 QARS reports). Drug susceptibility tests on 248 travelers' isolates found that 79.0% were susceptible, 9.3% had resistance to at least one drug, 11.3% had multidrug-resistant TB, and 0.4% had XDR TB. Federal travel restrictions were initiated for 45 travelers with possible TB, including 38 (84.4%) with active TB.
Further details regarding the travelers with TB show that males were predominant (62.8% of active TB reports), with air flights being the main mode of travel (312/415 or 75.2%). Nearly half of the cases who traveled by air required contact investigation. Median age was 36 for the cases of active TB, and 20.1% were U.S. citizens. The majority of travelers with active TB were identified after travel (77.9%).
In the second article, the authors reviewed risk factors for TB infection in travelers and current recommendations for preventing and screening for TB infection in travelers. They identified 5 previous reports that examined the risk of latent TB in travelers, including 4 that evaluated tuberculin skin test (TST) and one that used interferon-gamma release assay (IGRA).1-5 They summarized the following points, which are supported by data in travelers: 1) travel destination is the main determinant of risk; 2) incidence of infection in long-term travelers approaches that of the local population; 3) health care work overseas is associated with increased risk; and 4) travelers who are visiting friends and relatives (VFR) appear to have an increased risk.
The authors further discussed the utility of interferon-gamma release assays in screening for latent TB. The authors noted that "seroreversion" has occurred, possibly due to fluctuating immune response or suboptimal test reproducibility. Therefore, serial IGRA test results may be difficult to interpret.
Commentary
The two publications on TB and travelers address different issues. The paper by Modi et al. is particularly relevant to transmission of TB in-flight or through other conveyances where passengers are in closed quarters, having the potential to spread the disease widely and rapidly. Mycobacterium tuberculosis is spread by large droplets and droplet nuclei originating from a productive cough.6 In-flight transmission of TB has been documented with up to 6% tuberculin skin test (TST) conversion; passengers seated within 2 rows of the index case have the highest risk (31% TST conversion).7 This is of particular concern with regard to drug-resistant organisms. After the TB case with federal isolation order in May 2007, reports of TB in international travelers increased dramatically. The increased reporting is probably due to heightened awareness rather than an actual rise in incidence, but a causal effect is difficult to measure.
The review of TB testing in travelers seeks to answer whether IGRAs are useful for screening in travelers. IGRAs measure the interferon produced by T lymphocytes after exposure to Mycobacterium tuberculosis-specific antigens, and have better specificity compared to the TST. For example, an individual with past Bacille Calmette-Guérin vaccination may have a false-positive TST, but should test negative by IGRA. IGRAs are estimated to have a sensitivity of 76-90% and a specificity of 93-98%, whereas TST is estimated to have a sensitivity of 77% and specificity of 66%.8,9 However, little data exist to compare each test, specifically in travelers. The authors also noted that seroreversion (the appearance of a negative IGRA in a person who previously was positive) has occurred, possibly due to fluctuating immune responses or suboptimal test reproducibility.
Cobelens et al. showed that length of travel is associated with increased TB exposure; the risk of TB may reach that of the local population during longer stays.3,4 Additionally, travelers who worked in a healthcare settings overseas were more likely to be exposed and infected with TB, with a TST conversion rate of 7.9 per 1000 person-months of travel, compared to 2.8 per 1000 person-months of non-healthcare workers.3 An analysis of the GeoSentinel Surveillance Network data found that travelers visiting friends and relatives had proportionately higher rates of latent TB, based on TST, when compared to those who traveled for other purposes.10 Therefore, long-term travelers and VFR travelers are populations that deserve focus for studies on screening for latent TB.
Further research is needed to estimate TB risk accurately in travelers, to assess the efficacy of IGRAs in screening travelers, to understand reasons for seroreversion with IGRAs, to interpret sequential IGRAs, and to provide cost-effectiveness analysis.
References
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- Cobelens F, Van Deutekom H, Draayer-Jansen I, et al. Risk of infection with Mycobacterium tuberculosis in travelers to areas of high tuberculosis endemicity. Lancet 2000;356:461-465.
- Jung P, Banks R. Tuberculosis risk in US Peace Corps volunteers, 1996 to 2005. J Travel Med 2008;15:87-94.
- Wilder-Smith A, Foo W, Earnest A. High risk of Mycobacterium tuberculosis infection during the Hajj pilgrimage. Trop Med Int Health 2005;10:336-339.
- Musher DM. How contagious are common respiratory tract infections? N Engl J Med 2003;348(13):1256-66.
- Kenyon TA, Valway SE, Ihle WW, et al. Transmission of multidrug-resistant Mycobacterium tuberculosis during a long airplane flight. N Engl J Med 1996;334(15):933-8.
- Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: An update. Ann Intern Med 2008;149:177-184.
- Menzies D, Pai M, Comstock G. Meta-analysis: New tests for the diagnosis of latent tuberculosis infection: Areas of uncertainty and recommendations for research. Ann Intern Med 2007;146:340-354.
- Leder K, Tong S, Weld L, et al. Illness in travelers visiting friends and relatives: A review of the GeoSentinel surveillance network. Clin Infect Dis 2006;43:1185-1193.
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