Annals of the American Thoracic Society

Healthcare and humanitarian workers who travel to work where the incidence of multidrug-resistant tuberculosis (MDR TB) is high and potential transmission may occur are at risk of infection and disease due to these resistant strains. Transmission occurs due to inadequate transmission control practices and the inability to provide timely and accurate diagnosis and treatment of persons with MDR TB. Patients risk exposure if active TB is unrecognized in workers after they return to lower-risk settings. Guidance for risk reduction measures for workers in high-risk areas is limited, and no studies confirm the efficacy of treatment regimens for latent TB infection due to MDR TB. Bacille Calmette-Guérin (BCG) vaccination decreases the risk of active TB and possibly latent infection. IFN-γ release assays differentiate TB infection from BCG vaccination effect. A series of risk reduction measures are provided as a potential strategy. These measures include risk reductions before travel, including risk assessment, TB screening, education, respirator fit testing, and BCG vaccination. Measures during travel include use of respirators in settings where this may not be common practice, transmission control practices, triaging of patients with consistent symptoms, providing education for good cough etiquette, and provision of care in well-ventilated areas, including open air areas. Risk reduction measures after return include TB screening 8 to 10 weeks later and recommendations for management of latent TB infection in areas where the likelihood of MDR TB exposure is high.

An increasing number of students, physicians, researchers, other healthcare personnel, and humanitarian groups (referred to as “workers”) from areas of low risk (such as the United States) travel to work in areas of the world where the incidence of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis (referred to as “MDR TB”) is high. Work activities in these areas could involve exposure to patients with infectious TB in settings that lack effective transmission control practices. As a result, workers traveling to these areas are at increased risk for exposure and possible infection with Mycobacterium tuberculosis. The potential for further transmission of TB exists if workers develop TB disease after their return to the United States, with the added concern that active TB in a healthcare professional is also likely to place vulnerable (those with comorbid health conditions) patients exposed to that worker at risk.

Changes in technology, epidemiology, increasing global work, and TB drug resistance have prompted the development of this guidance for risk reduction for MDR TB transmission in workers serving in high-risk international settings. Changes include the availability of TB IFN-γ release assays (IGRA), modified global TB epidemiology, higher travel frequency of workers with humanitarian missions, healthcare and global health research, and the need to prescribe preventive measures (including the option for bacille Calmette-Guérin [BCG] vaccination) for a specific segment of the U.S. population and for workers from other low TB risk regions.

Members of the Advisory Council for the Elimination of Tuberculosis advised the Centers for Disease Control and Prevention (CDC) that new and expanded recommendations in the areas of infection control and worker vaccination were necessary and should be particularly addressed to workers traveling to international sites where they will have risk of exposure to MDR TB (1).

CDC convened a panel of persons (including CDC subject matter experts), each of whom had demonstrated TB-specific expertise in: diagnosis, treatment, prevention, vaccination, student health management, public health programs, surveillance, quarantine, epidemiology, clinical research, pulmonology, infectious diseases, occupational health, nosocomial transmission, or traveler’s health. The panel reviewed findings from reports, guidelines, surveillance, and other types of summary reports published from 1961 to 2011, interviewed experts, held discussions, and summarized the relevant evidence and opinions. The panel decided which information to include according to its relevance to reduce the risk of MDR TB for U.S. personnel serving in high-risk international settings and received full approval of these recommendations from the Advisory Council for the Elimination of Tuberculosis.

Recommended Risk Reduction Measures for Workers Traveling to MDR TB–Endemic Regions before Departure

Travel constituting a high likelihood of exposure to MDR TB was considered to be travel to the 2012 World Health Organization (WHO) classification of 27 countries “with a high burden of MDR TB and XDR TB” (2) (Figure 1). These countries represent more than 85% of the world’s estimated number of incident MDR TB cases. These countries are not the only locations where MDR TB transmission has been documented (3, 4). Limited data are available for much of Africa because drug susceptibility testing is not widely available, and the risk in Africa and in many other areas of the world remains unknown (5). WHO estimates that less than 25% of MDR cases were detected in 2012 (6). In addition, settings (such as prisons, hospitals) in countries without high MDR TB burden may amplify risk in exposed individuals. If a worker is traveling to a country not among the 27 listed here, but where there is a concern of an unquantified risk of MDR TB, the organization sponsoring the travel should seek the advice of experts from the CDC. Preventive risk reduction measures to be implemented before departure, during travel, and those relevant to the time after the worker’s return are listed in Table 1.

Table 1. Recommended risk reduction measures for workers traveling to tuberculosis-endemic regions

Risk reduction measures before travel*
 Risk assessment
 Testing for HIV infection
 Baseline TB screening and medical assessment
 Education on symptoms of TB
 Education on TB infection control measures
 Fit testing for respirator
 BCG vaccination
Risk reduction measures during travel (see Tables 3 and 4)
 Transmission control measures (see Table 3)
 Respirator use
Risk reduction measures after return to the United States
 TB screening 8–10 wk after return
 Recommendations for LTBI diagnosed after exposures in areas where the likelihood of exposure to MDR or XDR TB is high

Definition of abbreviations: BCG = bacille Calmette-Guérin; LTBI = latent tuberculosis infection; MDR = multidrug-resistant; TB = tuberculosis; XDR = extensively drug-resistant.

*Special considerations after extended or repeated travel to high-risk settings of MDR TB (see Table 5)

Risk assessment.

Activities in hospitals, clinics, prisons, refugee camps, facilities housing HIV-infected persons, and other congregate settings have an increased risk of TB transmission (710). Sputum collection, bronchoscopy, and regular contact with sick patients are associated with especially high risk. Rates of disease will differ with various socioeconomic determinants, and the risk of transmission will vary by site. Although precautions to prevent M. tuberculosis transmission focus on known cases, a greater risk exists for exposure to the unsuspected, untreated case or an inadequately treated known case of TB when drug resistance is unsuspected. Working in a TB-endemic, resource-limited setting carries an inherent risk of TB exposure and infection that cannot be eliminated. A decision by the worker or program to avoid travel or work at a site with inadequate protection and evidence of transmission of MDR TB may be the best approach until improvements in work safety can be accomplished (11). Sponsors of workers have an ethical responsibility to provide information regarding the risk of transmission of MDR TB and when possible work with the host site to reduce these risks (11).

Baseline TB assessment.

Baseline, serial follow-up screening and postexposure testing of workers, based on risk of TB exposure, are a necessary component of occupational health programs (12). These recommendations should be followed for workers planning service outside low TB risk areas. Although either a tuberculin skin test or IGRA can be used, IGRA diagnostic tests for latent TB infection (LTBI) are not affected by BCG vaccination history and are considered acceptable for monitoring occupational exposures in healthcare workers (13). When testing with a tuberculin skin test, the two-step testing method should be used (12). In the United States, two IGRAs are commercially available: QuantiFERON-TB Gold In-Tube and T-SPOT.TB. Several studies have demonstrated that an IGRA is more specific and equally sensitive when compared with a tuberculin skin test in populations that include BCG-vaccinated healthcare workers (14, 15) and other BCG-vaccinated populations from low- (14), intermediate- (16), and high-burden (17, 18) areas. We note that few longitudinal data exist on the ability of IGRAs to predict risk for subsequent active TB. Several studies suggest that these tests will be at least as useful as the tuberculin skin test for this purpose (1923). Persons at increased risk for the development of active disease if TB infected should be identified (Table 2). Recommendations are summarized in Figure 2.

Table 2. Persons at increased risk for progression from latent tuberculosis infection to tuberculosis disease

Persons with HIV infection*
Infants and children aged < 5 yr*
Persons who are receiving immunosuppressive therapy, such as TNF-α antagonists, systemic corticosteroids equivalent to ≥ 15 mg of prednisone/d, or immune suppressive drug therapy after organ transplantation*
Persons who were recently infected with Mycobacterium tuberculosis (within the past 2 yr)
Persons with a history of untreated or inadequately treated active TB, including persons with fibrotic changes on chest radiograph consistent with prior active TB
Persons with silicosis, diabetes mellitus, chronic renal failure, leukemia, lymphoma, or cancer of the head, neck, or lung
Persons who have had a gastrectomy or jejunoileal bypass
Persons who weigh < 90% of their ideal body weight
Cigarette smokers and persons who abuse drugs or alcohol
Populations defined locally as having an increased incidence of active TB, possibly including medically underserved or low-income populations

Definition of abbreviations: TB = tuberculosis; TNF = tumor necrosis factor.

Adapted by permission from reference 13.

*Indicates persons at increased risk for a poor outcome (e.g., meningitis, disseminated disease, or death) if active tuberculosis occurs.

Table 3. Tuberculosis transmission control measures for resource-limited settings

Workers should receive training on measures that might be available to them, including:
 Triaging of patients with TB symptoms
 Early diagnosis and effective treatment, especially of multidrug-resistant TB
 Cohorting infectious patients and separating them from other patient-care areas
 Provision of care to patients in well-ventilated areas or outside
 Interviewing patients in open air areas if weather, privacy, and space permit
 Opening windows and curtains in patient-care areas to facilitate natural ventilation and sunlight
 Placement of patients’ beds, when possible, to allow contaminated air to flow away from other patients and workers
 Minimizing time spent in high-risk areas (medical wards)
 Educating patients to use good cough etiquette
 Supplying surgical masks or other means of covering the mouth when coughing to all infectious patients
 Instructing patients to collect sputum samples outdoors if possible

Definition of abbreviation: TB = tuberculosis.

Infection control efforts can effectively reduce the risk of exposure when implemented, even within resource-limited TB-endemic settings.

Fit testing for respirators.

Personal respiratory protection is the third tier in the hierarchy of transmission control measures for TB in the United States and other countries with the ability to implement the first two (administrative and environmental) control strategies. Personal respiratory protection is an added strategy to optimize protection. In low-resource countries, it may be the only control available. Respiratory protection takes on particular importance for workers serving outside of low TB risk areas because it is a strategy that is within their control when other measures may be inadequate or absent. Use of an effective and properly fitted personal respirator can greatly reduce the risk of TB transmission (12, 24). There are two types of easily transported, nonpowered, tight-fitting respirators that are suitable for work with patients with TB: disposable filtering facepiece respirators (N95 or higher) or reusable elastomeric respirators. The protection provided by a personal respirator is a function of both the air-filtration efficacy of the filter material and leakage between the respirator and the face (face-seal leak). The biggest contributor to function failure is face-seal leakage. Without proper fit testing, the efficacy may be reduced due to a greater volume of unfiltered air reaching the person wearing the respirator. Approximately 10% of inhaled air does not pass through the filter in well-fitted disposable N95 models. Well-fitted reusable elastomeric respirators have approximately 2% face-seal leakage. Workers who are not clean shaven will not obtain an optimal face seal. Devices with higher levels of respiratory protection, such as powered air-purifying respirators, are more effective at reducing the risk of TB transmission compared with N95 respirators and reusable elastomeric half-mask respirators and address the issue of workers with facial hair (12). Such devices, however, are not commonly available in developing countries, particularly where resources are scarce and power supplies unreliable (Table 4).

Table 4. Recommendations for respiratory protection

Respirators that are suitable for work with patients with TB are either disposable filtering facepiece respirators (N95 or higher) or reusable elastomeric respirators.
Respirators should be fit tested by the issuer before use. Workers should be encouraged to limit facial hair to improve the respirator fit.
Workers should be issued respiratory protection (a sufficient supply of disposable respirators or an elastomeric respirator) to take with them to their destination.
Users of the respirators should be taught how to care for them, including how to pack them to prevent the respirator from becoming wet or crushed and how to clean and store them while in use.
Workers should be made aware that their local counterparts may not wear respiratory protection or may wear respiratory protection that is different from their own.
They should recognize that they may be at higher risk than their local counterpart due to lack of BCG vaccination at birth and no or limited prior TB exposure in home country and that respirator use is important even if not used by local workers.
Where appropriate, sponsors should facilitate implementation of administrative controls and encourage the use of appropriate respiratory protection by local staff at project sites
They should consider taking extra respirators with them that they can offer to local counterparts. Even though these will not be fit tested, they still will offer additional protection.

Definition of abbreviations: BCG = bacille Calmette-Guérin; TB = tuberculosis.

Workers from low-incidence areas may encounter clinical settings where local colleagues cannot or do not practice transmission control procedures, including use of a respirator. This may be due to inaccessibility of respirators or a perceived low risk of infection related to childhood BCG vaccination and/or TB immunity from repeated exposures. Workers should not refrain from using a respirator in this situation. These discordances require full explanation. Frank discussion with local colleagues about the differential risk and cultural differences in practice are often helpful in overcoming any tension that may be created by this situation. In the setting of a shortage of respirators, workers may wish to carry and offer additional respirators to colleagues who wish to use them. These need not be fitted for practical reasons, and the difference in protection provided by fit tested versus not may be only a small amount. Non–fit-tested respirators, although not optimal, will still provide additional protection.

Due to inherent limitations of personal respirators, protection is never total, and they should be used in conjunction with other transmission control strategies. A respirator reduces the level of exposure to the hazard; it does not eliminate the exposure completely (24, 25). A respirator should not give the worker a false sense of protection.

Special considerations for workers with extended or repeated travel to high-risk settings of MDR TB.

Baseline, serial, and follow-up TB screening post exposure is a standard component of occupational health programs (12). Workers with extended or repeated travel to high-risk settings have increased potential for exposure to MDR TB. Longer exposure times have been associated with an increased risk of infection in travelers and workers (2628). This group of workers should be screened at least as frequently as others with shorter stays. Guidelines for healthcare workers in medical facilities with evidence of ongoing transmission of TB support more frequent screening (12) (Table 5).

Table 5. Recommendations for workers with extended or repeated travel to high-risk settings for multidrug-resistant tuberculosis

A tuberculin skin test or IGRA should be performed as a baseline before initial travel and every 6 to 12 mo, depending on risk of TB exposure while traveling outside the low-risk area. An IGRA is preferred for those with a history of BCG vaccination. If a tuberculin skin test is used, two-step testing is recommended.
When a return to the low-risk area for an extended period is planned, a repeat test should be performed 8–10 wk after return to maximize the opportunity to detect recent conversion.
In general, LTBI treatment should not be delayed more than 6 mo. Thus, for those travelers planning stays of less than 6 mo, LTBI therapy can be started on their return to the low-risk area. Treatment should not be delayed if conditions are present that increase the risk of progression to active TB disease (see Table 2).
The sponsor should assure a mechanism is present for toxicity monitoring and a complete supply of medication while in the destination country. (These arrangements should be made before departure if possible.)
Those workers who are tuberculin skin test or IGRA positive and who decline treatment for LTBI should have periodic symptom screening (every 6–12 mo depending on risk) for early diagnosis of TB disease while on travel status and during an assessment scheduled 8–10 wk after the return to the United States.
The sponsor of workers with extended stays should arrange a mechanism to assure an adequate supply of respirators for the duration of the stay.

Definition of abbreviations: BCG = bacille Calmette-Guérin; IGRA = IFN-γ release antigen; TB = tuberculosis.

BCG vaccination.

Randomized controlled trials and case-controlled studies have consistently demonstrated high efficacy of the BCG vaccine in preventing meningeal and disseminated TB in children (29, 30). No strain has emerged as superior in human studies (3035). The estimated efficacy of BCG for protecting adults from pulmonary TB has been variable, ranging from a possibly detrimental effect (3638) to a protective efficacy of more than 80% (35). A metaanalysis of 14 prospective trials and 12 case-control studies found that BCG significantly reduces the risk of TB by an average of 50% (35). This effect persisted over all age groups and disease sites, including protection against adult pulmonary TB. However, some well-done studies showed a lack of TB protection with BCG vaccines (38, 39). The available cohort studies of the efficacy of BCG vaccine in healthcare workers in North America were reviewed. Rates of TB were substantially lower among healthcare workers receiving BCG vaccine than among those with negative tuberculin skin tests who were not vaccinated. Importantly, though, they showed that protection of BCG was not complete and that cases of TB did occur in some who were vaccinated (33). An analysis of eight prospective trials meeting rigorous methodological and statistical criteria concluded that although biased allocation of the vaccine did not appear to be a likely explanation for varying efficacy, unbiased detection of TB disease was present for only three trials, each of which reported 75% or greater protective efficacy (34). They also noted that in most trials reporting low efficacy, with the exception of the Chingleput BCG vaccine trial (39), the results had wide confidence intervals that could not exclude high efficacy, whereas the trials reporting high efficacy all had narrow confidence intervals that excluded low efficacy (34). Because contemporary data indicate that many adults are already exposed to mycobacteria and this likely has an impact on results of efficacy trials, von Reyn suggests that only prospective trials in mycobacteria-naive infants are valid for assessing the true efficacy of BCG and concludes, similarly, that the efficacy of BCG is 73% (40).

Several recent analyses offer new information. A randomized, placebo-controlled study of BCG vaccination among school-aged American Indians and Alaska Natives was conducted from 1935 to 1938, with follow-up to 1998. It concluded that BCG vaccine reduced the risk of pulmonary TB in adults by 52%, and this risk reduction was estimated to persist for 50 to 60 years (31). With the availability of IGRAs to distinguish TB infection from BCG immunization, several studies have explored the effect of BCG for protection against TB infection. One study analyzed the rates of LTBI in 979 children in Turkey with known TB household exposures and concluded that BCG was associated with a 24% relative risk reduction for TB infection (41). In the UK, among 199 junior school students exposed to TB, prior BCG vaccination was associated with a 74% reduction in the risk of TB infection (42). Similar results were noted in a nursery school outbreak in the UK, where calculated vaccine protection against TB infection was 66% (43), and in a community-based contact investigation that involved both children and adults, although this finding did not reach statistical significance (20). The suggestion that BCG vaccination may prevent primary infection and not just TB disease is a novel finding and has generated some controversy (44). Although no study has specifically evaluated BCG vaccine use to prevent MDR TB, there is no reason to expect vaccine efficacy to be affected by the drug sensitivity of M. tuberculosis strains.

The expert opinion of the panel is to offer the use of BCG vaccine to prevent MDR TB disease for traveling workers based on four principal points: (1) increased rates of MDR TB in areas where many United States workers travel and work; (2) development of IGRA tests that can discriminate between TB infection and BCG immunity; (3) clinical trial evidence that confirms protection provided by BCG vaccine not only against the most severe complications of TB disease (disseminated disease, meningitis, and death) but efficacy as well for prevention of adult pulmonary disease, and recent limited results that suggest possible protection against TB infection; and (4) absence of any proven effective treatment for LTBI due to MDR strains of M. tuberculosis and the clinical and management gravity of MDR TB disease. This use of BCG vaccine is consistent with the current CDC recommendation that BCG vaccination of healthcare workers should be considered on an individual basis in settings in which (1) a high percentage of patients with TB are infected with MDR TB, (2) there is ongoing transmission of drug-resistant TB strains, and (3) comprehensive TB infection control precautions have been implemented (45, 46) (Tables 6 and 7).

Table 6. Recommendations for bacille Calmette-Guérin vaccination in travelers

For otherwise healthy U.S.-born workers, a single dose of BCG vaccine may be considered as a pretravel preventive measure, unless contraindicated (Table 7).
Factors to consider include:
 The proposed vaccinee has no history or previous diagnosis of LTBI or TB disease.
 The patient population at the specific proposed site of work is likely infected with Mycobacterium tuberculosis strains with multiple-drug resistance.
 Transmission of such drug-resistant strains to the worker is likely.
 Comprehensive TB infection control precautions have not or cannot be implemented due to limited resources or other issues.
 BCG vaccination should not be relied on solely for risk reduction; thus, appropriate personal protective measures are recommended.
Vaccination with BCG should be offered before traveling but not be required for any worker. Information that should be discussed with the worker to aid in making the decision to vaccinate or not includes:
 The variable data on the efficacy of BCG vaccination
 The possible complications of BCG vaccine, especially in immunocompromised persons, such as those infected with HIV or with serious suppression of their immune system due to underlying disease or therapies
 The contraindications to BCG vaccination (Table 7)
 The effect of BCG vaccination on the tuberculin skin test and the advisability for post vaccination TB screening using IGRA and not a tuberculin skin test
Because optimal maturation of the immune response to BCG vaccination requires greater than 2 mo, and the vaccination site may not heal for up to 3 mo, when possible, BCG should be administered more than 2 mo before departure.
 This will allow immunity to develop and allow management of any adverse effects.
BCG vaccine can also be administered shortly before departure when the worker plans an extended stay, to offer the potential for protection during the latter part of the work assignment. Vaccine recipients should be aware that immunization just before departure could mean that they may have a draining skin lesion for several weeks when they arrive at their destination. The site of vaccination should be covered during this period.
Remind vaccinees that they are likely to test positive to a tuberculin skin test (but not IGRA) for years after successful vaccination.
 Lack of a positive tuberculin skin test should not be regarded as an indication of a failure of the vaccine.

Definition of abbreviations: BCG = bacille Calmette-Guérin; LTBI = latent tuberculosis infection; TB = tuberculosis.

Information on how to order both BCG vaccine and the applicator along with instructions for application can be found at: http://www.merck.com/product/usa/pi_circulars/b/bcg/bcg_pi.pdf.

Table 7. Bacille Calmette-Guérin vaccine adverse effects and contraindications

BCG vaccine adverse events
 Cutaneous
  Near universal
  Localized, self-limited at site
   Small papules Days 10–14; maximum size about 3 mm at 4–6 wk
   Resolve into flat scars after several mo
  Keloids develop at vaccine site in some individuals who tend to form these reactions
 Lymphadenitis
  Occurs in 0.5–5%
  Simple: nontender enlarged ipsilateral regional lymph node that resolves without treatment
  Suppurative adenitis
 Systemic symptoms
  Postvaccination self-limited fever, anorexia, myalgia, and neuralgia
 Disseminated BCG disease
  85% Occurs in immunocompromised
  Defined as:
   Isolation of BCG from two or more anatomic sites
   Positive blood or bone marrow culture
   Systemic syndrome consistent with mycobacterial disease
  Fatal disseminated disease 0.05–1.56 cases/million doses
  Disseminated disease in HIV-infected infants 4 – 13/1,000 vaccinated annually, many fatal
Contraindications to BCG vaccine
 Those allergic to any component of the vaccine or with serious reaction to a previous dose of BCG
 Persons with impaired immunity:
  HIV infection
  Congenital immunosuppression
  Immunosuppressive treatment including:
   Corticosteroids
   Alkylating agents
   Antimetabolites
   TNF-α–blocking drugs
   Radiation
 Pregnancy

Definition of abbreviations: BCG = bacille Calmette-Guérin; TNF = tumor necrosis factor.

Recommended Risk Reduction Measures for Workers Traveling to MDR TB–Endemic Regions While Working in High TB Risk Areas

See discussion of respirators above.

Transmission control measures.

Transmission control efforts can effectively reduce the risk of exposure when aggressively implemented, even within high risk of transmission settings. Significant reduction of TB infections in healthcare workers has been demonstrated with the implementation of TB control measures in a number of international settings, including Brazil (47), Thailand (48), and the United States (49, 50). Although there are limited data regarding the effectiveness of infection control in the spread of MDR TB to workers, several studies have demonstrated a significant decrease in healthcare worker MDR TB infection due to transmission control efforts (51, 52). Despite these studies documenting their effectiveness in preventing healthcare worker TB infection, implementation of transmission control policies and procedures is often inadequate or nonexistent, especially in resource-poor settings (53, 54).

For healthcare settings, guidelines for preventing the transmission of TB recommend that activities focus on a hierarchy of infection control measures, including (1) administrative controls, (2) environmental controls, and (3) respiratory protection (12). WHO and The International Union against Tuberculosis and Lung Disease guidelines for the prevention of TB in healthcare facilities in countries and areas with limited resources stress the importance of administrative controls and recommend the use of personal respiratory protection (24, 55). Administrative control strategies are designed to prevent TB transmission by minimizing or avoiding exposure. This may involve limiting the type of patients seen, adjusting the setting in which the patient is evaluated, and reducing the duration of contact with the patient. Surgical masks worn by patients were found to decrease transmission by 53% (56). Other low-technology measures that may be useful include cohorting infectious patients and separating them from other patient-care areas, opening windows and curtains in patient-care areas to facilitate natural ventilation and sunlight, and educating patients on cough etiquette (Table 3).

In low-income countries, resources to support transmission control may be absent and implementation ineffective. The most effective administrative control measures are intensified TB case finding and appropriate treatment. Effective chemotherapy works within days to reduce infectiousness among household contacts even before microbiologic sputum smear and culture conversion occurs (57). Preliminary observations using air sampling by sentinel guinea pigs suggests a rapid reduction in infectiousness also occurs among patients with MDR TB receiving effective therapy, but perhaps not among XDR TB cases (E. Nardell, personal communication). Individuals on medical wards with unrecognized TB disease and those with unrecognized MDR TB treated with standard first-line drug regimens or inadequate second-line regimens are a special source of transmission, especially as there may be a false sense of safety once a diagnosis is made and treatment started. Delayed diagnosis of MDR TB due to inadequate laboratory capacity is a significant factor contributing to ongoing risk of transmission in many countries.

A recent WHO publication on the ethics of TB prevention and care notes that “health care workers should not be expected to assume risk that can be avoided by the adoption of basic infection control measures, thus any discussion of health care worker obligations must also consider the reciprocal obligations of governments and health-care facilities to provide minimum standards of safety” (11).

Recommended Risk Reduction Measures for Workers Traveling to MDR TB–Endemic Regions after Return to the Lower-Risk Area
TB screening on return.

For those workers who are identified as having tuberculin skin test conversion or newly positive IGRAs after work in an area with known risk of transmission of MDR TB, LTBI due to an MDR TB strain is possible. Documentation of this 8 to 10 weeks after return helps to better identify this risk. It also identifies recent infections with an increased risk of progression to active TB (Figure 3).

Recommendations for management of LTBI diagnosed after exposures in areas where the likelihood of exposure to MDR TB is high.

CDC recommendations for treatment of LTBI in those likely to be infected with MDR TB are available; however, there are no data establishing any preventive regimen as effective against LTBI due to MDR TB (58). These regimens may potentially benefit those infected by strains with susceptibility to a fluoroquinolone, ethambutol, or pyrazinamide, but for those infected with an isolate that is resistant to two or three of these drugs, no reasonable regimen for treatment of LTBI is available. In some settings, totally resistant isolates have been reported (59). Although there are no proven treatments for preventing TB disease in persons likely to be infected with MDR TB, necessity has required the formulation of reasoned approaches when an individual has been exposed under conditions where drug resistance is prevalent and LTBI has been diagnosed. Consultation with an expert in the management of drug-resistant TB disease is strongly recommended (Figure 3) (58, 60, 61).

The authors thank Elsa Villarino, John Halpin, Emad Yanni, and Ken Castro from the CDC for their unwavering support and input in the development and writing of this document as well as Alysia Wayne and Kimberley Chapman for administrative assistance. They also thank John Grabenstein and Eddy Bresnitz of Merck & Co., Inc. for their input regarding BCG vaccine availability, access, and the applicator device.

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The content and views expressed in this publication are the sole responsibility of the authors and do not necessarily reflect the views or policies of the Department of Defense or the U.S. Government.

Correspondence and requests for reprints should be addressed to Barbara J. Seaworth, M.D., Heartland National TB Center, 2303 SE Military Drive, San Antonio, Texas 78223. E-mail:

Author disclosures are available with the text of this article at www.atsjournals.org.

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