Infectious Agent

Mycobacterium tuberculosis is a rod-shaped, nonmotile, slow-growing, acid-fast bacterium.


Tuberculosis (TB) transmission occurs when a contagious patient coughs, spreading bacilli through the air. Bovine TB (caused by the closely related M. bovis ) can be transmitted by consuming unpasteurized dairy products from infected cattle.


Globally, 10.4 million new TB cases and 1.7 million TB-related deaths are estimated to occur each year. TB occurs throughout the world, but the incidence varies (see Map 4-12). In the United States, the annual incidence is <3 per 100,000 population, but in some countries in sub-Saharan Africa and Asia, the annual incidence is several hundred per 100,000.

Map 4-12.Estimated tuberculosis incidence rates, 2016
Map 4-12.Estimated tuberculosis incidence rates, 2016
Data source: World Health Organization. Global Tuberculosis Report 2017 ( and Geneva: World Health Organization; 2017 [cited 2018 Feb 13].

Drug-resistant TB is of increasing concern. Multidrug-resistant (MDR) TB is resistant to the 2 most effective drugs, isoniazid and rifampin. Extensively drug-resistant (XDR) TB is resistant to isoniazid and rifampin, any fluoroquinolone, and ≥1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). MDR TB is less common than drug-susceptible TB, but globally approximately 490,000 new cases of MDR TB are diagnosed each year, and some countries have proportions of MDR TB >25% (Table 4-21). MDR and XDR TB are of particular concern among HIV-infected or other immunocompromised people. As of 2016, XDR TB had been reported in 123 countries.

Table 4-21. Estimated proportion of MDR TB cases in high MDR TB burden countries, 2016


% Of New TB Cases that are MDR

% Of Retreatment TB Cases that are MDR
















Democratic Republic of Congo
























Myanmar (Burma)









Papua New Guinea









Republic of Moldova






South Africa





















Before leaving the United States, travelers who anticipate possible prolonged exposure to TB (such as those spending time caring for patients or working in health care facilities, correctional facilities, or homeless shelters) or those who plan a prolonged stay in an endemic country should have a pretravel blood-based interferon-γ release assay (IGRA, such as QuantiFERON, T-SPOT.TB) or a 2-step tuberculin skin test (TST) (see Perspectives : Tuberculin Skin Testing of Travelers, later in this chapter).

If the predeparture test result is negative, the IGRA or single TST should be repeated 8–10 weeks after returning from travel. The predeparture test and follow-up test after traveler return should be the same test type to ensure accurate interpretation of results. Because people with HIV infection or other immunocompromising conditions are more likely to have an impaired response to either a skin or blood test, travelers should inform their clinicians about such conditions.

Although the risk of TB transmission on an airplane is low and dependent on infectiousness of the TB patient, seating proximity, flight duration and host factors, instances of transmission have occurred. To prevent TB transmission, people who have infectious TB (TB that can be spread to other people) should not travel by commercial airplanes or other commercial conveyances. Only TB of the lung or airway is infectious, and health department authorities determine whether a person is infectious based on the person’s chest radiograph, sputum tests, symptoms, and treatment received. The World Health Organization (WHO) has issued guidelines for notifying passengers potentially exposed to TB aboard airplanes. Passengers concerned about possible exposure to TB should see their primary health care provider or visit their local health department clinic for evaluation.

Bovine TB (M. bovis ) is a risk in travelers who consume unpasteurized dairy products in countries where M. bovis in cattle is common. Mexico is a common place of infection with M. bovis for US travelers.

Clinical Presentation

TB infection can be identified by a positive TST or IGRA result 8–10 weeks after exposure. Overall, only 5%–10% of otherwise healthy people have an infection that progresses to TB disease during their lifetime. Progression to disease can occur weeks to decades after initial infection. People with TB disease have symptoms or other manifestations of illness such as an abnormal chest radiograph. In the remainder, the infection remains in an inactive state (latent TB infection or LTBI) in which the infected person has no symptoms and cannot spread TB to others.

TB disease can affect any organ but most commonly the lungs (70%–80%). Typical TB symptoms include prolonged cough, fever, decreased appetite, weight loss, night sweats, and coughing up blood (hemoptysis). The most common sites for TB outside the lungs are the lymph nodes, pleura, bones and joints, brain and spinal cord lining (meningitis), kidneys, bladder, and genitalia.

The risk of progression to disease is much higher in immunosuppressed people (for example, 8%–10% per year in HIV-infected people not receiving antiretroviral therapy). People who are receiving tumor necrosis factor blockers to treat rheumatoid arthritis and other chronic inflammatory conditions are also at increased risk for disease progression.


CDC/American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) have published diagnostic recommendations for both TB disease and LTBI. Sputum or other respiratory cultures and smears for acid-fast bacilli (AFB) should be collected for suspected cases of pulmonary TB, and for AFB smear-positive pulmonary cases, a nucleic acid amplification test (NAAT) positive for M. tuberculosis complex rapidly confirms the diagnosis. Similarly, diagnosis of extrapulmonary TB disease can be confirmed with a NAAT positive for M. tuberculosis complex or a culture positive for M. tuberculosis from affected body tissues or fluids. On average, it takes about 2 weeks to culture and identify M. tuberculosis , even with rapid culture techniques.

A preliminary diagnosis of TB can be made when AFB are seen by microscope on sputum smear or in other body tissues or fluids. However, microscopy cannot distinguish between M. tuberculosis and nontuberculous mycobacteria. This is particularly problematic in countries such as the United States where TB incidence is low. NAATs are more rapid than culture and specific for M. tuberculosis . They are also more sensitive than the acid-fast bacillus smear but less sensitive than culture.

A diagnosis of TB disease can be made using clinical criteria in the absence of microbiologic confirmation. However, laboratory testing should be performed when feasible to confirm the diagnosis. Molecular tests for drug resistance can be performed directly on specimens and can guide initial treatment while culture results are pending. Culture-based susceptibility testing is recommended for all patients with a positive culture, regardless of the availability of molecular testing, to guide the final determination on the appropriate drug regimen.

LTBI is diagnosed by a positive IGRA or TST after further examinations (such as chest radiograph, symptom review) have excluded TB disease. TB is a nationally notifiable disease.


People with LTBI can be treated, and treatments are effective at preventing progression to TB disease. It is necessary to exclude TB disease before starting LTBI treatment. Current LTBI regimens in the United States for drug-susceptible TB include 3 months of once-weekly isoniazid and rifapentine (3HP), 4 months of daily rifampin, and 6–9 months of daily isoniazid. Given low completion rates of the 6- to 9-month isoniazid regimen, shorter-duration regimens are generally preferred. However, providers should choose the regimen on the basis of coexisting medical illness, potential for drug interactions, and drug-susceptibility results of the presumed source of exposure (if known). For example, rifampin has interactions with oral contraceptives and certain antiretroviral medications taken by people with HIV/AIDS.

For people who are at especially high risk for TB disease and may have difficulty adhering to treatment or are given an intermittent dosing regimen, directly observed therapy (DOT) for LTBI may be considered. Travelers who suspect that they have been exposed to TB should inform their health care provider of the possible exposure and receive a medical evaluation. Because drug resistance is relatively common in some parts of the world, travelers who have TST or IGRA conversion associated with international travel should consult experts in infectious diseases or pulmonary medicine.

Drug-susceptible TB disease is treated with a multiple-drug regimen administered by DOT for 6–9 months (usually isoniazid, rifampin, ethambutol, and pyrazinamide for 2 months, followed by isoniazid and rifampin for an additional 4 months). Patients with drug-resistant TB are more difficult to treat, requiring 4–6 drugs for 18–24 months, and should be managed by an expert in MDR/XDR TB. CDC/ATS/IDSA have published guidelines on treatment for drug-susceptible TB disease.


Travelers should avoid exposure to people with TB disease in crowded and enclosed environments (such as health care facilities, correctional facilities, or homeless shelters). Travelers who will be caring for patients or working in health care facilities where TB patients are likely to be encountered should be advised to consult infection control or occupational health experts about baseline LTBI screening and procedures for obtaining personal respiratory protective devices (such as N-95 respirators), along with respirator selection and training.

Based on WHO recommendations, bacillus Calmette-Guérin (BCG) vaccine is used once at birth in most developing countries to reduce the severe consequences of TB in infants and children. However, BCG vaccine has variable efficacy in preventing the adult forms of TB. Although not routinely recommended for use in the United States, some experts have advocated BCG vaccination for health care providers who are likely to be exposed to MDR or XDR TB patients in settings where the TB infection-control measures (such as those recommended in the United States) are not fully implemented. BCG may offer some protection in this circumstance; however, people who receive BCG vaccination must follow all recommended TB infection-control precautions to the greatest extent possible. Additionally, IGRA is preferred over the TST for pretravel and posttravel testing in people vaccinated with BCG, as BCG may result in false-positive TST results.

To prevent infections due to M. bovis , travelers should also avoid eating or drinking unpasteurized dairy products.

CDC website:


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Neela D. Goswami, Philip A. LoBue