Am Fam Physician. 2022;106(3):308-315
Author disclosure: No relevant financial relationships.
Approximately 10 million people worldwide were infected with tuberculosis (TB) in 2019, resulting in 1.4 million deaths. In the United States that same year, there were nearly 9,000 reported cases of TB disease and up to 13 million people were living with latent TB infection (LTBI), which is an asymptomatic, noncommunicable infection caused by Mycobacterium tuberculosis. Without treatment, LTBI will progress to active TB disease in approximately 5% to 10% of affected people. Individuals with symptoms of TB disease warrant testing. The U.S. Preventive Services Task Force recommends testing individuals at increased risk of LTBI with an interferon-gamma release assay or tuberculin skin testing. Because the incidence of LTBI in health care professionals is similar to that of the general population, periodic retesting is not recommended. After a positive test result, chest radiography should be performed and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis. Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively. Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), followed by a continuation phase lasting 18 weeks or more, with two drugs based on susceptibility testing results. Consultation with a TB expert is necessary if there is suspicion or confirmation of drug-resistant TB.
In 2019, approximately 10 million people worldwide were diagnosed with tuberculosis (TB), an infection caused by Mycobacterium tuberculosis, resulting in 1.4 million deaths.1 In the United States, there were nearly 9,000 reported cases of TB disease in 2019, with up to 13 million people living with latent TB infection (LTBI).2 Over the past decade, TB incidence in the United States has decreased by 2% to 3% annually, except in 2020 when the incidence was 20% lower compared with 2019.2,3 The COVID-19 pandemic may have affected the reporting of TB incidence in several ways, including underdiagnosis and a true reduction in the incidence of TB.2
| Clinical recommendation | Evidence rating | Comments |
|---|---|---|
| Screening for LTBI is recommended in individuals at increased risk.5 | B | U.S. Preventive Services Task Force recommendation |
| Interferon-gamma release assay and tuberculin skin testing are the preferred methods of testing for TB in at-risk individuals.6 | C | CDC recommendation |
| Preferred treatment regimens for LTBI are three to four months in duration.18 | C | National Tuberculosis Controllers Association and CDC recommendation |
| In active, drug-susceptible TB disease, four drugs (i.e., isoniazid, rifampin, pyrazinamide, and ethambutol) should be used for an intensive phase of eight weeks. This is followed by a continuation phase of four months with two drugs based on susceptibility test results (i.e., isoniazid and rifampin).24 | C | American Thoracic Society, CDC, and Infectious Diseases Society of America recommendation |
TB is caused by inhalation of respiratory droplets containing M. tuberculosis from a person with active respiratory disease. The M. tuberculosis bacilli multiply in the alveoli and can enter the bloodstream, spreading throughout the body (e.g., brain, larynx, lymph nodes, spine, bone, kidneys). The immune response to TB infection is the formation of granulomas resulting in LTBI. If the immune system cannot control the infection, the bacilli will multiply and progress to TB disease. Without treatment, LTBI will progress to active TB disease in 5% to 10% of affected people.4,5 Risk factors for progression include immunosuppression, diabetes mellitus, intravenous drug use, low body weight, and age younger than five years.6
Which Clinical Situations Warrant TB Testing?
| Employees of, or residents who live or have lived in, congregate settings (e.g., homeless shelters, correctional facilities, nursing homes)* |
| Health care workers who have been exposed to a patient with known TB disease* |
| Infants, children, and adolescents exposed to adults who are known to have latent TB infection or TB disease* |
| Patients known to have HIV, diabetes mellitus, gastrectomy or jejunoileal bypass, low body weight (< 90% of ideal body weight), silicosis, chronic renal failure, leukemia, or cancer of the head, neck, or lungs† |
| Patients taking active immunosuppressive therapy (e.g., tumor necrosis factor–alpha antagonists, systemic corticosteroids [15 mg or more of prednisone per day], immunosuppressive drug therapy following organ transplantation)† |
| People at increased risk of infection because of social determinants, including medically underserved or low-income populations or people who misuse drugs or alcohol*† |
| People born in or who frequently travel to Mexico, the Philippines, Vietnam, India, China, Haiti, Guatemala, sub-Saharan Africa, or other countries with high rates of TB* |
| People who have had contact with someone who has tested positive for or is presumed to have TB disease* |
| People with a history of untreated or inadequately treated TB disease† |
| People with recent Mycobacterium tuberculosis infection (within the past two years)† |
EVIDENCE SUMMARY
Testing should be performed in individuals with symptoms of TB disease and in asymptomatic individuals at increased risk of LTBI and progression to TB disease.5 Symptoms of TB disease include chronic cough (i.e., lasting three weeks or longer), hemoptysis, chest pain, fever, night sweats, anorexia, fatigue, and unexplained weight loss. People at increased risk include those who were born in, or are former residents of, countries with increased TB prevalence (e.g., immigrants, refugees), those who live or have lived in congregate settings (e.g., homeless shelters, correctional facilities), and people with known exposure to TB disease.5–7 People from sub-Saharan Africa and Southeast Asia are particularly at risk of LTBI.7–9 People at low risk of getting TB should not be tested because of the low positive predictive value of testing in low-risk populations.5,6
Initial testing is recommended for all health care professionals upon hire or preplacement. Repeat testing is recommended only for known exposure or based on risk assessments of the health care facility and setting.6 The incidence of LTBI in health care professionals is similar to that of the general population because of a substantial decline in the annual national TB rate in 2017 compared with previous decades.10 A screening questionnaire can be a useful tool in the assessment of health care workers at risk of TB.11
All suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. The health department will assist with diagnostic testing, follow-up, and treatment decisions.6
What Are the Recommended TB Tests?
Interferon-gamma release assay (IGRA) and tuberculin skin testing (TST) are recommended options in testing for TB in at-risk individuals.6
EVIDENCE SUMMARY
IGRA testing requires a blood sample. Two IGRA tests are currently approved for use in the United States: QuantiFERON-TB Gold+ (Qiagen) and T-SPOT.TB (Oxford Immunotec). Both indicate immune sensitization to M. tuberculosis.
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