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In view of the rapidity of rifampin resistance identification, the World Health Organization issued continued guidance in 2020 that rapid molecular testing is the ideal initial test for diagnosis and resistance profiling in persons in whom pulmonary or extrapulmonary tuberculosis is suspected.


  • Fatigue, weight loss, fever, night sweats, and productive cough.

  • Risk factors for acquisition of infection: household exposure, incarceration, drug use, travel to or residence in endemic area.

  • Chest radiograph: pulmonary opacities, including nodular or cavitating.

  • Acid-fast bacilli on smear of sputum, rapid molecular testing positive, or sputum culture positive for M tuberculosis.


Tuberculosis is one of the world’s most widespread and deadly illnesses and is the most deadly infectious disease. M tuberculosis, the organism that causes tuberculosis infection and disease, infects one-quarter of the world’s population, nearly 2 billion people. In 2019, there were 10 million new cases of tuberculosis worldwide with 1.4 million people dying of the disease. While most incident cases occur in low- and middle-income countries, tuberculosis is present in all regions of the world. In the United States, an estimated 13 million people are infected with M tuberculosis, and in 2019, there were 8914 reported active cases (a decrease from prior years), with the majority of incident cases in New York, California, Florida, and Texas. Tuberculosis occurs disproportionately among disadvantaged populations, such as the malnourished, homeless, and those living in overcrowded and substandard housing. There is an increased occurrence of tuberculosis among HIV-positive individuals.

Infection with M tuberculosis begins when a susceptible person inhales airborne droplet nuclei containing viable organisms. Tubercle bacilli that reach the alveoli are ingested by alveolar macrophages. Infection follows if the inoculum escapes alveolar macrophage microbicidal activity. Once infection is established, lymphatic and hematogenous dissemination of tuberculosis typically occurs before the development of an effective immune response. This stage of infection, primary tuberculosis, is usually clinically and radiographically silent. In most persons with intact cell-mediated immunity, T-cells and macrophages surround the organisms in granulomas that limit their multiplication and spread. The infection is contained but not eradicated, since viable organisms may lie dormant within granulomas for years to decades.

Individuals with latent tuberculosis infection do not have active disease and cannot transmit the organism to others. However, reactivation of disease may occur if the patient’s immune defenses are impaired. Active tuberculosis will develop in 5–15% of individuals with latent tuberculosis infection who are not given preventive therapy; half of these cases occur in the 2 years following primary infection. Diverse conditions such as gastrectomy, silicosis, diabetes mellitus, and an impaired immune response (eg, HIV infection; therapy with corticosteroids, tumor necrosis factor inhibitors or other immunosuppressive drugs) are associated with an increased risk of reactivation.

In approximately 5% of cases, the immune response is inadequate to contain the primary infection and progressive primary tuberculosis...

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