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ESSENTIALS OF DIAGNOSIS

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

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

  • Chest radiograph: pulmonary opacities, most often apical.

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

GENERAL CONSIDERATIONS

Tuberculosis is one of the world’s most widespread and deadly illnesses. M tuberculosis, the organism that causes tuberculosis infection and disease, infects one-third of the world’s population. In 2014, there were 9.6 million new cases of tuberculosis worldwide with 1.5 million people dying of the disease. In the United States, an estimated 11 million people are infected with M tuberculosis, and in 2014, there were 9421 active cases. By 2015, the number of cases of tuberculosis increased for the first time in 23 years in 29 US states, particularly in Texas, California, Florida, and New York. 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 host’s immune defenses are impaired. Active tuberculosis will develop in approximately 6% 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 develops, accompanied by both pulmonary and constitutional symptoms as described below. The clinical presentation does not definitively distinguish primary disease from reactivation of latent tuberculosis infection. Standard teaching has held that 90% of tuberculosis in adults represents activation of latent disease. However, DNA fingerprinting of the bacillus suggests that as many as one-third of new cases of tuberculosis in urban populations are primary infections resulting from person-to-person transmission.

The prevalence of drug-resistant strains is increasing worldwide; ...

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