A 40-year-old Indian immigrant presented to the emergency department with hemoptysis. He had had an intermittent productive cough for the past 4 weeks with increasing fatigue and lack of appetite. He also had intermittent fever with drenching night sweats. Chest radiograph and CT scan showed a left upper lobe cavitary lesion with infiltrate. He was admitted to the hospital with concern for pneumonia and to rule out possible active pulmonary tuberculosis.
Active pulmonary tuberculosis (APTB) remains an important but often missed diagnosis in hospitalized patients in the Western world.1,2 Because of its relative rarity, the diagnosis of APTB often is delayed in the United States, which can lead hospitalized patients to nosocomial transmission, unnecessary exposures, patient harm,3 and potentially avoidable cost to the health care system.4 The diagnosis and management can be challenging involving isolation needs, sputum clearance, treatment strategy, and criteria for discharge to home.
Any patient with risk factors presenting with signs and/or symptoms of APTB such as productive cough for more than 4 weeks, night sweats, weight loss, low-grade fevers, upper lobe cavitary lesions, or hemoptysis should be suspected. The diagnostic work-up for APTB should always begin with a thorough medical and social history. A chest radiograph or a CT scan should always be obtained. Risk factors for infection and for progression to active pulmonary TB are listed below.
Risk factors for TB infection:
- Close contacts of a person with APTB.
- Health care workers.
- Immigrants from high-burden countries.
- Homeless people.
- Individuals who have been incarcerated.
- International travelers.
- HIV patients.
- Intravenous drug users.
Risk factors for progression to APTB:
- HIV infection.
- Intravenous drug use.
- Younger than 5 years of age.
All patients with suspected or confirmed APTB who cannot be safely discharged home (see discharge considerations below) should be kept in negative-pressure airborne isolation rooms. Isolation can be discontinued once APTB has been ruled out or the patient is determined to be noninfectious based on three consecutive negative sputum smears.
Although rapid and inexpensive, acid-fast bacilli (AFB) smear microscopy has poor sensitivity (45%-80%, with culture-confirmed APTB cases) and poor positive predictive value (50%-80%) for TB in settings in which nontuberculous mycobacteria are commonly isolated. This makes an AFB smear nondiagnostic in the early diagnosis of APTB. The burden of mycobacteria seen in the sputum smear correlates with infectivity.
To improve sensitivity of testing, it is strongly recommended that three AFB smears be completed in 8- to 24-hour intervals and positive smears be accompanied by nucleic acid amplification (NAA) testing.5 If APTB is suspected, but the patient is unable to expectorate, induced sputum samples should be obtained, and, if unable to induce sputum samples, flexible bronchoscopy sampling should be pursued especially for the high-risk populations described above.
The Centers for Disease Control and Prevention recommends that at least one sputum specimen be tested with NAA to expedite the time to diagnosis of APTB. A negative NAA does NOT rule out TB. The turnaround time for this test is about 24-48 hours. NAA has better positive predictive value (greater than 95%) with AFB smear-positive specimens in settings in which nontuberculous mycobacteria are common. The ability to confirm rapidly the presence of Mycobacterium tuberculosis is 50%-80% in AFB smear-negative, culture-positive specimens.6
In patients with clinical or radiologic suspicion of APTB who are unable to produce sputum or have negative sputum smear microscopy results, bronchoscopy is a safe and reliable method for the diagnosis of pulmonary tuberculosis. For the diagnosis of tuberculosis, bronchoalveolar lavage has a sensitivity and specificity of 60% and 100%, respectively. Adding transbronchial biopsy further increases the sensitivity to 84%, and post-bronchoscopy sputum smear microscopy increases the sensitivity to 94%.6
In 2005, the CDC released guidelines for using interferon-gamma release assays (IGRA) to test for M. tuberculosis infection.7 Both tuberculin skin testing (TST) and IGRAs assess lymphocytes’ response to M. tuberculosis. Although these tests can be supportive of a previous tuberculosis infection, they are not diagnostic tests for APTB. Neither an IGRA nor a TST can distinguish latent from active tuberculosis.
Sputum AFB culture remains the preferred method for laboratory confirmation of APTB. Once APTB is confirmed, it is essential for susceptibility testing and genotyping. However, in the absence of a positive culture, APTB can be diagnosed based on signs and symptoms alone in a high-risk patient.