Tuberculosis (TB) has existed for billions of years, with evidence suggesting infection in dinosaurs. This long evolutionary history underscores the pathogen’s remarkable ability to survive and adapt. Through my work at the Massachusetts General Hospital Mycobacterial Center, I have developed a deep appreciation not only for the resilience of this organism, but also for the resilience of individuals affected by TB—many of whom face stigma, social isolation, work absences, financial strain from infection control measures, and adverse effects from prolonged treatment courses.
Despite being preventable and treatable, TB remains a leading cause of death worldwide. Global health initiatives, including the United Nations Sustainable Development Goals, have set an ambitious target of eliminating TB by 2030. Three issues remain critical to achieving this goal:
(1) Interpretation of TB testing in non–U.S.-born populations
In the United States, over 70% of TB cases occur in individuals born in TB-endemic countries, including the Philippines, India, Nigeria, and Haiti, many of whom received the BCG vaccine at birth. A common misconception among both patients and clinicians is that BCG vaccination causes false-positive TB blood tests. However, the TB blood tests that are available are Interferon-gamma release assays (IGRAs)—including T-SPOT.TB and QuantiFERON-TB Gold and they measure the immune responses to TB-specific antigens (ESAT-6 and CFP-10), which are not present in the BCG vaccine. Therefore, prior BCG vaccination does not cause a positive IGRA or TB blood test; a positive result instead indicates TB exposure. These tests do not distinguish between recent and remote infection, nor do they quantify disease burden. Individuals with positive tests require further evaluation to differentiate TB disease (typically symptomatic) from asymptomatic TB infection (formerly termed latent TB), recognizing that TB exists along a clinical spectrum.
In the United States, over 70% of TB cases occur in individuals born in TB-endemic countries, including the Philippines, India, Nigeria, and Haiti, many of whom received the BCG vaccine at birth. A common misconception among both patients and clinicians is that BCG vaccination causes false-positive TB blood tests. However, the TB blood tests that are available are Interferon-gamma release assays (IGRAs)—including T-SPOT.TB and QuantiFERON-TB Gold and they measure the immune responses to TB-specific antigens (ESAT-6 and CFP-10), which are not present in the BCG vaccine. Therefore, prior BCG vaccination does not cause a positive IGRA or TB blood test; a positive result instead indicates TB exposure. These tests do not distinguish between recent and remote infection, nor do they quantify disease burden. Individuals with positive tests require further evaluation to differentiate TB disease (typically symptomatic) from asymptomatic TB infection (formerly termed latent TB), recognizing that TB exists along a clinical spectrum.
(2) TB preventive therapy
Accurate interpretation of TB test results is essential for identifying individuals eligible for preventive therapy. Identifying those with TB infection and initiating preventive treatment can reduce the risk of progression to TB disease by up to 80%. This approach not only reduces morbidity and mortality but also helps prevent downstream consequences such as missed workdays, stigma, and treatment-related adverse effects.
Accurate interpretation of TB test results is essential for identifying individuals eligible for preventive therapy. Identifying those with TB infection and initiating preventive treatment can reduce the risk of progression to TB disease by up to 80%. This approach not only reduces morbidity and mortality but also helps prevent downstream consequences such as missed workdays, stigma, and treatment-related adverse effects.
(3) TB is not limited to pulmonary disease
TB is often incorrectly perceived as solely a pulmonary condition. While chest radiography is commonly used for screening, it may miss early or subtle disease detectable on more advanced imaging. Moreover, individuals may have microbiologically positive sputum even in the absence of symptoms or radiographic abnormalities. TB can disseminate via lymphohematogenous spread and affect virtually any organ system, including lymph nodes, the pericardium, and the eye. Comprehensive evaluation is therefore essential for individuals with evidence of infection.
TB is often incorrectly perceived as solely a pulmonary condition. While chest radiography is commonly used for screening, it may miss early or subtle disease detectable on more advanced imaging. Moreover, individuals may have microbiologically positive sputum even in the absence of symptoms or radiographic abnormalities. TB can disseminate via lymphohematogenous spread and affect virtually any organ system, including lymph nodes, the pericardium, and the eye. Comprehensive evaluation is therefore essential for individuals with evidence of infection.
Take-home points
- Most U.S. TB cases occur in non–U.S.-born individuals; clinicians can use World Health Organization TB country profiles data to identify regions with incidence rates >20 cases per 100,000, where screening is recommended.
- BCG vaccines do not cause false-positive Interferon-gamma release assays (TB blood tests).
- TB preventive therapy substantially reduces progression to TB disease.
- TB can involve multiple organ systems and requires comprehensive evaluation.
More information about TB
Harvard Medical School Infectious Disease in Adults Course:
Harvard Medical School Updates in General Medicine for Specialists
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