Introduction
Background
Tuberculosis is an infectious disease that has been known for centuries. Traditionally, the term tuberculosis has been used to indicate infections caused by Mycobacterium tuberculosis and Mycobacterium bovis; however, a multitude of causative mycobacteria are recognized.
Tuberculosis may involve multiple organs such as the lung, liver, spleen, kidney, brain, and bone. In endemic regions, the normal host immune response may be sufficient to contain the infection and prevent clinical presentation. Uncontrolled or uncontained infection may result in great morbidity and mortality.
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Pathophysiology
Mycobacteria are non–spore-forming bacilli that are obligate aerobes. They are recognized microscopically by an intense staining with aniline dyes (notably carbol-fuchsin) and resistance to decoloration with acid washing; therefore, the term acid-fast bacilli is used to describe them. Unlike other bacteria, mycobacteria require enriched culture media and extended incubation (usually 2-8 wk). Therefore, bacteriologic recognition of a mycobacterial infection is a protracted process that may delay appropriate medical therapy. The advent of polymerase chain reaction (PCR) techniques has increased the rapidity with which tuberculous infection is diagnosed.
Tuberculous infection occurs as a consequence of the inhalation of bacillus-laden droplets expelled from an infected host. Given the stringent growth requirements of the organism, the development of an infection depends on prolonged exposure (on the order of weeks) to an individual with active pulmonary tuberculosis. Once the organism is inhaled, it travels via the airways to the pulmonary parenchyma, where it is deposited. Although the organism may be deposited in any lobe, a predilection for the lower lobes exists.
The organism is ingested by alveolar macrophages, which then attempt to phagocytize the bacilli. As a result of the natural defenses of the tubercle bacillus, alveolar macrophages may be unsuccessful in attempting to completely destroy the bacilli, which then lie dormant within the macrophage. As a consequence, bacilli often remain viable within the macrophages in immunocompetent individuals. Subsequently, bacilli may travel via the pulmonary lymphatics, or they may enter the vascular system and seed distant sites such as the liver, spleen, or bone marrow.
In most immunocompetent individuals, macrophages are successful in containing the bacilli, and the infection is self-limited and often subclinical. The contained infection in immunocompetent hosts is called primary tuberculosis. Primary tuberculosis is seen most often in children in endemic regions.1,2 Since the advent of the AIDS era, adults may present with radiographic findings similar to those of primary tuberculosis.
In some patients, pulmonary macrophages are unable to contain the bacilli and are overwhelmed, leading to a clinically apparent infection. This is more common in patients who are immunocompromised, notably the population with HIV/AIDS.3 This form of tuberculosis is called progressive primary tuberculosis. Patients with progressive primary tuberculosis may present with pulmonary manifestations (often with miliary tuberculosis) or with manifestations of systemic or disseminated disease.
Postprimary (reactivation) tuberculosis is seen in patients in whom the initial infection was contained successfully by the pulmonary macrophages, with bacilli remaining viable within the macrophages. Infection results when the host's immune status (T cells) is compromised. This form may appear in the elderly population, for example.
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Frequency
United States
The incidence of tuberculosis markedly declined in the United States from the 1950s to the 1980s, largely as a result of improvements in public health programs, the development of effective chemotherapeutic agents, and improved living conditions. Subsequently, the incidence increased in 1985-1992, with an overall incidence of 10.5 cases per 100,000 population in 1992. The change has been attributed to the emergence of the HIV/AIDS epidemic during this decade. The incidence of tuberculosis again declined in the 1990s, with an incidence of 6.8 cases per 100,000 population in 1998.4
International
In 1997, the World Health Organization conducted a study to determine worldwide incidence and prevalence of tuberculosis.5 The total number of new cases in 1997 was estimated to be 7.96 million. This figure includes an estimated 3.52 million cases of infectious pulmonary tuberculosis. The death rate attributed to tuberculosis in 1997 was approximately 1.87 million.
Mortality/Morbidity
In immunocompetent patients in endemic regions, the primary infection is contained, and the patients remain asymptomatic. In some patients with relative immune compromise, primary infection may lead to fulminant pulmonary infection, with pulmonary necrosis leading to death. This is called progressive primary tuberculosis. Pulmonary manifestations of progressive pulmonary tuberculosis may be radiographically indistinguishable from manifestations of postprimary tuberculosis.
Postprimary tuberculosis is a significant cause of worldwide morbidity and mortality. Morbidity may result in any affected organ system. Pulmonary morbidity may result from a chronic cough, hemoptysis (which may be fatal), fibrosis, superinfection (eg, mycetoma), bronchial stenosis, repeated pulmonary infections from tuberculous bronchiectasis, or empyema.6,7 Significant morbidity also may arise from chronic tuberculous osteomyelitis, chronic renal insufficiency, or neurologic changes related to central nervous system (CNS) tuberculosis.
Race
Tuberculosis is a worldwide infection. Endemic areas include India, Southeast Asia, and sub-Saharan Africa.
Sex
No sex predilection exists for tuberculosis.
Age
Infection may occur at any age and is most significant at the extremes of age. Primary tuberculosis is usually seen in young children in endemic regions. The incidence is increasing in individuals in nonendemic regions who are immunocompromised.
Anatomy
Tuberculosis is transmitted via the spread of bacilli in aerosolized droplets. Infected droplets pass from the nasopharynx into the tracheobronchial tree and continue to the lung. As a result of gravity, droplets tend to be deposited in the lower lobes; therefore, primary tuberculosis is more common in the lower lobes. The oxygen tension is higher in the upper lobes, where reactivation tuberculosis usually occurs.
The intrapulmonary lymphatics and blood vessels play an important role in the manifestations of tuberculosis. The lymphatics and vasculature lie within the interstitium of the lung, and they drain (veins and lymphatics) and supply (arteries) the adjacent region of lung. This anatomy accounts for ipsilateral lymphadenopathy because infected lymph is drained along the interstitium to the hilar and mediastinal lymph nodes. Venous drainage allows hematogenous dissemination of the infection.
Presentation
Primary tuberculosis is usually a self-limited infection seen in children in endemic regions. As many as 60% of children and 5% of adults with primary tuberculosis are asymptomatic. Patients with primary pulmonary tuberculosis may be minimally symptomatic, with minimal constitutional symptoms. Children may present with fever, malaise, weight loss, cough, and occasional hemoptysis.
Progressive primary tuberculosis occurs in the setting of acute infection in patients with minimal or marked immune compromise. Patients with progressive primary tuberculosis become acutely ill, and they may have extensive lung parenchymal opacities and cavitation. Hypoxia and death may occur.
Patients with postprimary tuberculosis often manifest disease within 2 years of the initial infection or many years later, often as a result of comorbid states: old age, malnutrition, and/or neoplasm. These patients experience indolent clinical symptoms that include lethargy, anorexia, weight loss, low-grade fever, cough, hoarseness, and hemoptysis.
Preferred Examination
Diagnosis is based on a combination of tuberculin skin testing (purified protein derivative testing), sputum cultures, and radiography. Bronchoscopy may be required to obtain specimens.
Patients with primary tuberculosis may not undergo imaging; however, if imaging is performed, a conventional chest radiograph may be sufficient for diagnosis in the appropriate clinical setting.
In patients with progressive primary or postprimary tuberculosis, computed tomography (CT) is often performed, in addition to chest radiography. Magnetic resonance imaging (MRI) may be used to evaluate complications of thoracic disease. Patients with postprimary tuberculosis may also undergo bronchoscopy to evaluate endobronchial disease and to obtain sputum specimens for microbacteriologic cultures.8,9
Limitations of Techniques
With the purified protein derivative skin test, false-positive results may be seen in individuals who have been inoculated with bacillus Calmette-Guérin vaccine. False-negative results may occur in patients who are anergic, such as patients with HIV infection and decreased CD4 counts. These patients require an anergy panel.
As a result of the stringent growth requirements of the bacillus, culturing of the organisms is often a lengthy and difficult process. False-negative results may be seen if insufficient organisms are present in the specimen.
Conventional radiography is limited in its sensitivity and specificity. As many as 15% of patients with primary tuberculosis have normal chest radiographic findings. Clinical suspicion must remain high for prompt diagnosis in these individuals. Chest radiographic results are not specific for tuberculosis, and other entities must remain in the differential diagnosis,10
Differential Diagnoses
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References
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Lee KS, Song KS, Lim TH, et al. Adult-onset pulmonary tuberculosis: findings on chest radiographs and CT scans. AJR Am J Roentgenol. Apr 1993;160(4):753-8. [Medline].
Linh NN, Marks GB, Crawford AB. Radiographic predictors of subsequent reactivation of tuberculosis. Int J Tuberc Lung Dis. Oct 2007;11(10):1136-42. [Medline].
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Primack SL, Logan PM, Hartman TE, et al. Pulmonary tuberculosis and Mycobacterium avium-intracellulare: a comparison of CT findings. Radiology. Feb 1995;194(2):413-7. [Medline].
Eisenhuber E, Mostbeck G, Bankier A, Stadler A, Rumetshofer R. [Radiologic diagnosis of lung tuberculosis]. Radiologe. May 2007;47(5):393-400. [Medline].
Further Reading
Keywords
Mycobacterium tuberculosis, M tuberculosis, Mycobacterium bovis, M bovis, tuberculous infection, active pulmonary tuberculosis, progressive primary tuberculosis, postprimary tuberculosis, reactivation tuberculosis, infectious pulmonary tuberculosis
