Essentials of Diagnosis
- The cardinal symptoms of tuberculosis (TB) are fatigue, weight loss, fever, and night sweats.
- The most commonly infected populations include the homeless, institutionalized patients, and HIV-positive patients.
- In most cases, a TB skin test (PPD) is positive.
- To establish presence of infection, an acid-fast bacilli (AFB) smear demonstrates the acid-fast bacillus.
- In primary pulmonary TB, an infiltrate in the lower lobes of the lung is usually seen on chest x-ray. In contrast, apical lung infiltrates are commonly seen in the reactivation of pulmonary TB.
General Considerations
Mycobacterium tuberculosis is still an important pathogen.
Approximately one-third of the world’s population is infected with M tuberculosis, according to World Health Organization estimates, resulting in 2.9 million annual deaths. In the United States, tuberculosis is on the rise, after several decades of steady decline.
The disease develops in a subset of those who are infected. In most patients, the reason disease develops is unclear unless they are immunosuppressed by either HIV infection or other immunocompromising diseases. HIV has played a major role in the resurgence of tuberculosis in the United States and in the emergence of multidrug-resistant disease.
Prompt diagnosis and treatment of active disease is important in all patients to prevent severe disease and infection of the surrounding population. In those infected with the tuberculosis bacillus, the prevention of active tuberculosis disease is also important.
Epidemiology
In the United States, tuberculosis had been on the decline until 1985, when the number of cases began to increase. This increase was undoubtedly a result of the HIV epidemic. Cases continued to increase until 1995, when the 22,813 new cases documented in the United States constituted a 6.4% drop from 1994. This drop resulted from a decreased incidence in the U.S.-born population. The overall incidence of tuberculosis in the United States is quite low, but case rates are high among specific groups such as HIV-infected patients, the homeless, recent immigrants from countries that have a high prevalence of tuberculosis, intravenous drug users, inner-city dwellers, and minorities.
In the late 1980s, tuberculosis caused by organisms resistant to antimicrobial agents increased sharply, especially in New York City, where, in 1991, one-third of all cases were resistant to at least one agent. The rates of resistance in the United States began to decrease in 1995. Of cases reported, the isoniazid (INH) resistance rate was 7.6%, and the INH-rifampin resistance rate was 1.4%. The decrease in resistance rates was most likely caused by the introduction of directly observed therapy and intensive case management.
One lesson learned from the resurgence of tuberculosis and multidrug-resistant tuberculosis is the importance of tuberculosis control strategies and the importance of making sure patients adhere to the medication regimens. The Centers for Disease Control recommends that all tuberculosis patients be observed taking their medications by health care providers (“directly observed therapy,” [DOT]). The decrease in U.S. case rates has been attributed to the institution of DOT. Other factors thought to have decreased the case and resistance rates are improved laboratory methods for identifying tuberculosis, broader use of drug-susceptibility testing, expanded use of preventive therapy in high-risk groups, decreased transmission of tuberculosis in congregative settings, improved follow-up of persons with TB, and increased federal resources for state and local TB control efforts.
M tuberculosis is transmitted in the air. The bacillus is packaged in a droplet nucleus and coughed out into the surrounding air by one person and inhaled by another. Patients with bronchopulmonary TB with a productive cough are particularly infectious. Other factors that increase the infectivity of a person are the extent of cavitary disease of the lung, presence of AFB on the sputum smear, unprotected coughing, and crowding in a household. Generally, patients with extrapulmonary TB are not infectious.
Microbiology
M tuberculosis is an AFB that is curved or straight and nonmotile. It is slow growing, taking = 18 h for one replication. Typically, it may take 2-6 weeks to grow a significant colony. The bacillus is non-pigment producing, which can be used to differentiate it from some other atypical mycobacteria.
Pathogenesis
A person is infected with M tuberculosis by inhaling bacilli in droplet nuclei. The particles must be retained in the lung. Thus the inhaled particles, which are < 5 um in size, travel to the alveolus during inspiration and are retained in the lung. Larger particles are filtered out before they reach the alveoli. In the alveolus, the bacillus activates the immune system. The first line of defense is the alveolar macrophage. These macrophages engulf the bacilli. Some macrophages are capable of killing the bacillus, whereas others cannot. The bacilli multiply within the cells.
The factors controlling the macrophages’ ability to kill M tuberculosis are not all known and may be genetic. At any rate, T cells are then attracted to these macrophages and recognize the M tuberculosis protein presented by the macrophage. The T cell lyses the infected macrophage. Memory T cells then develop which are thought to contribute to the delayed hypersensitivity reaction relied on by the purified protein derivative (PPD) skin test. These memory T cells also enable patients previously infected with TB to resist reinfection.
Other factors that influence the progression of infection to disease include the intensity of exposure, interval since infection, age, and other coexisting or comorbid diseases. Extrapulmonary disease develops when the bacillus is not contained in the lungs and travels to other organs by way of the bloodstream.
Infection by M tuberculosis is reflected by a positive skin test reaction, although, in some immunocompromised patients, a PPD test result may be negative even though these patients are infected. Those who are immunosuppressed have an increased chance of developing illness, which may be caused by an ineffective cell-mediated response (Box 1). Cell-mediated immunity is thought to be the mechanism by which a contained TB infection is kept quiescent. Patients who are HIV positive (who have ineffective cell-mediated immunity) and are infected with TB have a 7% chance per year of developing active tuberculosis.
Active tuberculosis disease is defined as tissue involvement by the M tuberculosis bacillus that progresses to produce clinical symptoms and signs. On average, illness develops in 3-5% of infected patients. Of the other 95-97% of infected patients, 5% develop active tuberculosis in their lifetime. M tuberculosis infection can cause several clinical syndromes.