Tuberculosis (TB), which is one of the oldest diseases known to affect humans and is likely to have existed in prehominids, is a major cause of death worldwide. This disease is caused by bacteria of the Mycobacterium tuberculosis complex and usually affects the lungs, although other organs are involved in up to one-third of cases. If properly treated, TB caused by drug-susceptible strains is curable in virtually all cases. If untreated, the disease may be fatal within 5 years in 50–65% of cases. Transmission usually takes place through the airborne spread of droplet nuclei produced by patients with infectious pulmonary TB.
Mycobacteria belong to the family Mycobacteriaceae and the order Actinomycetales. Of the pathogenic species belonging to the M. tuberculosis complex, the most common and important agent of human disease is M. tuberculosis. The complex includes M. bovis (the bovine tubercle bacillus—characteristically resistant to pyrazinamide, once an important cause of TB transmitted by unpasteurized milk, and currently the cause of a small percentage of cases worldwide), M. caprae (related to M. bovis), M. africanum (isolated from cases in West, Central, and East Africa), M. microti (the “vole” bacillus, a less virulent and rarely encountered organism), M. pinnipedii (a bacillus infecting seals and sea lions in the Southern Hemisphere and recently isolated from humans), and M. canetti (a rare isolate from East African cases that produces unusual smooth colonies on solid media and is considered closely related to a supposed progenitor type).
M. tuberculosis is a rod-shaped, nonspore-forming, thin aerobic bacterium measuring 0.5 μm by 3 μm. Mycobacteria, including M. tuberculosis, are often neutral on Gram's staining. However, once stained, the bacilli cannot be decolorized by acid alcohol; this characteristic justifies their classification as acid-fast bacilli (AFB; Fig. 165-1). Acid fastness is due mainly to the organisms′ high content of mycolic acids, long-chain cross-linked fatty acids, and other cell-wall lipids. Microorganisms other than mycobacteria that display some acid fastness include species of Nocardia and Rhodococcus, Legionella micdadei, and the protozoa Isospora and Cryptosporidium. In the mycobacterial cell wall, lipids (e.g., mycolic acids) are linked to underlying arabinogalactan and peptidoglycan. This structure confers very low permeability of the cell wall, thus reducing the effectiveness of most antibiotics. Another molecule in the mycobacterial cell wall, lipoarabinomannan, is involved in the pathogen-host interaction and facilitates the survival of M. tuberculosis within macrophages. The complete genome sequence of M. tuberculosis comprises 4043 genes encoding 3993 proteins and 50 genes encoding RNAs; its high guanine-plus-cytosine content (65.6%) is indicative of an aerobic “lifestyle.” A large proportion of genes are devoted to the production of enzymes involved in cell wall metabolism.
Acid-fast bacillus smear showing M. tuberculosis bacilli. (Courtesy of the CDC, Atlanta.)
More than 5.8 million new cases of TB (all forms, both pulmonary and extrapulmonary) were reported to the World Health Organization (WHO) in 2009; 95% of cases were reported from developing countries. However, because of insufficient case detection and incomplete notification, reported cases represent only ∼63% (range, 60–67%) of total estimated cases. The WHO estimated that 9.4 million (range, 8.9–9.9 million) new cases of TB occurred worldwide in 2009, 95% of them in developing countries of Asia (5.2 million), Africa (2.8 million), the Middle East (0.7 million), and Latin America (0.3 million). It is further estimated that 1.7 million (range, 1.5–1.9 million) deaths from TB, including 0.4 million among people living with HIV infection, occurred in 2008, 96% of them in developing countries. Estimates of TB incidence rates (per 100,000 population) and numbers of TB-related deaths in 2008 are depicted in Figs. 165-2 and 165-3, respectively. During the late 1980s and early 1990s, numbers of reported cases of TB increased in industrialized countries. These increases were related largely to immigration from countries with a high prevalence of TB; infection with HIV; social problems, such as increased urban poverty, homelessness, and drug abuse; and dismantling of TB services. During the past few years, numbers of reported cases have begun to decline again or stabilized in industrialized nations. In the United States, with the implementation of stronger control programs, the decrease resumed in 1993. In 2009, 11,540 cases of TB (3.8 cases per 100,000 population) were reported to the Centers for Disease Control and Prevention (CDC).
Estimated tuberculosis incidence rates (per 100,000 population) in 2008. The designations employed and the presentation of material on this map do not imply the expression of any opinion whatsoever on the part of the WHO concerning the legal status of any country, territory, city, or area or of its authorities or concerning the delimitation of its frontiers or boundaries. White lines on maps represent approximate border lines for which there may not yet be full agreement. (Courtesy of the Stop TB Department, WHO; with permission.)
Estimated numbers of tuberculosis-related deaths in 2008. (See disclaimer in Fig. 165-2. Courtesy of the Stop TB Department, WHO; with permission.)
In the United States, TB is uncommon among young adults of European descent, who have only rarely been exposed to M. tuberculosis infection during recent decades. In contrast, because of a high risk of transmission in the past, the prevalence of M. tuberculosis infection is relatively high among elderly whites. Blacks, however, account for the highest proportion of cases (41.4% of 4499) among U.S.-born persons. TB in the United States is also a disease of adult members of the HIV-infected population, the foreign-born population (60% of all cases in 2009), and disadvantaged/marginalized populations. Overall, more TB cases were reported among Hispanics than among other ethnic groups; next in frequency were cases among Asians and blacks, with the highest ...