Tuberculosis was endemic in animals in the Paleolithic period, long before it ever affected humans. This disease (also called consumption) has been known in all ages and climates. For example, tuberculosis was the subject of a hymn in a sacred text from India dating from 2500 BC, and DNA unique to Mycobacterium tuberculosis was identified in lesions from the lung in 1000-year-old human remains found in Peru.

GENERAL CHARACTERISTICS

In the clinical microbiology laboratory, the term complex frequently is used to describe two or more species for which distinction is complicated and has little or no medical importance. The mycobacterial species that occur in humans and belong to the M. tuberculosis complex include M. tuberculosis, M. bovis, M. bovis BCG, M. africanum, M. caprae, M. microti, M. canettii, and M. pinnipedii. All of these species are capable of causing tuberculosis. It should be noted that species identification might be required for epidemiologic and public health reasons. The organisms that belong to the M. tuberculosis complex are considered slow growers, and colonies are nonpigmented.

EPIDEMIOLOGY AND PATHOGENESIS

 Epidemiology

M. tuberculosis is the cause of most cases of human tuberculosis, particularly in developed countries. An estimated 1.7 billion people, or one third of the world’s population, are infected with M. tuberculosis. This reservoir of infected individuals results in 8 million new cases of tuberculosis and 2.9 million deaths annually. Tuberculosis continues to be a public health problem in the United States. An additional complicating factor in the management of tuberculosis is the increasing incidence of co-infection with the human immunodeficiency virus (HIV). HIV associated tuberculosis remains a significant challenge to world health, with an estimated 1.1 million individuals living with HIV-associated tuberculosis. In the United States, tuberculosis typically is found among the poor, homeless, intravenous (IV) drug users, alcoholics, the elderly, or medically underserved populations. Although the organisms belonging to the M. tuberculosis complex have numerous characteristics in common, including extreme genetic homogeneity, they differ in certain epidemiologic aspects (Table 1).

Table1. Epidemiology of Organisms Belonging to M. tuberculosis Complex That Cause Human Infections

Pathogenesis

The pathogenesis of tuberculosis caused by organisms of the M. tuberculosis complex is discussed in Chapter 69. Inhalation of a single viable organism has been shown to lead to infection, although close contact is usually necessary. Of those who become infected with M. tuberculosis, 15% to 20% develop disease. The disease usually occurs some years after the initial infection, when the patient’s immune system breaks down for some reason other than the presence of tuberculosis bacilli in the lung. In a small percentage of infected hosts, the disease becomes systemic, affecting a variety of organs.

After ingestion of milk from infected cows, Mycobacterium bovis may penetrate the gastrointestinal mucosa or invade the lymphatic tissue of the oropharynx. An attenuated strain of M. bovis, bacillus Calmette-Guérin (BCG), has been used extensively in many parts of the world to immunize susceptible individuals against tuberculosis. Because mycobacteria are the classic examples of intra cellular pathogens and the body’s response to BCG hinges on cell-mediated immunoreactivity, immunized individuals are expected to react more aggressively against all antigens that elicit cell-mediated immunity. In rare cases, an unfortunate individual’s immune system is so compromised that it cannot handle the BCG, and systemic BCG infection may develop.

SPECTRUM OF DISEASE

Tuberculosis may mimic other diseases, such as pneumonia, neoplasm, or fungal infections. In addition, clinical manifestations in patients infected with M. tuberculosis complex may range from asymptomatic to acutely symptomatic. Patients who are symptomatic can have systemic symptoms, pulmonary signs and symptoms, signs and symptoms related to other organ involvement (e.g., the kidneys), or a combination of these features. Cases of pulmonary disease caused by M. tuberculosis complex organisms are clinically, radiologically, and pathologically indistinguishable.

Primary tuberculosis typically is considered a disease of the respiratory tract. Common presenting symptoms include low-grade fever, night sweats, fatigue, anorexia (loss of appetite), and weight loss. A patient who presents with pulmonary tuberculosis usually has a productive cough, along with low-grade fever, chills, myalgias (aches), and sweating; however, these signs and symptoms are similar for influenza, acute bronchitis, and pneumonia.

Upon respiratory infection with M. tuberculosis complex organisms, the cellular immune system T cells and macrophages migrate to the lungs, and the organisms are phagocytized by the macrophages. However, these organ isms are capable of intracellular multiplication in the macrophages. Often the host is unable to eliminate the organisms, and the result is a systemic hypersensitivity to Mycobacterium antigens. Granulomas or a hard tubercle forms in the lung from the lymphocytes, macrophages, and cellular pathology, including giant cell formation (cellular fusion displaying multiple nuclei). If the Mycobacterium antigen concentration is high, the hypersensitivity reaction may result in tissue necrosis, caused by enzymes released from the macrophages. In this case no granuloma forms, and a solid or semisolid, caseous mate rial is left at the primary lesion site.

In some patients infected with primary active tuberculosis, the disease may spread via the lymph system or hematogenously, leading to meningeal or miliary (disseminated) tuberculosis. This most often occurs in patients with depressed or ineffective cellular immunity.

As previously mentioned, in a small percentage of patients, organs besides the lungs can become involved after infection with M. tuberculosis complex organisms. These organs include the following:

 • Genitourinary tract

 • Lymph nodes (cervical lymphadenitis)

• Central nervous system (meningitis)

• Bone and joint (arthritis and osteomyelitis)

• Peritoneum

 • Pericardium

• Larynx

• Pleural lining (pleuritis) Disseminated tuberculosis may be diagnosed by a positive tuberculin skin test (described later in the chapter).

Patients also may have latent disease (i.e., they have no apparent signs, symptoms, or pathologic condition). A patient with latent tuberculosis is not infectious and does not have active disease, although the organism is present in granulomas. Patients with latent tuberculosis may progress to active disease (also referred to as reactivation of tuberculosis) at any time. Reactivation tuberculosis typically occurs after an incident in which cellular immunity is suppressed or damaged as a result of a change in life style or other health condition.

Individuals infected with HIV are particularly susceptible to developing active tuberculosis. These patients are likely to have rapidly progressive primary disease instead of a subclinical infection.

Diagnosing tuberculosis is more difficult in people infected with HIV, because chest radiographs of the pulmonary disease often lack specificity, and patients frequently are anergic (lack a biologic response) to tuberculin skin testing, a primary means of identifying individuals infected with M. tuberculosis. The tuberculin skin test, or purified protein derivative (PPD) test, is based on the premise that after infection with M. tuberculosis, an individual develops a delayed hypersensitivity cell-mediated immunity to certain antigenic components of the organism. To determine whether a person has been infected with M. tuberculosis, a culture extract of M. tuberculosis (i.e., PPD of tuberculin) is injected intracutaneously. After 48 to 72 hours, an infected individual shows a delayed hypersensitivity reaction to the PPD, characterized by erythema (redness) and, most important, induration (firmness as a result of influx of immune cells). The diameter of induration is measured and then interpreted as to whether the patient has been infected with M. tuberculosis; different interpretative criteria are used for different patient populations (e.g., immunosuppressed individuals, such as those infected with HIV). More recently, the T-Spot TB test (Oxford, Immunotec, United Kingdom) offers next-day results and does not require a follow-up visit with a physician. The assay measures T cells that have been activated by Mycobacterium tuberculosis antigens. Peripheral blood mononuclear cells are incubated with M. tuberculosis-specific antigens stimulating any sensitized T cells in the patient sample. T cell cytokines released in the sample are measured using antibody to capture them and then detected with a secondary antibody conjugated to alkaline phosphatase. This assay should be interpreted in correlation with the patient’s signs and symptoms.

The PPD test is not 100% sensitive or specific, and a positive reaction to the skin test does not necessarily signify the presence of disease. Because of these issues, a new test approved by the U.S. Food and Drug Administration (FDA) has become available. It is an enzyme-linked immunosorbent assay (ELISA) called QuantiFERON-TB Gold (Cellestis Limited, Carnegie, Victoria, Australia). The assay measures a component of the cell-mediated immune response to M. tuberculosis to diagnose latent tuberculosis infection and tuberculosis disease. It is based on the quantification of interferon gamma released from sensitized lymphocytes in heparinized whole blood that has been incubated overnight with a mixture of synthetic peptides simulating two proteins in M. tuberculosis. The test assesses responses to multiple antigens; it can be performed in a single patient visit; and it is less subject to reader bias and error. An important feature is that the results of the assay are unaffected by previous BCG vaccination. Guidelines published by the Centers for Disease Control and Prevention (CDC) recommend the use of this assay in all circumstances in which the tuberculin skin test currently is used (e.g., contact investigations and evaluation of recent immigrants). The guidelines also provide specific cautions for interpreting negative results in individuals from selected populations.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الفكرية يعلن مشاركة ممثلين من 18 دولة إفريقية في خدمة زائري الإمام العسكري (عليه السلام)

مصور في قسم إعلام العتبة العباسية المقدسة يحصد المركز الأول في مسابقة دولية

العتبة العباسية المقدسة تختتم مجالس العزاء بذكرى شهادة الإمام الحسن العسكري (عليه السلام)

مركز الكفيل يستأنف دوراته التدريبية في الإسعافات الأولية لمنتسبي العتبة العباسية المقدسة

المزيد

الآخبار الصحية

دون آثار جانبية.. زيت عشبة طبيعية قد يعالج القلق

"ليكانيماب".. علاج الزهايمر يطرح رسميا في السوق الألمانية

متى يجب تنظيف الأسنان في الصباح.. قبل أم بعد الإفطار؟

ارتفاع الوفيات.. منظمة الصحة تدق جرس الإنذار بشأن الكوليرا

المزيد

الآخبار التكنلوجية

أكبر مشروع طاقة رياح في نصف الكرة الجنوبي يحقق إنجازين جديدين

5 أمور لا تفعلها أثناء تشغيل مكيف سيارتك

ضوء إدارة المحرك: أسئلة مهمة لفهم عمله ومعانيه

"واتساب" يطلق خاصية جديدة لكتابة الرسائل بالذكاء الاصطناعي

المزيد

مواضيع ذات صلة

Rapidly Growing Nontuberculous mycobacteria (RGM)

Slow-growing Nontuberculous Mycobacteria

Anaerobic Gram-Positive and Gram-Negative Cocci

The Salmonellae

The shigellae

Diseases Caused by Enterobacteriaceae Other than Salmonella and Shigella

Antigenic Structure of Enterobacteriaceae

Gram-Negative Rods

Gram-Positive, non–Spore- Forming Bacilli

Gram-Positive, Spore Forming Bacilli

Morphology and Identification of Enterobacteriaceae

Clinical Findings of Enterococci