Tuberculosis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Tuberculosis (abbreviated as TB for 'Tubercle bacillus' or Tuberculosis) is a common and deadly infectious disease caused by mycobacteria, mainly Mycobacterium tuberculosis. Tuberculosis most commonly attacks the lungs (as pulmonary TB) but can also affect the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, bones, joints and even the skin. Other mycobacteria such as Mycobacterium bovis, Mycobacterium africanum, Mycobacterium canetti, and Mycobacterium microti can also cause tuberculosis, but these species do not usually infect healthy adults.[1] Over one-third of the world's population has been exposed to the TB bacterium, and new infections occur at a rate of one per second.[2] Not everyone infected develops the full-blown disease; asymptomatic, latent TB infection is most common. However, one in ten latent infections will progress to active TB disease, which, if left untreated, kills more than half of its victims.
Historical Perspective
Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium tuberculosis was in the remains of bison, dated 18,000 BC.[3] However, whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor, is currently unclear.[4] Through history tuberculosis had many names, such as phthisis and Wasting disease, which were mostly derived from its symptoms. The Mycobacterium tuberculosis was only identified in 1882 by Robert Koch. In the 19th and early 20th centuries, tuberculosis caused the most widespread public concern, being considered an endemic disease of the urban poor. It was only in 1946, with the development of the antibiotic streptomycin, that effective treatment and cure became possible. Since the rise of drug-resistant strains in the 1980s, hopes that the disease could be completely eliminated have been dashed.
Classification
Tuberculosis may be classified according to its pathogenesis into 6 categories. This classification divides patients from "class 0", in which the person hasn't had previous exposure to TB, and has a negative TST and IGRA, to "class 5", in which TB is suspected, there are signs and symptoms of the disease, but the evaluation is not complete to confirm the diagnosis. According to the U.S. Citizenship and Immigration Services, immigrants and refugees have a special classification system. This last classifies immigrants and refugees from "no class", in which the person has normal screening tests, to "class B3", in which the person is a recent contact of a known tuberculosis case.
Pathophysiology
Tuberculosis is a granulomatous infection which is chiefly transmitted through droplets. The granuloma prevents the dissemination of mycobacteria and provides a pathway for immune cell communication. Within the granuloma, T lymphocytes (CD4) secrete cytokines, such as interferon gamma, which activate local macrophages to kill the bacteria with which they are infected It is asymptomatic in 90% of immunocompetent individuals. In symptomatic patients it can present as pulmonary or extra pulmonary manifestations. The primary infection can progress to certain complications like disseminated infection. Tuberculosis can influence the progression of HIV if concomitantly present. Depending on the age of the patient, tuberculosis may have different clinical manifestations, progression, and prognosis.
Causes
Mycobacterium tuberculosis is the bacterium responsible for tuberculosis. It is an aerobic, non-encapsulated, non-motile, acid-fast bacillus. M. tuberculosis belongs to the Mycobacterium tuberculosis complex, that also includes bacteria, such as M. bovis and M. africanum. The bacterium has a very slow rate of replication, and its genetic variations account for the geographical distribution of different strains, and are involved in drug resistance. M. tuberculosis has tropism for different kinds of human cells, with preference for cells of the lung. It may infect different species, yet human beings are its frequent natural reservoir.
Epidemiology and Demographics
Tuberculosis is a bacterial infection that constitutes one of the world's deadliest diseases. In 2012, about 8.6 million people developed symptomatic TB and 1.3 million died from the disease. In 2013 there were 9 582 reported cases in the United States, with an incidence of 3.0 per 100 000 persons. Since 1990, the mortality rate of TB has been decreasing towards the goal of 50% reduction, planed for 2015. The prevalence of TB increases with age and is superior in older men. Racial and ethnic minorities have a higher prevalence of TB than non-Hispanic whites. TB is an important cause of death in people who are coinfected with HIV, with approximately 1/5 of deaths among these patients being due to TB.
Risk Factors
The risk factors for the development of tuberculosis include: weakened immune system (patients taking immunosuppressive medication or with immunosuppressive diseases, such as HIV or diabetes); history of contact with infected patients, bad hygiene conditions, and evidence of previous tuberculosis. Risk factors for multidrug-resistant TB include: non-adherence to treatment regimen, inadequate medication for that strain of bacteria, and contact with patients with multidrug-resistant TB.
Screening
Screening for tuberculosis is generally done with using a mantoux tuberculin skin test, also known as a tuberculin skin test or a PPD. The test involves injecting a small amount of a purified protein derivative of the tuberculosis bacterium intradermally, and watching for a reaction in the following days.
Natural history, complications and prognosis
Tuberculosis has been classified as primary or secondary (post primary) infection. It can have pulmonary and extra pulmonary manifestations as well as severe parenchymal, vascular, pleural and chest wall complications. Pulmonary complications include pleural effusions, cavitations, lymphadenopathy, airway obstruction, pneumonia and bronchietasis. The hematogenous dissemination of infection can lead to miliary tuberculosis. The post primary infection can be due to a recent infection or reactivation of an old infection. Without treatment, 1/3 of patients with active tuberculosis dies within 1 year of the diagnosis, and more than 50% during the first 5 years. But with early diagnosis and treatment it has a good prognosis.
Diagnosis
History and Symptoms
The general symptoms of tuberculosis include weakness, weight loss, fever, and night sweats. Symptoms of pulmonary tuberculosis include cough, chest pain, and hemoptysis. Tuberculosis is particularly difficult to diagnose in children, as these may not present with common findings.
Physical Examination
A physical examination can provide valuable information about the patient’s overall condition and other factors that may affect how tuberculosis is treated, such as HIV infection or other illnesses. The most common physical findings include fever, decreased breath sounds, tachypnea and tachycardia. Physical findings will depend on the location of the tuberculosis infection.
Laboratory findings
Routine laboratory exams are usually in the normal ranges. The presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates TB disease and a positive culture for M. tuberculosis confirms the diagnosis. Other laboratory test include peritoneal fluid or CSF analysis, urinalysis, and Interferon-Gamma release assays.
Electrocardiogram
Patients can develop a pericardial effusion secondary to TB and this might be manifested as low voltage and tachycardia on an EKG.
Chest X-Ray
A chest X ray is one of the important diagnostic tools in tuberculosis. A chest radiograph may be used to rule out the possibility of pulmonary TB in a person who are symptomatic or had a positive reaction to a tuberculin test or QFT-G and no symptoms of disease. The findings on chest x ray can be divided into parenchymal and pleural. The early parenchmal findings can be infiltrates, and cavity. A healed tuberculotic lesion can present as fibrosis, and calcification. Pleural lesions in form of pleral effusion can also be seen. An advanced tuberculosis lesion can present as combination of these early lesions and termed as fibrocavitatory lesions.
Echocardiography or Ultrasound
Echocardiography or ultrasound: Patients can develop a pericardial effusion secondary to TB.
Other Diagnostic Studies
Because of difficulties with the Tuberculin skin test, many laboratory methods of diagnosis are emerging [5] [6].
Treatment
Medical Therapy
If there is a high probability of infection, presumptively treat the patient even if the stain is negative, while waiting for the culture results. The patient should be brought back in few weeks. Patients usually feel better a few weeks post-treatment. In the U.S., all TB is tested for drug resistance. Isoniazid (INH) resistant TB can be treated in same way as non-MDR TB.
Surgery
Surgery may be necessary, especially to drain spinal abscesses or to stabilize the spine in case of Pott's disease.
Primary Prevention
Many countries use BCG vaccine as part of their TB control programs, especially for infants. This was the first vaccine for TB and developed at the Pasteur Institute in France between 1905 and 1921.[7] However, mass vaccination with BCG did not start until after World War II.[8] The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is greater than 80%; its protective efficacy for preventing pulmonary TB in adolescents and adults is variable, ranging from 0 to 80%.[9]
Secondary Prevention
All health-care settings need an infection-control program designed to ensure prompt 1) detection, 2) airborne precautions and 3) treatment of persons who have suspected or confirmed tuberculosis (TB) disease (or prompt referral of persons who have suspected TB disease for settings where persons with TB disease are not expected to be encountered). In order to be effective, the primary emphasis of the TB infection-control program should be on achieving these three goals.
In all health-care settings, particularly those in which persons who are at high risk for exposure to Mycobacterium tuberculosis work or receive care, policies and procedures for TB control should be developed, reviewed periodically, and evaluated for effectiveness to determine the actions necessary to minimize the risk for transmission of M. tuberculosis.
References
- ↑ Raviglione MC, O'Brien RJ (2004). "Tuberculosis". In Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL, Isselbacher KJ, eds. Harrison's Principles of Internal Medicine (16th ed. ed.). McGraw-Hill Professional. pp. 953–66. doi:10.1036/0071402357. ISBN 0071402357.
- ↑ World Health Organization (WHO). Tuberculosis Fact sheet N°104 - Global and regional incidence. March 2006, Retrieved on 6 October 2006.
- ↑ Rothschild B, Martin L, Lev G, Bercovier H, Bar-Gal G, Greenblatt C, Donoghue H, Spigelman M, Brittain D (2001). "Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present". Clin Infect Dis. 33 (3): 305–11. PMID 11438894.
- ↑ Pearce-Duvet J (2006). "The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease". Biol Rev Camb Philos Soc. 81 (3): 369–82. PMID 16672105.
- ↑ Drobniewski F, Caws M, Gibson A, Young D (2003). "Modern laboratory diagnosis of tuberculosis". Lancet Infect Dis. 3 (3): 141–7. PMID 12614730.
- ↑ Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A (2007). "A systematic review of rapid diagnostic tests for the detection of tuberculosis infection". Health Technol Assess. 11 (3): 1–314. PMID 17266837.
- ↑ Bonah C (2005). "The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921–1933". Stud Hist Philos Biol Biomed Sci. 36 (4): 696–721. PMID 16337557.
- ↑ Comstock G (1994). "The International Tuberculosis Campaign: a pioneering venture in mass vaccination and research". Clin Infect Dis. 19 (3): 528–40. PMID 7811874.
- ↑ Bannon M (1999). "BCG and tuberculosis". Arch Dis Child. 80 (1): 80–3. PMID 10325767.