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Tuberculosis
Classifications and external resources

Image:Tuberculosis-x-ray-1.jpg
Chest X-ray of a patient with advanced pulmonary tuberculosis
ICD-10	A15.-A19.
ICD-9	010-018
OMIM	607948
DiseasesDB	8515
MedlinePlus	000077 000624
eMedicine	med/2324  emerg/618 radio/411
MeSH	C01.252.410.040.552.846

Tuberculosis (abbreviated as TB for Tubercle Bacillus) is a common and deadly infectious disease caused by the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system, lymphatic system, circulatory system, genitourinary system, bones and joints.

Over one-third of the world's population now has the TB bacterium in their bodies and new infections are occurring at a rate of one per second.<ref name="WHO2004data">World Health Organization (WHO). Tuberculosis Fact sheet N°104 - Global and regional incidence. March 2006, Retrieved on 6 October 2006.</ref> Not everyone who is infected develops the disease and asymptomatic latent TB infection is most common. However, one in ten latent infections will progress to active TB disease which, if left untreated, will kill more than half of its victims. In 2004, 14.6 million people had active TB and there were 8.9 million new cases and 1.7 million deaths,<ref name="WHO2004data"/> mostly in developing countries. A rising number of people in the developed world contract tuberculosis because their immune systems are compromised by immunosuppressive drugs, substance abuse, or HIV/AIDS.

The rise in HIV infection levels and the neglect of TB control programs have caused a resurgence of tuberculosis, and drug-resistant strains of TB are also emerging.<ref name="MMWR2006">Centers for Disease Control (CDC). Emergence of Mycobacterium tuberculosis with Extensive Resistance to Second-Line Drugs — Worldwide, 2000–2004. MMWR Weekly, March 24, 2006 / 55(11);301-305.</ref> The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership proposed a Global Plan to Stop Tuberculosis which aims to save 14 million lives between 2006 and 2015.<ref>World Health Organization (WHO). Stop TB Partnership. Retrieved on 3 October 2006.</ref>

Contents 1 Other names 2 Symptoms 3 Bacterial species 4 Transmission 5 Pathogenesis 6 Diagnosis 7 Progression 8 Treatment 9 Prevention 9.1 Vaccines 10 Epidemiology 11 History 12 Infection of other animals 13 See also 14 References 15 Further reading 16 External links

Other names

In the past, tuberculosis was called consumption, because it seemed to consume people from within, with a bloody cough, fever, pallor, and long relentless wasting. Other names included phthisis (Greek for consumption) and phthisis pulmonalis; scrofula, affecting the lymphatic system and resulting in swollen neck glands; tabes mesenterica, TB of the abdomen and lupus vulgaris, TB of the skin; wasting disease; white plague, because sufferers appear markedly pale; king's evil, because it was believed that a king's touch would heal scrofula; and Pott's disease of the spine and joints.<ref name=Britannica1911>Tuberculosis The 11th edition of the Encyclopedia Britannica, (1911)</ref><ref>Rudy's List of Archaic Medical Terms English Glossary of Archaic Medical Terms, Diseases and Causes of Death. Accessed 09 Oct 06</ref> Miliary TB is an archaic term that is still occasionally used, and is when the infection invades the circulatory system resulting in x-ray lesions with the appearance of millet seeds.<ref name=Britannica1911/><ref>Disseminated tuberculosis NIH Medical Encyclopedia. Accessed 09 Oct 06</ref> This form of TB is now more commonly named disseminated TB.

Symptoms

Further information: Tuberculosis classification

In the patients where TB becomes an active disease, 75% of these cases affect the lungs, where the disease is called pulmonary TB. Symptoms include a productive, prolonged cough of more than three weeks duration, chest pain, and coughing up blood. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, and easy fatigability.<ref name="WHO2004data"/>

When the infection spreads out of the lungs, extrapulmonary sites include the pleura, central nervous system in meningitis, lymphatic system in scrofula of the neck, genitourinary system in urogenital tuberculosis, and bones and joints in Pott's disease of the spine. An especially serious form is disseminated, or miliary tuberculosis. Extrapulmonary forms are more common in immunosuppressed persons and in young children. Infectious pulmonary TB may co-exist with extrapulmonary TB, which is not contagious.<ref name=CDCcourse>Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated Aug 2003.</ref>

Bacterial species

The cause of tuberculosis, Mycobacterium tuberculosis (MTB), is a slow-growing aerobic bacterium that divides every 16 to 20 hours; this is extremely slow compared to other bacteria that have division times measured in minutes.<ref>Cox RA. "Quantitative relationships for specific growth rates and macromolecular compositions of Mycobacterium tuberculosis, Streptomyces coelicolor A3(2) and Escherichia coli B/r: an integrative theoretical approach." Microbiology. 2004 May;150(Pt 5):1413-26. PMID 15133103</ref> In contrast, one of the fastest growing bacteria is a strain of E. coli that can divide roughly every 20 minutes. As MTB only has one phospholipid outer membrane, it is classified as a Gram-positive bacteria. However, if a Gram stain is performed, MTB either stains very weakly Gram-positive, or does not retain dye, due to the high lipid content of its cell wall.<ref>Madison B (2001). "Application of stains in clinical microbiology.". Biotech Histochem 76 (3): 119-25. PMID 11475314.</ref> MTB is a small rod-like bacillus which can withstand weak disinfectants and can survive in a dry state for weeks. Normally, the bacteria can only grow within a host organism, so in vitro culture of M. tuberculosis took a long time to develop, but is now a routine laboratory procedure.<ref>Parish T, Stoker NG. Mycobacteria: bugs and bugbears (two steps forward and one step back). Mol Biotechnol. 1999 Dec 15;13(3):191-200. PMID 10934532</ref>

MTB is identified microscopically by its staining characteristics: it retains certain stains after being treated with acidic solution, and is thus classified as an "acid-fast bacillus" or AFB.<ref>Madison BM. Application of stains in clinical microbiology. Biotech Histochem. 2001 May;76(3):119-25. PMID 11475314</ref> In the most common staining technique, the Ziehl-Neelsen stain, AFB are stained a bright red which stands out clearly against a blue background. Acid-fast bacilli can also be visualized by fluorescent microscopy, and by an auramine-rhodamine stain.

The M. tuberculosis complex includes 3 other mycobacteria which can cause tuberculosis: M. bovis, M. africanum and M. microti. The first two are very rare causes of disease in immunocompetent people, and M. microti is not usually pathogenic, although it is possible that the prevalence of M. microti infections has been underestimated.<ref>Niemann S, Richter E, Dalugge-Tamm H, Schlesinger H, Graupner D, Konigstein B, Gurath G, Greinert U, Rusch-Gerdes S. "Two cases of Mycobacterium microti derived tuberculosis in HIV-negative immunocompetent patients." Emerg Infect Dis. 2000 Sep-Oct;6(5):539-42. PMID 10998387</ref> Other pathogenic mycobacteria are known, such as Mycobacterium leprae, Mycobacterium avium and M. kansasii. The last two are part of the group defined as Nontuberculous mycobacteria (NTM). Nontuberculous mycobacteria are mycobacteria that are not part of the M. tuberculosis complex, and do not cause leprosy, but do cause pulmonary diseases resembling tuberculosis.<ref>Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Official statement of the American Thoracic Society Am J Respir Crit Care Med. 1997 Aug;156(2 Pt 2):S1-25. PMID 9279284</ref>

Transmission

TB is spread by aerosol droplets expelled by people with the active disease of the lungs when they cough, sneeze, speak, or spit. These infectious droplets are 0.5 to 5 µm in diameter and about 40,000 can be produced by a single sneeze.<ref>Cole EC, Cook CE. Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies. Am J Infect Control. 1998 Aug;26(4):453-64. PMID 9721404</ref> People with prolonged, frequent, or intense contact are at highest risk of becoming infected, with an estimated 22% infection rate. A person with untreated, active tuberculosis can infect 10-15 other people per year.<ref name="WHO2004data"/> Others at risk include those from areas where TB is common, patients immunocompromised by conditions such as HIV/AIDS, residents and employees of high-risk congregate settings, health care workers who serve high-risk clients, medically underserved, low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, and people who inject illicit drugs.<ref>Griffith DE, Kerr CM. Tuberculosis: disease of the past, disease of the present. J Perianesth Nurs. 1996 Aug;11(4):240-5. PMID 8964016</ref>

Transmission can only occur from people with active—not latent— TB disease. The probability of transmission from one person to another depends upon the quantity of the infectious droplets expelled by the patient, the effectiveness of ventilation, the duration of exposure, and the virulence of the Mycobacterium tuberculosis strain.<ref name=CDCcourse/> The chain of transmission can therefore be broken by isolating patients with active disease and starting effective anti-tuberculous therapy.

Pathogenesis

Image:TB in sputum.png About 90% of those infected with Mycobacterium tuberculosis have asymptomatic, latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease. However, if untreated, the death rate for these active TB cases is more than 50%.<ref name =TDRreport>Onyebujoh, Phillip and Rook, Graham A. W. World Health Organization Disease Watch: Focus: Tuberculosis. December 2004. Accessed 07 October 2006.</ref>

TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within alveolar macrophages.<ref name=Houben>Houben EN, Nguyen L, Pieters J. Interaction of pathogenic mycobacteria with the host immune system. Curr Opin Microbiol. 2006 Feb;9(1):76-85. PMID 16406837</ref> The primary site of infection in the lungs is called the Ghon focus. Bacteria are picked up by dendritic cells, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph nodes. Further spread is through the bloodstream to the more distant tissues and organs where secondary TB lesions can develop in lung apexes, peripheral lymph nodes, kidneys, brain, and bone.<ref>Herrmann JL, Lagrange PH. Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse? Pathol Biol (Paris). 2005 Feb;53(1):35-40. PMID 15620608</ref>

Tuberculosis is classified as one of the granulomatous inflammatory conditions. Macrophages, T lymphocytes, B lymphocytes and fibroblasts are among the cells that aggregate to form a granuloma, with lymphocytes surrounding the infected macrophages. The granuloma functions not only to prevent dissemination of the mycobacteria, but also provides a local environment for communication of cells of the immune system. Within the granuloma, T lymphocytes (CD4+) secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected.<ref>Kaufmann SH. "Protection against tuberculosis: cytokines, T cells, and macrophages." Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii54-8. PMID 12379623</ref> T lymphocytes (CD8+) can also directly kill infected cells.<ref name=Houben/>

Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of cell death, also called necrosis, in the center of tubercles. To the naked eye this has the texture of soft white cheese and was termed caseous necrosis.<ref name=Grosset>Grosset J. Mycobacterium tuberculosis in the extracellular compartment: an underestimated adversary. Antimicrob Agents Chemother. 2003 Mar;47(3):833-6. PMID 12604509</ref>

If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called miliary tuberculosis. Patients with this disseminated TB have a fatality rate of approximately 20%, even with intensive treatment.<ref>Kim JY, Park YB, Kim YS, Kang SB, Shin JW, Park IW, Choi BW. "Miliary tuberculosis and acute respiratory distress syndrome." Int J Tuberc Lung Dis. 2003 Apr;7(4):359-64. PMID 12733492</ref>

In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis.<ref name=Grosset/> Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. During active disease, some of these cavities are joined to the air passages bronchi and this material can be coughed up. It contains living bacteria and can therefore pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.<ref name=Grosset/>

Diagnosis

Tuberculosis can be a difficult disease to diagnose, due mainly to the difficulty in culturing this slow-growing organism in the laboratory. A complete medical evaluation for TB must include a medical history, a chest X-ray, and a physical examination. Tuberculosis radiology is used in the diagnosis of TB. It may also include a tuberculin skin test, a serological test, microbiological smears and cultures. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immunosuppression.<ref name=CDCcourse/>

Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to purified protein derivatives of M. tuberculosis. Those immunized for TB or with past-cleared infection will respond with parallel delayed hypersensitivity to those currently in a state of infection and thus must be used with caution, particularly with regard to persons from countries where TB immunization is common.<ref>Rothel JS, Andersen P. "Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent?" Expert Rev Anti Infect Ther. 2005 Dec;3(6):981-93. PMID 16307510</ref> New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These use polymerase chain reaction detection of bacterial DNA and antibody assays to detect the release of interferon gamma in response to mycobacteria.<ref>Nahid P, Pai M, Hopewell PC. Advances in the diagnosis and treatment of tuberculosis. Proc Am Thorac Soc. 2006;3(1):103-10. PMID 16493157</ref> Rapid and cheap diagnosis will be particularly valuable in the developing world.

Progression

Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system defenses and begin to multiply. In primary TB disease—1 to 5% of cases—this occurs soon after infection; in post-primary TB, secondary TB, or reactivation TB disease of dormant bacilli— 5 to 9% of cases—it occurs many years after infection. The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In patients co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.<ref name =TDRreport/>

Other conditions that increase risk include drug injection, mainly because of the life style of IV drug users; recent TB infection or a history of inadequately treated TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules; diabetes mellitus; silicosis; prolonged corticosteroid therapy and other immunosuppressive therapy; head and neck cancers; hematologic and reticuloendothelial diseases, such as leukemia and Hodgkin's disease; end-stage kidney disease; intestinal bypass or gastrectomy; chronic mal-absorption syndromes; or low body weight.<ref name=CDCcourse/>

Some drugs, including rheumatoid arthritis drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine), raise the risk of activating a latent infection due to the importance of this cytokine in the immune defense against TB.<ref>Mutlu GM, Mutlu EA, Bellmeyer A, Rubinstein I. Pulmonary adverse events of anti-tumor necrosis factor-alpha antibody therapy. Am J Med. 2006 Aug;119(8):639-46. PMID 16887405</ref>

Treatment

Treatment for TB uses antibiotics to kill the bacteria. The two antibiotics most commonly used are rifampicin and isoniazid. However, these treatments are more difficult than the short courses of antibiotics used to cure most bacterial infections as long periods of treatment (around 6 to 12 months) are needed to entirely eliminate mycobacteria from the body.<ref name=CDCcourse/> Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance.<ref name=OBrien>O'Brien RJ. "Drug-resistant tuberculosis: etiology, management and prevention." Semin Respir Infect. 1994 Jun;9(2):104-12. PMID 7973169</ref> People with these latent infections are treated to prevent them from progressing to active TB disease later in life. However, treatment using Rifampin and Pyrazinamide is not risk-free. The Centers for Disease Control and Prevention (CDC) notified healthcare professionals of revised recommendations against the use of rifampin plus pyrazinamide for treatment of latent tuberculosis infection, due to high rates of hospitalization and death from liver injury associated with the combined use of these drugs.<ref>Update: Adverse Event Data and Revised American Thoracic Society/CDC Recommendations Against the Use of Rifampin and Pyrazinamide for Treatment of Latent Tuberculosis Infection---United States, 2003 MMWR Weekly August 8, 2003 52(31);735-739</ref>

Drug resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons who are infected with a resistant strain of TB. A patient with fully-susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low quality medication.<ref name=OBrien/> Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug resistant TB (MDR-TB) is defined as resistance to the two most effective first line TB drugs: rifampicin and isoniazid. Extensively drug-resistant TB (XDR-TB) is also resistant to three or more of the six classes of second-line drugs.<ref name="MMWR2006"/>

Prevention

TB prevention and control takes two parallel approaches. In the first, people with TB and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for TB. In the second approach, children are vaccinated to protect them from TB. Unfortunately, no vaccine is available that provides reliable protection for adults. However, in tropical areas where the incidence of atypical mycobacteria is high, exposure to nontuberculous mycobacteria gives some protection against TB.<ref>Fine PE, Floyd S, Stanford JL, Nkhosa P, Kasunga A, Chaguluka S, Warndorff DK, Jenkins PA, Yates M, Ponnighaus JM. "Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy." Epidemiol Infect. 2001 Jun;126(3):379-87. PMID 11467795</ref>

Vaccines

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.<ref name=Bonah>Bonah C. "The 'experimental stable' of the BCG vaccine: safety, efficacy, proof, and standards, 1921-1933." Stud Hist Philos Biol Biomed Sci. 2005 Dec;36(4):696-721. PMID 16337557</ref> However, mass vaccination with BCG did not start until after World War II.<ref name=Comstock>Comstock GW. The International Tuberculosis Campaign: a pioneering venture in mass vaccination and research. Clin Infect Dis. 1994 Sep;19(3):528-40. PMID 7811874</ref> 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 from 0 to 80%.<ref>Bannon MJ. BCG and tuberculosis. Arch Dis Child. 1999 Jan;80(1):80-3. PMID 10325767</ref>

In South Africa, the country with the highest prevelance of TB, BCG is given to all children under the age of three.<ref>WHO/UNICEF Review of National Immunization Coverage 1980-2005: South Africa. Accessed 11 October 06.</ref> However, the effectiveness of BCG is lower in areas where mycobacteria are less prevalent, therefore BCG is not given to the entire population in these countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria:<ref name=CDCcourse/>

• Infants or children with negative skin-test result who are continually exposed to untreated or ineffectively treated patients or will be continually exposed to multidrug-resistant TB.
• Healthcare workers considered on an individual basis in settings in which high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and not successful.

Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID).<ref>National Institute of Allergy and Infectious Diseases (NIAID).First U.S. Tuberculosis Vaccine Trial in 60 Years Begins. National Institutes of Health News 26 January 2004. Retrieved on 8 May 2006.</ref> A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take four to five years to be available in humans.<ref>Ha SJ, Jeon BY, Youn JI, Kim SC, Cho SN, Sung YC. Protective effect of DNA vaccine during chemotherapy on reactivation and reinfection of Mycobacterium Tuberculosis. Gene Ther. 2005 Apr;12(7):634-8. PMID 15690060</ref> The only TB vaccine currently in phase III trials is MVA85A, which is being trialed in South Africa by a group led by Oxford University,<ref>Ibanga HB, Brookes RH, Hill PC, et al. Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design. Lancet Infect Dis. 2006 6(8):522–28. PMID 16870530</ref> and is based on a genetically modified vaccinia virus. Because of the limitations of current vaccines, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.<ref>Webber, David and Kremer, Michael. Stimulating Industrial R&D for Neglected Infectious Diseases: Economic Perspectives (PDF). Bulletin of the World Health Organization 79(8), 2001, pp. 693-801.</ref><ref>Barder, Owen; Kremer, Michael; Williams, Heidi. "Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases," The Economists' Voice, Vol. 3 (2006) Issue 3.</ref>

Epidemiology

Image:TB incidence.pngImage:World tb.pngAccording to the World Health Organization (WHO), nearly 2 billion people—one–third of the world's population—have tuberculosis.<ref>National Institute of Allergy and Infectious Diseases (NIAID). Microbes in Sickness and in Health. 26 October 2005. Retrieved on 3 October 2006. "According to the World Health Organization (WHO), nearly 2 billion people, one-third of the world's population, have TB."</ref> Annually, 8 million people become ill with tuberculosis, and 2 million people die from the disease worldwide.<ref name=CDC>Centers for Disease Control. Fact Sheet: Tuberculosis in the United States. 17 March 2005, Retrieved on 6 October 2006.</ref> In 2004, around 14.6 million people had active TB disease with 9 million new cases. The annual incidence rate varies from 356 per 100,000 in Africa to 41 per 100,000 in the Americas.<ref name="WHO2004data"/> Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS.<ref>Stop TB Partnership. London tuberculosis rates now at Third World proportions. PR Newswire Europe Ltd. 4 December 2002. Retrieved on 3 October 2006.</ref>

In 2004, the country with the highest incidence of TB was South Africa, with 718 cases per 100,000 people. India has the largest number of infections, with over 1.8 million cases.<ref name=WHOreport/> In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, TB incidences range from 40 per 100,000 in London to less than 5 per 100,000 in the rural South West of England.<ref>Notification rates of tuberculosis: by NHS Regional Office area, 1990-2001: Regional Trends 37 Office for National Statistics Retrieved on 13 October 2006.</ref>; the national average is 13 per 100,000. The highest rates in Western Europe are in Portugal (42 per 100,000) and Spain (20 per 100,000). These rates compare with 113 per 100,000 in China and 64 per 100,000 in Brazil. In the United States, the overall tuberculosis case rate was 4.9 per 100,000 persons in 2004.<ref name=CDC/>

The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults.<ref>World Health Organization (WHO). Global Tuberculosis Control Report, 2006 - Annex 1 Profiles of high-burden countries. (PDF) Retrieved on 13 October 2006.</ref> However, in countries where TB has gone from high to low incidence, such as America, TB is mainly a disease of older people.<ref>Centers for Disease Control and Prevention (CDC). 2005 Surveillance Slide Set. (September 12, 2006) Retrieved on 13 October 2006.</ref>

There are a number of known factors that make people more susceptible to TB infection: worldwide the most important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to the high incidence of HIV in these countries.<ref name=WHOreport/> Smoking more than 20 cigarettes a day also increases the risk of TB by two- to four-times.<ref>Davies PDO, Yew WW, Ganguly D, et al. (2006). "Smoking and tuberculosis: the epidemiological association and pathogenesis". Trans R Soc Trop Med Hyg 100: 291–8. PMID 16325875</ref>

History

Tuberculosis has been present in humans since antiquity. The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 17,000 years before the present.<ref>Rothschild BM, Martin LD, Lev G, Bercovier H, Bar-Gal GK, Greenblatt C, Donoghue H, Spigelman M, Brittain D. "Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present." Clin Infect Dis. 2001 Aug 1;33(3):305-11. PMID 11438894</ref> However, whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor, is currently unclear.<ref>Pearce-Duvet JM."The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease." Biol Rev Camb Philos Soc. 2006 Aug;81(3):369-82. PMID 16672105</ref> Skeletal remains show prehistoric humans (4000 BCE) had TB, and tubercular decay has been found in the spines of Egyptian mummies from 3000-2400 BCE.<ref>Zink AR, Sola C, Reischl U, Grabner W, Rastogi N, Wolf H, Nerlich AG. Characterization of Mycobacterium tuberculosis complex DNAs from Egyptian mummies by spoligotyping. J Clin Microbiol. 2003 Jan;41(1):359-67. PMID 12517873</ref> Phthisis is a Greek term for tuberculosis; around 460 BCE, Hippocrates identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal.<ref>Hippocrates. Aphorisms. Accessed 07 October 2006.</ref> Genetic studies suggest that TB was present in The Americas from about the year 100 CE.<ref>Konomi N, Lebwohl E, Mowbray K, Tattersall I, Zhang D. Detection of mycobacterial DNA in Andean mummies. J Clin Microbiol. 2002 Dec;40(12):4738-40. PMID 12454182</ref>

Before the Industrial Revolution, tuberculosis may sometimes have been regarded as vampirism. When one member of a family died from it, the other members that were infected would lose their health slowly. People believed that this was caused by the original victim draining the life from the other family members. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often have symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood.<ref>Sledzik, Paul S. and Nicholas Bellantoni Bioarcheological and Biocultural Evidence for the New England Vampire Folk Belief. Am J Phys Anthropol. 1994 Jun;94(2):269-74. PMID 8085617</ref>

Although it was established that the pulmonary form was associated with 'tubercles' by Dr Richard Morton in 1689,<ref name="WhoNamedIt-Calmette">Who Named It? Léon Charles Albert Calmette. Retrieved on 6 October 2006.</ref><ref name="MedHist1970-Trail">Trail, RR. Richard Morton (1637-1698). Med Hist. 14(2):166–174. PMID 4914685</ref> due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was not named 'tuberculosis' until 1839 by J. L. Schönlein.<ref>Zur Pathogenie der Impetigines. Auszug aus einer brieflichen Mitteilung an den Herausgeber. [Müller’s] Archiv für Anatomie, Physiologie und wissenschaftliche Medicin. 1839, page 82.</ref> During the years 1838-1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of tuberculosis sufferers into the cave in the hope of curing the disease with the constant temperature and purity of the cave air: they died within a year.<ref>Kentucky: Mammoth Cave long on history. CNN. 27 February 2004. Accessed 08 October 2006.</ref> The first TB sanatorium opened in 1859 in Sokołowsko, Poland by Hermann Brehmer.<ref name =sanatoria>McCarthy OR. The key to the sanatoria. J R Soc Med. 2001 Aug;94(8):413-7. PMID 11461990</ref>

The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on March 24, 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery.<ref>Nobel Foundation. The Nobel Prize in Physiology or Medicine 1905. Accessed 07 October 2006.</ref> Koch did not believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was eliminated by the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it 'tuberculin'. It was not effective, but was later adapted as a test for pre-symptomatic tuberculosis.<ref>Waddington K. To stamp out "so terrible a malady": bovine tuberculosis and tuberculin testing in Britain, 1890-1939. Med Hist. 2004 Jan;48(1):29-48. PMID 14968644</ref>

The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Guerin in 1906. It was called 'BCG' (Bacillus of Calmette and Guerin). The BCG vaccine was first used on humans in 1921 in France,<ref name=Bonah/> but it wasn't until after World War II that BCG received widespread acceptance in the USA, Great Britain, and Germany.<ref name=Comstock/>

Tuberculosis, or 'consumption' as it was commonly known, caused the most widespread public concern in the 19th and early 20th centuries as an endemic disease of the urban poor. In 1815, one in four deaths in England was of consumption; by 1918 one in six deaths in France were still caused by TB. After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were "encouraged" to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention.<ref name =sanatoria/> Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916).<ref name =sanatoria/>

The promotion of Christmas Seals began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907-08 to help the National Tuberculosis Association (later called the American Lung Association).

In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons.

In Europe, deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in public health were reducing tuberculosis even before the arrival of antibiotics, although the disease remained a significant threat to public health, such that when the Medical Research Council was formed in Britain in 1913 its initial focus was tuberculosis research.<ref>Medical Research Council. Origins of the MRC. Accessed 07 October 2006.</ref>

It was not until 1946 with the development of the antibiotic streptomycin that effective treatment and cure became possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including the pneumothorax technique—collapsing an infected lung to "rest" it and allow lesions to heal—a technique that was of little benefit and was largely discontinued by the 1950s.<ref>Wolfart W. [Surgical treatment of tuberculosis and its modifications--collapse therapy and resection treatment and their present-day sequelae] [Article in German] Offentl Gesundheitswes. 1990 Aug-Sep;52(8-9):506-11. PMID 2146567</ref> The emergence of multidrug-resistant TB has again introduced surgery as part of the treatment for these infections. Here, surgical removal of chest cavities will reduce the number of bacteria in the lungs, as well as increasing the exposure of the remaining bacteria to drugs in the bloodstream, and is therefore thought to increase the effectiveness of the chemotherapy.<ref>Lalloo UG, Naidoo R, Ambaram A. "Recent advances in the medical and surgical treatment of multidrug-resistant tuberculosis." Curr Opin Pulm Med. 2006 May;12(3):179-85. PMID 16582672</ref>

Hope that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, tuberculosis cases in Britain, numbering around 50,000 in 1955, had fallen to around 5,500 in 1987, but in 2000 there were over 7,000 confirmed cases.^{[citation needed]} Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence in the late 1980s.<ref>Paolo WF Jr, Nosanchuk JD. Tuberculosis in New York city: recent lessons and a look ahead. Lancet Infect Dis. 2004 May;4(5):287-93. PMID 15120345</ref> The number of those failing to complete their course of drugs is high. NY had to cope with more than 20,000 "unnecessary" TB-patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid). The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization in 1993.<ref>World Health Organization (WHO). Frequently asked questions about TB and HIV. Retrieved 6 October 2006.</ref>

Infection of other animals

Tuberculosis can be carried by mammals; domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers. In some places, regulations aiming to prevent the spread of TB restrict the ownership of novelty pets; for example, the U.S. state of California forbids the ownership of pet gerbils.<ref>14 CA ADC § 671 Barclays official California code of regulations; Title 14. Natural resources; Division 1. Fish and game commission – Department of fish and game; Subdivision 3. General regulations; Chapter 3. Miscellaneous.</ref>

Mycobacterium bovis causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of New Zealand is underway. It has been found that herd infection is more likely in areas where infected vector species such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush borders.<ref>Tweddle NE, Livingstone P. Bovine tuberculosis control and eradication programs in Australia and New Zealand. Vet Microbiol. 1994 May;40(1-2):23-39. PMID 8073626</ref> Controlling the vectors through possum eradication and monitoring the level of disease in livestock herds through regular surveillance are seen as a "two-pronged" approach to ridding New Zealand of the disease.

In both the Republic of Ireland and Northern Ireland, badgers have been identified as a vector species for the transmission of bovine tuberculosis. As a result, the government in both regions has mounted an active campaign of eradication of the species in an effort to reduce the incidence of the disease. Badgers have been culled primarily by snaring and gassing. It remains a contentious issue, with proponents and opponents of the scheme citing their own studies to support their position.<ref>The Department of Agriculture & Food (Ireland). Disease Eradication Schemes - Bovine Tuberculosis and Brucellosis. Retrieved on 8 May 2006.</ref><ref>Cassidy, Martin. Badgers targeted over bovine TB. BBC News 2 December, 2004. Retrieved on 8 May 2006.</ref><ref>National Federation of Badger Groups (Ireland). Cattle blamed for massive increase in bovine TB. Retrieved on 8 May 2006.</ref>

See also

• Abreugraphy
• ATC code J04 Drugs for treatment of TB
• Buruli ulcer and leprosy: other diseases caused by mycobacteria
• Latent tuberculosis
• List of tuberculosis victims
• Mycobacterium Tuberculosis Structural Genomics Consortium
• National Center for HIV, STD, and TB Prevention
• Nontuberculous mycobacteria
• Overcrowding
• Tuberculosis in history and art
• Philip D'Arcy Hart

References

Further reading

External links

• BioHealthBase Bioinformatics Resource Center. Database of Mycobacterium tuberculosis genome sequences and related information.
• Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Core Curriculum on Tuberculosis: What the Clinician Should Know. 4th edition (2000). Updated Aug 2003.
• Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. News and updates.
• Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. Questions and Answers About TB, 2005.
• Tuberculosis at the Open Directory Project
• Kaiser Family Foundation. Tuberculosis. Globalhealthfacts.org.
• The Nobel Price Website. Tuberculosis Educational Game
• United States Agency for International Development (USAID). The Tuberculosis Coalition for Technical Assistance (TBCTA).
• Walton, David and Farmer, Paul. The New White Plague. JAMA. 2000;284:2789.
• World Health Organization (WHO). Tuberculosis.

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