Tuberculosis

Tuberculosis, MTB, or TB (short for tubercle bacillus) is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis.[1] Tuberculosis usually attacks the lungs but can also affect other parts of the body. It is spread through the air when people who have an active MTB infection cough, sneeze, or otherwise transmit their saliva through the air.[2] Most infections in humans result in an asymptomatic, latent infection, and about one in ten latent infections eventually progress to active disease, which, if left untreated, kills more than 50% of those infected. The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss (the last giving rise to the formerly prevalent colloquial term "consumption"). Infection of other organs causes a wide range of symptoms. Diagnosis relies on radiology (commonly chest X-rays), a tuberculin skin test, blood tests, as well as microscopic examination and microbiological culture of bodily fluids. Treatment is difficult and requires long courses of multiple antibiotics. Social contacts are also screened and treated if necessary. Antibiotic resistance is a growing problem in (extensively) multi-drug-resistant tuberculosis. Prevention relies on screening programs and vaccination, usually with Bacillus Calmette-Guérin vaccine. One third of the world's population is thought to have been infected with M. tuberculosis,[3][4] and new infections occur at a rate of about one per second.[3] In 2007 there were an estimated 13.7 million chronic active cases,[5] and in 2010 there where 8.8 million new cases, and 1.5 million deaths, mostly in developing countries.[6] The absolute number of tuberculosis cases has been decreasing since 2006 and new cases since 2002.[6] In addition, more people in the developing world contract tuberculosis because their immune systems are more likely to be compromised due to higher rates of AIDS.[7] The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5–10% of the U.S. population test positive.[1 Signs and symptoms [pic] [pic] Main symptoms of variants and stages of tuberculosis,[8] with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. Multiple variants may be present simultaneously. Only about 5-10% of those without HIV, infected with tuberculosis develop active disease during their lifetime.[9] In contrast 30% of those co-infected with HIV develop active disease.[9] Tuberculosis may infect any part of the body but most commonly occurs in the lungs (known as pulmonary tuberculosis).[10] Extrapulmonary TB is when tuberculosis occurs outside of the lungs and may co-exist with pulmonary TB.[10] General symptoms such as: fever, chills, night sweats, appetite loss, weight loss, fatigue,[10] and finger clubbing may also occur.[9] Pulmonary If tuberculosis does become active, it most commonly involves infection in the lungs. Symptoms may include chest pain and a productive, prolonged cough. About a quarter of people however may not have any symptoms.[7] Occasionally people may cough up blood in small amounts and in very rare cases the infection may erode into the pulmonary artery resulting in massive bleeding known as Rasmussen's aneurysm. Spitting up stones known as lithoptysis has been described due to bronchial lymph nodes communicated with the airways.Tuberculosis may become chronic with scarring usually in the upper lobes of the lungs. It is believed that the upper lungs are more frequently affected due to their poor lymph supply rather than more air flow.[10] Extrapulmonary In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted extrapulmonary tuberculosis.[11] This occurs more commonly in immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculous pleurisy, the central nervous system in meningitis, the lymphatic system in scrofula of the neck, the genitourinary system in urogenital tuberculosis, and the bones and joints in Pott's disease of the spine. When spread to the bones it is also known as "osseous tuberculosis",[12] a form of osteomyelitis (as a complication of tuberculosis[1]). A potentially more serious form is disseminated TB, more commonly known as miliary tuberculosis.[10] Causes Mycobacterium Main article: Mycobacterium tuberculosis [pic] [pic] Scanning electron micrograph of Mycobacterium tuberculosis The main cause of TB is, Mycobacterium tuberculosis, a small aerobic non-motile bacillus or less commonly the closely related Mycobacterium bovis.[10] The high lipid content of this pathogen accounts for many of its unique clinical characteristics.[13] It divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour.[14] Mycobacteria have an outer membrane lipid bilayer, yet microbiology textbooks continue to classify them as a Gram-positive bacteria.[15][16] If a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall.[17] MTB can withstand weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of a host organism, but M. tuberculosis can be cultured in the laboratory.[18] Using histological stains on expectorate samples from phlegm (also called sputum), scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB).[1][17] The most common acid-fast staining technique, the Ziehl-Neelsen stain, dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an auramine-rhodamine stain and fluorescent microscopy. The M. tuberculosis complex includes four other TB-causing mycobacteria: M. bovis, M. africanum, M. canetti, and M. microti.[19] M. africanum is not widespread, but in parts of Africa it is a significant cause of tuberculosis.[20][21] M. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries.[1][22] M. canetti is rare and seems to be limited to Africa, although a few cases have been seen in African emigrants.[23] M. microti is mostly seen in immunodeficient people, although it is possible that the prevalence of this pathogen has been underestimated.[24] Other known pathogenic mycobacteria include Mycobacterium leprae, Mycobacterium avium, and M. kansasii. The latter two are part of the nontuberculous mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB nor leprosy, but they do cause pulmonary diseases resembling TB.[25] Risk factors Main article: Risk factors for tuberculosis There are a number factors that make people more susceptible to TB infections. Worldwide the most important of these is HIV with co-infection present in about 13% of cases.[6] This is a particular problem in Sub-Saharan Africa where rates of HIV are high.[26][27] Tuberculosis is closely linked to both overcrowding and malnutrition making it one of the principal diseases of poverty.[7] Chronic lung disease is a risk factor with smoking more than 20 cigarettes a day increasing the risk by two to four times[28] and silicosis increasing the risk about 30 fold.[29] Other disease states that increase the risk of developing tuberculosis include alcoholism[7] and diabetes mellitus (threefold increase).[30] Certain medications such as corticosteroids and Infliximab (an anti-αTNF monoclonal antibody) are becoming increasingly important risk factors, especially in the developed world.[7] There is also a genetic susceptibility[31] for which overall importance is still undefined.[7] Mechanism [pic] [pic] Public health campaigns in the 1920s tried to halt the spread of TB. Transmission When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5 µm in diameter. A single sneeze can release up to 40,000 droplets.[32] Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low and inhaling fewer than ten bacteria may cause an infection.[33] People with prolonged, frequent, or close contact are at particularly high risk of becoming infected, with an estimated 22% infection rate.[34] A person with active but untreated tuberculosis can infect 10–15 other people per year.[3] Others at risk include people in areas where TB is common, people who inject illicit drugs, inhabitants and employees of vulnerable congregate settings, medically under-privileged and resource poor populations, high-risk racial or ethnic minority groups, children in close contact with high-risk category patients, those who are immunocompromised by conditions such as HIV/AIDS, people who take immunosuppressant drugs, and health care providers and nurses serving these clients.[35] Transmission can only occur from people with active—not latent—TB.[1] The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence of the M. tuberculosis strain.[36] The cascade of person to person spread can be circumvented by effective segregation of those with active (overt) TB and putting them on recommended anti-TB regimen. After about two weeks of such treatment, subjects with non-resistant active infection generally do not remain as potential source of infection for contacts.[34] If someone does become infected, then it will take three to four weeks before the newly infected person can transmit the disease to others.[37] Pathogenesis 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.[1] However, if untreated, the death rate for these active TB cases is more than 50%.[3] TB infection begins when the mycobacteria reach the pulmonary alveoli, where they invade and replicate within the endosomes of alveolar macrophages.[1][38] The primary site of infection in the lungs is called the Ghon focus, and is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe.[1] Simon foci may also be present. 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 other tissues and organs where secondary TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes, kidneys, brain, and bone.[1][39] All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.[40] 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 granulomas, with lymphocytes surrounding the infected macrophages. The granuloma prevents dissemination of the mycobacteria and provides a local environment for interaction of cells of the immune system. Bacteria inside the granuloma can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of abnormal cell death (necrosis) in the center of tubercles. To the naked eye this has the texture of soft white cheese and is termed caseous necrosis.[41] 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. People with this disseminated TB have a fatality rate near 100% if untreated. However, if treated early, the fatality rate is reduced to about 10%.[42] In many people the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis.[41] 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 spread the infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.[41] Diagnosis Main articles: Tuberculosis diagnosis and Tuberculosis classification [pic] [pic] Mycobacterium tuberculosis (stained red) in sputum Diagnosing tuberculosis based on signs and symptoms is difficult.[43] A definitive diagnosis is made by identifying the causative organism (Mycobacterium tuberculosis) in a clinical sample (for example, sputum or pus). When this is not possible, a probable—although sometimes inconclusive[2]—diagnosis may be made using imaging (X-rays or scans), a tuberculin skin test (Mantoux test),[2] or a, Interferon Gamma Release Assay (IGRA). The main problem with tuberculosis diagnosis is the difficulty in culturing this slow-growing organism in the laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB must include a medical history, a physical examination, a chest X-ray, microbiological smears, and cultures. It may also include a tuberculin skin test, a serological test. 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.[36] Nucleic acid amplification tests and adenosine deaminase may allow rapid diagnosis.[43] Serology tests to detect tuberculosis however are not very accurate.[44] Screening [pic] [pic] Mantoux tuberculin skin test Mantoux tuberculin skin tests are often used for routine screening of high risk individuals.[45] Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to an extract made from M. tuberculosis.[1] Those immunized for TB or with past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection, so the test must be used with caution, particularly with regard to persons from countries where TB immunization is common.[46] Tuberculin tests have the disadvantage of producing false negatives, especially when the person is co-morbid with sarcoidosis, Hodgkins lymphoma, malnutrition, or most notably active tuberculosis disease.[1] The newer interferon release assays (IGRAs) such as T-SPOT.TB and QuantiFERON-TB Gold In Tube overcome many of these problems. IGRAs are in vitro blood tests that are more specific than the skin test. IGRAs detect the release of interferon gamma in response to mycobacterial proteins such as ESAT-6.[47] These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results.[48] There is also evidence that IGRAs are more sensitive than the skin test.[49] Prevention Tuberculosis prevention and control efforts primarily rely on the vaccination of infants and the detection and appropriate treatment of active cases.[7] The World Health Organization has achieved some success with improved treatment success and a small decrease in case numbers.[7] Vaccines The only currently available vaccine as of 2011 is Bacillus Calmette-Guérin (BCG) which while effective against disseminated disease in childhood, confers inconsistent protection against pulmonary disease.[50] It is the most widely used vaccine worldwide with more than 90% of children vaccinated.[7] However the immunity that it induces, decreases after about ten years.[7] As tuberculosis is uncommon in most of Canada, the United Kingdom and the United States, BCG is only administered to people at high risk.[51][52][53] Part of the reason against the use of vaccine is that it makes the tuberculin skin test falsely positive and thus of no use in screening.[53] A number of new vaccines are in development.[7] Public health The World Health Organization (WHO) declared TB a global health emergency in 1993.[7] and in 2006 the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between its launch and 2015.[54] A number of targets that they have set are not likely to be achieved by 2015 due to the increase in HIV associated tuberculosis and multi-drug resistant tuberculosis.[7] Management Main article: Tuberculosis management Treatment for TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which makes many antibiotics ineffective and hinders the entry of drugs.[55] The two antibiotics most commonly used are isoniazid and rifampicin and treatments can be prolonged.[36] 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.[56] People with latent infections are treated to prevent them from progressing to active TB disease later in life. New onset The recommended treatment of new onset pulmonary tuberculosis as of 2010 is six months of a combination of antibiotics containing rifampin, isoniazid, pyrazinamide and ethambutol for the first two months and just rifampin and isoniazid for the last four months.[7] Where resistance to insoniazid is high ethambutol may be added for the last four months.[7] Recurrent disease If tuberculosis recurs, testing to determine what antibiotics it is sensitive to is important before determining treatment.[7] If multi-drug-resistant tuberculosis is detected, treatment with at least four effective antibiotics for 18-24 month is recommended.[7] Medication resistance Primary resistance occurs in persons infected with a resistant strain of TB. A person 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.[56] Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis (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.[57] Totally drug-resistant TB (TDR-TB), which was first observed in 2003 in Italy, but not widely reported until 2012, is resistant to all currently-used drugs.[58] Prognosis 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—1–5% of cases—this occurs soon after infection.[1] However, in the majority of cases, a latent infection occurs that has no obvious symptoms.[1] These dormant bacilli can produce tuberculosis in 2–23% of these latent cases, often many years after infection.[59] The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.[1] Studies utilizing DNA fingerprinting of M. tuberculosis strains have shown that reinfection contributes more substantially to recurrent TB than previously thought,[60] with estimates that it might account for more than 50% in areas where TB is common.[61] The chance of death from a case of tuberculosis is about 4%.[7] Epidemiology [pic] [pic] Age-standardized death from tuberculosis per 100,000 inhabitants in 2004.[62] |  no data |   250–500 | |   ≤ 10 |   500–750 | |   10–25 |   750–1000 | |   25–50 |   1000–2000 | |   50–75 |  2000–3000 | |   75–100 |  ≥ 3000 | |   100–250 | | [pic] [pic] In 2007, the prevalence of TB per 100,000 people was highest in Sub-Saharan Africa, and was also relatively high in Asia.[63] [pic] [pic] Annual number of new reported TB cases. Data from WHO.[64] Roughly a third of the world's population has been infected with M. tuberculosis, and new infections occur at a rate of one per second.[3] However, not all infections with M. tuberculosis cause TB disease and many infections are asymptomatic.[65] In 2007 there were an estimated 13.7 million chronic active cases,[5] and in 2010 there were 8.8 million new cases, and 1.45 million deaths, mostly in developing countries.[6] 0.35 million of these deaths occur in those co-infected with HIV.[66] Tuberculosis is the second most common cause of death from infectious disease (after HIV).[10] The absolute number of tuberculosis cases has been decreasing since 2005 and new cases since 2002.[6] China has achieved particularly dramatic progress, with an 80 percent decline in its TB mortality rate.[67] The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5–10% of the U.S. population test positive.[1] In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases.[5] In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, the national average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe were 30 per 100,000 in Portugal and Spain. These rates compared with 98 per 100,000 in China and 48 per 100,000 in Brazil. In the United States, the overall tuberculosis case rate was 4 per 100,000 persons in 2007.[63] In Canada, tuberculosis is still endemic in some rural areas.[68] The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults.[69] However, in countries where TB has gone from high to low incidence, such as the United States, TB is mainly a disease of older people, or of the immunocompromised.[1][70] 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.[71] History Main article: History of tuberculosis [pic] [pic] Egyptian mummy in the British Museum. Tubercular decay has been found in the spines of Egyptian mummies. Tuberculosis has been present in humans since antiquity.[7] The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 17,000 years before the present.[72] However, whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor, is currently unclear.[73] Although, there is evidence following a comparative genomic approach of MTBC in humans to MTBC in animals that suggests that humans did not acquire MTBC from animals during animal domestication as previously believed. Both strains of the tuberculosis bacteria are shown to share a common ancestor, which could have infected humans as early as the Neolithic transition.[74] Skeletal remains show prehistoric humans (4000 BCE) had TB, and researchers have found tubercular decay in the spines of Egyptian mummies dating from 3000-2400 BCE.[75] Phthisis is a Greek term for consumption; 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.[76] Genetic studies suggest that TB was present in The Americas from about the year 100 CE.[77] Before the Industrial Revolution, folklore often associated tuberculosis with vampires. 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.[78] Although it was established that the pulmonary form was associated with 'tubercles' by Dr Richard Morton in 1689,[79][80] 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.[81] 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.[82] Hermann Brehmer opened the first TB sanatorium in 1859 in Sokołowsko, Poland.[83] [pic] [pic] Dr. Robert Koch discovered the tuberculosis bacilli. The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on 24 March 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine in 1905 for this discovery.[84] 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.[85] Albert Calmette and Camille Guerin achieved the first genuine success in immunizing against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called 'BCG' (Bacillus of Calmette and Guerin). The BCG vaccine was first used on humans in 1921 in France,[86] but it wasn't until after World War II that BCG received widespread acceptance in the USA, Great Britain, and Germany.[87] Tuberculosis 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.[83] 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).[83] 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.[88] 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.[89] Hopes of completely eliminating the disease were dashed following 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.[90] 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.[91] Society and culture One molecular diagnostics test which gives results in 100 minutes is currently being offered to 116 low- and middle-income countries at a discount with support from the World Health Organization and the Bill and Melinda Gates Foundation.[92] Many resource poor places as of 2011 still only have access to sputum microscopy.[93] In part due to poor disease management within the private health care sector, India had the highest total number of TB cases worldwide in 2010 and implementation is pending for programs similar to the Revised National Tuberculosis Control Program that has helped reduce TB levels amongst patients receiving public health care.[94] In 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.[95] Mycobacterium bovis causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of New Zealand is under way. 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.[96] 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.[97][98][99] Research There is ongoing research to develop new TB vaccines to address the limitations of BCG.[100] A number of potential candidates are currently in phase I and II trials.[100] Two main approaches are being attempted to improve the efficacy of available vaccines, one is to add a subunit vaccines to BCG and the other is to create new better live vaccines.[100] A TB vaccine, MVA85A, is currently in phase II trials in South Africa,[101] and is based on a genetically modified vaccinia virus. To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives, and advance market commitments.[102][103] An experimental vaccine, with positive results in mouse models, may be effective not only in preventing infection, but also in eradicating the infection once it has been established.[104] A tuberculosis vaccine aimed at sterile Mtb eradication should be able to target latent Mtb as well as Mtb that causes early-stage tuberculosis.[105] The vaccine is a combination of antigens Ag85B and ESAT-6 as well as the protein Rv2660c. Ag85B and ESAT-6 together form the vaccine Hybrid-1, while Rv2660c is a protein that is expressed even in late-stage infections, when protein transcription is generally reduced. The novel combination of Ag85B, ESAT-6, and Rv2660c allows for both short- and long-term protection as a result of the continued expression of target proteins. The new vaccine, currently referred to as H56, works by promoting a polyfunctional CD4+ T cell response against tuberculosis protein components.[104] Phase I clinical trials began in Cape Town, South Africa, in December 2011.[106] A number of groups including the Mycobacterium Tuberculosis Structural Genomics Consortium and The Tuberculosis Vaccine Initiative (TBVI) are involved with research. References 1. ^ a b c d e f g h i j k l m n o p q Kumar V, Abbas AK, Fausto N, Mitchell RN (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 516–522. ISBN 978-1-4160-2973-1.  2. ^ a b c Konstantinos A (2010). "Testing for tuberculosis". Australian Prescriber 33 (1): 12–18. http://www.australianprescriber.com/magazine/33/1/12/18/.  3. ^ a b c d e "Tuberculosis Fact sheet N°104". World Health Organization. November 2010. http://www.who.int/mediacentre/factsheets/fs104/en/index.html. Retrieved 26 July 2011.  4. ^ Jasmer RM, Nahid P, Hopewell PC (2002). "Clinical practice. Latent tuberculosis infection". N. Engl. J. Med. 347 (23): 1860–6. doi:10.1056/NEJMcp021045. PMID 12466511. http://jasoncartermd.com/resources/pdf/Latent%20TB%20Infection.pdf. , which cites Dolin PJ, Raviglione MC, Kochi A (1994). "Global tuberculosis incidence and mortality during 1990-2000". Bull World Health Organ 72 (2): 213–20. PMC 2486541. PMID 8205640. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2486541.  5. ^ a b c World Health Organization (2009). "Epidemiology". Global tuberculosis control: epidemiology, strategy, financing. pp. 6–33. ISBN 9789241563802. http://who.int/entity/tb/publications/global_report/2009/pdf/chapter1.pdf. Retrieved 12 November 2009.  6. ^ a b c d e "The sixteenth global report on tuberculosis". 2011. http://www.who.int/tb/publications/global_report/2011/gtbr11_executive_summary.pdf.  7. ^ a b c d e f g h i j k l m n o p q r s Lawn, SD; Zumla, AI (2 July 2011). "Tuberculosis". Lancet 378 (9785): 57–72. doi:10.1016/S0140-6736(10)62173-3. PMID 21420161.  8. ^ Schiffman G (15 January 2009). "Tuberculosis Symptoms". eMedicineHealth. http://www.emedicinehealth.com/tuberculosis/page3_em.htm.  9. ^ a b c al.], edited by Peter G. Gibson ; section editors, Michael Abramson ... [et (2005). Evidence-based respiratory medicine (1. publ. ed.). Oxford: Blackwell. pp. 321. ISBN 9780727916051. http://books.google.ca/books'id=sDIKJ1s9wEQC&pg=PA321.  10. ^ a b c d e f g Dolin, [edited by] Gerald L. Mandell, John E. Bennett, Raphael (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases (7th ed.). Philadelphia, PA: Churchill Livingstone/Elsevier. pp. Chapter 250. ISBN 978-0443068393.  11. ^ Golden MP, Vikram HR (2005). "Extrapulmonary tuberculosis: an overview". American family physician 72 (9): 1761–8. PMID 16300038.  12. ^ Mile WA (September 1974). "Osseous tuberculosis". J Natl Med Assoc. 66 (5): 400–3. PMC 2609260. PMID 4414957. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2609260.  13. ^ Southwick F (10 December 2007). "Chapter 4: Pulmonary Infections". Infectious Diseases: A Clinical Short Course, 2nd ed.. McGraw-Hill Medical Publishing Division. p. 104. ISBN 0071477225. http://pharma-books.blogspot.com/2009/01/infectious-disease-clinical-short.html.  14. ^ Cox R (2004). "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 150 (Pt 5): 1413–26. doi:10.1099/mic.0.26560-0. PMID 15133103. http://mic.sgmjournals.org/cgi/content/full/150/5/1413'view=long&pmid=15133103#R35.  15. ^ Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H (March 2010). "Mycobacterial outer membranes: in search of proteins". Trends Microbiol. 18 (3): 109–16. doi:10.1016/j.tim.2009.12.005. PMC 2931330. PMID 20060722. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2931330.  16. ^ Niederweis M (March 2008). "Nutrient acquisition by mycobacteria". Microbiology (Reading, Engl.) 154 (Pt 3): 679–92. doi:10.1099/mic.0.2007/012872-0. PMID 18310015.  17. ^ a b Madison B (2001). "Application of stains in clinical microbiology". Biotech Histochem 76 (3): 119–25. doi:10.1080/714028138. PMID 11475314.  18. ^ Parish T, Stoker N (1999). "Mycobacteria: bugs and bugbears (two steps forward and one step back)". Mol Biotechnol 13 (3): 191–200. doi:10.1385/MB:13:3:191. PMID 10934532.  19. ^ van Soolingen D et al (1997). "A novel pathogenic taxon of the Mycobacterium tuberculosis complex, Canetti: characterization of an exceptional isolate from Africa". Int. J. Syst. Bacteriol. 47 (4): 1236–45. doi:10.1099/00207713-47-4-1236. PMID 9336935.  20. ^ Niemann S et al (2002). "Mycobacterium africanum Subtype II Is Associated with Two Distinct Genotypes and Is a Major Cause of Human Tuberculosis in Kampala, Uganda". J. Clin. Microbiol. 40 (9): 3398–405. doi:10.1128/JCM.40.9.3398-3405.2002. PMC 130701. PMID 12202584. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=130701.  21. ^ Niobe-Eyangoh SN et al (2003). "Genetic Biodiversity of Mycobacterium tuberculosis Complex Strains from Patients with Pulmonary Tuberculosis in Cameroon". J. Clin. Microbiol. 41 (6): 2547–53. doi:10.1128/JCM.41.6.2547-2553.2003. PMC 156567. PMID 12791879. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=156567.  22. ^ Thoen C, Lobue P, de Kantor I (2006). "The importance of Mycobacterium bovis as a zoonosis". Vet. Microbiol. 112 (2–4): 339–45. doi:10.1016/j.vetmic.2005.11.047. PMID 16387455.  23. ^ Pfyffer GE, Auckenthaler R, van Embden JD, van Soolingen D (1998). "Mycobacterium canettii, the smooth variant of M. tuberculosis, isolated from a Swiss patient exposed in Africa". Emerging Infect. Dis. 4 (4): 631–4. doi:10.3201/eid0404.980414. PMC 2640258. PMID 9866740. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2640258.  24. ^ Niemann S, Richter E, Dalügge-Tamm H, Schlesinger H, Graupner D, Königstein B, Gurath G, Greinert U, Rüsch-Gerdes S (2000). "Two cases of Mycobacterium microti derived tuberculosis in HIV-negative immunocompetent patients". Emerg Infect Dis 6 (5): 539–42. doi:10.3201/eid0605.000516. PMC 2627952. PMID 10998387. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2627952.  25. ^ American Thoracic Society (1997). "Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association". Am J Respir Crit Care Med 156 (2 Pt 2): S1–25. PMID 9279284.  26. ^ World Health Organization. "Global tuberculosis control–surveillance, planning, financing WHO Report 2006". http://www.who.int/tb/publications/global_report/en/index.html. Retrieved 13 October 2006.  27. ^ Chaisson, RE; Martinson, NA (13 March 2008). "Tuberculosis in Africa--combating an HIV-driven crisis". The New England Journal of Medicine 358 (11): 1089–92. doi:10.1056/NEJMp0800809. PMID 18337598.  28. ^ Davies, PD; Yew, WW, Ganguly, D, Davidow, AL, Reichman, LB, Dheda, K, Rook, GA (2006 Apr). "Smoking and tuberculosis: the epidemiological association and immunopathogenesis". Transactions of the Royal Society of Tropical Medicine and Hygiene 100 (4): 291–8. doi:10.1016/j.trstmh.2005.06.034. PMID 16325875.  29. ^ ATS/CDC Statement Committee on Latent Tuberculosis Infection (June 200). "Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society". MMWR Recomm Rep 49 (RR–6): 1–51. PMID 10881762. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4906a1.htm#tab3.  30. ^ Restrepo, BI (15 August 2007). "Convergence of the tuberculosis and diabetes epidemics: renewal of old acquaintances". Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 45 (4): 436–8. doi:10.1086/519939. PMC 2900315. PMID 17638190. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2900315.  31. ^ Möller, M; Hoal, EG (2010 Mar). "Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis". Tuberculosis (Edinburgh, Scotland) 90 (2): 71–83. doi:10.1016/j.tube.2010.02.002. PMID 20206579.  32. ^ Cole E, Cook C (1998). "Characterization of infectious aerosols in health care facilities: an aid to effective engineering controls and preventive strategies". Am J Infect Control 26 (4): 453–64. doi:10.1016/S0196-6553(98)70046-X. PMID 9721404.  33. ^ Nicas M, Nazaroff WW, Hubbard A (2005). "Toward understanding the risk of secondary airborne infection: emission of respirable pathogens". J Occup Environ Hyg 2 (3): 143–54. doi:10.1080/15459620590918466. PMID 15764538.  34. ^ a b Ahmed N, Hasnain S (2011). "Molecular epidemiology of tuberculosis in India: Moving forward with a systems biology approach". Tuberculosis 91 (5): 407–3. doi:10.1016/j.tube.2011.03.006. PMID 21514230.  35. ^ Griffith D, Kerr C (1996). "Tuberculosis: disease of the past, disease of the present". J Perianesth Nurs 11 (4): 240–5. doi:10.1016/S1089-9472(96)80023-2. PMID 8964016.  36. ^ a b c "Core Curriculum on Tuberculosis: What the Clinician Should Know". Centers for Disease Control and Prevention (CDC), Division of Tuberculosis Elimination. 2000, updated August 2003. http://www.cdc.gov/tb/'404;http://www.cdc.gov:80/tb/pubs/corecurr/default.htm.  37. ^ "Causes of Tuberculosis". Mayo Clinic. 21 December 2006. http://www.mayoclinic.com/health/tuberculosis/DS00372/DSECTION=3. Retrieved 19 October 2007.  38. ^ Houben E, Nguyen L, Pieters J (2006). "Interaction of pathogenic mycobacteria with the host immune system". Curr Opin Microbiol 9 (1): 76–85. doi:10.1016/j.mib.2005.12.014. PMID 16406837.  39. ^ Herrmann J, Lagrange P (2005). "Dendritic cells and Mycobacterium tuberculosis: which is the Trojan horse'". Pathol Biol (Paris) 53 (1): 35–40. doi:10.1016/j.patbio.2004.01.004. PMID 15620608.  40. ^ Agarwal R, Malhotra P, Awasthi A, Kakkar N, Gupta D (2005). "Tuberculous dilated cardiomyopathy: an under-recognized entity'". BMC Infect Dis 5 (1): 29. doi:10.1186/1471-2334-5-29. PMC 1090580. PMID 15857515. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=1090580.  41. ^ a b c Grosset J (2003). "Mycobacterium tuberculosis in the Extracellular Compartment: an Underestimated Adversary". Antimicrob Agents Chemother 47 (3): 833–6. doi:10.1128/AAC.47.3.833-836.2003. PMC 149338. PMID 12604509. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=149338.  42. ^ Kim J, Park Y, Kim Y, Kang S, Shin J, Park I, Choi B (2003). "Miliary tuberculosis and acute respiratory distress syndrome". Int J Tuberc Lung Dis 7 (4): 359–64. PMID 12733492.  43. ^ a b Bento, J; Silva, AS, Rodrigues, F, Duarte, R (2011 Jan-Feb). "[Diagnostic tools in tuberculosis].". Acta medica portuguesa 24 (1): 145–54. PMID 21672452.  44. ^ Steingart, KR; Flores, LL, Dendukuri, N, Schiller, I, Laal, S, Ramsay, A, Hopewell, PC, Pai, M (2011 Aug). "Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis.". PLoS medicine 8 (8): e1001062. doi:10.1371/journal.pmed.1001062. PMC 3153457. PMID 21857806. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=3153457.  45. ^ Bloch, Alan B.; Advisory Council for the Elimination of Tuberculosis (September 1995). "Screening for tuberculosis and tuberculosis infection in high-risk populations. Recommendations of the Advisory Council for the Elimination of Tuberculosis". MMWR Recomm Rep 44 (RR–11): 19–34. PMID 7565540. http://www.cdc.gov/mmwr/preview/mmwrhtml/00038873.htm.  46. ^ Rothel J, Andersen P (2005). "Diagnosis of latent Mycobacterium tuberculosis infection: is the demise of the Mantoux test imminent'". Expert Rev Anti Infect Ther 3 (6): 981–93. doi:10.1586/14787210.3.6.981. PMID 16307510.  47. ^ Nahid P, Pai M, Hopewell P (2006). "Advances in the Diagnosis and Treatment of Tuberculosis". Proc Am Thorac Soc 3 (1): 103–10. doi:10.1513/pats.200511-119JH. PMC 2658675. PMID 16493157. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2658675.  48. ^ Pai M, Zwerling A, Menzies D (2008). "Systematic Review: T-Cell–based Assays for the Diagnosis of Latent Tuberculosis Infection: An Update". Ann. Intern. Med. 149 (3): 1–9. PMC 2951987. PMID 18593687. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2951987.  49. ^ Lalvani A, Richeldi L, Kunst H (2005). "Interferon gamma assays for tuberculosis". Lancet Infect Dis 5 (6): 322–4; author reply 325–7. doi:10.1016/S1473-3099(05)70118-3. PMID 15919613.  50. ^ McShane, H (12 October 2011). "Tuberculosis vaccines: beyond bacille Calmette–Guérin". Philosophical transactions of the Royal Society of London. Series B, Biological sciences 366 (1579): 2782–9. doi:10.1098/rstb.2011.0097. PMC 3146779. PMID 21893541. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=3146779.  51. ^ "Vaccine and Immunizations: TB Vaccine (BCG)". Centers for Disease Control and Prevention. 2011. http://www.cdc.gov/tb/topic/vaccines/. Retrieved 26 July 2011.  52. ^ "BCG Vaccine Usage in Canada - Current and Historical". Public Health Agency of Canada. September 2010. http://www.phac-aspc.gc.ca/tbpc-latb/bcgvac_1206-eng.php. Retrieved 30 December 2011.  53. ^ a b Teo, SS; Shingadia, DV (2006 Jun). "Does BCG have a role in tuberculosis control and prevention in the United Kingdom'". Archives of Disease in Childhood 91 (6): 529–31. doi:10.1136/adc.2005.085043. PMC 2082765. PMID 16714729. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=2082765.  54. ^ "The Global Plan to Stop TB". World Health Organization. 2011. http://www.stoptb.org/global/plan/. Retrieved 13 June 2011.  55. ^ Brennan PJ, Nikaido H (1995). "The envelope of mycobacteria". Annu. Rev. Biochem. 64: 29–63. doi:10.1146/annurev.bi.64.070195.000333. PMID 7574484.  56. ^ a b O'Brien R (1994). "Drug-resistant tuberculosis: etiology, management and prevention". Semin Respir Infect 9 (2): 104–12. PMID 7973169.  57. ^ Centers for Disease Control and Prevention (CDC) (2006). "Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000–2004". MMWR Morb Mortal Wkly Rep 55 (11): 301–5. PMID 16557213. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5511a2.htm.  58. ^ Maryn McKenna (12 January 2012). "Totally Resistant TB: Earliest Cases in Italy". Wired. http://www.wired.com/wiredscience/2012/01/tdr-first-italy/. Retrieved 12 January 2012.  59. ^ Parrish N, Dick J, Bishai W (1998). "Mechanisms of latency in Mycobacterium tuberculosis". Trends Microbiol 6 (3): 107–12. doi:10.1016/S0966-842X(98)01216-5. PMID 9582936.  60. ^ Lambert M et al (2003). "Recurrence in tuberculosis: relapse or reinfection'". Lancet Infect Dis 3 (5): 282–7. doi:10.1016/S1473-3099(03)00607-8. PMID 12726976.  61. ^ Wang, JY; Lee, LN, Lai, HC, Hsu, HL, Liaw, YS, Hsueh, PR, Yang, PC (15 July 2007). "Prediction of the tuberculosis reinfection proportion from the local incidence". The Journal of infectious diseases 196 (2): 281–8. doi:10.1086/518898. PMID 17570116.  62. ^ "WHO Disease and injury country estimates". World Health Organization. 2004. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved 11 November 2009.  63. ^ a b World Health Organization (2009). "The Stop TB Strategy, case reports, treatment outcomes and estimates of TB burden". Global tuberculosis control: epidemiology, strategy, financing. pp. 187–300. ISBN 9789241563802. http://who.int/tb/publications/global_report/2009/annex_3/en/index.html. Retrieved 14 November 2009.  64. ^ World Health Organization. "WHO report 2008: Global tuberculosis control". http://www.who.int/tb/publications/global_report/2008/annex_3/en/index.html. Retrieved 13 April 2009.  65. ^ "Fact Sheets: The Difference Between Latent TB Infection and Active TB Disease". Centers for Disease Control. 20 June 2011. http://www.cdc.gov/tb/publications/factsheets/general/LTBIandActiveTB.htm. Retrieved 26 July 2011.  66. ^ http://www.who.int/tb/publications/global_report/2011/gtbr11_full.pdf 67. ^ Global Tuberculosis Control, World Health Organization, 2011 68. ^ Al-Azem A, Kaushal Sharma M, Turenne C, Hoban D, Hershfield E, MacMorran J, Kabani A (1998). "Rural outbreaks of Mycobacterium tuberculosis in a Canadian province". Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother 38: 555. abstract no. L-27. http://gateway.nlm.nih.gov/MeetingAbstracts/ma'f=102188560.html.  69. ^ World Health Organization. "Global Tuberculosis Control Report, 2006 – Annex 1 Profiles of high-burden countries" (PDF). http://www.who.int/tb/publications/global_report/2006/pdf/full_report_correctedversion.pdf. Retrieved 13 October 2006.  70. ^ Centers for Disease Control and Prevention (12 September 2006). "2005 Surveillance Slide Set". http://www.cdc.gov/nchstp/tb/pubs/slidesets/surv/surv2005/default.htm. Retrieved 13 October 2006.  71. ^ Medical Research Council.Origins of the MRC. Accessed 7 October 2006. 72. ^ Rothschild BM, Martin LD, Lev G et al (August 2001). "Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present". Clin. Infect. Dis. 33 (3): 305–11. doi:10.1086/321886. PMID 11438894. http://www.journals.uchicago.edu/cgi-bin/resolve'CID001531.  73. ^ 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. doi:10.1017/S1464793106007020. PMID 16672105.  74. ^ Comas, Iñaki, and Sebastien Gagneux. 2009,"The Past And Future Of Tuberculosis Research." Plos Pathogens 5.10 (2009): 2. Web.9 Nov. 2011 75. ^ Zink A, Sola C, Reischl U, Grabner W, Rastogi N, Wolf H, Nerlich A (2003). "Characterization of Mycobacterium tuberculosis Complex DNAs from Egyptian Mummies by Spoligotyping". J Clin Microbiol 41 (1): 359–67. doi:10.1128/JCM.41.1.359-367.2003. PMC 149558. PMID 12517873. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=149558.  76. ^ Hippocrates. Aphorisms. Accessed 7 October 2006. 77. ^ Konomi N, Lebwohl E, Mowbray K, Tattersall I, Zhang D (2002). "Detection of Mycobacterial DNA in Andean Mummies". J Clin Microbiol 40 (12): 4738–40. doi:10.1128/JCM.40.12.4738-4740.2002. PMC 154635. PMID 12454182. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=154635.  78. ^ Sledzik, Paul S.; Nicholas Bellantoni (June 1994). "Bioarcheological and biocultural evidence for the New England vampire folk belief" (PDF). American Journal of Physical Anthropology 94 (2): 269–274. doi:10.1002/ajpa.1330940210. ISSN 0002-9483. PMID 8085617. http://www.ceev.net/biocultural.pdf.  79. ^ Léon Charles Albert Calmette at Who Named It' 80. ^ Trail RR (April 1970). "Richard Morton (1637-1698)". Med Hist 14 (2): 166–74. PMC 1034037. PMID 4914685. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=1034037.  81. ^ Zur Pathogenie der Impetigines. Auszug aus einer brieflichen Mitteilung an den Herausgeber. [Müller’s] Archiv für Anatomie, Physiologie und wissenschaftliche Medicin. 1839, page 82. 82. ^ Kentucky: Mammoth Cave long on history. CNN. 27 February 2004. Accessed 8 October 2006. 83. ^ a b c McCarthy OR (August 2001). "The key to the sanatoria". J R Soc Med 94 (8): 413–7. PMC 1281640. PMID 11461990. http://www.jrsm.org/cgi/pmidlookup'view=long&pmid=11461990.  84. ^ Nobel Foundation. The Nobel Prize in Physiology or Medicine 1905. Accessed 7 October 2006. 85. ^ Waddington K (January 2004). "To stamp out "So Terrible a Malady": bovine tuberculosis and tuberculin testing in Britain, 1890–1939". Med Hist 48 (1): 29–48. PMC 546294. PMID 14968644. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=546294.  86. ^ 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. doi:10.1016/j.shpsc.2005.09.003. PMID 16337557.  87. ^ Comstock G (1994). "The International Tuberculosis Campaign: a pioneering venture in mass vaccination and research". Clin Infect Dis 19 (3): 528–40. doi:10.1093/clinids/19.3.528. PMID 7811874.  88. ^ Wolfart W (1990). "[Surgical treatment of tuberculosis and its modifications—collapse therapy and resection treatment and their present-day sequelae]" (in German). Offentl Gesundheitswes 52 (8–9): 506–11. PMID 2146567.  89. ^ Lalloo UG, Naidoo R, Ambaram A (May 2006). "Recent advances in the medical and surgical treatment of multi-drug resistant tuberculosis". Curr Opin Pulm Med 12 (3): 179–85. doi:10.1097/01.mcp.0000219266.27439.52. PMID 16582672. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm'issn=1070-5287&volume=12&issue=3&spage=179.  90. ^ Paolo WF, Nosanchuk JD (May 2004). "Tuberculosis in New York city: recent lessons and a look ahead". Lancet Infect Dis 4 (5): 287–93. doi:10.1016/S1473-3099(04)01004-7. PMID 15120345. http://linkinghub.elsevier.com/retrieve/pii/S1473309904010047.  91. ^ World Health Organization (WHO). Frequently asked questions about TB and HIV. Retrieved 6 October 2006. 92. ^ "WHO says Cepheid rapid test will transform TB care". Reuters. 8 December 2010. http://www.reuters.com/article/idUSTRE6B71RF20101208.  93. ^ Lienhardt, C; Espinal, M, Pai, M, Maher, D, Raviglione, MC (2011 Nov). "What research is needed to stop TB' Introducing the TB Research Movement.". PLoS medicine 8 (11): e1001135. doi:10.1371/journal.pmed.1001135. PMC 3226454. PMID 22140369. http://www.pubmedcentral.nih.gov/articlerender.fcgi'tool=pmcentrez&artid=3226454.  94. ^ Anurag Bhargava, Lancelot Pinto, Madhukar Pai (2011). "Mismanagement of tuberculosis in India: Causes, consequences, and the way forward". Hypothesis 9 (1): e7. http://www.hypothesisjournal.com/'p=989.  95. ^ 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. 96. ^ Tweddle N, Livingstone P (1994). "Bovine tuberculosis control and eradication programs in Australia and New Zealand". Vet Microbiol 40 (1–2): 23–39. doi:10.1016/0378-1135(94)90044-2. PMID 8073626.  97. ^ "Disease Eradication Schemes - Bovine Tuberculosis and Brucellosis". The Department of Agriculture & Food (Ireland). http://www.agriculture.ie/index.jsp'file=animal_health/TB.xml. Retrieved 8 May 2006.  98. ^ Cassidy, Martin (2 December 2004). "Badgers targeted over bovine TB". BBC News. http://news.bbc.co.uk/1/hi/northern_ireland/4044897.stm. Retrieved May 2006.  99. ^ National Federation of Badger Groups (Ireland). Cattle blamed for massive increase in bovine TB. Retrieved on 8 May 2006. 100. ^ a b c Martín Montañés, C; Gicquel, B (2011 Mar). "New tuberculosis vaccines.". Enfermedades infecciosas y microbiologia clinica 29 Suppl 1: 57–62. doi:10.1016/S0213-005X(11)70019-2. PMID 21420568.  101. ^ Ibanga H, Brookes R, Hill P, Owiafe P, Fletcher H, Lienhardt C, Hill A, Adegbola R, McShane H (2006). "Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design". Lancet Infect Dis 6 (8): 522–8. doi:10.1016/S1473-3099(06)70552-7. PMID 16870530.  102. ^ Webber D, Kremer M (2001). "Stimulating Industrial R&D for Neglected Infectious Diseases: Economic Perspectives". Bulletin of the World Health Organization 79 (8): 693–801. http://www.who.int/bulletin/archives/79(8)735.pdf.  103. ^ Barder O, Kremer M, Williams H (2006). "Advance Market Commitments: A Policy to Stimulate Investment in Vaccines for Neglected Diseases". The Economists' Voice 3 (3). doi:10.2202/1553-3832.1144. http://www.bepress.com/ev/vol3/iss3/art1.  104. ^ a b Aagaard C, Hoang T, Dietrich J, Cardona PJ, Izzo A, Dolganov G, Schoolnik GK, Cassidy JP, Billeskov R, Andersen P (2011). "A multistage tuberculosis vaccine that confers efficient protection before and after exposure". Nature Medicine 17 (2): 189–94. doi:10.1038/nm.2285. PMID 21258338.  105. ^ Kaufmann SH (2010). "Future vaccination strategies against tuberculosis: Thinking outside the box". Immunity 33 (4): 567–77. doi:10.1016/j.immuni.2010.09.015. PMID 21029966.  106. ^ Leadman, Annmarie. Vaccine targeting latent TB enters clinical testing. Eurekalert. 01 Dec 2011. Last accessed 25 Jan 2012. External links |[pic] |Wikimedia Commons has media related to: Tuberculosis | • Tuberculosis at the Open Directory Project • "Tuberculosis (TB)". Centers for Disease Control. http://www.cdc.gov/tb/default.htm. Retrieved 6 April 2011.  • "Tuberculosis (TB)". UK Health Protection Agency. http://www.hpa.org.uk/infections/topics_az/tb/menu.htm. Retrieved 6 April 2011.  |[show] | |v | |t | |e | |Actinobacteria (high-G+C) Infectious diseases · Bacterial diseases: G+ (primarily A00–A79, 001–041, 080–109) | | | | | | | | | |Actinomycineae | |Actinomycetaceae | |Actinomyces israelii (Actinomycosis, Cutaneous actinomycosis) · Tropheryma whipplei (Whipple's disease) · Arcanobacterium | |haemolyticum (Arcanobacterium haemolyticum infection) | | | | | | | | | |Propionibacteriaceae | |Propionibacterium acnes | | | | | | | | | | | | | |Corynebacterineae | |Mycobacteriaceae | |M. tuberculosis/ | |M. bovis | |Tuberculosis: Ghon focus/Ghon's complex · Pott disease · brain (Meningitis, Rich focus) · Tuberculous lymphadenitis (Tuberculous | |cervical lymphadenitis) · cutaneous (Scrofuloderma, Erythema induratum, Lupus vulgaris, Prosector's wart, Tuberculosis cutis | |orificialis, Tuberculous cellulitis, Tuberculous gumma) · Lichen scrofulosorum · Tuberculid (Papulonecrotic tuberculid) · Primary| |inoculation tuberculosis · Miliary · Tuberculous pericarditis · Urogenital tuberculosis · Multi-drug-resistant tuberculosis · | |Extensively drug-resistant tuberculosis | | | | | | | | | |M. leprae | |Leprosy: Tuberculoid leprosy · Borderline tuberculoid leprosy · Borderline leprosy · Borderline lepromatous leprosy · Lepromatous| |leprosy · Histoid leprosy | | | | | | | | | |Nontuberculous | |R1: M. kansasii · M. marinum (Aquarium granuloma) | |R2: M. gordonae | |R3: M. avium complex/Mycobacterium avium/Mycobacterium intracellulare/MAP (MAI infection) · M. ulcerans (Buruli ulcer) · M. | |haemophilum | |R4/RG: M. fortuitum · M. chelonae · M. abscessus | | | | | | | | | | | | | |Nocardiaceae | |Nocardia asteroides/Nocardia brasiliensis (Nocardiosis) · Rhodococcus equi | | | | | | | | | |Corynebacteriaceae | |Corynebacterium diphtheriae (Diphtheria) · Corynebacterium minutissimum (Erythrasma) · Corynebacterium jeikeium (Group JK | |corynebacterium sepsis) | | | | | | | | | | | | | |Bifidobacteriaceae | |Gardnerella vaginalis | | | | | | | | | |M: BAC | |bact (clas) | |gr+f/gr+a(t)/gr-p(c)/gr-o | |drug(J1p, w, n, m, vacc) | | | | | | | | | | | |[show] | |v | |t | |e | |Tuberculosis | | | | | | | | | |Treatment/ | |vaccines | |ATC code J04 · Isoniazid · 4-Aminosalicylic acid · Ethambutol · Capreomycin · Cycloserine · Rifampicin · Thioacetazone · | |Streptomycin · R207910 · RBCG30 · Pyrazinamide · MVA85A · Rifater | | | | | | | | | |People/ | |History | |Manuel de Abreu · Hermann Brehmer · Albert Calmette · Philip D'Arcy Hart · Christopher Dye · George M. Heath · Max Gerson · F. R.| |G. Heaf · Robert Koch · Marcos Espinal · Friedrich Franz Friedmann · Charles Mantoux · Richard Morton · Edward Livingston | |Trudeau · Carl Rüedi · Lucius Rüedi · Mario Raviglione · Madonna Swan | | | | | | | | | |Conditions/ | |symptoms/signs | |Caseous necrosis · Ghon focus/Ghon's complex · Giant multinucleated cell · Pott disease · Canga's bead symptom · Prosector's | |wart · Latent tuberculosis · Paronychia · Lupus vulgaris · Tuberculous lymphadenitis · Tuberculous meningitis · Miliary | |tuberculosis | | | | | | | | | |Mycobacterium species | |Mycobacterium tuberculosis · Mycobacterium africanum · Mycobacterium bovis · Mycobacterium bovis BCG · Mycobacterium caprae | | | | | | | | | |Type by resistance | |Multi-drug-resistant tuberculosis · Extensively drug-resistant tuberculosis · Totally drug-resistant tuberculosis | | | | | | | | | |Tests/diagnosis | |Ziehl–Neelsen stain · Auramine phenol stain · Culture on Lowenstein-Jensen medium and/or MGIT · GeneXpert · Chest | |photofluorography · Tuberculin (Heaf test, Mantoux test, Tine test) · Interferon-γ release assays (QuantiFERON, T-SPOT.TB) · | |Microscopic Observation Drug Susceptibility assay | | | | | | | | | |Organizations | |Adirondack Cottage Sanitarium · Aeras Global TB Vaccine Foundation · Friends of the Global Fight Against AIDS, Tuberculosis, and | |Malaria · Glen Lake Children's Camp · Glen Lake Sanatorium · Glenn Dale Hospital · The Global Fund to Fight AIDS, Tuberculosis | |and Malaria · Global Plan to Stop Tuberculosis · Unitaid · TB Alliance · Seattle Biomedical Research Institute · Stop TB | |Partnership · Millennium Foundation · Mycobacterium Tuberculosis Structural Genomics Consortium · National Jewish Medical and | |Research Center · Phipps Institute for the Study, Treatment and Prevention of Tuberculosis · Campaign for Access to Essential | |Medicines · Cure Cottages of Saranac Lake · International Congress on Tuberculosis | | | | | | | | | |Other/ungrouped | |2007 tuberculosis scare · 72F fusion protein · Tuberculosis in popular culture · Baumgarten-Tangl law · CFP-10 · Tuberculosis in | |China · ESAT-6 · Iowa Cow War · List of tuberculosis victims · Plombage · Preventorium · Sanatorium · Sunshine Way · Tuberculosis| |classification · Tuberculosis radiology · Tygerberg score · World Tuberculosis Day | | | | | | | | | |M: BAC | |bact (clas) | |gr+f/gr+a(t)/gr-p(c)/gr-o | |drug(J1p, w, n, m, vacc) | | | | | | | | | | | |[show] | |v | |t | |e | |Diseases of poverty | | | | | | | | | |Diseases of poverty | |AIDS | |Malaria | |Tuberculosis | |Measles | |Pneumonia | |Diarrheal diseases | | | | | | | | | |Neglected diseases | |Cholera | |Chagas disease | |African Sleeping Sickness | |Schistosomiasis | |Guinea worm | |River blindness | |Leishmaniasis | | | | | | | | | |Miscellaneous | |Malnutrition | |Priority Review Voucher | | | Retrieved from "http://en.wikipedia.org/w/index.php'title=Tuberculosis&oldid=486637556" View page ratings Rate this page Rate this page Page ratings What's this' Current average ratings. Trustworthy [pic] Objective [pic] Complete [pic] Well-written [pic] [pic]I am highly knowledgeable about this topic (optional) [pic]I have a relevant college/university degree [pic]It is part of my profession [pic]It is a deep personal passion [pic]The source of my knowledge is not listed here [pic]I would like to help improve Wikipedia, send me an e-mail (optional)[pic] We will send you a confirmation e-mail. We will not share your e-mail address with outside parties as per our feedback privacy statement. Submit ratings Saved successfully Your ratings have not been submitted yet Your ratings have expired Please reevaluate this page and submit new ratings. An error has occurred. Please try again later. Thanks! Your ratings have been saved. Please take a moment to complete a short survey. Start surveyMaybe later Thanks! Your ratings have been saved. Do you want to create an account' An account will help you track your edits, get involved in discussions, and be a part of the community. Create an accountorLog inMaybe later Thanks! Your ratings have been saved. Did you know that you can edit this page' Edit this pageMaybe later Categories: • Tuberculosis • Health in Africa • Health in India • Mycobacterium-related cutaneous conditions Hidden categories: • Wikipedia indefinitely semi-protected pages • Wikipedia indefinitely move-protected pages • All articles with unsourced statements • Articles with unsourced statements from September 2011 • Use dmy dates from August 2010