Tuberculosis or TB (short for tubercles bacillus ) is a common and often deadly infectious disease caused by various strains of mycobacteria , usually Mycobacterium tuberculosis in humans. Most infections in humans result in an asymptomatic, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of its victims.

The classic symptoms are a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss. 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. 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-Gu??rin vaccine.

One third of the world's population is thought to be infected with M. tuberculosis , and new infections occur at a rate of about one per second.

The current clinical classification system for tuberculosis (TB) is based on the pathogenesis of the disease.

Classification System for TB

Type |> Description
0	No TB exposure Not infected	No history of exposure Negative reaction to tuberculin skin test
1	TB exposure No evidence of infection	History of exposure Negative reaction to tuberculin skin test Ghon complex
2	TB infection No disease	Positive reaction to tuberculin skin test Negative bacteriologic studies (if done) Fibrocaseous cavitary lesion (usually in upper lobe of lungs)
3	TB, clinically active	''M. tuberculosis'' cultured (if done) Clinical, bacteriologic, or radiographic evidence of current disease
4	TB Not clinically active	History of episode(s) of TB '''or''' Abnormal but stable radiographic findings Positive reaction to the tuberculin skin test Negative bacteriologic studies (if done) '''and''' No clinical or radiographic evidence of current disease
5	TB suspect	Diagnosis pending TB disease should be ruled in or out within 3 months

When the disease becomes active, 75% of the cases are pulmonary TB, that is, TB in the lungs. Symptoms include chest pain, coughing up blood , and a productive, prolonged cough for more than three weeks. Systemic symptoms include fever, chills , night sweats, appetite loss, weight loss, pallor, and often a tendency to fatigue very easily.

In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted extrapulmonary tuberculosis. This occurs more commonly in immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculosis pleurisy, the central nervous system in meningitis, the lymphatic system in scrofula of the neck, the genitourinary system in urogenital tuberculosis, and bones and joints in Pott's disease of the spine. An especially serious form is disseminated TB, more commonly known as miliary tuberculosis. Extrapulmonary TB may co-exist with pulmonary TB as well.

The primary cause of TB, Mycobacterium tuberculosis, is a small aerobic non-motile bacillus. High lipid content of this pathogen accounts for many of its unique clinical characteristics. It divides every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour.

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). 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 . M. africanum is not widespread, but in parts of Africa it is a significant cause of tuberculosis. 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.

Other known pathogenic mycobacteria include Mycobacterium leprae, Mycobacterium avium and M. kansasii . The last two are part of the nontuberculous mycobacteria (NTM) group. Nontuberculous mycobacteria cause neither TB nor leprosy, but they do cause pulmonary diseases resembling TB.

Risk factors

Persons with silicosis have an approximately 30-fold greater risk for developing TB. Silica particles irritate the respiratory system, causing immunogenic responses such as phagocytosis, which, as a consequence, results in high lymphatic vessel deposits. It is this interference and blockage of macrophage function that increases the risk of tuberculosis. Persons with chronic renal failure and also on hemodialysis have an increased risk: 10???25 times greater than the general population. Persons with diabetes mellitus have a risk for developing active TB that is two to four times greater than persons without diabetes mellitus, and this risk is likely greater in persons with insulin-dependent or poorly controlled diabetes. Other clinical conditions that have been associated with active TB include gastrectomy with attendant weight loss and malabsorption, jejunoileal bypass, renal and cardiac transplantation, carcinoma of the head or neck, and other neoplasms (e.g., lung cancer, lymphoma, and leukemia).

Given that silicosis greatly increases the risk of tuberculosis, more research about the effect of various indoor or outdoor air pollutants on the disease would be necessary. Some possible indoor source of silica includes paint, concrete and Portland cement. Crystalline silica is found in concrete, masonry, sandstone, rock, paint, and other abrasives. The cutting, breaking, crushing, drilling, grinding, or abrasive blasting of these materials may produce fine silica dust. It can also be in soil, mortar, plaster, and shingles. When you wear dusty clothing at home or in your car, you may be carrying silica dust that your family will breathe.

Low body weight is associated with risk of tuberculosis as well. A body mass index (BMI) below 18.5 increases the risk by 2???3 times. On the other hand, an increase in body weight lowers the risk. Patients with diabetes mellitus are at increased risk of contracting tuberculosis, and they have a poorer response to treatment, possibly due to poorer drug absorption

Other conditions that increase risk include IV drug abuse ; recent TB infection or a history of inadequately treated TB; chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules; prolonged corticosteroid therapy and other immunosuppressive therapy; Immunocompromised patients (30-40% of AIDS patients in the world also have TB) hematologic and reticuloendothelial diseases, such as leukemia and Hodgkin's disease; end-stage kidney disease; intestinal bypass; chronic malabsorption syndromes; vitamin D deficiency; and low body weight.

Twin studies in the 1940s showed that susceptibility to TB was heritable. If one of a pair of twins got TB, then the other was more likely to get TB if he was identical than if he was not. These findings were more recently confirmed by a series of studies in South Africa. Specific gene polymorphisms in IL12B have been linked to tuberculosis susceptibility.

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.

Transmission

When people suffering from active pulmonary TB cough, sneeze, speak, or spit, they expel infectious aerosol droplets 0.5 to 5 ??m in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very low and inhaling less than ten bacteria may cause an infection.

People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10???15 other people per year. Others at risk include people in areas where TB is common, people who inject drugs using unsanitary needles, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, patients immunocompromised by conditions such as HIV/ AIDS, people who take immunosuppressant drugs, and health care workers serving these high-risk clients.

Transmission can only occur from people with active ??? not latent ??? TB. The chain of transmission can, therefore, be broken by isolating patients with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with non-resistant active TB generally cease to be contagious. If someone does become infected, then it will take at least 21 days, or three to four weeks, before the newly infected person can transmit the disease to others.

TB can also be transmitted by eating meat infected with TB. Mycobacterium bovis causes TB in cattle. (See details below.)

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.

TB infection begins when the mycobacteria reach the pulmonary alveoli , where they invade and replicate within the endosomes of alveolar macrophages. All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.

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 secrete cytokines such as interferon gamma, which activates macrophages to destroy the bacteria with which they are infected. Cytotoxic T cells can also directly kill infected cells, by secreting perforin and granulysin.

Importantly, bacteria are not always eliminated within the granuloma, but can become dormant, resulting in a latent infection.

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 near 100% if untreated. However, If treated early, the fatality rate is reduced to near 10%.

In many patients the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis.

If untreated, infection with Mycobacterium tuberculosis can become lobar pneumonia.

Tuberculosis is diagnosed definitively 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 - diagnosis may be made using imaging (X-rays or scans) and/or a tuberculin skin test (Mantoux test) .

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.

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 . These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results. There is also evidence that the T-SPOT. TB IGRA is more sensitive than the skin test.

New TB tests are being developed that offer the hope of cheap, fast and more accurate TB testing. These include polymerase chain reaction assays for the detection of bacterial DNA. The development of a rapid and inexpensive diagnostic test would be particularly valuable in the developing world.

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. No vaccine is available that provides reliable protection for adults. However, in tropical areas where the levels of other species of mycobacteria are high, exposure to nontuberculous mycobacteria gives some protection against TB.

The World Health Organization (WHO) declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis that aims to save 14 million lives between 2006 and 2015. Since humans are the only host of Mycobacterium tuberculosis , eradication would be possible. This goal would be helped greatly by an effective vaccine.

Vaccines

Many countries use Bacillus Calmette-Gu??rin (BCG) vaccine as part of their TB control programmes, especially for infants. According to the WHO, this is the most often used vaccine worldwide, with 85% of infants in 172 countries immunized in 1993.

In South Africa, the country with the highest prevalence of TB, BCG is given to all children under age three. However, BCG is less effective 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:

• Infants or children with negative skin test results 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 a high percentage of MDR-TB patients has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and were not successful.

BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective vaccine that would prevent all forms of TB???including drug resistant strains???in all age groups and among people with HIV.

Several new vaccines to prevent TB infection are being developed. The first recombinant tuberculosis vaccine rBCG30, entered clinical trials in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). 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. and is based on a genetically modified vaccinia virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines (fusion molecules composed of two recombinant proteins delivered in an adjuvant ) such as Hybrid-1, HyVac4 or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles, making them preferable for areas where HIV is very common. All of these vaccines have been successfully tested in humans and are now in extended testing in TB-endemic regions. To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives and advance market commitments.

Mantoux tuberculin skin tests are often used for routine screening of high risk individuals.

Interferon-?? release assays are blood tests used in the diagnosis of some infectious diseases. There are currently two interferon-?? release assays available for the diagnosis of tuberculosis:

• QuantiFERON-TB Gold (licensed in US, Europe and Japan); and

• T-SPOT.TB, a form of ELISPOT (licensed in Europe).

Chest photofluorography has been used in the past for mass screening for tuberculosis.

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. People with latent infections are treated to prevent them from progressing to active TB disease later in life.

Drug-resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons 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. 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.

The DOTS (Directly Observed Treatment Short-course) strategy of tuberculosis treatment recommended by WHO was based on clinical trials done in the 1970s by Tuberculosis Research Centre, Chennai, India. The country in which a person with TB lives can determine what treatment they receive. This is because multidrug-resistant tuberculosis is resistant to most first-line medications, the use of second-line antituberculosis medications is necessary to cure the patient. However, the price of these medications is high; thus poor people in the developing world have no or limited access to these treatments.

Studies utilizing DNA fingerprinting of M. tuberculosis strains have shown that reinfection contributes more substantially to recurrent TB than previously thought, with between 12% and 77% of cases attributable to reinfection (instead of reactivation).

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. 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.

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. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/ AIDS.

The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis. The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs .

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. In Canada tuberculosis is still endemic in some rural areas.

The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults. 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.

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. Smoking more than 20 cigarettes a day also increases the risk of TB by two to four times. Diabetes mellitus is also an important risk factor that is growing in importance in developing countries. Other disease states that increase the risk of developing tuberculosis are Hodgkin lymphoma, end-stage renal disease , chronic lung disease, malnutrition, and alcoholism.

Diet may also modulate risk. For example, among immigrants in London from the Indian subcontinent, vegetarian Hindu Asians were found to have an 8.5 fold increased risk of tuberculosis, compared to Muslims who ate meat and fish daily. Although a causal link is not proved by this data, this increased risk could be caused by micronutrient deficiencies: possibly iron, vitamin B12 or vitamin D. Further studies have provided more evidence of a link between vitamin D deficiency and an increased risk of contracting tuberculosis. Globally, the severe malnutrition common in parts of the developing world causes a large increase in the risk of developing active tuberculosis, due to its damaging effects on the immune system. Along with overcrowding, poor nutrition may contribute to the strong link observed between tuberculosis and poverty.

Prisoners, especially in poor countries, are particularly vulnerable to infectious diseases such as HIV/AIDS and TB. Prisons provide a conditions that allow TB to spread rapidly, due to overcrowding, poor nutrition and a lack of health services. Since the early 1990s, TB outbreaks have been reported in prisons in many countries in Eastern Europe. The prevalence of TB in prisons is much higher than among the general population ??? in some countries as much as 40 times higher.

Tuberculosis has been present in humans since antiquity . The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 18,000 years before the present.

Skeletal remains from a Neolithic Settlement in the Eastern Mediterranean show prehistoric humans (7000 BC ) had TB,

Other names

In the past, tuberculosis has been 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 (in adults), 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, or gibbus of the spine and joints.

Miliary tuberculosis???now commonly known as disseminated TB???occurs when the infection invades the circulatory system, resulting in millet-like seeding of TB bacilli in the lungs as seen on an X-ray. TB is also called Koch's disease, after the scientist Robert Koch.

Folklore

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, extremely low body heat, a weak heart and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood. Similarly, but less commonly, it was attributed to the victims being "hagridden"???being transformed into horses by witches (hags) to travel to their nightly meetings, again resulting in a lack of rest.

TB was romanticized in the nineteenth century. Many people believed TB produced feelings of euphoria referred to as Spes phthisica ("hope of the consumptive"). It was believed that TB sufferers who were artists had bursts of creativity as the disease progressed. It was also believed that TB sufferers acquired a final burst of energy just before they died that made women more beautiful and men more creative. In the early 20th century, some believed TB to be caused by masturbation.

Study and treatment

The study of tuberculosis, sometimes known as phthisiatry, dates back to The Canon of Medicine written by Ibn Sina (Avicenna) in the 1020s. He was the first physician to identify pulmonary tuberculosis as a contagious disease , the first to recognise the association with diabetes, and the first to suggest that it could spread through contact with soil and water. He developed the method of quarantine in order to limit the spread of tuberculosis. In ancient times, treatments focused on sufferers' diets. Pliny the Elder described several methods in his Natural History : "wolf's liver taken in thin wine, the lard of a sow that has been fed upon grass, or the flesh of a she-ass taken in broth".

Although it was established that the pulmonary form was associated with "tubercles" by Dr Richard Morton in 1689,

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. 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.

The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette and Camille Gu??rin in 1906. It was called "BCG" ( Bacillus of Calmette and Gu??rin ). The BCG vaccine was first used on humans in 1921 in France,

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. In the 20th century, tuberculosis killed an estimated 100 million people. 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 pressured to enter sanatoria that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention. 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).

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 ??? 1908 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. The disease remained such a significant threat to public health, that when the Medical Research Council was formed in Britain in 1913, its initial focus was tuberculosis research.

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 bronchoscopy and suction as well as the pneumothorax or plombage technique ??? collapsing an infected lung to "rest" it and allow lesions to heal ??? a technique that was of little benefit and was mostly discontinued by the 1950s.

Hopes 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 117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose again, reaching 6,300 in 2000 and 7,600 cases in 2005. Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence of TB in the late 1980s. The number of patients failing to complete their course of drugs is high. New York had to cope with more than 20,000 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 (WHO) in 1993. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.

Evolution

Tuberculosis has co-evolved with humans for many thousands of years, and perhaps for several million years. The oldest known human remains showing signs of tuberculosis infection are 9,000 years old. During this evolution, M. tuberculosis has lost numerous coding and non-coding regions in its genome, losses that can be used to distinguish between strains of the bacteria. The implication is that M. tuberculosis strains differ geographically, so their genetic differences can be used to track the origins and movement of each strain.

A new species has recently been discovered for the first time in 20 years.

Through its affecting important historical figures, tuberculosis has influenced particularly European history, and become a theme in art ??? mostly literature, music, and film.

Public health

Tuberculosis is one of the three primary diseases of poverty along with AIDS and malaria. The Global Fund to Fight AIDS, Tuberculosis and Malaria was started in 2002 to raise finances to address these infectious diseases. Globalization has led to increased opportunities for disease spread. A tuberculosis scare occurred in 2007 when Andrew Speaker flew on a transatlantic flight infected with multi-drug-resistant tuberculosis.

In the United States, the National Center for HIV, STD, and TB Prevention, as part of the Centers for Disease Control and Prevention (CDC), is responsible for public health surveillance and prevention research.

Notable victims

The Mycobacterium Tuberculosis Structural Genomics Consortium is a global consortium of scientists conducting research regarding the diagnosis and treatment of tuberculosis. They are attempting to determine the 3-dimensional structures of proteins from M. Tuberculosis .

Tuberculosis can be carried by mammals; domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers.

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 natural reservoir such as Australian brush-tailed possums come into contact with domestic livestock at farm/bush borders. 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 Ireland and the United Kingdom, badgers have been identified as one vector species for the transmission of bovine tuberculosis. As a result, governments have come under pressure from some quarters, primarily dairy farmers, to mount an active campaign of eradication of badgers in certain areas with the purpose of reducing the incidence of bovine TB. The effectiveness of culling on the incidence of TB in cattle is a contentious issue, with proponents and opponents citing their own studies to support their position. For instance, a study by an Independent Study Group on badger culling reported on 18 June 2007 that it was unlikely to be effective and would only make a ???modest difference??? to the spread of TB and that "badger culling cannot meaningfully contribute to the future control of cattle TB"; in contrast, another report concluded that this policy would have a significant impact. On 4 July 2008, the UK government decided against a proposed random culling policy.

• General information, public health websites and epidemiology

• * Special Issue of Future Medicinal Chemistry on TB drug development

• * World Health Organization (WHO) - Tuberculosis

• *

• * The Stop TB Partnership - established in 2000 with the goal of eliminating tuberculosis as a public health problem

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• * Central Asia Health Review (CAHR). High Prevalence of Multi-Drug-Resistant Tuberculosis in Uzbekistan

• * Tuberculosis on the CDC website

• * Tuberculosis information from the Health Protection Agency in the UK

• * Kaiser Family Foundation. Tuberculosis. Globalhealthfacts.org.

• * United States Agency for International Development (USAID). The Tuberculosis Coalition for Technical Assistance (TBCTA).

• * Tuberculosis and HIV: HIV InSite Knowledge Base chapter and related resources .

• Patient information on tuberculosis

• * Tuberculosis on Medicinenet.com (HON code compliant)

• * (CDC) - TB Questions and Answers

• * Nobel Prize Website Tuberculosis Educational Game

• Professional information and scientific research

• * Tuberculosis Database is an integrated platform for tuberculosis research, hosting genomic and gene expression data for Mycobacterium tuberculosis and other related species.

• * Mycobacterium tuberculosis in the BioHealthBase (TB genomics and proteomics database)

• * Tuberculosis 2007 - a textbook that focuses on research, diagnosis and treatment of tuberculosis

• * Tuberculosis: A Persistent Threat to Global Health on-line lecture by John McKinney

• Sir John Crofton - Daily Telegraph obituary