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Tuberculosis

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Tuberculosis, also called TB, phthisis, consumption, and nicknamed the white plague, is the most common infectious disease in the world today. It is caused by the bacterium Mycobacterium tuberculosis and can lead to death if untreated. It causes about 2-3 million deaths per year and is especially prevalent in undeveloped, tropical countries.

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The Disease

The T.B. bacillus can attack different parts of the body and so produce a series of different symptoms but always creating the distinctive tubercles or tuberculous nodules, small lesions consisting of dead grayish matter and containing many T.B. bacteria.

Infection is usually from one of three sources - infected milk, droplet infection from an infected person or breathing infected dust.

In children, infection of the lungs is not common; the bones , abdomen, kidneys or spine (Pott's disease) are more common sites of infection. Tuberculous meningitis is also possible. Miliary tuberculosis[?] (the lesions formed resemble millet seeds), a form of T.B. septicaemia[?] is also more common in the young than the old.

The form most common in adults is pulmonary tuberculosis, the 'classic' form of T.B., in which the lungs or pleura are infected. The disease begins gradually with coughing and later traces of blood in the sputum (haemoptysis). If untreated, it leads to fever, weight-loss, and death. The term consumption arose because sufferers appear as if consumed by the disease.

Primary tuberculosis is a person's first exposure to T.B. Assuming the infection was not completely cleared by the immune system (which sometimes happens if the bacterial load was small enough), reactivation tuberculosis can occur - this is a reactivation of T.B. following primary tuberculosis (symptomatic or asymptomatic). Reactivation can occur as long as decades after a primary infection.

Primary tuberculosis is more dangerous than reactivation (or post-primary) tuberculosis because if the immune system is compromised or deficient, there is the threat of miliary tuberculosis, which infiltrates all the organs of the body and carries a high mortality rate. This is why contact tracing is so important whenever someone is diagnosed with tuberculosis. All his/her close contacts should be screened for T.B. with a Mantoux test and a chest x-ray.

The Bacterium

The cause of tuberculosis, Mycobacterium tuberculosis is a Gram-positive aerobic bacterium[?] that divides every 16-20 hours. This is extremely slow compared to other bacteria which tend to have division times measured in minutes. It is a small rod-like bacillus which can withstand weak disinfectants and can survive in a dry state for months. Close relatives of the bacterium infect cattle (Mycobacterium bovis), swine and fowl. Infection occurs if the bacterium is ingested. MTB is identified microscopically by its staining characteristics: it retains certain stains after being treated with acidic solution, and is thus classified as an "acid-fast bacillus[?]" or "AFB". In the most common staining technique, the Ziehl-Neelsen stain[?], AFB are stained a bright red which stands out clearly against a blue background. Acid-fast bacilli can also be visualized by fluorescent microscopy, and by auramine-rhodamine stain[?].

Diagnosis

A chest X-ray[?] is essential in all cases of suspected pulmonary tuberculosis. The classical X-ray picture of post-primary tuberculosis is of bilateral, posterior apical, cavitating, caseous lesions.

Sputum smears and cultures should be done for acid-fast bacili if the patient is producing sputum. If no sputum is being produced, bronchoscopy or fine needle aspiration should be considered.

The Mantoux test should be done in all cases of suspected tuberculosis, although the results must be interpreted carefully. Tuberculin units are injected intradermally (into the skin) and read at 48 to 72 hours. Tuberculin is the purified proteins of the M. tuberculosis bacteria; thus a patient exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins. An induration (hardened spot of skin) of more than 10mm to 10 Mantoux units is considered a positive result, indicating T.B. A negative test does not exclude active tuberculosis, especially if the test was done within 6 to 8 weeks of acquiring the infection, if the infection is overwhelming or if the patient is immunocompromised.

Tuberculosis should be suspected when a persistent respiratory illness in an otherwise healthy individual does not respond to regular antibiotics (such as penicillin, or amoxacillin).

Treatment

The current accepted first-line therapy is a combination of the drugs rifampicin[?], isoniazid[?], pyrizinamide[?] and ethambutol[?].

Why four drugs? If only one drug is given, what ends up happening is that all the bacteria sensitive to that drug are killed and three months later, the patient will be infected with progeny of the bacteria that were resistant to that particular drug. Rifampicin and isoniazid are bactericidal agents that kill the bacteria, pyrizinamide acts well against the intracellular bacteria which are dormant inside macrophages and other cells and ethambutol is a bacteriostatic agent that inhibits bacterial proliferation while the other drugs kill off the TB.

The World Health Organization (WHO) currently recommends DOTS[?] or Directly Observed Treatment, Short-course. The mainstay of this is the DOT or Directly Observed Treatment portion which involves health care workers directly monitoring tuberculosis patients actually swallowing their anti-tuberculous therapy for at least the first two months of treatment. Treatment with properly implemented DOTS has a success rate exceeding 95% and prevents the emergence of further multi-drug resistant strains of tuberculosis. [1] (http://www.who.int/gtb/dots/index.htm)

Streptomycin is used if the initial 4-drug therapy fails, often in conjunction with other second-line drugs such as capreomycin[?], cycloserine[?], new macrolides, quinolones and protionamide[?]. Streptomycin and capreomycin are not available as oral medications and must be injected.

Adverse drug reactions[?] are expected in 20-25% of patients but only 5% of all patients will have a severe enough reaction to warrant a change in their drug regimen. Hepatic damage is the most significant of the drug reactions.

Supervised therapy, in which the patient's continued use of his prescribed medication is ensured by direct observation, has a cure rate of about 98%.

Prevention

BCG immunization gives the receiver between 0-70% resistance to TB. In tropical areas where the incidence of atypical mycobacteria are high (exposure to non-TB mycobacteria[?] give some protection against TB), the effectiveness of BCGs are much lower than in areas where mycobacteria are much less prevalent.

History

The different symptoms meant that tuberculosis was not identified as a unified disease until the 1820s and was not named tuberculosis until 1839 by J.L. Schoenlein. Some forms of the disease were probably known to the ancient Greeks, if not before, as the origins of the disease are in the first domestication of cattle (which also gave humanity viral poxes).

The bacillus causing tuberculosis, Mycobacterium tuberculosis, was described on March 24, 1882 by Robert Koch. He received the Nobel Prize in physiology or medicine for this discovery in 1905. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which held back the recognition of infected milk as a source of infection. Later, this source was eliminated by pasteurization. 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 for a test for pre-symptomatic tuberculosis.

The first genuine success was in immunizing against tuberculosis. Developed from attenuated bovine strain tuberculosis by Albert Calmette[?] and Camille Guerin[?] in 1906 - BCG (Bacillus of Calmette and Guerin). It was first used on humans on July 18, 1921 in France, although national arrogance prevented its widespread use in either the USA, Great Britain or Germany until after WW II.

Tuberculosis has caused the most widespread public concern in the 19th and early 20th centuries as the endemic disease of the urban poor. In 1815 England one in four deaths were of consumption, by 1918 one in six deaths in France were still caused by T.B. After the establishment in the 1880s that the disease was contagious, T.B. 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 rather resembled prisons. Whatever the purported benefits of the fresh air and labour in the sanatoria, 75 per cent of those who entered were dead within five years (1908).

However from killing 500 out of 100,000 Europeans in 1850 the number had fallen to 50 out of 100,000 by 1950. Improvements in public health were impacting tuberculosis even before the arrival of antibiotics, although the disease's significance was still such that when the Medical Research Council[?] was formed in Britain in 1913 its first project was tuberculosis.

It was not until 1946 with the development of the antibiotic streptomycin that treatment rather than prevention became a possibility. Prior to then only surgical intervention was possible as supposed treatment (other than sanatoria), including the pneumothorax technique - collapsing an infected lung to 'rest' it and allow lesions to heal, although it was an accomplished technique it was of little benefit and was discontinued after 1946.

Hopes that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, T.B. cases in Britain, numbering around 50,000 in 1955, had fallen to around 5,500 in 1987, but for 2001 there were over 7,000 confirmed cases.

Tuberculosis as a subtext in art and literature

It has been speculated that the real-life ubiquity of illness and death due to tuberculosis affected the portrayal of these issues in European art and literature.

The titular heroine of La Boheme suffers from tuberculosis (a theme carried over in the modern film adaptation Moulin Rouge).

The pale, "haunted" appearance of tuberculosis sufferers has been seen as an influence on the works of Edgar Allan Poe and in vampire tales. In recent years, this aesthetic has been revived by the "Goth" subculture.

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