Tuberculosis

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Introduction and History

Also called TB, phthsis, consumption, or the 'white plague'.

The T.B. bacillus can attack different parts of the body and so produce a series of different symptoms but always creating the distinctive tubercle (tuberculous nodule). 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.

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

In children infecton of the lungs is not common; the bones (Pott's Disease), abdomen, kidneys or spine are more common sites of infection. Tuberculous meningitis is also possible and until the development of antibiotics it was invariably fatal. Miliary tuberculosis (the lesions formed resemble millet seeds), a form of T.B. septicaemia is also more common in young than the old.

The 'classic' form of T.B. is the form most common in adults where the lungs or pleura are infected - pulmonary tuberculosis. The disease begins gradually with coughing and later traces of blood in the sputum (haemotysis), untreated leading to fever and death, the term consumption arising because sufferers are literally consumed.


The discovery of the bacillus causing tuberculosis was announced by Robert Koch on 24 March 1882 as mycobacterium tuberculosis. But the disease itself was 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).

Koch mis-used his authority as discoverer to squash the idea that bovine and human tuberculosis were similiar. This held back the recognition of infected milk as a source of infection which could then be remedied by pastuerization. Even more shamefully 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 was in immunizing against tuberculosis. Developed from attenuated bovine strain tuberculosis by A. Calmette and J. M. Guerin in 1906 - BCG (Bacilli-Calmette-Guerin). It was first used on humans in 1924 in France, although national arrogance prevented its widespread use in either the US, 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 that the disease was contagious in the 1880s 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 stilll such that when the Medical Research Council was formed in Britain in 1911 it's 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 a 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.



Infection

The cause of tuberculosis, Mycobacterium tuberculosis is an 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.

TB is the most common infectious disease in the world. It is more common in undeveloped, tropical countries. In Australia, the incidence of TB is currently 6 per 100,000. Of Australians born in Australia, the rate is 1.8 per 100,000.

Primary tuberculosis is a person's first exposure to M. TB. Assuming the infection was not completely cleared by the immune system (which sometimes happens if the bacterial load was small enough), post primary tuberculosis can occur - this is a reactivation of TB following primary tuberculosis (symptomatic or asymptomatic). In 40% of patients with primary TB, this may take more than 10 years.

Primary tuberculosis is more dangerous than 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 TB with a Mantoux test and a chest x-ray.

A persistent respiratory illness that does not respond to regular antibiotics (e.g. penicillin, amoxil) in an otherwise healthy individual is tuberculosis until proven otherwise.



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 and read at 48 to 72 hours. An induration of more than 10mm to 10 Mantoux units is considered a positive test. 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.


Treatment

The current accepted first-line therapy is the combination of rifampicin, isoniazid, pyrizinamide and ethambutol.

Why four drugs? If only one drug is given, what ends up happening is that you end up killing all the bacteria sensitive to that drug and three months later, you get a bunch of bacteria which were resistant. 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.

Adverse drug reactions are expected in 20-25% of patients but only 5% 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 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.

Tuberculosis as a subtext in art and literature

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

In particular, 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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External links:

Center for Disease Control Division of Tuberculosis Elimination http://www.cdc.gov/nchstp/tb/faqs/qa.htm