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Bacillus Calmette-Guérin
Bacille Calmette-Guérin (BCG) is a vaccine against tuberculosis that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially cultured in an artificial medium for years. The bacilli have retained enough strong antigenicity to become a somewhat effective vaccine for the prevention of human tuberculosis. At best, the BCG vaccine is 80% effective in preventing tuberculosis for a duration of 15 years, however, its protective effect appears to vary according to geography. Additional recommended knowledge
HistoryThe history of BCG is tied to that of smallpox. Jean Antoine Villemin first recognised bovine tuberculosis in 1854 and transmitted it, and Robert Koch first distinguished Mycobacterium bovis from Mycobacterium tuberculosis. After the success of vaccination in preventing small pox, scientists thought to find a corollary in tuberculosis. A parallel was drawn between bovine tuberculosis and cow pox, and it was hypothesised that infection with bovine tuberculosis might protect against infection with human tuberculosis. In the late 19th century, clinical trials using M. bovis were conducted in Italy with disastrous results, because M. bovis was found to be just as virulent as M. tuberculosis. Albert Calmette, a French bacteriologist, and his assistant and later colleague, Camille Guérin, a veterinarian, were working at the Pasteur Institute in Lille in 1908. Their work included the subculturing of virulent strains of the tuberculosis bacillus and the testing of different culture media. They noted that a glycerin-bile-potato mixture grew bacilli that seemed less virulent. They changed the course of their research to see if repeated subculturing would produce a strain that was attenuated to be considered for use as a vaccine. Throughout World War I, the research continued until 1919 when the now non-virulent bacilli were unable to cause tuberculosis disease in research animals. They transferred to the Paris Pasteur Institute in 1919. In 1921, the BCG vaccine was first used in humans.[1] Public acceptance was slow and one disaster in particular did much to harm public acceptance of the vaccine. In Lubeck, 240 infants were vaccinated in the first 10 days of life; almost all developed tuberculosis and 72 infants died. It was subsequently discovered that the BCG administered had been contaminated with a virulent strain that was being stored in the same incubator, and led to legal action being taken against the manufacturers of BCG.[2] In 1928 it was adopted by the Health Committee of the League of Nations. However, because of opponents of vaccination, it was not widely used until after World War II. From 1945 to 1948 , relief organizations (International Tuberculosis Campaign or Joint Enterprises) vaccinated over 8 million babies in eastern Europe and prevented the predicted increase of TB after a major war. The vaccine proved to be the safest and the most widely used vaccine. The vaccine is very efficacious against tuberculous meningitis in the pediatric age group, but its efficacy against pulmonary tuberculosis appears to be variable. As of 2006, a few countries do not use BCG for routine vaccination, and the USA and the Netherlands have never used it routinely. In the United States, BCG vaccination is not routinely given to adults because it is felt that having a reliable Mantoux test, and being able to accurately detect active disease, is more beneficial to society than vaccinating against a relatively rare (in the US) condition.[citation needed] Variable efficacyThe most controversial aspect of BCG is the variable efficacy found in different clinical trials that appears to depend on geography. Clinical trials conducted in the UK have consistently shown a protective effect of 60 to 80%, but trials conducted elsewhere have shown no protective effect, and efficacy appears to fall the closer one gets to the equator.[3] The first large scale trial evaluating the efficacy of BCG was conducted from 1956 to 1963 and involved almost 60,000 school children who received BCG at the age of 14 or 15; this study showed an efficacy of 84% up to 5 years after immunization.[4] However, a US Public Health Service trial of BCG in Georgia and Alabama published in 1966 showed an efficacy of only 14%,[5] and did much to convince the US that it did not want to implement mass immunisation with BCG. A further trial conducted in South India and published in 1979 (the "Chingleput trial"), showed no protective effect.[6] The duration of protection of BCG is not clearly known. In those studies that have shown a protective effect, the data is inconsistent. The MRC study showed that protection waned to 59% after 15 years and to less than zero after 20 years; a study looking at native Americans immunised in the 1930's found evidence of protection even 60 years after immunisation with only a slight waning in efficacy.[7] BCG seems to have its greatest effect in preventing miliary TB or TB meningitis,[8] for which reason, it is still extensively used even in countries where efficacy against pulmonary tuberculosis is negligible. Reasons for variable efficacyThe reasons for the variable efficacy of BCG in different countries is difficult to understand. A number of possible reasons have been proposed but none have been proven.
UsesTuberculosis The main use of BCG is for vaccination against tuberculosis. It is recommended that the BCG vaccination be given intradermally by a nurse skilled in the technique. Having had a previous BCG vaccination is a cause of a false positive Mantoux test, although a very high-grade reading is usually due to active disease. The age and frequency that BCG is given has always varied from country to country.
Method of administrationExcept in neonates, a tuberculin skin test should always be done before administering BCG. A reactive tuberculin skin test is a contraindication to BCG. If someone with a positive tuberculin reaction is given BCG, there is a high risk of severe local inflammation and scarring. It is a common misconception that tuberculin reactors are not offered BCG because "they are already immune" and therefore do not need BCG. People found to have reactive tuberculin skin tests should be screened for active tuberculosis. BCG is given as a single intradermal injection at the insertion of the deltoid. If BCG is accidentally given subcutaneously, then a local abscess may form (a BCG-oma) that may ulcerate and often requires treatment with antibiotics. However, it is important to note that an abscess is not always associated with incorrect administration, and it is one of the more common complications that can occur with the vaccination. Numerous medical studies on treatment of these abscesses with antibiotics have been done with varying results, but the general consensus of opinion is that once pus is aspirated and analysed, providing there are no unusual bacilli present, the abscess will generally heal spontaneously in a matter of weeks.[15] BCG immunisation leaves a characteristic raised scar that is often used as proof of prior immunisation. The scar of BCG immunisation must be distinguished from that of small pox vaccination which it may resemble. Other uses
Adverse effectsBCG is one of the most widely used vaccines in the world, with an unparalleled safety record. BCG immunisation causes pain and scarring at the site of injection. The main adverse effect are keloids or large, ugly scars. The insertion of deltoid is most frequently used because the local complication rate is smallest when that site is used. If given subcutaneously, BCG causes a local skin infection that may spread to the regional lymph nodes causing a suppurative lymphadenitis. If BCG is accidentally given to an immunocompromised patient (e.g., an infant with SCID), it can cause disseminated or life-threatening infection. The documented incidence of this happening is less than 1 per million immunisations given.[19] Other tuberculosis vaccines
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References
Categories: Vaccines | Live vaccines | Tuberculosis |
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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Bacillus_Calmette-Guérin". A list of authors is available in Wikipedia. |