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Bacillus Calmette-Guérin

Bacillus Calmette-Guérin

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Bacillus Calmette-Guérin (or Bacille Calmette-Guérin, BCG) is a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

 against tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 that is prepared from a strain of the attenuated (weakened) live bovine tuberculosis bacillus, Mycobacterium bovis
Mycobacterium bovis
Mycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...

, that has lost its virulence in humans by being specially subcultured (230 passages) in an artificial medium for 13 years, and also prepared from Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. The bacilli have retained enough strong antigenicity to become a somewhat effective vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

 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.

History


The history of BCG is tied to that of smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...

. Jean Antoine Villemin
Jean Antoine Villemin
Jean-Antoine Villemin was a French physician born in Prey, Vosges. In 1865 he demonstrated that tuberculosis was an infectious disease.-Biography:...

 first recognized bovine tuberculosis in 1854 and transmitted it, and Robert Koch
Robert Koch
Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis , the Tuberculosis bacillus and the Vibrio cholerae and for his development of Koch's postulates....

 first distinguished Mycobacterium bovis
Mycobacterium bovis
Mycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...

from Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. After the success of vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

 in preventing smallpox, scientists thought to find a corollary in tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 by drawing a parallel between bovine tuberculosis and cowpox
Cowpox
Cowpox is a skin disease caused by a virus known as the Cowpox virus. The pox is related to the vaccinia virus and got its name from the distribution of the disease when dairymaids touched the udders of infected cows. The ailment manifests itself in the form of red blisters and is transmitted by...

: It was hypothesized 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
Albert Calmette
Léon Charles Albert Calmette ForMemRS was a French physician, bacteriologist and immunologist, and an important officer of the Pasteur Institute. He discovered the Bacillus Calmette-Guérin, an attenuated form of Mycobacterium used in the BCG vaccine against tuberculosis...

, a French bacteriologist, and his assistant and later colleague, Camille Guérin
Camille Guérin
Jean-Marie Camille Guérin was a French veterinarian, bacteriologist and immunologist who, together with Albert Calmette, developed the Bacillus Calmette-Guérin , a vaccine for immunization against tuberculosis....

, a veterinarian, were working at the Institut Pasteur de Lille
Institut Pasteur de Lille
The Institut Pasteur de Lille is a research centre, membre of the Pasteur Institute network.It includes 14 research units, 1150 employees including 626 researchers located in Lille . 300 employees located outside the Pasteur site come in addition...

 (Lille
Lille
Lille is a city in northern France . It is the principal city of the Lille Métropole, the fourth-largest metropolitan area in the country behind those of Paris, Lyon and Marseille. Lille is situated on the Deûle River, near France's border with Belgium...

, France) in 1908. Their work included subculturing virulent strains of the tubercle bacillus and testing different culture media. They noted a glycerin-bile-potato mixture grew bacilli that seemed less virulent, and changed the course of their research to see if repeated subculturing would produce a strain that was attenuated enough to be considered for use as a vaccine. The research continued throughout World War I until 1919, when the now avirulent bacilli were unable to cause tuberculosis disease in research animals. They transferred to the Paris Pasteur Institute
Pasteur Institute
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...

 in 1919. The BCG vaccine was first used in humans in 1921.

Public acceptance was slow, and one disaster, in particular, did much to harm public acceptance of the vaccine. In the summer of 1930 in Lübeck
Lübeck
The Hanseatic City of Lübeck is the second-largest city in Schleswig-Holstein, in northern Germany, and one of the major ports of Germany. It was for several centuries the "capital" of the Hanseatic League and, because of its Brick Gothic architectural heritage, is listed by UNESCO as a World...

, 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.

Dr. R.G. Ferguson, working at the Fort Qu'Appelle Sanatorium in Saskatchewan, was among the pioneers in developing the practice of vaccination against tuberculosis. In 1928, BCG was adopted by the Health Committee of the League of Nations
League of Nations
The League of Nations was an intergovernmental organization founded as a result of the Paris Peace Conference that ended the First World War. It was the first permanent international organization whose principal mission was to maintain world peace...

 (predecessor to the WHO
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

). Because of opposition, however, it did not become 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
Eastern Europe
Eastern Europe is the eastern part of Europe. The term has widely disparate geopolitical, geographical, cultural and socioeconomic readings, which makes it highly context-dependent and even volatile, and there are "almost as many definitions of Eastern Europe as there are scholars of the region"...

 and prevented the predicted increase of TB after a major war.

BCG is very efficacious against tuberculous meningitis
Tuberculous meningitis
Tuberculous meningitis is also known as TB meningitis or tubercular meningitis.Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelops the central nervous system. It is the most common form of CNS tuberculosis.-Clinical features:Fever...

 in the pediatric age group, but its efficacy against pulmonary tuberculosis appears to be variable. As of 2006, only a few countries do not use BCG for routine vaccination. The USA and the Netherlands have never used it routinely. In both countries, BCG vaccination is not routinely given to adults because it is felt that having a reliable Mantoux test
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

 and being able to accurately detect active disease is more beneficial to society than vaccinating against a relatively rare (in those countries) condition.

Recent research by the Imperial College London
Imperial College London
Imperial College London is a public research university located in London, United Kingdom, specialising in science, engineering, business and medicine...

 has focused on finding new cellwall proteins which trigger an immune response and are suitable for use in a vaccine that can provide long-term protection against Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. The study has revealed a few such proteins, the most promising of which has been dubbed EspC, elicits a very strong immune reaction, and is specific to M. tuberculosis.

Variable efficacy


The most controversial aspect of BCG is the variable efficacy found in different clinical trials that appears to depend on geography. Trials conducted in the UK have consistently shown a protective effect of 60 to 80%, but those conducted elsewhere have shown no protective effect, and efficacy appears to fall the closer one gets to the equator.

The first large scale trial evaluating the efficacy of BCG was conducted from 1956 to 1963, and involved 54,239 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. However, a US Public Health Service trial of BCG in Georgia
Georgia (U.S. state)
Georgia is a state located in the southeastern United States. It was established in 1732, the last of the original Thirteen Colonies. The state is named after King George II of Great Britain. Georgia was the fourth state to ratify the United States Constitution, on January 2, 1788...

 and Alabama
Alabama
Alabama is a state located in the southeastern region of the United States. It is bordered by Tennessee to the north, Georgia to the east, Florida and the Gulf of Mexico to the south, and Mississippi to the west. Alabama ranks 30th in total land area and ranks second in the size of its inland...

 published in 1966 showed an efficacy of only 14%, and did much to convince the US it did not want to implement mass immunization with BCG. A further trial conducted in South India and published in 1979 (the "Chingleput trial"), showed no protective effect.

The duration of protection of BCG is not clearly known. In those studies showing a protective effect, the data are inconsistent. The MRC study showed protection waned to 59% after 15 years and to zero after 20 years; however, a study looking at native Americans immunized in the 1930s found evidence of protection even 60 years after immunization, with only a slight waning in efficacy.

BCG seems to have its greatest effect in preventing miliary TB or TB meningitis, for which reason, it is still extensively used even in countries where efficacy against pulmonary tuberculosis is negligible.

Reasons for variable efficacy


The reasons for the variable efficacy of BCG in different countries are difficult to understand. A number of possible reasons have been proposed, but none have been proven, and none can explain the lack of efficacy in both low TB burden countries (US) and high TB burden countries (India). The reasons for variable efficacy have been discussed at length in a WHO
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 document on BCG.
  1. Background frequency of exposure to tuberculosis It has been hypothesized that in areas with high levels of background exposure to tuberculosis, every susceptible individual is already exposed prior to BCG, and that the natural immunizing effect of background tuberculosis duplicates any benefit of BCG.
  2. Genetic variation in BCG strains There is genetic variation in the BCG strains used, and this may explain the variable efficacy reported in different trials.
  3. Genetic variation in populations Differences in genetic make-up of different populations may explain the difference in efficacy. The Birmingham BCG trial was published in 1988. The trial was based in Birmingham
    Birmingham
    Birmingham is a city and metropolitan borough in the West Midlands of England. It is the most populous British city outside the capital London, with a population of 1,036,900 , and lies at the heart of the West Midlands conurbation, the second most populous urban area in the United Kingdom with a...

    , United Kingdom, and examined children born to families who originated from the Indian subcontinent (where vaccine efficacy had previously been shown to be zero). The trial showed a 64% protective effect, which is very similar to the figure derived from other UK trials, thus arguing against the genetic variation hypothesis.
  4. Interference by nontuberculous mycobacteria Exposure to environmental mycobacteria (especially M. avium, M. marinum and M. intracellulare) results in a nonspecific immune response against mycobacteria. Administering BCG to someone who already has a nonspecific immune response against mycobacteria does not augment the response already there. BCG will therefore appear not to be efficacious, because that person already has a level of immunity and BCG is not adding to that immunity. This effect is called masking, because the effect of BCG is masked by environmental mycobacteria. There is clinical evidence for this effect from a series of studies performed in parallel in adolescent school children in the UK and Malawi. In this study, the UK school children had a low baseline cellular immunity to mycobacteria which was increased by BCG; in contrast, the Malawi school children had a high baseline cellular immunity to mycobacteria and this was not significantly increased by BCG. Whether this natural immune response is protective is not known. An alternative explanation is suggested by mouse studies: immunity against mycobacteria stops BCG from replicating and so stops it from producing an immune response. This is called the blocking hypothesis.
  5. Interference by concurrent parasitic infection Another hypothesis is that simultaneous infection with parasites changes the immune response to BCG, making it less effective. A Th1
    T helper cell
    T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...

     response is required for an effective immune response to tuberculous infection; one hypothesis is that concurrent infection with various parasites produces a simultaneous Th2-response which blunts the effect of BCG.
  6. Exposure to ultraviolet light Concentration of ultraviolet light (particularly UVB light) from the Sun
    Sun
    The Sun is the star at the center of the Solar System. It is almost perfectly spherical and consists of hot plasma interwoven with magnetic fields...

     may have some effect on efficacy of the BCG vaccine. UVB has been demonstrated to reduce efficacy of BCG vaccine in laboratory guinea pigs. The concentration gradient of UVB light increases geographically closer to the Earth's equator. It is possible, though currently unresearched, that this effect may occur as a result of sunlight-dependent Vitamin D
    Vitamin D
    Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....

     production.

Uses


Tuberculosis The main use of BCG is for vaccination against tuberculosis. It is recommended 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
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

, although a very high-grade reading is usually due to active disease.

The age of the patient and the frequency with which BCG is given has always varied from country to country.
  • WHO BCG policy The WHO
    World Health Organization
    The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

     recommend BCG be given to all children born in countries highly endemic for TB because it protects against miliary TB and TB meningitis.
  • United States The US has never used mass immunization of BCG, relying instead on the detection and treatment of latent tuberculosis
    Latent tuberculosis
    Also called latent tuberculosis infection, latent TB or LTBI.Latent tuberculosis is where a patient is infected with Mycobacterium tuberculosis, but does not have active tuberculosis disease. Patients with latent tuberculosis are not infectious, and it is not possible to get TB from someone with...

    .
  • United Kingdom The UK introduced universal BCG immunization in 1953, and until 2005, the UK policy was to immunize all school children at the age of 13, and all neonates born into high risk groups. The injection was only given once during an individual's lifetime (as there is no evidence of additional protection from more than one vaccination). BCG was also given to protect people who had been exposed to tuberculosis. The peak of tuberculosis incidence is in adolescence and early adulthood, and the evidence from the MRC trial was that efficacy lasted only 15 years at most. Styblo and Meijer argued neonatal immunization protected against miliary TB and other noncontagious forms of TB, and not pulmonary TB which was a disease of adults, and that mass immunization campaigns with BCG would therefore not be expected to have a significant public health impact. For these and other reasons, BCG was therefore given to time with the peak incidence of pulmonary disease. Routine immunization with BCG was withdrawn in 2005 because of falling cost-effectiveness: whereas in 1953, 94 children would have to be immunized to prevent one case of TB, by 1988, the annual incidence of TB in the UK had fallen so much that 12,000 children would have to be immunized to prevent one case of TB.
  • India and Pakistan India and Pakistan introduced BCG mass immunization in 1948, the first countries outside Europe to do so.
  • Brazil Brazil introduced universal BCG immunization in 1967-1968, and the practice continues until now. According to Brazilian law, BCG is given again to professionals of the health sector and to people close to patients with tuberculosis or leprosy.
  • Other countries In some countries, such as the former USSR, BCG was given regularly throughout life. In South Korea
    South Korea
    The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...

    , Singapore
    Singapore
    Singapore , officially the Republic of Singapore, is a Southeast Asian city-state off the southern tip of the Malay Peninsula, north of the equator. An island country made up of 63 islands, it is separated from Malaysia by the Straits of Johor to its north and from Indonesia's Riau Islands by the...

    , Taiwan
    Taiwan
    Taiwan , also known, especially in the past, as Formosa , is the largest island of the same-named island group of East Asia in the western Pacific Ocean and located off the southeastern coast of mainland China. The island forms over 99% of the current territory of the Republic of China following...

     and Malaysia, BCG was given at birth and again at the age of 12. But in Malaysia and Singapore, from 2001, this policy was changed to once only at birth, and it was discontinued in South Korea.

Method of administration



Except in neonates, a tuberculin skin test should always be done before administering BCG. A reactive tuberculin skin test is a contraindication to BCG. Someone with a positive tuberculin reaction is not given BCG, because there is a high risk of severe local inflammation and scarring, not because of the common misconception that tuberculin reactors "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
BCG-oma
A BCG-oma is an abscess caused by the BCG strain of Mycobacterium bovis. It follows incorrect administration of BCG . It is treated as for any Mycobacterium bovis infection ....

) that can sometimes ulcerate, and may require treatment with antibiotics. However, it is important to note 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 consensus is that once pus is aspirated and analysed, providing there are no unusual bacilli present, the abscess will generally heal on its own in a matter of weeks.

BCG immunization leaves a characteristic raised scar that is often used as proof of prior immunization. The scar of BCG immunization must be distinguished from that of small pox vaccination which it may resemble.

Other uses


  • Leprosy
    Leprosy
    Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...

    : BCG has a small protective effect against leprosy of around 26%, although it is not used specifically for this purpose.
  • Buruli ulcer
    Mycobacterium ulcerans
    Mycobacterium ulcerans is a slow-growing mycobacterium that classically infects the skin and subcutaneous tissues, giving rise to indolent nonulcerated and ulcerated lesions. After tuberculosis and leprosy, Buruli ulcer is the third most common mycobacteriosis of humans. M...

    : It is possible that BCG may protect against or delay the onset of Buruli ulcer.
  • Cancer immunotherapy
    Cancer immunotherapy
    Cancer immunotherapy is the use of the immune system to reject cancer. The main premise is stimulating the patient's immune system to attack the malignant tumor cells that are responsible for the disease...

    : BCG is used in the treatment
    BCG as a treatment for bladder cancer
    BCG , a live attenuated form of Mycobacterium bovis, is the most commonly used agent for intravesical therapy. A number of other intravesical agents have been compared to BCG, but none has proved consistently superior....

     of superficial forms of bladder cancer
    Bladder cancer
    Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...

    . Since the late 1980s, evidence has become available that instillation of BCG into the bladder is an effective form of immunotherapy
    Immunotherapy
    Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...

     in this disease. While the mechanism is unclear, it appears a local immune reaction is mounted against the tumor. Immunotherapy with BCG prevents recurrence in up to 67% of cases of superficial bladder cancer. BCG also finds use for immunotherapy of colorectal cancer
    Colorectal cancer
    Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....

     and for the treatment of equine sarcoid in horses. A number of cancer vaccines in development use BCG as an adjuvant to provide an initial stimulation of the patients' immune system.
  • Diabetes, Type I
    Diabetes mellitus type 1
    Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...

    : Clinical trials based on the work of Denise Faustman
    Denise Faustman
    Denise L. Faustman, is a U.S. physician and medical researcher. An Associate Professor of Medicine at Harvard University and Director of the Immunobiology Laboratory at Massachusetts General Hospital, her work specializes in diabetes mellitus type 1 and other autoimmune diseases...

     use BCG to induce production of TNF-α, which can kill the T-cells responsible for type 1 diabetes. Studies using mice have shown a similar treatment results in a permanent cure for about a third of the test subjects.
  • Interstitial cystitis
    Interstitial cystitis
    Interstitial cystitis or bladder pain syndrome is a chronic, oftentimes severely debilitating disease of the urinary bladder...

     (IC) / painful bladder syndrome (PBS): BCG has been useful in treating some people with IC and/or PBS, which are chronic inflammatory bladder problems with unknown etiology. It is instilled directly into the bladder. It is not clear how it works, but the mechanism is likely immunotherapeutic, as the chronic inflammation could be the result of an autoimmune problem.
  • Multiple sclerosis
    Multiple sclerosis
    Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

     (MS): In humans, BCG has been shown to substantially reduce recurrence of symptoms in multiple sclerosis patients. The frequency of new enhancing lesions as detected by Gd-enhanced MRI was reduced by more than half in 12 patients, comparing the six-month run-in phase to the six-month post BCG phase of the experiment. Persistence at subsequent MR scan was reduced from 18 to 1 lesion, and evolution to black holes was reduced from 28 to 6 lesions. The conventional explanation of such protection is that parasites (including bacteria) modulate the sensitivity of the immune system. BCG appears safe as a treatment for multiple sclerosis although it is not commonly used.
  • Parkinson's disease
    Parkinson's disease
    Parkinson's disease is a degenerative disorder of the central nervous system...

     (PD): In a mouse model of Parkinson's disease, BCG vaccination partially preserved striatal dopaminergic markers. The neuroprotective effect is associated with suppression in microglia activation and proliferation in mouse mid-brain area.

Adverse effects


BCG is one of the most widely used vaccines in the world, with an unparalleled safety record. BCG immunization generally causes some pain and scarring at the site of injection. The main adverse effects are keloid
Keloid
A keloid is a type of scar, which depending on its maturity, is composed mainly of either type III or type I collagen. It is a result of an overgrowth of granulation tissue at the site of a healed skin injury which is then slowly replaced by collagen type 1...

s—large, raised scars. The insertion of deltoid is most frequently used because the local complication rate is smallest when that site is used. Nonetheless, buttock is an alternative site of administration because it provides better cosmetic outcomes.

BCG vaccine should be given intradermally. If given subcutaneously, BCG may induce local infection and spread to the regional lymph nodes causing lymphadenitis. It can be classified into suppurative and non-suppurative lymphadenitis. Conservative management is usually adequate for non-suppurative lymphadenitis. If suppuration occurs, it may need needle aspiration. For non resolving suppuration, surgical excision is required but not incision. Uncommonly, breast and gluteal abscess can occur due to haematogenous and lymphangiomatous spread. Regional bone infection (BCG osteomyelitis or osteitis) and disseminated BCG infection are rare complications of BCG vaccination but potentially life threatening. Systemic anti-tuberculous therapy may be helpful in severe complications.

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 immunizations given. In 2007, The WHO
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 stopped recommending BCG for infants with HIV, even if there is a high risk of exposure to TB, because of the risk of disseminated BCG infection (which is approximately 400 per 100,000).

Manufacturers


There are a number of different manufacturers of BCG, and each manufacturer uses a different genetic strain. This may result in different vaccine potency.
1) OncoTICE (used for bladder instillation for bladder cancer), developed by Organon laboratories, acquired by Schering-Plough, in turn acquired by Merck, Inc.
2) Statens Serum Institut in Denmark
3) Pacis BCG. Apparently the original BCG strain. First marketed by Urocor in about 2002. Urocor since acquired by Dianon Systems
4) Evans vaccines (subsidiary of PowderJect Pharmaceuticals Plc, London: PJP)

See also

  • Heaf test
    Heaf test
    The Heaf test is a diagnostic skin test performed in order to determine whether or not a child has been exposed to tuberculosis. Also known as the Sterneedle test, it is administered by a Heaf gun which is a spring-loaded instrument with six needles arranged in a circular formation.Patients who...

  • Mantoux test
    Mantoux test
    The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

  • Tuberculosis
    Tuberculosis
    Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

  • Tuberculosis vaccines
    Tuberculosis vaccines
    Tuberculosis vaccines are vaccinations intended for the prevention of tuberculosis. There is currently only one tuberculosis vaccine available, bacille Calmette-Guérin .Other tuberculosis vaccines currently in development are:* MVA85A* rBCG30...

  • Philip D'Arcy Hart
    Philip D'Arcy Hart
    Philip Montagu D’Arcy Hart, CBE, was a British medical researcher and pioneer in tuberculosis treatment. Grandson of Samuel Montagu, 1st Baron Swaythling, he became a consultant physician at University College Hospital at the age of 34...

  • BCG disease outbreak in Finland in the 2000's
    BCG disease outbreak in Finland in the 2000's
    BCG disease is an adverse effect of the Bacillus Calmette-Guérin vaccine. The vaccine contains living Mycobacterium bovis BCG, and in BCG disease, the bacterium causes a disease in persons vaccinated...


External links