カルメット・ゲラン桿菌、Calmette-Guerin桿菌、ウシ型弱毒結核菌ワクチン

関: BCG、Calmette-Guerin bacillus

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/08/15 15:37:40」(JST)

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Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis.^[1] In countries where tuberculosis is common one dose is recommended in healthy babies as close to the time of birth as possible.^[1] Babies with HIV/AIDS should not be vaccinated.^[2] In areas where tuberculosis is not common, only babies at high risk are typically immunized while suspected cases of tuberculosis are individually tested for and treated. Adults who do not have tuberculosis and have not been previously immunized but are frequently exposed to drug resistant tuberculosis may be immunized as well.^[1] It is also often used as part of the treatment of bladder cancer.^[3]

Rates of protection against tuberculosis infection vary widely and protection lasts between ten and twenty years.^[1] Among children it prevents about 20% from getting infected and among those who do get infected it protects half from developing disease.^[4] The vaccine is given by injection into the skin.^[1] Additional doses are not supported by evidence.^[1] It may also be used in the treatment of some types of bladder cancers.^[5]

Serious side effects are rare. Often there is redness, swelling, and mild pain at the site of injection. A small ulcer may also form with some scarring after healing. Side effects are more common and potentially more severe in those with poor immune function. It is not safe for use during pregnancy. The vaccine was originally developed from Mycobacterium bovis which is commonly found in cows. While it has been weakened, it is still live.^[1]

The BCG vaccine was first used medically in 1921.^[1] It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system.^[6] Between 2011 and 2014 the wholesale price was $0.16 to $1.11 USD a dose in the developing world.^[7]^[8] In the United States it costs $100 to $200 USD.^[9] As of 2004 the vaccine is given to about 100 million children per year globally.^[1]

1 Medical uses
- 1.1 Tuberculosis
  - 1.1.1 Recommendations
  - 1.1.2 Reasons
- 1.2 Mycobacteria
- 1.3 Cancer
- 1.4 Method of administration
2 Adverse effects
3 Usage
4 Manufacturer
- 4.1 BCG supply shortage 2012-
- 4.2 Preparation
- 4.3 Dried
5 History
6 Research
7 Other tuberculosis vaccines
8 References
9 External links

Medical uses

Tuberculosis

The main use of BCG is for vaccination against tuberculosis. BCG vaccine can be administered after birth intradermally.^[10] BCG vaccination is recommended to be given intradermally. A previous BCG vaccination can cause a false positive Mantoux test, although a very high-grade reading is usually due to active disease.

The most controversial aspect of BCG is the variable efficacy found in different clinical trials, which 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.^[11]^[12]

A 1994 systematic review found that BCG reduces the risk of getting TB by about 50%.^[11] There are differences in effectiveness, depending on region, due to factors such as genetic differences in the populations, changes in environment, exposure to other bacterial infections, and conditions in the lab where the vaccine is grown, including genetic differences between the strains being cultured and the choice of growth medium.^[13]^[14]

A systematic review and meta analysis conducted in 2014 demonstrated that the BCG vaccine reduced infections by 19–27% and reduced progression to active TB by 71%.^[15] The studies included in this review were limited to those that used interferon gamma release assay.

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.^[16]

BCG seems to have its greatest effect in preventing miliary TB or TB meningitis, so it is still extensively used even in countries where efficacy against pulmonary tuberculosis is negligible.^[17]

Recommendations

In countries where tuberculosis is common one dose is recommended in healthy babies as close to the time of birth as possible.^[1] Babies with HIV/AIDS should not be vaccinated.^[2] In areas where tuberculosis is not common, only babies at high risk are typically immunized while suspected cases of tuberculosis are individually tested for and treated. Adults who do not have tuberculosis and have not been previously immunized but are frequently exposed to drug resistant tuberculosis may be immunized as well.^[1]^[18]

Reasons

A number of possible reasons for the variable efficacy of BCG in different countries have been proposed. None have been proven, some have been disproved, 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 document on BCG.^[19]

Genetic variation in BCG strains: Genetic variation in the BCG strains used may explain the variable efficacy reported in different trials.^[20]
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, based in Birmingham, United Kingdom, 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.^[21]
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. Clinical evidence for this effect was found in a series of studies performed in parallel in adolescent school children in the UK and Malawi.^[22] 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.^[23] 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 block hypothesis.^[24]
Interference by concurrent parasitic infection: In another hypothesis, simultaneous infection with parasites changes the immune response to BCG, making it less effective. As Th1 response is required for an effective immune response to tuberculous infection, concurrent infection with various parasites produces a simultaneous Th2 response, which blunts the effect of BCG.^[25]

Mycobacteria

Leprosy: BCG has a protective effect against leprosy in the range of 26 to 41% based on controlled trials. The protective effect is somewhat larger based on case control and cohort studies—about 60%.^[26]^[27] However BCG vaccine is not used specifically to control leprosy.
Buruli ulcer: BCG may protect against or delay the onset of Buruli ulcer.^[28]

Cancer

Micrograph showing granulomatous inflammation of bladder neck tissue due to Bacillus Calmette-Guérin used to treat bladder cancer, H&E stain

BCG has been one of the most successful immunotherapies.^[18] BCG vaccine has been the "standard of care for patients with bladder cancer (NMIBC)" since 1977.^[18]^[29] By 2014 there were more than eight different considered biosimilar agents or strains used for the treatment of non–muscle-invasive bladder cancer (NMIBC).^[18] ^[29]

A number of cancer vaccines use BCG as an additive to provide an initial stimulation of the person's immune systems.
BCG is used in the treatment of superficial forms of bladder cancer. Since the late 1970s, evidence has become available that instillation of BCG into the bladder is an effective form of immunotherapy in this disease.^[30] 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 has been evaluated in a number of studies as a therapy for colorectal cancer.^[31] The US biotech company Vaccinogen is evaluating BCG as an adjuvant to autologous tumour cells used as a cancer vaccine in stage II colon cancer.

Method of administration

An apparatus (4–5 cm length, with 9 short needles) used for BCG vaccination in Japan, shown with ampules of BCG and saline

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 the risk of severe local inflammation and scarring is high, 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 also contraindicated in certain people who have IL-12 receptor pathway defects.

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 can sometimes ulcerate, and may require treatment with antibiotics immediately, otherwise without treatment it could spread the infection causing severe damage to vital organs. 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 once pus is aspirated and analysed, provided no unusual bacilli are present, the abscess will generally heal on its own in a matter of weeks.^[32]

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

Adverse effects

BCG immunization generally causes some pain and scarring at the site of injection. The main adverse effects are keloids—large, raised scars. The insertion of deltoid is most frequently used because the local complication rate is smallest when that site is used. Nonetheless, the buttock is an alternative site of administration because it provides better cosmetic outcomes.

BCG vaccine should be given intradermally. If given subcutaneously, it may induce local infection and spread to the regional lymph nodes, causing either suppurative and nonsuppurative lymphadenitis. Conservative management is usually adequate for nonsuppurative lymphadenitis. If suppuration occurs, it may need needle aspiration. For nonresolving suppuration, surgical excision may be required. Evidence for the treatment of these complications is scarce.^[33]

Uncommonly, breast and gluteal abscesses 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 antituberculous therapy may be helpful in severe complications.^[34]

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 one per million immunizations given.^[35] In 2007, The WHO stopped recommending BCG for infants with HIV, even if there is a high risk of exposure to TB,^[36] because of the risk of disseminated BCG infection (which is approximately 400 per 100,000 in that higher risk context).^[37]^[38]

Usage

The age of the person and the frequency with which BCG is given has always varied from country to country.

WHO BCG policy: The WHO recommend BCG be given to all children born in countries highly endemic for TB because it protects against miliary TB and TB meningitis.^[39]
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.
Central and South America: Most countries in Central and South America have universal BCG immunizations. In Ecuador, a child cannot receive their birth certificate without having the BCG vaccine in their medical record along with other vaccinations.^[40]
France: The BCG was mandatory for school children between 1950 and 2007,^[41]^[42] and for healthcare professionals between 1947 and 2010. Vaccination is still available for French healthcare professionals and social workers but is now decided on a case by case basis.^[43]
India and Pakistan: India and Pakistan introduced BCG mass immunization in 1948, the first countries outside Europe to do so.^[44]
Mongolia: All newborns are vaccinated with BCG. Previously, the vaccine was also given at ages 8 and 15, although this is no longer common practice.^[45]
Norway: In Norway the BCG vaccine was mandatory from 1947 to 1995. It is still available and recommended for high-risk groups.^[46]
Philippines: BCG vaccine started in the Philippines in 1979 with the Expanded Program on Immunization
South Africa: In South Africa, the BCG Vaccine is given routinely at birth, to all newborns, except those with clinically symptomatic AIDS. The vaccination site in the right shoulder.^[47]
Sri Lanka: In Sri Lanka, The National Policy of Sri Lanka is to give BCG vaccination to all newborn babies immediately after birth. BCG vaccination is carried out under the Expanded Programme of Immunisation (EPI).^[48]
Thailand: In Thailand, the BCG Vaccine is given routinely at birth.^[49]
United Kingdom: The UK introduced universal BCG immunization in 1953, and until July 2005, the UK policy was to immunize all school children between 10 and 14 years of age, and all neonates born into high-risk groups. The injection was given only 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 MRC trial showed efficacy lasted a maximum of 15 years.^[50] Routine immunization with BCG for all school children was scrapped in July 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, 12,000 children would have to be immunized to prevent one case of TB.^[51] The vaccine is still given to certain healthcare professionals, however.^[52]
United States: The US has never used mass immunization of BCG, relying instead on the detection and treatment of latent tuberculosis.
Other countries: In some countries, such as the former Soviet Union, BCG was given regularly throughout life. In South Korea, Singapore, Taiwan and Malaysia, BCG was given at birth and again at age 12. But in Malaysia and Singapore, from 2001, this policy was changed to once only at birth. South Korea also stopped the re-vaccination in 2008.

Manufacturer

BCG is prepared from a strain of the attenuated (virulence-reduced) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its ability to cause disease in humans. Because the living bacilli evolve to make the best use of available nutrients, they become less well-adapted to human blood and can no longer induce disease when introduced into a human host. Still, they are similar enough to their wild ancestors to provide some degree of immunity against human tuberculosis. The BCG vaccine can be anywhere from 0 to 80% effective in preventing tuberculosis for a duration of 15 years; however, its protective effect appears to vary according to geography and the lab in which the vaccine strain was grown.^[13]

A number of different companies make BCG, sometimes using different genetic strains of the bacterium. This may result in different product characteristics. OncoTICE, used for bladder instillation for bladder cancer, was developed by Organon Laboratories (since acquired by Schering-Plough, and in turn acquired by Merck, Inc.). Pacis BCG, made from the Montréal (Institut Armand-Frappier) strain,^[53] was first marketed by Urocor in about 2002. Urocor was since acquired by Dianon Systems. Evans Vaccines (a subsidiary of PowderJect Pharmaceuticals). Statens Serum Institut in Denmark markets BCG vaccine prepared using Danish strain 1331.^[54] Japan BCG Laboratory markets its vaccine, based on the Tokyo 172 substrain of Pasteur BCG, in 50 countries worldwide.

According to a UNICEF report published in December 2015 on BCG vaccine supply security, global demand increased in 2015 from 123 to 152.2 million doses. In order to improve security and to [diversify] sources of affordable and flexible supply," UNICEF awarded seven new manufacturers contracts to produce BCG. Along with supply availability from existing manufacturers, and a "new WHO prequalified vaccine" the total supply will be "sufficient to meet both suppressed 2015 demand carried over to 2016, as well as total forecast demand through 2016-2018."^[55]

BCG supply shortage 2012-

In the fall of 2011 the Sanofi Pasteur plant flooded causing problems with mold.^[56] The facility, located in Toronto, Ontario, Canada, produced BCG vaccine products, made with substrain Connaught, such as a tuberculosis vaccine ImmuCYST, a BCG Immunotherapeutic -a bladder cancer drug.^[57] By April 2012 the FDA had found dozens of documented problems with sterility at the plant including mold, nesting birds and rusted electrical conduits.^[56] The resulting closure of the plant for over two years resulting in shortages of bladder cancer and tuberculosis vaccines.^[58]^[59] On October 29, 2014 Health Canada gave the permission for Sanofi to resume production of BCG.^[60]

Preparation

A weakened strain of bovine tuberculosis bacillus, Mycobacterium bovis is specially subcultured in a culture medium, usually Middlebrook 7H9.

Dried

Some BCG vaccines are freeze dried and become fine powder. Sometimes the powder are sealed with vacuum in a glass ampoule. Such a glass ampoule has to be opened slowly to prevent the airflow from blowing out the powder. Then the powder has to be diluted with saline water before injecting.

History

The history of BCG is tied to that of smallpox. Jean Antoine Villemin first recognized bovine tuberculosis in 1854 and transmitted it, and Robert Koch first distinguished Mycobacterium bovis from Mycobacterium tuberculosis. Following the success of vaccination in preventing smallpox, established during the 18th century, scientists thought to find a corollary in tuberculosis by drawing a parallel between bovine tuberculosis and cowpox: 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, a French physician and bacteriologist, and his assistant and later colleague, Camille Guérin, a veterinarian, were working at the Institut Pasteur de Lille (Lille, 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 BCG strain was isolated after subculturing 239 times during 13 years from virulent strain on glycerine potato medium. 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 in 1919. The BCG vaccine was first used in humans in 1921.^[61]

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, 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 there had been contaminated with a virulent strain that was being stored in the same incubator, which led to legal action against the manufacturers of the vaccine.^[62]

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 (predecessor to the WHO). Because of opposition, however, it only became widely used 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 typical increase of TB after a major war.

BCG is very efficacious against tuberculous meningitis 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. Two countries that have never used it routinely are the USA and the Netherlands (in both countries, 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 condition that is now relatively rare there).^[63]^[64]

Other names include "Vaccin Bilié de Calmette et Guérin vaccine" and "Bacille de Calmette et Guérin vaccine".

Research

Tentative evidence exists for a beneficial non-specific effect of BCG vaccination on overall mortality in low income countries, or for its reducing other health problems including sepsis and respiratory infections when given early,^[65] with greater benefit the earlier it is used.^[66]

Other tuberculosis vaccines

See: Tuberculosis vaccines

References

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^ [2] Archived May 11, 2013, at the Wayback Machine.
^ "Role Of BC Vaccination". The National Programme for TB Control & Chest Diseases.
^ "Thai Pediatrics". Thai Pediatrics.
^ Styblo, K; Meijer, J (March 1976). "Impact of BCG vaccination programmes in children and young adults on the tuberculosis problem.". Tubercle. 57 (1): 17–43. doi:10.1016/0041-3879(76)90015-5. PMID 1085050.
^ "School 'TB jabs' to be scrapped". BBC News. July 2005. Retrieved 24 September 2014.
^ http://www.nhs.uk/conditions/vaccinations/pages/bcg-tuberculosis-tb-vaccine.aspx
^ "Pharmaceutical Information - PACIS". RxMed. Retrieved 2014-02-02.
^ "BCG Vaccine Danish Strain 1331 - Statens Serum Institut". Ssi.dk. 2013-09-19. Retrieved 2014-02-02.
^ "Bacillus Calmette-Guérin Vaccine Supply & Demand Outlook" (PDF), UNICEF Supply Division, p. 5, December 2015, retrieved 29 January 2016
^ ^a ^b "April 2012 Inspectional Observations (form 483)", U.S. Food and Drug Administration, Vaccines, Blood & Biologics, 12 April 2012, retrieved 29 January 2016
^ "Sanofi Pasteur Product Monograph - Immucyst" (PDF). Sanofi Pasteur Canada. Retrieved 11 February 2016.
^ Palmer, Eric (10 September 2014), "Merck again shipping BCG cancer treatment but Sanofi still is not: Shortages of bladder cancer and tuberculosis treatment have persisted for two years", FiercePharma |access-date= requires |url= (help)
^ Palmer, Eric (12 July 2012), "Merck again shipping BCG cancer treatment but Sanofi still is not: Shortages of bladder cancer and tuberculosis treatment have persisted for two years", FiercePharma |access-date= requires |url= (help)
^ Palmer, Eric (31 March 2015), "Sanofi Canada vax plant again producing ImmuCyst bladder cancer drug", FiercePharma, retrieved 29 January 2016
^ Fine PE, Carneiro IA, Milstein JB, Clements CJ (1999). Issues relating to the use of BCG in immunization programs. Geneva: WHO.
^ Rosenthal SR. (1957). BCG vaccination against tuberculosis. Boston: Little, Brown & Co.
^ "Fact Sheets: BCG Vaccine". Centers for Disease Control and Prevention. 28 October 2011. Retrieved 18 July 2013.
^ "Vaccination of young children against tuberculosis" (PDF) (2011/04). The Hague:Health Council of the Netherlands. 17 March 2011. ISBN 978-90-5549-844-4. Retrieved 12 July 2013.
^ Aaby, P; Roth, A; Ravn, H; Napirna, BM; Rodrigues, A; Lisse, IM; Stensballe, L; Diness, BR; Lausch, KR; Lund, N; Biering-Sørensen, S; Whittle, H; Benn, CS (15 July 2011). "Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?". The Journal of Infectious Diseases. 204 (2): 245–52. doi:10.1093/infdis/jir240. PMID 21673035.
^ Biering-Sørensen, S; Aaby, P; Napirna, BM; Roth, A; Ravn, H; Rodrigues, A; Whittle, H; Benn, CS (March 2012). "Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guérin vaccination at first health center contact.". The Pediatric Infectious Disease Journal. 31 (3): 306–8. doi:10.1097/inf.0b013e3182458289. PMID 22189537.

External links

Frequently Asked Questions about BCG Professor P D O Davies, Tuberculosis Research Unit, Cardiothoracic Centre, Liverpool, UK.
BCG World Atlas BCG policy by country, past and present.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. BCG膀胱内注入療法の感染性合併症infectious complications of intravesical bcg immunotherapy [show details]
…developed complications from BCG treatment . Systemic sepsis and even death can also develop early following local instillation of BCG . During the initial clinical experience with BCG as an intravesical agent …
2. 結核の予防接種vaccines for prevention of tuberculosis [show details]
… these include booster vaccines (designed to boost the effect of Bacille Calmette-Guerin [BCG]) and priming vaccines (intended to replace BCG) . Candidate booster vaccines include subunit vaccines (in which …
3. 筋層非浸潤性膀胱癌の再発癌あるいは残存癌のマネージメントmanagement of recurrent or persistent non muscle invasive bladder cancer [show details]
… (AUA) . "BCG failure" refers to patients with either intermediate- or high-risk non-muscle invasive bladder cancer who received a single round of induction BCG without maintenance therapy . "BCG unresponsive" …
4. 原発性筋層非浸潤性膀胱癌の治療treatment of primary non muscle invasive urothelial bladder cancer [show details]
… epirubicin, and gemcitabine, are widely used as alternatives. Bacillus Calmette-Guerin (BCG) is a live attenuated form of Mycobacterium bovis; BCG is the most commonly used agent for intravesical therapy. …
5. 国際養子縁組：感染症の側面international adoption infectious disease aspects [show details]
…T-SPOT.TB, with an overall agreement of 71 percent . A positive TST was not associated with Bacille Calmette-Guerin (BCG) vaccination or scar. Given the high rate of false negative TST tests shortly after arrival …

English Journal

Expression and regulatory networks of Mycobacterium tuberculosis PE/PPE family antigens.

Li W, Deng W, Xie J.
Journal of cellular physiology. 2019 Jun;234(6)7742-7751.
PE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major source
PMID 30478834

Cell Wall Hydrolytic Enzymes Enhance Antimicrobial Drug Activity Against Mycobacterium.

Gustine JN, Au MB, Haserick JR, Hett EC, Rubin EJ, Gibson FC, Deng LL.
Current microbiology. 2019 Apr;76(4)398-409.
Cell wall hydrolases are enzymes that cleave bacterial cell walls by hydrolyzing specific bonds within peptidoglycan and other portions of the envelope. Two major sources of hydrolases in nature are from hosts and microbes. This study specifically investigated whether cell wall hydrolytic enzymes co
PMID 30603964

Clinical Manifestations, Management, and Outcomes of Osteitis/Osteomyelitis Caused by Mycobacterium bovis Bacillus Calmette-Guérin in Children: Comparison by Site(s) of Affected Bones.

Huang CY, Chiu NC, Chi H, Huang FY, Chang PH.
The Journal of pediatrics. 2019 Apr;207()97-102.
To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis. We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, l
PMID 30577978

Japanese Journal

症例 BCG注入療法後に両側多発性腎腫瘤として発症した腎結核性肉芽腫の1例

臨床放射線 62(3), 479-481, 2017-03
NAID 40021138416

BCG 接種後に生じた丘疹状結核疹の1例

皮膚の科学 16(3), 201-204, 2017
NAID 130005830359

がん免疫療法を促進するDrug Delivery Systemの開発

薬学雑誌 136(11), 1477-1484, 2016
NAID 130005267659

Related Pictures

★リンクテーブル★

リンク元	「Calmette-Guerin桿菌」「ウシ型弱毒結核菌ワクチン」

「Calmette-Guerin桿菌」

BCG vaccine
	Microscopic image of the Calmette-Guérin bacillus, Ziehl–Neelsen stain, magnification:1,000nn
Vaccine description
Target disease	Tuberculosis
Type	Live bacteria
Clinical data
AHFS/Drugs.com	FDA Professional Drug Information
Pregnancy; category	US: C (Risk not ruled out); ;
Routes of; administration	Percutaneous
Legal status
Legal status	US: ℞-only;
Identifiers
ATC code	J07AN01 (WHO)
ChemSpider	none

　　[★]

英: Bacille Calmette-Guerin
関: ウシ型弱毒結核菌ワクチン、カルメット・ゲラン桿菌

「ウシ型弱毒結核菌ワクチン」

　　[★]

英: Bacille Calmette-Guerin、BCG
関: カルメット・ゲラン桿菌、Calmette-Guerin桿菌

[WHO2004-1] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k "BCG Vaccine: WHO position paper" (PDF). Weekly epidemiological record. 4 (79): 25–40. Jan 23, 2014.

[WHO2007-2] "Revised BCG vaccination guidelines for infants at risk for HIV infection." (PDF). Wkly Epidemiol Rec. 82 (21): 193–196. May 25, 2007. PMID 17526121.

[3] Fuge, O; Vasdev, N; Allchorne, P; Green, JS (2015). "Immunotherapy for bladder cancer.". Research and reports in urology. 7: 65–79. doi:10.2147/RRU.S63447. PMC 4427258. PMID 26000263.

[4] Roy, A; Eisenhut, M; Harris, RJ; Rodrigues, LC; Sridhar, S; Habermann, S; Snell, L; Mangtani, P; Adetifa, I; Lalvani, A; Abubakar, I (5 August 2014). "Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis.". BMJ (Clinical research ed.). 349: g4643. doi:10.1136/bmj.g4643. PMC 4122754. PMID 25097193.

[5] Houghton, BB; Chalasani, V; Hayne, D; Grimison, P; Brown, CS; Patel, MI; Davis, ID; Stockler, MR (May 2013). "Intravesical chemotherapy plus bacille Calmette-Guérin in non-muscle invasive bladder cancer: a systematic review with meta-analysis.". BJU international. 111 (6): 977–83. doi:10.1111/j.1464-410x.2012.11390.x. PMID 23253618.

[6] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[7] "Vaccine, Bcg". International Drug Price Indicator Guide. Retrieved 6 December 2015.

[8] "Vaccine, Bcg". ERC. Retrieved 13 June 2016.

[Ric2015-9] Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 312. ISBN 9781284057560.

[10] "BCG Vaccine | TB Symptoms | Tuberculin Skin Test | PPD | TB Signs". TB Symptoms. 2013-01-18. Retrieved 2014-02-02.

[Colditz-11] Colditz, Graham A.; Brewer, TF; Berkey, CS; Wilson, ME; Burdick, E; Fineberg, HV; Mosteller, F (1994). "Efficacy of BCG Vaccine in the Prevention of Tuberculosis". JAMA. 271 (9): 698–702. doi:10.1001/jama.1994.03510330076038. PMID 8309034.

[12] Fine PEM (1995). "Variation in protection by BCG: implications of and for heterologous immunity". Lancet. 346 (8986): 1339–45. doi:10.1016/S0140-6736(95)92348-9. PMID 7475776.

[Venkataswamy-13] Venkataswamy, Manjunatha M.; Goldberg, Michael F.; Baena, Andres; Chan, John; Jacobs, William R., Jr.; Porcelli, Steven A. (1 February 2012). "In vitro culture medium influences the vaccine efficacy of Mycobacterium bovis BCG". Vaccine. 30 (6): 1038–1049. doi:10.1016/j.vaccine.2011.12.044. PMC 3269512. PMID 22189700. |access-date= requires |url= (help)

[Fine-14] FINE, P (1 November 1995). "Variation in protection by BCG: implications of and for heterologous immunity". The Lancet. 346 (8986): 1339–1345. doi:10.1016/S0140-6736(95)92348-9. PMID 7475776.

[pmid25097193-15] Roy A, Eisenhut M, Harris RJ, et al. (2014). "Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis". BMJ. 349: g4643. doi:10.1136/bmj.g4643. PMC 4122754. PMID 25097193.

[16] Aronson NE, Santosham M, Comstock GW (2004). "Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study". JAMA. 291 (17): 2086–91. doi:10.1001/jama.291.17.2086. PMID 15126436.

[17] Rodrigues LC, Diwan VK, Wheeler JG (1993). "Protective Effect of BCG against Tuberculous Meningitis and Miliary Tuberculosis: A Meta-Analysis". Int J Epidemiol. 22 (6): 1154–8. doi:10.1093/ije/22.6.1154. PMID 8144299.

[BDG_2016-18] Rentsch, Cyrill A.; Birkhäuser, Frédéric D.; Biot, Claire; Gsponer, Joël R.; Bisiaux, Aurélie; Wetterauer, Christian; Lagranderie, Micheline; Marchal, Gilles; Orgeur, Mickael; Bouchier, Christiane; Bachmann, Alexander; Ingersoll, Molly A.; Brosch, Roland; Albert, Matthew L.; Thalmann, George N. (1 October 2014). "Bacillus Calmette-Guérin Strain Differences Have an Impact on Clinical Outcome in Bladder Cancer Immunotherapy". European Urology. 66 (4): 677–688. doi:10.1016/j.eururo.2014.02.061.

[19] Fine PE, Carneiro IA, Milstein JB, Clements CJ (1999). "Chapter 8: Reasons for variable efficacy". Issues relating to the use of BCG in immunization programmes (PDF). Geneva, Switzerland: World Health Organization.

[20] Brosch R, Gordon SV, Garnier T, Eiglmeier K (2007). "Genome plasticity of BCG and impact on vaccine efficacy". Proceedings of the National Academy of Sciences of the United States of America. 104 (13): 5596–601. doi:10.1073/pnas.0700869104. PMC 1838518. PMID 17372194.

[21] Packe GE, Innes JA (1988). "Protective effect of BCG vaccination in infant Asians: a case-control study". Archives of Disease in Childhood. 63 (3): 277–281. doi:10.1136/adc.63.3.277. PMC 1778792. PMID 3258499.

[22] Black GF, Weir RE, Floyd S (2002). "BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malai and the UK: two randomized controlled studies". Lancet. 359 (9315): 1393–401. doi:10.1016/S0140-6736(02)08353-8. PMID 11978337.

[23] Palmer CE, Long MW (1966). "Effects of infection with atypical mycobacteria on BCG vaccination and tuberculosis". Am Rev Respir Dis: 553–68.

[24] Brandt L, Feino Cunha J, Weinreich Olsen A (2002). "Failure of Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis". Infection and Immunity. 70 (2): 672–78. doi:10.1128/IAI.70.2.672-678.2002. PMC 127715. PMID 11796598.

[25] Rook GAW; Dheda K; Zumla A. (2005). "Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?". Vaccine. 23 (17–18): 2115–20. doi:10.1016/j.vaccine.2005.01.069. PMID 15755581.

[26] Setia MS, Steinmaus C, Ho CS, Rutherford GW (2006). "The role of BCG in prevention of leprosy: a meta-analysis". Lancet Infect Dis. 6 (3): 162–70. doi:10.1016/S1473-3099(06)70412-1. PMID 16500597.

[Merle2010-27] Merle, Corinne SC; Cunha, Sergio S; Rodrigues, Laura C (2010). "BCG vaccination and leprosy protection: Review of current evidence and status of BCG in leprosy control". Expert Review of Vaccines. 9 (2): 209–22. doi:10.1586/ERV.09.161. PMID 20109030.

[28] Tanghe, A.; J. Content; J. P. Van Vooren; F. Portaels; K. Huygen (2001). "Protective efficacy of a DNA vaccine encoding antigen 85A from Mycobacterium bovis BCG against Buruli ulcer". Infection and Immunity. 69 (9): 5403–11. doi:10.1128/IAI.69.9.5403-5411.2001. PMC 98650. PMID 11500410.

[BCG_success_2007-29] Brandau, S.; Suttmann, H. (2007). "Thirty years of BCG immunotherapy for non-muscle invasive bladder cancer: a success story with room for improvement". Biomed Pharmacother. 61: 299–305. doi:10.1016/j.biopha.2007.05.004.

[30] Lamm DL, Blumenstein BA, Crawford ED (1991). "A randomized trial of intravesical doxorubicin and immunotherapy with bacille Calmette-Guerin for transitional-cell carcinoma of the bladder". N Engl J Med. 325 (2): 1205–9. doi:10.1056/NEJM199110243251703. PMID 1922207.

[31] Mosolits S, Nilsson B, Mellstedt H (2005). "Towards therapeutic vaccines for colorectal carcinoma: a review of clinical trials". Expert Rev Vaccines. 4 (3): 329–50. doi:10.1586/14760584.4.3.329. PMID 16026248.

[32] Nick Makwana and Andrew Riordan (2004), "Is medical therapy effective in the treatment of BCG abscesses?", Birmingham Heartlands Hospital [1]

[33] Cuello-García, Carlos A.; Pérez-Gaxiola, Giordano; Jiménez Gutiérrez, Carlos (2013-01-01). "Treating BCG-induced disease in children". The Cochrane Database of Systematic Reviews. 1: CD008300. doi:10.1002/14651858.CD008300.pub2. ISSN 1469-493X. PMID 23440826.

[34] Govindarajan KK, Chai FY (2011). "BCG adenitis — need for increased awareness". Mal J Med Sci. 18 (2): 67–70. Malaysian Journal of Medical Sciences

[35] Centers for Disease Control and Prevention (1996). "The role of BCG vaccine in the prevention and control of tuberculosis in the United States: a joint statement of the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices". MMWR Recomm Rep. 45 (RR-4): 1–18. PMID 8602127.

[36] WHO (2007). "Revised BCG vaccination guidelines for infants at risk for HIV infection". Wkly Epidemiol Rec. 82 (21): 193–6. PMID 17526121.

[37] Trunz BB, Fine P, Dye C (2006). "Effect of BCG vaccination on childhood tuberculous meningitis and miliary tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness". Lancet. 367 (9517): 1173–80. doi:10.1016/S0140-6736(06)68507-3. PMID 16616560.

[38] Mak TK, Hesseling AC, Hussey GD, Cotton MF (2008). "Making BCG vaccination programs safer in the HIV era". Lancet. 372 (9641): 786–7. doi:10.1016/S0140-6736(08)61318-5. PMID 18774406.

[39] WHO (2004). WHO Position Paper on BCG Vaccination (PDF). Geneva: WHO.

[40] ttp://www.siise.gob.ec/siiseweb/PageWebs/SALUD/ficsal_S21.htm

[41] Loi n° 50-7 du 5 janvier 1950

[42] écret n° 2007-1111 du 17 juillet 2007

[43] "relatif à l'obligation de vaccination par le BCG des professionnels listés aux articles L" (PDF). Retrieved 2014-02-02.

[44] Mahler HT, Mohamed Ali P (1955). "Review of mass B.C.G. project in India". Ind J Tuberculosis. 2 (3): 108–16.

[45] C. Oyunsolong, personal communication. Vaccine Specialist, Selenge Province Health Department, Mongolia. 14 January 2015.

[46] ttp://www.fhi.no/eway/default.aspx?pid=239&trg=Content_6493&Main_6157=6287:0:25,5501&MainContent_6287=6493:0:25,6826&Content_6493=6441:68710::0:6446:1:::0:0#eHandbook687100

[47] [2] Archived May 11, 2013, at the Wayback Machine.

[48] "Role Of BC Vaccination". The National Programme for TB Control & Chest Diseases.

[49] "Thai Pediatrics". Thai Pediatrics.

[50] Styblo, K; Meijer, J (March 1976). "Impact of BCG vaccination programmes in children and young adults on the tuberculosis problem.". Tubercle. 57 (1): 17–43. doi:10.1016/0041-3879(76)90015-5. PMID 1085050.

[51] "School 'TB jabs' to be scrapped". BBC News. July 2005. Retrieved 24 September 2014.

[52] ttp://www.nhs.uk/conditions/vaccinations/pages/bcg-tuberculosis-tb-vaccine.aspx

[53] "Pharmaceutical Information - PACIS". RxMed. Retrieved 2014-02-02.

[54] "BCG Vaccine Danish Strain 1331 - Statens Serum Institut". Ssi.dk. 2013-09-19. Retrieved 2014-02-02.

[UNICEF_2015-55] "Bacillus Calmette-Guérin Vaccine Supply & Demand Outlook" (PDF), UNICEF Supply Division, p. 5, December 2015, retrieved 29 January 2016

[FDA_2012-56] "April 2012 Inspectional Observations (form 483)", U.S. Food and Drug Administration, Vaccines, Blood & Biologics, 12 April 2012, retrieved 29 January 2016

[57] "Sanofi Pasteur Product Monograph - Immucyst" (PDF). Sanofi Pasteur Canada. Retrieved 11 February 2016.

[Sanofi_2014_BCG_vaccine-58] Palmer, Eric (10 September 2014), "Merck again shipping BCG cancer treatment but Sanofi still is not: Shortages of bladder cancer and tuberculosis treatment have persisted for two years", FiercePharma |access-date= requires |url= (help)

[Sanofi_2012_BCG_vaccine-59] Palmer, Eric (12 July 2012), "Merck again shipping BCG cancer treatment but Sanofi still is not: Shortages of bladder cancer and tuberculosis treatment have persisted for two years", FiercePharma |access-date= requires |url= (help)

[FiercePharma_mar_2015-60] Palmer, Eric (31 March 2015), "Sanofi Canada vax plant again producing ImmuCyst bladder cancer drug", FiercePharma, retrieved 29 January 2016

[61] Fine PE, Carneiro IA, Milstein JB, Clements CJ (1999). Issues relating to the use of BCG in immunization programs. Geneva: WHO.

[62] Rosenthal SR. (1957). BCG vaccination against tuberculosis. Boston: Little, Brown & Co.

[63] "Fact Sheets: BCG Vaccine". Centers for Disease Control and Prevention. 28 October 2011. Retrieved 18 July 2013.

[64] "Vaccination of young children against tuberculosis" (PDF) (2011/04). The Hague:Health Council of the Netherlands. 17 March 2011. ISBN 978-90-5549-844-4. Retrieved 12 July 2013.

[65] Aaby, P; Roth, A; Ravn, H; Napirna, BM; Rodrigues, A; Lisse, IM; Stensballe, L; Diness, BR; Lausch, KR; Lund, N; Biering-Sørensen, S; Whittle, H; Benn, CS (15 July 2011). "Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?". The Journal of Infectious Diseases. 204 (2): 245–52. doi:10.1093/infdis/jir240. PMID 21673035.

[66] Biering-Sørensen, S; Aaby, P; Napirna, BM; Roth, A; Ravn, H; Rodrigues, A; Whittle, H; Benn, CS (March 2012). "Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guérin vaccination at first health center contact.". The Pediatric Infectious Disease Journal. 31 (3): 306–8. doi:10.1097/inf.0b013e3182458289. PMID 22189537.

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Bacille Calmette-Guerin