Bacillus Calmette-Guérin (BCG) is the live attenuated vaccine form of Mycobacterium bovis used to prevent tuberculosis and other mycobacterial infections. The vaccine was developed by Calmette and Guérin and was first administered to human beings in 1921. BCG is the only vaccine against tuberculosis. It is the most widely administered vaccine and usually a part of the routine newborn immunization schedule. BCG vaccine also offers protection against non-tuberculous mycobacteria infection like leprosy and Buruli ulcer. It is also used in the treatment of superficial carcinoma of the bladder.
BCG vaccine is safe and is not associated with severe complications. Prior to the mycobacterial infection, vaccine-induced or acquired naturally can protect against subsequent infection due to mycobacteria including tuberculosis . Prior infection with nontuberculous mycobacteria and Mycobacterium tuberculosis can confer natural protection against tuberculosis infection . Protection against tuberculosis infection is usually due to the immune response to mycobacterial antigens. Prior contained latent infection with Mycobacterium tuberculosis can provide up to 80 percent protection against disease with subsequent exposure . In patients with previous active disease, there is an increased risk of recurrence of active tuberculosis due to distinct strain in both HIV-uninfected and HIV-infected patients . Bacille Calmette-Guérin (BCG) has been associated with a reduction in childhood mortality which is not attributable to tuberculosis. Reduction in childhood mortality may be due to epigenetic reprogramming of the NOD2 receptor 
BCG vaccine can be given either intracutaneously or intradermally. Research is currently being conducted on respiratory administration since natural infection, and sensitization to Mycobacterium tuberculosis in humans tend to occur in the respiratory system .
Groups to consider for BCG vaccination include
Children: Newborns and infants have the greatest benefit from BCG vaccination
Exposure to MDR-TB:
Health care workers: Routine vaccination of health care workers is not recommended since in the United States since infection with tuberculosis is low. BCG vaccine also interferes with the result of a tuberculin skin test that is used to detect Mycobacterium tuberculosis infection. In health care workers, the efficacy of BCG vaccination is not definite . Strict adherence to tuberculosis infection control practices should be emphasized in areas with a high incidence of disease transmission.
BCG immunization guidelines depend on the prevalence of tuberculosis infection . Childhood BCG immunization should be routine in countries with high prevalence of tuberculosis. In countries with low to intermediate rates of TB (<5/100,000 smear-positive cases per year), BCG immunization should be administered to children at particular risk of TB exposure  ( ie children exposed to multidrug-resistant disease).
BCG vaccination policy is determined by the regional prevalence of tuberculosis infection. Routine neonatal vaccination is recommended by the WHO in countries with moderate to severe prevalence of tuberculosis. Close contacts of patients with TB infection and healthcare workers exposed to patients multidrug-resistant tuberculosis infections with negative tuberculin tests should receive BCG vaccination. Routine BCG vaccination is not recommended in countries with a low prevalence of tuberculosis. Routine BCG vaccination has never been recommended in the United States given a low prevalence of tuberculosis infection. Routine BCG vaccination of children at age 13 and all neonates in high-risk groups was implemented between 1953 and 2005 in the United Kingdom. Routine vaccination was later discontinued in 2005 due decrease incidence of tuberculosis infection.
Groups not to vaccinate include
Immunocompromised patients: BCG is a live vaccine and should not be given to:
Adults with HIV infection living in areas of low TB prevalence
BCG vaccination after infancy has a substantial effect on tuberculin skin test (TST) reactivity. BCG trial in the United States showed that individuals who received BCG after infancy had tuberculin skin test reactions ≥10 mm up to 55 years post immunization .
Prior BCG vaccination should not affect the interpretation of TST results in individuals vaccinated at birth more than ten years earlier given that most individuals who receive BCG vaccine come from areas where there is a high incidence of TB. Interferon-gamma release assays (IGRAs) should be used to interpret positive TSTs in persons with a history of BCG immunization since this test is not affected by BCG administration. In individuals exposed to serial tuberculin testing, previous BCG vaccination may be increased, leading to a positive skin test in an individual with a prior negative skin test. Greater than 50 percent of patients that received intravesical BCG for bladder cancer has been reported to result in conversion to positive tuberculin skin test  This exposure to intravesical BCG should not result in a positive IGRA result .
The rationale for the development of a booster vaccine is due to decreasing immunity about 15-20 years after the initial immunization at infancy . However, studies done in Brazil and Malawi have shown that a booster dose of BCG vaccine is not very effective against TB disease . BCG vaccine may offer protection against infections due to nontuberculous mycobacteria .
Studies have shown that BCG vaccine decreases the risk of disease due to Mycobacterium leprae by 50 to 80 percent and this effect is increased with booster doses of BCG . Prior studies had shown that the vaccine is also 50 percent effective in preventing Buruli ulcer disease due to M. ulcerans, but a more recent retrospective study failed to show evidence that BCG protected against Buruli ulcer disease .
BCG vaccination also protects against childhood lymphadenitis due to M. avium complex  has been an increase in childhood adenitis due to non-tuberculous mycobacteria since the cessation of childhood BCG immunization .
Tuberculin skin test (TST) reaction of 3 to 19 mm in size is expected in most individuals that received BCG immunization two to three months after vaccination. In a study of 5952 individuals who had BCG vaccination and subsequently underwent tuberculin skin testing 10 to 25 years later, only 8 percent had positive skin test results .
BCG vaccination policy is determined by the regional prevalence of tuberculosis infection. Routine neonatal vaccination is recommended by the WHO in countries with moderate to a severe incidence of tuberculosis. Conversion of tuberculin skin test should not be used to determine the efficacy of BCG vaccine among recipients .
Routine BCG vaccination is not generally recommended in the United States due to a low incidence of tuberculosis infection and also due to an interference of immunization with the PPD test. BCG vaccination is not recommended for health care workers in the low-risk area. Vaccination is also contraindicated in immunosuppressed patients.
BCG vaccination may be considered in situations where a high percentage of patients are infected with TB strains that are resistant to isoniazid and rifampin Vaccination can also be found in cases where implementation of general infection precautions have failed and when transmission of multi-drug resistant strain of Mycobacterium tuberculosis is likely . Nurses practitioners, physician assistants, and physicians that administer BCG should work together in an interprofessional team to assure safe and effective administration. [Level V]
|||von Reyn CF,Vuola JM, New vaccines for the prevention of tuberculosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2002 Aug 15; [PubMed PMID: 12145732]|
|||Edwards LB,Palmer CE, Biology of the mycobacterioses. Identification of the tuberculous-infected by skin tests. Annals of the New York Academy of Sciences. 1968 Sep 5; [PubMed PMID: 5266317]|
|||Fine PE, Variation in protection by BCG: implications of and for heterologous immunity. Lancet (London, England). 1995 Nov 18; [PubMed PMID: 7475776]|
|||Andrews JR,Noubary F,Walensky RP,Cerda R,Losina E,Horsburgh CR, Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2012 Mar; [PubMed PMID: 22267721]|
|||Bjartveit K, Olaf Scheel and Johannes Heimbeck: their contribution to understanding the pathogenesis and prevention of tuberculosis. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2003 Apr; [PubMed PMID: 12729334]|
|||HEIMBECK J, BCG vaccination of nurses. Tubercle. 1948 Apr; [PubMed PMID: 18909014]|
|||Verver S,Warren RM,Beyers N,Richardson M,van der Spuy GD,Borgdorff MW,Enarson DA,Behr MA,van Helden PD, Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. American journal of respiratory and critical care medicine. 2005 Jun 15; [PubMed PMID: 15831840]|
|||von Reyn CF,Horsburgh CR, Reinfection with Mycobacterium tuberculosis. American journal of respiratory and critical care medicine. 2006 Jan 1; [PubMed PMID: 16368796]|
|||Lahey T,Mackenzie T,Arbeit RD,Bakari M,Mtei L,Matee M,Maro I,Horsburgh CR,Pallangyo K,von Reyn CF, Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior active tuberculosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2013 Jan; [PubMed PMID: 22972862]|
|||Zumla A,Raviglione M,Hafner R,von Reyn CF, Tuberculosis. The New England journal of medicine. 2013 Feb 21; [PubMed PMID: 23425167]|
|||Roth AE,Stensballe LG,Garly ML,Aaby P, Beneficial non-targeted effects of BCG--ethical implications for the coming introduction of new TB vaccines. Tuberculosis (Edinburgh, Scotland). 2006 Nov; [PubMed PMID: 16901755]|
|||Roth A,Jensen H,Garly ML,Djana Q,Martins CL,Sodemann M,Rodrigues A,Aaby P, Low birth weight infants and Calmette-Gu�rin bacillus vaccination at birth: community study from Guinea-Bissau. The Pediatric infectious disease journal. 2004 Jun; [PubMed PMID: 15194836]|
|||Kristensen I,Aaby P,Jensen H, Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ (Clinical research ed.). 2000 Dec 9; [PubMed PMID: 11110734]|
|||Kleinnijenhuis J,Quintin J,Preijers F,Joosten LA,Ifrim DC,Saeed S,Jacobs C,van Loenhout J,de Jong D,Stunnenberg HG,Xavier RJ,van der Meer JW,van Crevel R,Netea MG, Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proceedings of the National Academy of Sciences of the United States of America. 2012 Oct 23; [PubMed PMID: 22988082]|
|||Jeyanathan M,Heriazon A,Xing Z, Airway luminal T cells: a newcomer on the stage of TB vaccination strategies. Trends in immunology. 2010 Jul; [PubMed PMID: 20542470]|
|||Horvath CN,Shaler CR,Jeyanathan M,Zganiacz A,Xing Z, Mechanisms of delayed anti-tuberculosis protection in the lung of parenteral BCG-vaccinated hosts: a critical role of airway luminal T cells. Mucosal immunology. 2012 Jul; [PubMed PMID: 22453678]|
|||Lutwama F,Kagina BM,Wajja A,Waiswa F,Mansoor N,Kirimunda S,Hughes EJ,Kiwanuka N,Joloba ML,Musoke P,Scriba TJ,Mayanja-Kizza H,Day CL,Hanekom WA, Distinct T-cell responses when BCG vaccination is delayed from birth to 6 weeks of age in Ugandan infants. The Journal of infectious diseases. 2014 Mar; [PubMed PMID: 24179111]|
|||Pereira SM,Barreto ML,Pilger D,Cruz AA,Sant'Anna C,Hijjar MA,Ichihara MY,Santos AC,Genser B,Rodrigues LC, Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial. The Lancet. Infectious diseases. 2012 Apr; [PubMed PMID: 22071248]|
|||The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports. 1996 Apr 26; [PubMed PMID: 8602127]|
|||Dara M,Acosta CD,Rusovich V,Zellweger JP,Centis R,Migliori GB, Bacille Calmette-Gu�rin vaccination: the current situation in Europe. The European respiratory journal. 2014 Jan; [PubMed PMID: 24381321]|
|||Brewer TF,Colditz GA, Bacille Calmette-Gu�rin vaccination for the prevention of tuberculosis in health care workers. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 1995 Jan; [PubMed PMID: 7727639]|
|||Criteria for discontinuation of vaccination programmes using Bacille Calmette-Guerin (BCG) in countries with a low prevalence of tuberculosis. A statement of the International Union Against Tuberculosis and Lung Disease. Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 1994 Jun; [PubMed PMID: 7919307]|
|||Fine P, Stopping routine vaccination for tuberculosis in schools. BMJ (Clinical research ed.). 2005 Sep 24; [PubMed PMID: 16179677]|
|||Mancuso JD,Mody RM,Olsen CH,Harrison LH,Santosham M,Aronson NE, The Long-term Effect of Bacille Calmette-Gu�rin Vaccination on Tuberculin�Skin Testing: A 55-Year Follow-Up Study. Chest. 2017 Aug; [PubMed PMID: 28087302]|
|||Lamm DL, Bacillus Calmette-Guerin immunotherapy for bladder cancer. The Journal of urology. 1985 Jul; [PubMed PMID: 3892050]|
|||Silverman MS,Reynolds D,Kavsak PA,Garay J,Daly A,Davis I, Use of an interferon-gamma based assay to assess bladder cancer patients treated with intravesical BCG and exposed to tuberculosis. Clinical biochemistry. 2007 Aug; [PubMed PMID: 17512514]|
|||von Reyn CF, Correcting the record on BCG before we license new vaccines against tuberculosis. Journal of the Royal Society of Medicine. 2017 Nov; [PubMed PMID: 28949270]|
|||Black GF,Weir RE,Floyd S,Bliss L,Warndorff DK,Crampin AC,Ngwira B,Sichali L,Nazareth B,Blackwell JM,Branson K,Chaguluka SD,Donovan L,Jarman E,King E,Fine PE,Dockrell HM, BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet (London, England). 2002 Apr 20; [PubMed PMID: 11978337]|
|||Randomised controlled trial of single BCG, repeated BCG, or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Karonga Prevention Trial Group. Lancet (London, England). 1996 Jul 6; [PubMed PMID: 8691924]|
|||Rodrigues LC,Pereira SM,Cunha SS,Genser B,Ichihara MY,de Brito SC,Hijjar MA,Dourado I,Cruz AA,Sant'Anna C,Bierrenbach AL,Barreto ML, Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial. Lancet (London, England). 2005 Oct 8; [PubMed PMID: 16214599]|
|||Zimmermann P,Finn A,Curtis N, Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A Systematic Review and Meta-Analysis. The Journal of infectious diseases. 2018 Jul 24; [PubMed PMID: 29635431]|
|||Merle CS,Cunha SS,Rodrigues LC, BCG vaccination and leprosy protection: review of current evidence and status of BCG in leprosy control. Expert review of vaccines. 2010 Feb; [PubMed PMID: 20109030]|
|||Phillips RO,Phanzu DM,Beissner M,Badziklou K,Luzolo EK,Sarfo FS,Halatoko WA,Amoako Y,Frimpong M,Kabiru AM,Piten E,Maman I,Bidjada B,Koba A,Awoussi KS,Kobara B,Nitschke J,Wiedemann FX,Kere AB,Adjei O,L�scher T,Fleischer B,Bretzel G,Herbinger KH, Effectiveness of routine BCG vaccination on buruli ulcer disease: a case-control study in the Democratic Republic of Congo, Ghana and Togo. PLoS neglected tropical diseases. 2015 Jan; [PubMed PMID: 25569674]|
|||Katila ML,Brander E,Backman A, Neonatal BCG vaccination and mycobacterial cervical adenitis in childhood. Tubercle. 1987 Dec; [PubMed PMID: 3138802]|
|||Romanus V,Hallander HO,W�hl�n P,Olinder-Nielsen AM,Magnusson PH,Juhlin I, Atypical mycobacteria in extrapulmonary disease among children. Incidence in Sweden from 1969 to 1990, related to changing BCG-vaccination coverage. Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 1995 Aug; [PubMed PMID: 7579311]|
|||Kontturi A,Soini H,Ollgren J,Salo E, Increase in Childhood Nontuberculous Mycobacterial Infections After Bacille Calmette-Gu�rin Coverage Drop: A Nationwide, Population-Based Retrospective Study, Finland, 1995-2016. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2018 Sep 28; [PubMed PMID: 29584893]|
|||Leung CC,Tam CM,Chan SL,Chan-Yeung M,Chan CK,Chang KC, Efficacy of the BCG revaccination programme in a cohort given BCG vaccination at birth in Hong Kong. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease. 2001 Aug; [PubMed PMID: 11495262]|