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BCG vaccination

INTRODUCTION

Bacille Calmette-Guérin (BCG) is a live strain of Mycobacterium bovis developed by Calmette and Guérin for use as an attenuated vaccine to prevent tuberculosis and other mycobacterial infections. The vaccine was first administered to humans in 1921 and remains the only vaccine against tuberculosis in general use. Several new vaccines against tuberculosis are also in development, and many are designed to boost the effects of BCG [1,2]. One investigational vaccine has been shown effective in a phase III trial [3].

BCG is the most widely administered vaccine in the world; it has been given to over 3 billion individuals, principally in the setting of routine newborn immunization (as dictated by guidelines of the World Health Organization) [4]. In the United States, BCG was sometimes administered to healthcare workers at risk for tuberculosis (TB) until the middle of the twentieth century but was never adopted for routine childhood immunization.

Issues related to host immunity, vaccine efficacy, administration, safety, and policy will be reviewed here. Although the major role of BCG is TB prevention, BCG vaccine is also effective for protection against leprosy, Buruli ulcer, and disease due to nontuberculous mycobacteria. In addition, it is used as an immunostimulant in the treatment of superficial carcinoma of the bladder. These topics are discussed in detail separately. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of leprosy" and "Buruli ulcer (Mycobacterium ulcerans infection)" and "Complications of intravesical BCG immunotherapy".)

MYCOBACTERIA AND HOST IMMUNITY

Virtually any prior mycobacterial infection (whether naturally acquired or vaccine induced) appears to produce some level of protection against subsequent disease due to tuberculosis and, in some cases, to other mycobacteria [1]. Natural infections that confer protection against tuberculosis (TB) include prior contained infection with M. tuberculosis itself or prior infection with nontuberculous mycobacteria (NTM) [5,6]. These observations suggest that protection is conferred by the immune response to common mycobacterial antigens.

Prior latent infection with M. tuberculosis that has been contained provides as much as 80 percent protection against disease after subsequent exposure [7]. However, prior active disease is associated with an increased risk of a second episode of active tuberculosis due to a different strain in both HIV-positive and HIV-negative persons [8-14]. (See "Microbiology and pathogenesis of tuberculosis", section on 'Host factors'.)

                         

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Literature review current through: Sep 2014. | This topic last updated: Sep 8, 2014.
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References
Top
  1. von Reyn CF, Vuola JM. New vaccines for the prevention of tuberculosis. Clin Infect Dis 2002; 35:465.
  2. Hoft DF. Tuberculosis vaccine development: goals, immunological design, and evaluation. Lancet 2008; 372:164.
  3. von Reyn CF, Mtei L, Arbeit RD, et al. Prevention of tuberculosis in Bacille Calmette-Guérin-primed, HIV-infected adults boosted with an inactivated whole-cell mycobacterial vaccine. AIDS 2010; 24:675.
  4. Fine PE, Carneiro IA, Milstien JB, Clements CJ. Issues relating to the use of BCG in immunization programs: a discussion document. Geneva, Switzerland: Department of Vaccines and Biologicals, World Health Organization 1999. p.1.
  5. Edwards LB, Palmer CE. Biology of the mycobacterioses. Identification of the tuberculous-infected by skin tests. Ann N Y Acad Sci 1968; 154:140.
  6. Fine PE. Variation in protection by BCG: implications of and for heterologous immunity. Lancet 1995; 346:1339.
  7. Andrews JR, Noubary F, Walensky RP, et al. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin Infect Dis 2012; 54:784.
  8. Flahiff, EW. The occurrence of tuberculosis in persons who failed to react to tuberculin, and in persons with positive tuberculin reactions. Am Jour Hyg 1939; 30:69.
  9. Bjartveit K. Olaf Scheel and Johannes Heimbeck: their contribution to understanding the pathogenesis and prevention of tuberculosis. Int J Tuberc Lung Dis 2003; 7:306.
  10. HEIMBECK J. BCG vaccination of nurses. Tubercle 1948; 29:84.
  11. Verver S, Warren RM, Beyers N, et al. Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am J Respir Crit Care Med 2005; 171:1430.
  12. von Reyn CF, Horsburgh CR. Reinfection with Mycobacterium tuberculosis. Am J Respir Crit Care Med 2006; 173:133.
  13. Lahey T, Mackenzie T, Arbeit RD, et al. Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior active tuberculosis. Clin Infect Dis 2013; 56:151.
  14. Zumla A, Raviglione M, Hafner R, von Reyn CF. Tuberculosis. N Engl J Med 2013; 368:745.
  15. 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 (Edinb) 2006; 86:397.
  16. Roth A, Jensen H, Garly ML, et al. Low birth weight infants and Calmette-Guérin bacillus vaccination at birth: community study from Guinea-Bissau. Pediatr Infect Dis J 2004; 23:544.
  17. Kristensen I, Aaby P, Jensen H. Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ 2000; 321:1435.
  18. Kleinnijenhuis J, Quintin J, Preijers F, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A 2012; 109:17537.
  19. Aronson NE, Santosham M, Comstock GW, et al. Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study. JAMA 2004; 291:2086.
  20. Mangtani P, Abubakar I, Ariti C, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis 2014; 58:470.
  21. Wilson ME, Fineberg HV, Colditz GA. Geographic latitude and the efficacy of bacillus Calmette-Guérin vaccine. Clin Infect Dis 1995; 20:982.
  22. Black GF, Weir RE, Floyd S, et al. 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 2002; 359:1393.
  23. Behr MA, Small PM. Has BCG attenuated to impotence? Nature 1997; 389:133.
  24. Colditz GA, Brewer TF, Berkey CS, et al. Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA 1994; 271:698.
  25. Clemens JD, Chuong JJ, Feinstein AR. The BCG controversy. A methodological and statistical reappraisal. JAMA 1983; 249:2362.
  26. Colditz GA, Berkey CS, Mosteller F, et al. The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics 1995; 96:29.
  27. Rodrigues LC, Diwan VK, Wheeler JG. Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol 1993; 22:1154.
  28. ARONSON JD. Protective vaccination against tuberculosis with special reference to BCG vaccination. Am Rev Tuberc 1948; 58:255.
  29. FERGUSON RG, SIMES AB. BCG vaccination of Indian infants in Saskatchewan. Tubercle 1949; 30:5.
  30. ROSENTHAL SR, LOEWINSOHN E, GRAHAM ML, et al. BCG vaccination in tuberculous households. Am Rev Respir Dis 1961; 84:690.
  31. ROSENTHAL SR, GRAHAM ML, LIVERIGHT D, et al. BCG vaccination against tuberculosis in Chicago. A twenty-year study statistically analyzed. Pediatrics 1961; 28:622.
  32. Levine, MI, Sackett, MF. Results of BCG immunization in New York City. Am Rev Tuberc 1948; 53:517.
  33. Brandt L, Feino Cunha J, Weinreich Olsen A, et al. Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis. Infect Immun 2002; 70:672.
  34. Baily GV. Tuberculosis prevention Trial, Madras. Indian J Med Res 1980; 72 Suppl:1.
  35. Tripathy SP. Fifteen year follow-up of the Indian BCG prevention trial. In: International Union Against Tuberculosis. Singapore: Professional Postgraduate Services KK, 1986.
  36. Hart PD, Sutherland I. BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Br Med J 1977; 2:293.
  37. Narayanan PR. Influence of sex, age & nontuberculous infection at intake on the efficacy of BCG: re-analysis of 15-year data from a double-blind randomized control trial in South India. Indian J Med Res 2006; 123:119.
  38. Pereira SM, Barreto ML, Pilger D, et al. 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. Lancet Infect Dis 2012; 12:300.
  39. Soysal A, Millington KA, Bakir M, et al. Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet 2005; 366:1443.
  40. Eisenhut M, Paranjothy S, Abubakar I, et al. BCG vaccination reduces risk of infection with Mycobacterium tuberculosis as detected by gamma interferon release assay. Vaccine 2009; 27:6116.
  41. Chan PC, Yang CH, Chang LY, et al. Lower prevalence of tuberculosis infection in BCG vaccinees: a cross-sectional study in adult prison inmates. Thorax 2013; 68:263.
  42. Roy A, Eisenhut M, Harris RJ, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta-analysis. BMJ 2014; 349:g4643.
  43. Marsh BJ, von Reyn CF, Edwards J, et al. The risks and benefits of childhood bacille Calmette-Guérin immunization among adults with AIDS. International MAC study groups. AIDS 1997; 11:669.
  44. Waddell RD, Lishimpi K, von Reyn CF, et al. Bacteremia due to Mycobacterium tuberculosis or M. bovis, Bacille Calmette-Guérin (BCG) among HIV- positive children and adults in Zambia. AIDS 2001; 15:55.
  45. 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 1996; 348:17.
  46. Rodrigues LC, Pereira SM, Cunha SS, et al. Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial. Lancet 2005; 366:1290.
  47. Hawkridge A, Hatherill M, Little F, et al. Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial. BMJ 2008; 337:a2052.
  48. Kemp EB, Belshe RB, Hoft DF. Immune responses stimulated by percutaneous and intradermal bacille Calmette-Guérin. J Infect Dis 1996; 174:113.
  49. Leung CC, Tam CM, Chan SL, et al. Efficacy of the BCG revaccination programme in a cohort given BCG vaccination at birth in Hong Kong. Int J Tuberc Lung Dis 2001; 5:717.
  50. Turnbull FM, McIntyre PB, Achat HM, et al. National study of adverse reactions after vaccination with bacille Calmette-Guérin. Clin Infect Dis 2002; 34:447.
  51. Kröger L, Korppi M, Brander E, et al. Osteitis caused by bacille Calmette-Guérin vaccination: a retrospective analysis of 222 cases. J Infect Dis 1995; 172:574.
  52. Brewer MA, Edwards KM, Palmer PS, Hinson HP. Bacille Calmette-Guérin immunization in normal healthy adults. J Infect Dis 1994; 170:476.
  53. Caglayan S, Yegin O, Kayran K, et al. Is medical therapy effective for regional lymphadenitis following BCG vaccination? Am J Dis Child 1987; 141:1213.
  54. Goraya JS, Virdi VS. Treatment of Calmette-Guérin bacillus adenitis: a metaanalysis. Pediatr Infect Dis J 2001; 20:632.
  55. Grange JM. Complications of bacille Calmette-Guérin (BCG) vaccination and immunotherapy and their management. Commun Dis Public Health 1998; 1:84.
  56. Cuello-García CA, Pérez-Gaxiola G, Jiménez Gutiérrez C. Treating BCG-induced disease in children. Cochrane Database Syst Rev 2013; 1:CD008300.
  57. Segal S, Pollard AJ, Watts C, et al. Osteomyelitis of the humerus complicating BCG vaccination. Arch Dis Child 2006; 91:244.
  58. von Reyn CF. Routine childhood bacille Calmette Guérin immunization and HIV infection. Clin Infect Dis 2006; 42:559.
  59. Talbot EA, Perkins MD, Silva SF, Frothingham R. Disseminated bacille Calmette-Guérin disease after vaccination: case report and review. Clin Infect Dis 1997; 24:1139.
  60. Hesseling AC, Cotton MF, Fordham von Reyn C, et al. Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants. Int J Tuberc Lung Dis 2008; 12:1376.
  61. Hesseling AC, Rabie H, Marais BJ, et al. Bacille Calmette-Guérin vaccine-induced disease in HIV-infected and HIV-uninfected children. Clin Infect Dis 2006; 42:548.
  62. Nuttall JJ, Davies MA, Hussey GD, Eley BS. Bacillus Calmette-Guérin (BCG) vaccine-induced complications in children treated with highly active antiretroviral therapy. Int J Infect Dis 2008; 12:e99.
  63. Hong DN, Huyen MN, Lan NT, et al. Rifampin-resistant Mycobacterium bovis BCG-induced disease in HIV-infected infant, Vietnam. Emerg Infect Dis 2013; 19:1168.
  64. Hesseling AC, Schaaf HS, Hanekom WA, et al. Danish bacille Calmette-Guérin vaccine-induced disease in human immunodeficiency virus-infected children. Clin Infect Dis 2003; 37:1226.
  65. Ninane J, Grymonprez A, Burtonboy G, et al. Disseminated BCG in HIV infection. Arch Dis Child 1988; 63:1268.
  66. Centers for Disease Control (CDC). Disseminated Mycobacterium bovis infection from BCG vaccination of a patient with acquired immunodeficiency syndrome. MMWR Morb Mortal Wkly Rep 1985; 34:227.
  67. Lumb R, Shaw D. Mycobacterium bovis (BCG) vaccination. Progressive disease in a patient asymptomatically infected with the human immunodeficiency virus. Med J Aust 1992; 156:286.
  68. Pentel P, O'Connell MB. The pressor effect of phenylpropanolamine. JAMA 1989; 262:2386.
  69. Wells CL, Jechorek RP, Twiggs LB, Brooker DC. Recovery of viable bacteria from pelvic lymph nodes of patients with gynecologic tumors. J Infect Dis 1990; 162:1216.
  70. Puthanakit T, Oberdorfer P, Punjaisee S, et al. Immune reconstitution syndrome due to bacillus Calmette-Guérin after initiation of antiretroviral therapy in children with HIV infection. Clin Infect Dis 2005; 41:1049.
  71. Menzies R, Vissandjee B. Effect of bacille Calmette-Guérin vaccination on tuberculin reactivity. Am Rev Respir Dis 1992; 145:621.
  72. WHO Weekly Epidemiological Record 23 January 2004; 79:27. http://www.who.int/wer.
  73. Lutwama F, Kagina BM, Wajja A, et al. Distinct T-cell responses when BCG vaccination is delayed from birth to 6 weeks of age in Ugandan infants. J Infect Dis 2014; 209:887.
  74. 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. Tuber Lung Dis 1994; 75:179.
  75. Hersh AL, Tala-Heikkilä M, Tala E, et al. A cost-effectiveness analysis of universal versus selective immunization with Mycobacterium bovis bacille Calmette-Guérin in Finland. Int J Tuberc Lung Dis 2003; 7:22.
  76. Fine P. Stopping routine vaccination for tuberculosis in schools. BMJ 2005; 331:647.
  77. O'Brien KL, Ruff AJ, Louis MA, et al. Bacillus Calmette-Guérin complications in children born to HIV-1-infected women with a review of the literature. Pediatrics 1995; 95:414.
  78. Muram D. Labial adhesions in sexually abused children. JAMA 1988; 259:352.
  79. Lallemant-Le Coeur S, Lallemant M, Cheynier D, et al. Bacillus Calmette-Guérin immunization in infants born to HIV-1-seropositive mothers. AIDS 1991; 5:195.
  80. WHO Weekly Epidemiological Record 25 May 2007; 82:181. Available at: http://www.who.int/wer.
  81. 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 Recomm Rep 1996; 45:1.
  82. Felten MK, Leichsenring M. Use of BCG in high prevalence areas for HIV. Trop Med Parasitol 1995; 46:69.
  83. Dara M, Acosta CD, Rusovich V, et al. Bacille Calmette-Guérin vaccination: the current situation in Europe. Eur Respir J 2014; 43:24.
  84. Brewer TF, Colditz GA. Bacille Calmette-Guérin vaccination for the prevention of tuberculosis in health care workers. Clin Infect Dis 1995; 20:136.
  85. Brewer TF, Heymann SJ, Krumplitsch SM, et al. Strategies to decrease tuberculosis in us homeless populations: a computer simulation model. JAMA 2001; 286:834.
  86. Cobelens FG, van Deutekom H, Draayer-Jansen IW, et al. Risk of infection with Mycobacterium tuberculosis in travellers to areas of high tuberculosis endemicity. Lancet 2000; 356:461.