Background Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. Methods/Findings We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Limitations Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. Conclusions/Significance All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration should be given to prevention effectiveness of BCG preparations.
References
[1]
Colditz GA, Brewer TF, Berkey CS, Wilson ME, Burdick E, et al. (1994) Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of published literature. JAMA 271: 698–702.
[2]
Comstock GW (2000) Simple, practical ways to assess the protective efficacy of a new tuberculosis vaccine. Clin Infect Dis 30: Suppl 3S250–253.
[3]
Romanus V (1987) Tuberculosis in bacillus Calmette-Guérin immunized and non-immunized children in Sweden: a ten years evaluation following cessation of general bacillus Calmette-Guérin immunization of the newborn in 1975. Pediatr Infect Dis J 6: 272–280.
[4]
Hart PD, Sutherland I (1977) BCG and vole bacillus vaccine in the prevention of tuberculosis in adolescence and early adult life. Br Med J 2(6082): 293–5.
[5]
Tuberculosis Research Centre (ICMR), Chennai (1999) Fifteen year follow up of trial of BCG vaccines in south India for tuberculosis prevention. Indian J Med Res 110: 56–69.
[6]
Clemens JD, Chuong JJ, Feinstein AR (1983) The BCG controversy. A methodological and statistical reappraisal. JAMA 249: 2362–2369.
[7]
Padungchan S, Konjanart S, Kasiratta S, Daramas S, ten Dam HG (1986) The effectiveness of BCG vaccination of the newborn against childhood tuberculosis in Bangkok. Bull World Health Organ 64: 247–258.
[8]
Tidjani O, Amedome A, ten Dam HG (1986) The protective effect of BCG vaccination of the newborn against childhood tuberculosis in an African community. Tubercle 67: 269–281.
[9]
World Health Organization (2011) WHO-UNICEF Estimates of Immunization Coverage: the Republic of Kazakhstan, 2011. Available: http://apps.who.int/immunization_monitor？ing/en/globalsummary/timeseries/tswucove？ragebycountry.cfm?country=KAZ.
[10]
National Center for Tuberculosis (2007) [Ismailov SS, Baimukhanova KX, Belinskaya GD, Tursynbaeva GS, eds.] Annual tuberculosis statistical review, Republic of Kazakhstan [in Russian]. Almaty, Kazakhstan: Etamp Asia Publishers, 2007. [and annual editions of this report from 2002–2006].
[11]
Agency of Statistics of the Republic of Kazakhstan (2011) Multiple websites; Available: http://www.stat.kz/digital/naselsenie/Pa？ges/default.aspx.
[12]
Smith PG, Morrow RH, editors. (1996) Field Trials of Health Interventions in Developing Countries. A Toolbox. 2nd edition. London: Macmillan Education Limited.
[13]
Shapiro C, Cook N, Evans D, Willett W, Fajardo I, et al. (1985) A case-control study of BCG and childhood tuberculosis in Cali, Colombia. Int J Epidemiol 14: 441–446.
[14]
Sirinavin S, Chotpitayasunondh T, Suwanjutha S, Sunakorn P, Chantarojanasiri T (1991) Protective efficacy of neonatal Bacillus Calmette-Guérin vaccination against tuberculosis. Pediatr Infect Dis J 10: 359–365.
[15]
Comstock GW (1994) Field trials of tuberculosis vaccines: how could we have done them better? Control Clin Trials 15: 247–276.
[16]
von Reyn CF (2006) Routine childhood Bacillus Calmette-Guérin immunization and HIV infection. Clin Infect Dis 42: 559–561.
[17]
Fine PE (1988) BCG vaccination against tuberculosis and leprosy. Br Med Bull 44: 691–703.
[18]
Rodrigues LC, Diwan VK, Wheeler JG (1993) Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol 22: 1154–1158.
[19]
Fine PE (2001) BCG: the challenge continues. Scand J Infect Dis 33: 243–245.
[20]
Delogu G, Fadda G (2009) The quest for a new vaccine against tuberculosis. J Infect Dev Ctries 3: 5–15.
[21]
Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, et al. (1999) Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 284: 1520–1523.
[22]
Brosch R, Gordon SV, Garnier T, Eiglmeier K, Frigui W, et al. (2007) Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci USA 104: 5596–5601.
[23]
Ritz N, Dutta B, Donath S, Casalaz D, Connell TG, et al. (2012) The influence of Bacille Calmette-Guérin vaccine strain on the immune response against tuberculosis. Am J Respir Crit Care Med 185: 213–222.
[24]
Svenson S, K？llenius G, Pawlowski A, Hamasur B (2010) Towards new tuberculosis vaccines. Hum Vaccin 6: 309–317.
[25]
Russell DG, Barry CE 3rd, Flynn JL (2010) Tuberculosis: What we don't know can, and does, hurt us. Science 328: 852–856.
