BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life. Bacille Calmette-Guérin vaccine-induced disease in HIV-infected and HIV-uninfected children. Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial Pathogenesis of tuberculosis and effectiveness of BCG vaccination. Quality control of BCG vaccine by WHO: a review of factors that may influence vaccine effectiveness and safety.
The Medical Research Council 's trial of BCG and vole bacillus vaccines in the prevention of  tuberculosis in Great Britain has ended after 20 years ' follow-up of the 54 239 participants , who were aged 14 to 15 years when the entered the trial in 1950 - 2 . Participants who were tuberculin positive on entry were left unvaccinated ; those who were tuberculin negative were allocated at r and om to an unvaccinated or to a vaccinated group . The protective efficacy of each of the two vaccines , among those initially tuberculin negative , was 84 % during the first five years , and gradually decreased , averaging 77 % for each vaccine over the whole period . The incidence of tuberculosis decreased substantially in all groups during the trial , however , and of the total of 610 cases of tuberculosis only 27 developed between 15 and 20 years . Thus we can not make a reliable assessment of efficacy during this final period . The prevalence and incidence of tuberculosis in Great Britain have decreased radically since this trial began . The expected benefit from large-scale BCG-vaccination of children is now far less , and may decrease further if the incidence of tuberculosis continues to decline BACKGROUND Bacille Calmette-Guérin (BCG)--a live , attenuated vaccine -- is routinely given to neonates in setting s where tuberculosis is endemic , irrespective of human immunodeficiency virus ( HIV ) exposure . HIV-infected infants and other immunodeficient infants are at risk of BCG-related complications . We report the presentation , treatment , and mortality of children who develop BCG disease , with emphasis on HIV-infected children . In addition , we present a revised classification of BCG disease in children and propose st and ard diagnostic and management guidelines . METHODS This retrospective , hospital-based study was conducted in the Western Cape Province , South Africa . Mycobacterium tuberculosis complex isolates recovered from children aged < 13 years during the period of August 2002 through January 2005 were speciated by polymerase chain reaction to confirm Mycobacterium bovis BCG . Clinical data were collected through medical file review . BCG disease was classified according to st and ard and revised disease classifications . Mortality was assessed at the end of the study period . RESULTS BCG disease was diagnosed in 25 children ; 22 ( 88 % ) had local disease , and 8 ( 32 % ) had distant or disseminated disease ; 5 children ( 20 % ) had both local and distant or disseminated disease . Seventeen children were HIV infected ; 2 children had other immunodeficiencies . All 8 children with distant or disseminated disease were immunodeficient ; 6 were HIV infected . The mortality rate was 75 % for children with distant or disseminated disease . CONCLUSIONS BCG vaccination poses a risk to infants perinatally infected with HIV and to other primary immunodeficient children . The proposed pediatric BCG disease classification reflects clinical ly relevant disease categories in HIV-infected children . The suggested diagnostic and treatment guidelines should improve existing case management and surveillance . Prospect i ve evaluation of management strategies for BCG disease in HIV-infected and HIV-uninfected children is essential BACKGROUND Many countries offer a second BCG vaccination to prevent tuberculosis , although there is little evidence of whether this confers additional protection . BCG vaccination is routine in Brazil but BCG revaccination procedures vary by state . We studied revaccination efficacy in two Brazilian cities with tuberculosis prevalence representative of Brazil . METHODS We did a cluster-r and omised trial of the protection against tuberculosis from BCG revaccination in school-aged children who had had one BCG vaccination as infants . 767 schools in the cities of Salvador and Manaus , Brazil , participated ; schools were the unit of r and omisation . The study was open label with no placebo . Cases of tuberculosis were identified through record linkage to the Tuberculosis Control Programme . Revaccination status was masked during linkage and validation of cases . The incidence of tuberculosis was the primary outcome . Analysis was by intention to treat . FINDINGS 386 schools ( 176,846 children ) were assigned BCG revaccination and 365 ( 171,293 children )  no revaccination .  42,053 children in the vaccine group and 47,006 in the control group were absent from school on the day of the visit and were excluded . 31,163 and 27,146 , respectively were also excluded because they had no BCG scar , two or more scars , or a doubtful scar on assessment . The crude incidence of tuberculosis in the intervention group was 29.3 per 100,000 person years and in the control group 30.2 per 100,000 person-years ( crude-rate ratio 0.97 ; 95 % CI 0.76 - 1.28 ) . The efficacy of BCG revaccination was 9 % ( -16 to 29 % ) . INTERPRETATION Revaccination given to children aged 7 - 14 years in this setting does not provide substantial additional protection and should not be recommended . Follow-up is ongoing and needed to assess the effect of other factors on revaccination efficacy : time since vaccination , age at vaccination , and high or low prevalence of environmental mycobacteria Among the hypotheses offered to explain the conflicting results of various trials of  BCG vaccination  , the one invoking gross differences in the immunogenic properties of the various BCG vaccines ( strains ) has received most attention . Indeed , for many years research in BCG vaccination has been directed almost entirely towards improving the quality of vaccines . the anticipated benefit of this work , however , is not borne out by the results of the latest trial in India . Whereas it can not be excluded that technological advances may have result ed in the worst vaccines ever , it also remains possible that the basic hypothesis was less relevant than presumed . the quality of the vaccine may be of little importance and a different explanation should be sought for the observed differences in protection . One possible lead is the observation that BCG vaccination consistently appeared to be of poor efficacy under conditions where , in a vaccination programme , even an effective vaccine would have little impact on the tuberculosis problem , i.e. where the majority of cases originated from the population already infected . The hypothesis offered is that in such population s the pathogenesis of tuberculosis is different from that prevailing under the clearly exceptional conditions under which BCG vaccination was effective . Rather than being the direct result of primary infection , tuberculous disease ( observed ) may be the result of reinfection . In this case BCG vaccination can not be expected to have a protective effect WHO oversees the quality control of BCG vaccine via a system that includes regular testing of products by in vitro methods and clinical trials . Three parent strains of BCG ( Glaxo-1077 , Tokyo-172 , and Pasteur-1173P2 )  account for over 90 % of the vaccines currently in use worldwide . Important characteristics of the vaccine preparations are summarized here , along with their physical-chemical properties . In instances where diagnostic criteria for tuberculosis are stringent , there is no evidence that when administered to newborns different preparations of BCG vaccine exhibit different efficacies ; however , the incidence of BCG-associated adverse reactions does correlate with the type of preparation . Other factors , including dose , administration technique , and recipient characteristics are also important in determining vaccine-associated reactions
OBJECTIVE The BCG vaccine has been in use since 1921 , but still arouses controversy and uncertainties .
The objective was to analyze the protective effect of the BCG vaccine in its first and second doses and the accompanying vaccination policies .