human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 
    Output:
    