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Causes of variation in BCG vaccine efficacy : examining evidence from the BCG REVAC cluster randomized trial to explore the masking and the blocking hypotheses . BCG protection varies and in some places ( nearest the equator ) is low or absent . Understanding this variation can inform the efforts to develop new vaccines against tuberculosis . Two main hypotheses are used to explain this variation : under masking , new vaccines are unlikely to increase protection ; under blocking new vaccines have a greater potential to be effective when BCG is not . We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second ( revaccination ) time at school age in two sites ( Manaus close and Salvador further south from the equator ) . Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine ( BCG vaccination at school age ) or control group . Protection by first BCG vaccination at school age was high in Salvador ( 34 % , 95 % CI 7-53 % , p=0.017 ) but low in Manaus ( 8 % , 95 % CI t0 39-40 % , p=0.686 ) . For revaccination at school age , protection was modest in Salvador ( 19 % , 95 % CI 3-33 % , p=0.022 ) and absent in Manaus ( 1 % , 95 % CI to 27-23 % , p=0.932 ) . Vaccine efficacy for neonatal vaccination was similar in Salvador ( 40 % , 95 % CI 22-54 % , p < 0.001 ) and Manaus ( 36 % , 95 % CI 11-53 % , p=0.008 ) . Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth , which points towards blocking as the dominant mechanism . New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective .
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Intervention_Pharmacological
BCG vaccine
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Intervention_Pharmacological
BCG vaccine
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Intervention_Pharmacological
BCG vaccination
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Intervention_Control
control group
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Intervention_Pharmacological
BCG vaccination
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Intervention_Pharmacological
BCG
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Outcome_Other
efficacy :
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Outcome_Physical
protection ;
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Outcome_Physical
Protection by first BCG vaccination
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Outcome_Mental
revaccination at school age
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Outcome_Other
Vaccine efficacy
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Outcome_Other
Variation in BCG efficacy
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Participant_Age
school age
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Participant_Sample-size
239,934
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Participant_Age
children