Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial

Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adul...

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Autores: Pittet, Laure F., Messina, Nicole L., McDonald, Ellie, Orsini, Francesca, Barry, Simone, Bonten, Marc, Campbell, John, Croda, Julio, Croda, Mariana G., Dalcolmo, Margareth, Gardiner, Kaya, Gwee, Amanda, Jardim, Bruno, Lacerda, Marcus V.G., Lucas, Michaela, Lynn, David J., Manning, Laurens, Fariñas Álvarez, María del Carmen, Gutiérrez Cuadra, Manuel, Arnáiz de las Revillas Almajano, Francisco|||0000-0002-0611-6309
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universidad de Cantabria (UC)
Repositorio:UCrea Repositorio Abierto de la Universidad de Cantabria
Idioma:inglés
OAI Identifier:oai:repositorio.unican.es:10902/36035
Acceso en línea:https://hdl.handle.net/10902/36035
Access Level:acceso abierto
Palabra clave:Bacille Calmette-Guérin (BCG) vaccine
Immunity
Heterologous
Health personnel
Randomised controlled trial
Primary prevention
Placebo
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network_name_str España
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dc.title.none.fl_str_mv Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
title Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
spellingShingle Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
Pittet, Laure F.
Bacille Calmette-Guérin (BCG) vaccine
Immunity
Heterologous
Health personnel
Randomised controlled trial
Primary prevention
Placebo
title_short Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
title_full Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
title_fullStr Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
title_full_unstemmed Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
title_sort Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trial
dc.creator.none.fl_str_mv Pittet, Laure F.
Messina, Nicole L.
McDonald, Ellie
Orsini, Francesca
Barry, Simone
Bonten, Marc
Campbell, John
Croda, Julio
Croda, Mariana G.
Dalcolmo, Margareth
Gardiner, Kaya
Gwee, Amanda
Jardim, Bruno
Lacerda, Marcus V.G.
Lucas, Michaela
Lynn, David J.
Manning, Laurens
Fariñas Álvarez, María del Carmen
Gutiérrez Cuadra, Manuel
Arnáiz de las Revillas Almajano, Francisco|||0000-0002-0611-6309
author Pittet, Laure F.
author_facet Pittet, Laure F.
Messina, Nicole L.
McDonald, Ellie
Orsini, Francesca
Barry, Simone
Bonten, Marc
Campbell, John
Croda, Julio
Croda, Mariana G.
Dalcolmo, Margareth
Gardiner, Kaya
Gwee, Amanda
Jardim, Bruno
Lacerda, Marcus V.G.
Lucas, Michaela
Lynn, David J.
Manning, Laurens
Fariñas Álvarez, María del Carmen
Gutiérrez Cuadra, Manuel
Arnáiz de las Revillas Almajano, Francisco|||0000-0002-0611-6309
author_role author
author2 Messina, Nicole L.
McDonald, Ellie
Orsini, Francesca
Barry, Simone
Bonten, Marc
Campbell, John
Croda, Julio
Croda, Mariana G.
Dalcolmo, Margareth
Gardiner, Kaya
Gwee, Amanda
Jardim, Bruno
Lacerda, Marcus V.G.
Lucas, Michaela
Lynn, David J.
Manning, Laurens
Fariñas Álvarez, María del Carmen
Gutiérrez Cuadra, Manuel
Arnáiz de las Revillas Almajano, Francisco|||0000-0002-0611-6309
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad de Cantabria
dc.subject.none.fl_str_mv Bacille Calmette-Guérin (BCG) vaccine
Immunity
Heterologous
Health personnel
Randomised controlled trial
Primary prevention
Placebo
topic Bacille Calmette-Guérin (BCG) vaccine
Immunity
Heterologous
Health personnel
Randomised controlled trial
Primary prevention
Placebo
description Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ?1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ?3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10902/36035
url https://hdl.handle.net/10902/36035
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv eClinicalMedicine, 2024, 72, 102616
reponame:UCrea Repositorio Abierto de la Universidad de Cantabria
instname:Universidad de Cantabria (UC)
instname_str Universidad de Cantabria (UC)
reponame_str UCrea Repositorio Abierto de la Universidad de Cantabria
collection UCrea Repositorio Abierto de la Universidad de Cantabria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Bacille Calmette-Guérin vaccination to prevent febrile and respiratory illness in adults (BRACE): secondary outcomes of a randomised controlled phase 3 trialPittet, Laure F.Messina, Nicole L.McDonald, EllieOrsini, FrancescaBarry, SimoneBonten, MarcCampbell, JohnCroda, JulioCroda, Mariana G.Dalcolmo, MargarethGardiner, KayaGwee, AmandaJardim, BrunoLacerda, Marcus V.G.Lucas, MichaelaLynn, David J.Manning, LaurensFariñas Álvarez, María del CarmenGutiérrez Cuadra, ManuelArnáiz de las Revillas Almajano, Francisco|||0000-0002-0611-6309Bacille Calmette-Guérin (BCG) vaccineImmunityHeterologousHealth personnelRandomised controlled trialPrimary preventionPlaceboBackground: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ?1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%-68.2%), compared with 63.4% in the control group (95% CI 61.8%-65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ?3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%-20.7%), compared with 18.8% in the control group (95% CI 17.4%-20.2%) a difference of +0.6 percentage points (95% CI -1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children’s Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donorsElsevierUniversidad de Cantabria20242024-01-01journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articlehttps://hdl.handle.net/10902/36035eClinicalMedicine, 2024, 72, 102616reponame:UCrea Repositorio Abierto de la Universidad de Cantabriainstname:Universidad de Cantabria (UC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositorio.unican.es:10902/360352026-06-02T12:39:31Z
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