Autor(es)
Afiliação
Resumo em Inglês
Background BCG vaccines are given to more than 100 million children every year, but there is considerable debate
regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older
children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on
tuberculosis (pulmonary and extrapulmonary) development and mortality. Methods In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of
Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts
published between Jan 1, 1998, and April 7, 2018. Search terms included “mycobacterium tuberculosis”, “TB”,
“tuberculosis”, and “contact”. We excluded cohort studies that did not provide information on BCG vaccination or
were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a
prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and
the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of
prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline)
tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis,
extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary,
multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest,
baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We
stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with
PROSPERO, CRD42020180512.. Findings We identified 14 927 original records from our database searches. We included participant-level data from
26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed
tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants).
The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74–0·91).
When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger
than 5 years (aOR 0·63, 95% CI 0·49–0·81). Among contacts with a positive tuberculin skin test or IFNγ release
assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI
0·69–0·96), participants younger than 5 years (0·68, 0·47–0·97), and participants aged 5–9 years (0·62, 0·38–0·99).
There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54,
0·32–0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG
vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in
41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70–0·94) but not
against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated
participants; 0·96, 0·65–1·41). In the four studies with mortality data, BCG vaccination was significantly protective
against death (0·25, 0·13–0·49). Interpretation Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children
but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations.
Editor
Elsevier
Referência
MARTINEZ, Leonardo et al. Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis. Lancet Glob Health, v. 10, e1307-16, p. 1 - 10, 2022.
ISSN
2214-109X
Notas
AUTOR - Ana Cristina Carvalho . Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Educação e Bioprodutos. Rio de Janeiro, RJ, Brasil.
AUTOR - Julia Croda. Fundação Oswaldo Cruz. Campo Grande, MS, Brasil / Universidade Federal do Mato Grosso do Sul. Campo Grande, MS, Brasil / Department of Epidemiology
of Microbial Diseases, Yale School of Public Health. New Haven, CT, USA.
OUTROS AUTORES:
Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J Fox, Anna Cristina C Carvalho, Pei-Chun Chan,
Julio Croda, Philip C Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M Graham, Marcos A Espinal, Beate Kampmann,
Arthur Reingold, Helena Huerga, Julian A Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu,
Christian Lienhardt, Justin T Denholm, James A Seddon, Christopher C Whalen, Alberto L García-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh,
Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena del Corral, Anna M Mandalakas, LaShaunda L Malone, Du-Lin Ling, Afrânio Kritski,
Catherine M Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos,
Anneke C Hesseling, Alexander Kay, Edward C Jones-López, C Robert Horsburgh, Christoph Lange, Jason R Andrews, Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J Fox, Anna Cristina C Carvalho, Pei-Chun Chan,
Julio Croda, Philip C Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M Graham, Marcos A Espinal, Beate Kampmann,
Arthur Reingold, Helena Huerga, Julian A Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu,
Christian Lienhardt, Justin T Denholm, James A Seddon, Christopher C Whalen, Alberto L García-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh,
Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena del Corral, Anna M Mandalakas, LaShaunda L Malone, Du-Lin Ling, Afrânio Kritski,
Catherine M Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos,
Anneke C Hesseling, Alexander Kay, Edward C Jones-López, C Robert Horsburgh, Christoph Lange, Jason R AndrewsLeonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J Fox, Anna Cristina C Carvalho, Pei-Chun Chan,
Julio Croda, Philip C Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M Graham, Marcos A Espinal, Beate Kampmann,
Arthur Reingold, Helena Huerga, Julian A Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu,
Christian Lienhardt, Justin T Denholm, James A Seddon, Christopher C Whalen, Alberto L García-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh,
Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena del Corral, Anna M Mandalakas, LaShaunda L Malone, Du-Lin Ling, Afrânio Kritski,
Catherine M Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos,
Anneke C Hesseling, Alexander Kay, Edward C Jones-López, C Robert Horsburgh, Christoph Lange, Jason R Andrews.Leonardo Martinez, Olivia Cords, Qiao Liu, Carlos Acuna-Villaorduna, Maryline Bonnet, Greg J Fox, Anna Cristina C Carvalho, Pei-Chun Chan,
Julio Croda, Philip C Hill, Elisa Lopez-Varela, Simon Donkor, Katherine Fielding, Stephen M Graham, Marcos A Espinal, Beate Kampmann,
Arthur Reingold, Helena Huerga, Julian A Villalba, Louis Grandjean, Giovanni Sotgiu, Uzochukwu Egere, Sarman Singh, Limei Zhu,
Christian Lienhardt, Justin T Denholm, James A Seddon, Christopher C Whalen, Alberto L García-Basteiro, Rina Triasih, Cheng Chen, Jitendra Singh,
Li-Min Huang, Surendra Sharma, Djohar Hannoun, Helena del Corral, Anna M Mandalakas, LaShaunda L Malone, Du-Lin Ling, Afrânio Kritski,
Catherine M Stein, Richa Vashishtha, Fadila Boulahbal, Chi-Tai Fang, W Henry Boom, Eduardo Martins Netto, Antonio Carlos Lemos,
Anneke C Hesseling, Alexander Kay, Edward C Jones-López, C Robert Horsburgh, Christoph Lange, Jason R Andrews.
AUTORES E AFILIAÇÕES:
Department of Epidemiology,
School of Public Health, Boston
University, Boston, MA, USA
(L Martinez PhD,
Prof C R Horsburgh MD); Center
for Animal Disease Modeling
and Surveillance, School of
Veterinary Medicine,
University of California, Davis,
Davis, CA, USA (O Cords MS);
Department of Chronic
Communicable Disease, Center
for Disease Control and
Prevention of Jiangsu Province,
Nanjing, China (Q Liu PhD,
L Zhu MSc, C Chen PhD); Section
of Infectious Diseases,
Department of Medicine,
Boston University Medical
Center, Boston, MA, USA
(C Acuna-Villaorduna MD);
Université de Montpellier, IRD,
INSERM, TransVIHMI,
Montpellier, France
(M Bonnet MD,
Prof C Lienhardt MD); Faculty of
Medicine and Health, The
University of Sydney,
Camperdown, NSW, Australia
(G J Fox PhD); Woolcock
Institute of Medical Research,
Glebe, NSW, Australia (G J Fox);
Laboratory of Innovations in
Therapies, Education and
Bioproducts, Oswaldo Cruz
Institute, Oswaldo Cruz
Foundation, Rio de Janeiro,
Brazil (A C C Carvalho MD);
Division of Chronic Infectious
Disease (P-C Chan MD) and
Taichung Regional Center
(D-L Ling MSc), Taiwan Centers
for Disease Control, Taipei,
Taiwan; Department of
Pediatrics, National Taiwan
University Hospital and National Taiwan University
College of Medicine, Taipei,
Taiwan (P-C Chan,
Prof L-M Huang MD); Institute
of Epidemiology and
Preventive Medicine, College of
Public Health, National Taiwan
University, Taipei, Taiwan
(P-C Chan, Prof C-T Fang MD);
Oswaldo Cruz Foundation
Mato Grosso do Sul, Campo
Grande, Brazil (Prof J Croda MD);
Federal University of Mato
Grosso do Sul, Campo Grande,
Brazil (Prof J Croda);
Department of Epidemiology
of Microbial Diseases, Yale
School of Public Health,
New Haven, CT, USA
(Prof J Croda); Centre for
International Health, Division
of Health Sciences, University
of Otago, Dunedin, New
Zealand (Prof P C Hill MD);
Centro de Investigação em
Saúde de Manhiça, Maputo,
Mozambique
(E Lopez-Varela MD,
A L García-Basteiro MD);
ISGlobal, Hospital Clínic,
Universitat de Barcelona,
Barcelona, Spain
(E Lopez-Varela,
A L García-Basteiro); Vaccines
and Immunity Theme, Medical
Research Council Unit The
Gambia, Banjul, The Gambia
(Prof B Kampmann PhD,
S Donkor MSc); Department of
Infectious Disease
Epidemiology, Faculty of
Epidemiology and Population
Health, London School of
Hygiene & Tropical Medicine,
London, UK (Prof K Fielding PhD,
Prof C Lienhardt); Centre for
International Health,
University of Melbourne
Department of Paediatrics and
Murdoch Children’s Research
Institute, Royal Children’s
Hospital, Melbourne, VIC,
Australia (Prof S M Graham MD);
Communicable Diseases and
Environmental Determinants
of Health, Pan American Health
Organization, Washington, DC,
USA (M A Espinal MD); Division
of Epidemiology, University of
California, Berkeley, Berkeley,
CA, USA (Prof A Reingold MD);
Epicentre, Paris, France
(H Huerga MD); Laboratorio de
Tuberculosis, Instituto de
Biomedicina, Universidad
Central de Venezuela, Caracas,
Venezuela (J A Villalba MD);
Department of Pathology,
Massachusetts General
Hospital, Harvard Medical
School, Boston, MA, USA. (J A Villalba); Department of
Infection, Inflammation and
Immunity, Institute of Child
Health, University College
London, London, UK
(L Grandjean MD); Clinical
Epidemiology and Medical
Statistics Unit, Department of
Medical, Surgical and
Experimental Sciences,
University of Sassari, Sassari,
Italy (Prof G Sotgiu MD);
Department of International
Public Health, Liverpool School
of Tropical Medicine, Liverpool,
UK (U Egere PhD); Department
of Microbiology
(Prof S Singh MD, J Singh PhD)
and Translational Medicine
Centre (J Singh), All India
Institute of Medical Sciences,
Bhopal, India; Victorian
Tuberculosis Program,
Melbourne Health, Melbourne,
VIC, Australia (J T Denholm MD);
Department of Infectious
Diseases, Peter Doherty
Institute for Infection and
Immunity, University of
Melbourne, Parkville, VIC,
Australia (J T Denholm);
Desmond Tutu TB Centre,
Department of Paediatrics and
Child Health, Stellenbosch
University, Cape Town, South
Africa (J A Seddon MD,
A C Hesseling MD); Department
of Epidemiology and
Biostatistics, College of Public
Health (Prof C C Whalen MD)
and Global Health Institute
(Prof C C Whalen), University of
Georgia, Athens, GA, USA;
Department of Pediatrics,
Faculty of Medicine, Public
Health and Nursing,
Universitas Gadjah Mada and
Dr. Sardjito Hospital,
Yogyakarta, Indonesia
(R Triasih PhD); Department of
Molecular Medicine, Jamia
Hamdard Institute of Molecular
Medicine, New Delhi, India
(Prof S Sharma MD);
Department of General
Medicine (Prof S Sharma) and
Department of Respiratory
Medicine (Prof S Sharma),
Jawaharlal Nehru Medical
College, Datta Meghe Institute
of Medical Sciences, Wardha,
India; Department of
Information, National Institute
of Public Health, Algiers,
Algeria (Prof D Hannoun MD);
Grupo de Inmunología Celulare
Inmunogenética, Facultad de
Medicina, Sede de
Investigación Universitaria
(H del Corral PhD) and Grupo de
Epidemiologıa (H del Corral),
Universidad de Antioquia,
Medellin, Colombia; The Global
TB Program, Texas Children’s
Hospital, Houston, TX, USA
(Prof A M Mandalakas MD,
A Kay MD); Department of
Pediatrics, Baylor College of
Medicine, Houston, TX, USA
(Prof A M Mandalakas, A Kay,
Prof C Lange MD); Uganda-
CWRU Research Collaboration,
Kampala, Uganda
(L L Malone MSPH,
C M Stein PhD,
Prof W H Boom MD);
Tuberculosis Academic
Program, Medical School,
Federal University of Rio de
Janeiro, Rio de Janeiro, Brazil
(Prof A Kritski PhD);
Tuberculosis Research Unit,
Case Western Reserve
University, Cleveland, OH, USA
(C M Stein, Prof W H Boom);
Department of Medicine,
University Hospitals Cleveland
Medical Center, Cleveland, OH,
USA (C M Stein, Prof W H Boom,
L L Malone); Groupe de
recherche sur la tuberculose
latente, Laboratoire National
de Référence pour la
Tuberculose, Institut Pasteur
d’Algérie, Algiers, Algeria
(F Boulahbal MD); Department
of Internal Medicine, National
Taiwan University Hospital,
Taipei, Taiwan (Prof C-T Fang);
Medicine Department,
University Hospital Professor
Edgard Santos, Federal
University of Bahia, Salvador,
Brazil (E M Netto MD,
Prof A C Lemos MD); Division of
Clinical Infectious Diseases,
Medical Clinic, Research Center
Borstel, Borstel, Germany
(Prof C Lange,
Prof A M Mandalakas);
Respiratory Medicine and
International Health,
University of Lübeck, Lübeck,
Germany (Prof C Lange);
Tuberculosis Unit, German
Center for Infection Research,
Borstel, Germany (Prof C Lange,
Prof A M Mandalakas); Division
of Infectious Diseases and
Geographic Medicine, Stanford
University School of Medicine,
Stanford, CA, USA
(J R Andrews MD); Department
of Laboratory Medicine and
Pathology, Mayo Clinic,
Rochester, MN, USA
(J A Villalba); Department of
Infectious Disease, Imperial
College London, London, UK
(J A Seddon); Centro de
Investigación Biomédica en Red
de Enfermedades Infecciosas.
Barcelona, Spain
(A L García-Basteiro);
Department of Internal
Medicine (R Vashishtha PhD)
and Department of Laboratory
Medicine (Prof S Singh, J Singh),
All India Institute of Medical
Sciences, New Delhi, India;
Division of Infectious Diseases,
Keck School of Medicine,
University of Southern
California, Los Angeles, CA, USA
(E C Jones-López MD); Medical
Science and Engineering
Research Centre, Indian
Institute of Science Education
and Research, Bhopal, India
(Prof S Singh)
Correspondence to:
Leonardo Martinez, Department
of Epidemiology, School of
Public Health, Boston University,
Boston, MA 02118, USA
leomarti@bu.edu
See Online for appendix.
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