Evidence map›Paper›PMID 39709975›Full record

SynthesisThe Lancet. Microbe2025

Effectiveness of the primary Bacillus Calmette-Guérin vaccine against the risk of Mycobacterium tuberculosis infection and tuberculosis disease: a meta-analysis of individual participant data.

Puck T Pelzer, Logan Stuck, Leonardo Martinez, Alexandra S Richards, Carlos Acuña-Villaorduña, Naomi E Aronson, Maryline Bonnet, Anna C Carvalho, Pei-Chun Chan, Li-Min Huang and 32 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
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  4. Review
  5. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

42 authors.

Puck T PelzerAmsterdam University Medical Centres, Amsterdam, Netherlands; KNCV Tuberculosis Foundation, The Hague, Netherlands; London School of Hygiene & Tropical Medicine, London, UK; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands. Electronic address: ppelzer@iavi.org.
Logan StuckAmsterdam University Medical Centres, Amsterdam, Netherlands; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.
Leonardo MartinezDepartment of Epidemiology, School of Public Health, Boston University, Boston, MA, USA.
Alexandra S RichardsLondon School of Hygiene & Tropical Medicine, London, UK.
Carlos Acuña-VillaorduñaBoston University Medical Center, Boston, MA, USA.
Naomi E AronsonUniformed Services University of the Health Sciences, Bethesda, MD, USA.
Maryline BonnetTransVIHMI, University of Montpellier, IRD, INSERM, Montpellier, France.
Anna C CarvalhoLaboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Pei-Chun ChanDivision of Chronic Infectious Disease, Taiwan Centers for Disease Control, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Li-Min HuangInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Chi-Tai FangDepartment of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Gavin ChurchyardAurum Institute, Johannesburg, South Africa; School of Public Health, University of the Witwatersrand, Johannesburg, South Africa; Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Helena Del Corral-LondoñoUniversidad de Antioquia, National School of Public Health, Medellin, Colombia.
Manjula DattaA Society for Primary Health Care Intervention, Research and Education, Chennai, India.
Marcos A EspinalNational Centre for Research on Maternal and Child Health, Santo Domingo, Dominican Republic.
Katherine FieldingLondon School of Hygiene & Tropical Medicine, London, UK; nfectious Disease Epidemiology Department, Epicentre, Paris, France.
Andrew J Fiore-GartlandFred Hutchinson Cancer Center, Seattle, WA, USA.
Alberto Garcia-BasteiroBarcelona Institute for Global Health, Barcelona, Spain.
Willem HanekomAfrica Health Research Institute, Durban, South Africa.
Mark HatherillSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Phillip C HillCentre for International Health, University of Otago, Dunedin, New Zealand.
Helena HuergaField Epidemiology Department, Epicentre, Paris, France.
Edward C Jones-LópezDivision of Infectious Diseases, Department of Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Afranio KritskiPrograma Acadêmico de Tuberculose, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Anna M MandalakasBaylor College of Medicine, Houston, TX, USA; Research Center Borstel, Sülfeld, Germany.
Punam MangtaniLondon School of Hygiene & Tropical Medicine, London, UK; nfectious Disease Epidemiology Department, Epicentre, Paris, France.
Eduardo Martins NettoFaculdade de Medicina da Bahia, Salvador, Brazil; Hospital Universitário Professor Edgard Santos, Salvador, Brazil; Universidade Federal da Bahia, Salvador, Brazil.
Harriet MayanjaMakerere University Infectious Diseases Institute, Kampala, Uganda.
Rufaida MazahirNehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Megan MurrayDepartment of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA.
Molebogeng RangakaInstitute for Global Health and MRC Clinical Trials Unit, University College London, London, UK.
Thomas ScribaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Jitendra SinghDepartment of Translational Medicine, All India Institute of Medical Sciences Bhopal, Madhya Pradesh, India.
Sarman SinghDepartment of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India; All India Institute of Medical Sciences, New Delhi, India; All India Institute of Medical Sciences, Bhopal, India; Aaarupadai Veedu Medical College, Pondicherry, India.
Catherine M SteinDepartment of Population and Quantitative Health Sciences, and Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Johan VekemansIAVI, New York, NY, USA.
Lilly M VerhagenDepartment of Pediatric Infectious Diseases and Immunology, Radboud Community for Infectious Diseases, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, Netherlands; Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, Netherlands; Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Julian A VillalbaLaboratorio de Tuberculosis, Instituto de Biomedicina, Universidad Central de Venezuela, Caracas, Venezuela; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Anne WajjaMakerere University Infectious Diseases Institute, Kampala, Uganda.
Basilea WatsonICMR-National Institute for Research in Tuberculosis, Chennai, India.
Richard G WhiteLondon School of Hygiene & Tropical Medicine, London, UK.
Frank G J CobelensAmsterdam University Medical Centres, Amsterdam, Netherlands; Department of Global Health and Amsterdam Institute for Global Health and Development, Amsterdam, Netherlands.

Funding

Aurum Clinical Trials UnitUM1AI154463 · NIAID · AURUM INSTITUTE NPC · PI Gavin John Churchyard · 2021 to 2026
$8.1M
Seattle Tuberculosis Research Advancement CenterP30AI168034 · NIAID · UNIVERSITY OF WASHINGTON · PI Rhea N Coler, CHETAN SESHADRI · 2022 to 2026
$6.3M
Quantifiable stool-based TB PCR to Improve Diagnostics and Treatment MonitoringR01AI137527 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI MANDALAKAS, ANNA M · 2019 to 2022
$2.7M
Defining drivers of TB transmission in the era of universal ART, and implications for finding the walking wellR01AI147321 · NIAID · LONDON SCH/HYGIENE & TROPICAL MEDICINE · PI GRANT, ALISON · 2019 to 2024
$2.3M
Bill & Melinda Gates Foundation INV-035506NIAID NIH HHS P30 AI168034NIAID NIH HHS R01 AI137527NIAID NIH HHS R01 AI147321NIAID NIH HHS UM1 AI154463Wellcome Trust
6 · The paper itself

Abstract

backgroundTuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

methodsWe conducted an individual participant data (IPD) meta-analysis on experimental and observational longitudinal studies before April 6, 2018, identified through systematic reviews, known to us through expert knowledge in the field, reporting on BCG vaccination status, M tuberculosis infection test (QuantiFERON IFN-γ release assay [IGRA] and tuberculin skin test [TST]), and tuberculosis incidence. Cohort studies were included only for countries with a mandatory neonatal BCG vaccination policy. Exclusion criteria were previous or current tuberculosis disease, HIV infection, tuberculosis preventive treatment usage, and for household contacts, a positive baseline IGRA or TST test and young children aged 0-2 years; for randomised controlled trials, TST results within 2 years after random assignation were excluded. We contacted the investigators of the identified studies to provide IPD. We compared the protective efficacy of the BCG vaccine against M tuberculosis infection with that against tuberculosis disease using mixed-effects, multivariable proportional hazards modelling, by study type, M tuberculosis infection test (IGRA and TST), cutoff for defining test positivity, age, sex, and latitude.

findingsWe identified 79 studies eligible for full screening and of these, IPD datasets from 14 studies were included in our analysis: 11 household contact studies (29 147 participants), two adolescent cohort studies (11 368 participants), and one randomised controlled trial (2963 participants). Among 28 188 participants we found no protection by the BCG vaccine against TST conversion regardless of cutoff in any type of study. Among 1491 household contacts, but not among 5644 adolescents, the BCG vaccine protected against QuantiFERON conversion at the primary cutoff of 0·7 IU/mL or more with the adjusted hazard ratio (0·65, 95% CI 0·51-0·82) being consistent with that for protection against disease (0·68, 0·18-2·59). Protection against QuantiFERON conversion at cutoff of 0·35 IU/mL or more (0·64, 0·51-0·81) was similar.

interpretationProtection from the BCG vaccination against M tuberculosis infection, measured as QuantiFERON conversion, is inconsistent across different groups. Among groups with recent household exposure, QuantiFERON conversion is consistent with protection against disease and could be evaluated as a proxy for disease in tuberculosis vaccine trials. We found that TST lacks value for prevention in phase 2b proof-of-concept trials.

fundingBill & Melinda Gates Foundation.

Indexed as

BCG VaccineMycobacterium tuberculosisTuberculosisAdolescentAdultChildChild, PreschoolFemaleHumansIncidenceInfantInterferon-gamma Release TestsLongitudinal StudiesMaleTuberculin TestVaccinationBCG Vaccine

Identifiers

PMID39709975
PMCPMC12778190

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.