Evidence map›Paper›PMID 37719417›Full record

ArticleEClinicalMedicine2023

Bacillus Calmette-Guérin vaccination for protection against recurrent herpes labialis: a nested randomised controlled trial.

Laure F Pittet, Cecilia L Moore, Ellie McDonald, Simone Barry, Marc Bonten, John Campbell, Julio Croda, Margareth Dalcolmo, Andrew Davidson, Mark W Douglas and 18 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.0field-weighted citation impact, top 22% of its field
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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
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

28 authors at 18 institutions in 7 countries.

Laure F PittetInfectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Cecilia L MooreDepartment of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
Ellie McDonaldInfectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Simone BarryPrecision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Marc BontenJulius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, the Netherlands.
John CampbellExeter Collaboration for Academic Primary Care, University of Exeter Medical School, Exeter, United Kingdom.
Julio CrodaFiocruz Mato Grosso do Sul, Fundação Oswaldo Cruz, Campo Grande, Brazil.
Margareth DalcolmoHelio Fraga Reference Center, Oswaldo Cruz Foundation Ministry of Health, Curicica, Brazil.
Andrew DavidsonMelbourne Children's Trial Centre, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Mark W DouglasStorr Liver Centre, The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales, Australia.
Kaya GardinerInfectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Amanda GweeInfectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Bruno JardimInstitute of Clinical Research Carlos Borborema, Doctor Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil.
Marcus V G LacerdaInstitute of Clinical Research Carlos Borborema, Doctor Heitor Vieira Dourado Tropical Medicine Foundation, Manaus, Brazil.
Michaela LucasDepartment of Immunology, Pathwest, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.
David J LynnPrecision Medicine Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
Laurens ManningSchool of Medicine, University of Western Australia, Perth, Western Australia, Australia.
Roberto D de OliveiraNursing Course, State University of Mato Grosso do Sul, Dourados, Brazil.
Kirsten P PerrettDepartment of Paediatrics, The University of Melbourne, Parkville, Victoria, Australia.
Cristina Prat-AymerichJulius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, the Netherlands.
Peter C RichmondDepartment of Immunology and General Paediatrics, Perth Children's Hospital, Nedlands, Western Australia, Australia.
Jorge L RochaHelio Fraga Reference Center, Oswaldo Cruz Foundation Ministry of Health, Curicica, Brazil.
Jesus Rodriguez-BañoDivision of Infectious Diseases and Microbiology, Department of Medicine, Hospital Universitario Virgen Macarena, University of Seville, Biomedicines Institute of Seville-Consejo Superior de Investigaciones Científicas, Seville, Spain.
Adilia WarrisMedical Research Council Centre for Medical Mycology, University of Exeter, Exeter, United Kingdom.
Nicholas J WoodFaculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Nicole L MessinaInfectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Nigel CurtisInfectious Diseases Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
BRACE Trial Consortium Group
Royal Children's Hospital · AUThe Kids Research Institute Australia · AUThe University of Melbourne · AUUniversity of Exeter · GBFundação de Medicina Tropical · BRMurdoch Children's Research Institute · AUThe University of Sydney · AUUniversidade Federal da Grande Dourados · BRMinistério da Saúde · BRThe University of Western Australia · AUUniversity of Geneva · CHFlinders University · AUPontifícia Universidade Católica do Rio de Janeiro · BRRoyal Adelaide Hospital · AUUniversidade Federal de Mato Grosso do Sul · BRUniversitat Autònoma de Barcelona · ESInstituto de Salud Carlos III · ESUtrecht University · NL

Funding

Medical Research Council MR/V033417/1
6 · The paper itself

Abstract

Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2-8 x 10 Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27-2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32-0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69-3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26-0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3-2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the 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, and individual donors.

Indexed as

Bacille Calmette-GuérinCold soreHerpes labialisHerpes simplex virusHeterologous immunityMycobacterium bovisNon-specific effectsOff-target effectsPreventionSecondary prophylaxis

Identifiers

PMID37719417
PMCPMC10500555
OpenAlexW4386617876

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.