Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

Paola Villanueva^{1

2

3

4}, Nigel W Crawford^{1

2

4

5}, Mariana Garcia Croda⁶, Simone Collopy⁷, Bruno Araújo Jardim⁸, Tyane de Almeida Pinto Jardim⁸, Laurens Manning^{9

10

11}, Michaela Lucas^{10

12

13

14}, Helen Marshall¹⁵, Cristina Prat-Aymerich^{16

17}, Alice Sawka¹⁸, Ketaki Sharma^{19

20}, Darren Troeman¹⁶, Ushma Wadia⁹, Adilia Warris^{21

22}, Nicholas Wood^{19

20

23}, Nicole L Messina^{1

2}, Nigel Curtis^{1

2

3}, Laure F Pittet^{1

2

3

24}

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
² Infection and Immunity, Murdoch Children's Research Institute, Parkville, VIC, Australia.
³ Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁴ Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁵ Immunisation Service, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁶ School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil.
⁷ Department of Pediatrics, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil.
⁸ Carlos Borborema Clinical Research Institute, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
⁹ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia.
¹⁰ School of Medicine, University of Western Australia, Perth, WA, Australia.
¹¹ Department of Infectious Diseases, Fiona Stanley Hospital, Perth, WA, Australia.
¹² Department of Immunology, Sir Charles Gairdner Hospital, Perth, WA, Australia.
¹³ Departments of Immunology, Perth Children's Hospital, Perth, WA, Australia.
¹⁴ Department of Immunology, Pathwest, QE2 Medical Centre, Perth, WA, Australia.
¹⁵ Robinson Research Institute and Adelaide Medical School, The University of Adelaide and Department of Paediatrics, The Women's and Children's Health Network, Australia.
¹⁶ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
¹⁷ Institut d'Investigació Germans Trias i Pujol, Departament de Genètica i Microbiologia, CIBER de enfermedades respiratorias (CIBERES), Instituto de Salud Carlos III, Universitat Autònoma de Barcelona, Catalunya, Badalona, Spain.
¹⁸ Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia.
¹⁹ National Centre for Immunisation Research and Surveillance, Westmead, NSW, Australia.
²⁰ The Children's Hospital at Westmead, Westmead, NSW, Australia.
²¹ Medical Research Council Centre for Medical Mycology, University of Exeter, UK.
²² Great Ormond Street Hospital, London, UK.
²³ The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
²⁴ Infectious Diseases Unit, Department of Paediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva and University Hospitals of Geneva, Geneva, Switzerland.

PMID: 37113782
PMCID: PMC10126857
DOI: 10.1016/j.heliyon.2023.e15241

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

Paola Villanueva et al. Heliyon. 2023.

. 2023 Apr 6;9(4):e15241.

doi: 10.1016/j.heliyon.2023.e15241. eCollection 2023 Apr.

Authors

Affiliations

¹ Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
² Infection and Immunity, Murdoch Children's Research Institute, Parkville, VIC, Australia.
³ Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁴ Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁵ Immunisation Service, Royal Children's Hospital Melbourne, Parkville, VIC, Australia.
⁶ School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil.
⁷ Department of Pediatrics, Universidade Estadual do Rio de Janeiro, Rio de Janeiro, Brazil.
⁸ Carlos Borborema Clinical Research Institute, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
⁹ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia.
¹⁰ School of Medicine, University of Western Australia, Perth, WA, Australia.
¹¹ Department of Infectious Diseases, Fiona Stanley Hospital, Perth, WA, Australia.
¹² Department of Immunology, Sir Charles Gairdner Hospital, Perth, WA, Australia.
¹³ Departments of Immunology, Perth Children's Hospital, Perth, WA, Australia.
¹⁴ Department of Immunology, Pathwest, QE2 Medical Centre, Perth, WA, Australia.
¹⁵ Robinson Research Institute and Adelaide Medical School, The University of Adelaide and Department of Paediatrics, The Women's and Children's Health Network, Australia.
¹⁶ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.
¹⁷ Institut d'Investigació Germans Trias i Pujol, Departament de Genètica i Microbiologia, CIBER de enfermedades respiratorias (CIBERES), Instituto de Salud Carlos III, Universitat Autònoma de Barcelona, Catalunya, Badalona, Spain.
¹⁸ Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia.
¹⁹ National Centre for Immunisation Research and Surveillance, Westmead, NSW, Australia.
²⁰ The Children's Hospital at Westmead, Westmead, NSW, Australia.
²¹ Medical Research Council Centre for Medical Mycology, University of Exeter, UK.
²² Great Ormond Street Hospital, London, UK.
²³ The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, NSW, Australia.
²⁴ Infectious Diseases Unit, Department of Paediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva and University Hospitals of Geneva, Geneva, Switzerland.

PMID: 37113782
PMCID: PMC10126857
DOI: 10.1016/j.heliyon.2023.e15241

Erratum in

Erratum: Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination.
Villanueva P, Crawford NW, Croda MG, Collopy S, Jardim BA, de Almeida Pinto Jardim T, Manning L, Lucas M, Marshall H, Prat-Aymerich C, Sawka A, Sharma K, Troeman D, Wadia U, Warris A, Wood N, Messina NL, Curtis N, Pittet LF. Villanueva P, et al. Heliyon. 2023 Apr 26;9(6):e15821. doi: 10.1016/j.heliyon.2023.e15821. eCollection 2023 Jun. Heliyon. 2023. PMID: 37484338 Free PMC article.

Abstract

The prevalence of scar formation following Bacille Calmette-Guérin (BCG) vaccination varies globally. The beneficial off-target effects of BCG are proposed to be stronger amongst children who develop a BCG scar. Within an international randomised trial ('BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers'; BRACE Trial), this nested prospective cohort study assessed the prevalence of and factors influencing scar formation, as well as participant perception of BCG scarring 12 months following vaccination . Amongst 3071 BCG-recipients, 2341 (76%) developed a BCG scar. Scar prevalence was lowest in Spain and highest in UK. Absence of post-injection wheal (OR 0.4, 95%CI 0.2-0.9), BCG revaccination (OR 1.7, 95%CI 1.3-2.0), female sex (OR 2.0, 95%CI 1.7-2.4), older age (OR 0.4, 95%CI 0.4-0.5) and study country (Brazil OR 1.6, 95%CI 1.3-2.0) influenced BCG scar prevalence. Of the 2341 participants with a BCG scar, 1806 (77%) did not mind having the scar. Participants more likely to not mind were those in Brazil, males and those with a prior BCG vaccination history. The majority (96%) did not regret having the vaccine. Both vaccination-related (amenable to optimisation) and individual-related factors affected BCG scar prevalence 12 months following BCG vaccination of adults, with implications for maximising the effectiveness of BCG vaccination.

Keywords: BCG scar; BCG vaccine; Vaccination technique; Vaccine safety.

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Figures

**Figure 1**
BCG scar description at 12 months. Representative photographs for BCG scar descriptions. (A) skin colour mark without redness (normal scar formation), (B) red mark, (C) red mark with crusting, (D) red mark with discharge, (E) purple mark, (F) inflamed appearance with surrounding swelling and/or redness, (G) abnormal thick scar.

**Figure 2**
BRACE participants who received BCG in A) Stage 1 and B) Stage 2. Abbreviations: BCG, Bacille Calmette-Guérin; BRACE trial, BCG vaccination to reduce the impact of coronavirus disease 2019 (COVID-19) in healthcare workers; dTpa, diphtheria-tetanus-acellular pertussis vaccine, reduced antigen formulation; 12MQ, 12-month questionnaire.

**Figure 3**
BCG scar prevalence at 12 months by recruitment country, with 95% confidence interval.

**Figure 4**
Scar prevalence by vaccinator, grouped by study country. Proportion of scar positive vaccinees at 12 months, per vaccinator. Each data point represents an individual vaccinator. Horizontal lines represent medians.

**Figure 5**
BCG scar perception at 12 months by study country.

See this image and copyright information in PMC

References

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Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

Affiliations

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

Authors

Affiliations

Erratum in

Abstract

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources