Accelerated Bacille Calmette-Guérin reactions: More than meets the eye
Paola Villanueva,
Nigel W. Crawford,
Mariana Garcia Croda,
Julio Croda,
Margareth Dalcolmo,
Bruno Araújo Jardim,
Tyane de Almeida Pinto Jardim,
Helen Marshall,
Cristina Prat-Aymerich,
Alice Sawka,
Ketaki Sharma,
Darren Troeman,
Adilia Warris,
Nicholas Wood,
Nicole L. Messina,
Laure F. Pittet,
Nigel Curtis
Affiliations
Paola Villanueva
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Parkville, VIC, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, VIC, Australia; Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia; Corresponding author. Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
Nigel W. Crawford
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Parkville, VIC, Australia; Department of General Medicine, Royal Children's Hospital Melbourne, Parkville, VIC, Australia; Immunisation Service, Royal Children's Hospital Melbourne, Parkville, VIC, Australia
Mariana Garcia Croda
School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil
Julio Croda
School of Medicine, Federal University of Mato Grosso do Sul, Campo Grande, MS, Brazil; Oswaldo Cruz Foundation, Campo Grande, Mato Grosso do Sul, Brazil; Yale School of Public Health, New Haven, CT, USA
Margareth Dalcolmo
Helio Fraga Reference Center, Oswaldo Cruz Foundation Ministry of Health, Rio de Janeiro, Brazil
Bruno Araújo Jardim
Carlos Borborema Clinical Research Institute, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
Tyane de Almeida Pinto Jardim
Carlos Borborema Clinical Research Institute, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil
Helen Marshall
Robinson Research Institute and Adelaide Medical School, The University of Adelaide and Department of Paediatrics, The Women's and Children's Health Network, Australia
Cristina Prat-Aymerich
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands; 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, Badalona, Catalunya, Spain
Alice Sawka
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia
Ketaki Sharma
National Centre for Immunisation Research and Surveillance, Westmead, NSW, Australia; The Children's Hospital at Westmead, Westmead, NSW, Australia
Darren Troeman
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
Adilia Warris
Medical Research Council Centre for Medical Mycology, University of Exeter, UK; Great Ormond Street Hospital, London, UK
Nicholas Wood
National Centre for Immunisation Research and Surveillance, Westmead, NSW, Australia; The Children's Hospital at Westmead, Westmead, NSW, Australia; The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, NSW, Australia
Nicole L. Messina
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Parkville, VIC, Australia
Laure F. Pittet
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Parkville, VIC, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, VIC, Australia; Infectious Diseases Unit, Department of Paediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva and University Hospitals of Geneva, Geneva, Switzerland; Corresponding author. Infectious Diseases Unit, Department of Paediatrics, Gynaecology and Obstetrics, Faculty of Medicine, University of Geneva and University Hospitals of Geneva, Geneva, Switzerland.
Nigel Curtis
Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia; Infection, Immunity and Global Health, Murdoch Children's Research Institute, Parkville, VIC, Australia; Infectious Diseases, Royal Children's Hospital Melbourne, Parkville, VIC, Australia
An accelerated local injection site reaction following Bacille Calmette-Guérin (BCG) vaccination has been associated with underlying active tuberculosis (TB) in high TB-prevalence settings. The clinical significance of this accelerated BCG reaction in individuals without TB symptoms, particularly in low TB-prevalence countries, is unclear.Using safety surveillance data and baseline interferon-gamma release assays (IGRA) within an international randomised trial of BCG vaccination in healthcare workers (the BRACE trial), we aimed to determine the incidence, and investigate for clinical implications, of an accelerated BCG reaction in asymptomatic adults in low and high TB-prevalence settings.An accelerated BCG reaction occurred in 755/1984 (38 %) of BCG-vaccinees. Although more frequently painful, tender, erythematous and/or swollen within the first fourteen days of vaccination, compared with non-accelerated reactions, the majority of injection site reactions were mild and did not meet criteria for an adverse event.Prior mycobacterial exposure, through prior BCG vaccination (OR 2.46, 95%CI 1.93–3.13, p < 0.001) or latent TB infection (OR 4.17, 95%CI 1.16–14.93, p = 0.03), and female sex (OR 1.27, 95%CI 1.03–1.57, p = 0.02), were key determinants for the occurrence of an accelerated BCG reaction.The development of an accelerated local reaction to BCG vaccination in an individual without prior history of BCG vaccination, should prompt consideration of further investigations for potential underlying TB infection.
