title: BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.
abstract: BACKGROUND
  Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected.
  
  
  OBJECTIVE
  We sought to describe the complications and risks associated with BCG vaccination in patients with SCID.
  
  
  METHODS
  An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed.
  
  
  RESULTS
  Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/μL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/μL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001).
  
  
  CONCLUSIONS
  BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Beatriz E
authors.initials: BE
authors.lastname: Marciano
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Chiung-Yu
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Gyan
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authors.lastname: Joshi
authors.affiliation: Pediatric Center of Excellence, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nima
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authors.lastname: Rezaei
authors.affiliation: Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Beatriz Costa
authors.initials: BC
authors.lastname: Carvalho
authors.affiliation: Immunology Department, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Allwood
authors.affiliation: Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey.
authors.forename: Aydan
authors.initials: A
authors.lastname: Ikinciogullari
authors.affiliation: Department of Pediatric Allergy and Immunology, Children's Hospital, Ain Shams University, Cairo, Egypt.
authors.forename: Shereen M
authors.initials: SM
authors.lastname: Reda
authors.affiliation: Paediatric Immunology Department, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew
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authors.lastname: Gennery
authors.affiliation: Department of Clinical Immunology and Allergy, Medical Faculty of Masaryk University, St Anne's University Hospital, Brno, Czech Republic.
authors.forename: Vojtech
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authors.lastname: Thon
authors.affiliation: National Institute of Pediatrics, Mexico City Federal District, Mexico City, Mexico.
authors.forename: Francisco
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authors.lastname: Espinosa-Rosales
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Kuwait University, Al-Sabah Hospital, Kuwait City, Kuwait.
authors.forename: Waleed
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authors.lastname: Al-Herz
authors.affiliation: Department of Immunology and Rheumatology, National Children's Hospital "Dr. Carlos Sáenz Herrera", San Jose, Costa Rica.
authors.forename: Oscar
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authors.lastname: Porras
authors.affiliation: Department of Clinical Immunology, Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Anna
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authors.lastname: Shcherbina
authors.affiliation: Department of Clinical Immunology and Transplantology, Children's University Hospital, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Szaflarska
authors.affiliation: Pediatric Immunology Division, Uludag University Medical Faculty, Bursa, Turkey.
authors.forename: Şebnem
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authors.affiliation: Primary Immunodeficiency Group, University of Antioquia, Medellin, Colombia.
authors.forename: Jose L
authors.initials: JL
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authors.affiliation: Immunology Unit, Children's Hospital Ricardo Gutierrez, Buenos Aires, Argentina.
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authors.initials: AC
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authors.affiliation: Faculty of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
authors.forename: Persio
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authors.lastname: Roxo
authors.affiliation: Primary Immunodeficiency Center, Lisbon Academic Center, Santa María Hospital, Lisbon, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Esteves
authors.affiliation: Cairo University, Cairo, Egypt.
authors.forename: Nermeen
authors.initials: N
authors.lastname: Galal
authors.affiliation: Faculty of Medicine of ABC, Santo André, São Paulo, Brazil.
authors.forename: Anete Sevciovic
authors.initials: AS
authors.lastname: Grumach
authors.affiliation: Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Salem
authors.initials: S
authors.lastname: Al-Tamemi
authors.affiliation: Department of Pediatric Immunology-Allergy, Ondokuz Mayis University, Atakum-Samsun, Turkey.
authors.forename: Alisan
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authors.lastname: Yildiran
authors.affiliation: Division of Allergy and Clinical Immunology, Santísima Trinidad Children's Hospital, Córdoba, Argentina.
authors.forename: Julio C
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authors.lastname: Orellana
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masafumi
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authors.lastname: Yamada
authors.affiliation: Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomohiro
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authors.lastname: Morio
authors.affiliation: Pediatric Immunology, Italian Hospital, Buenos Aires, Argentina.
authors.forename: Diana
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authors.lastname: Liberatore
authors.affiliation: Hyogo College of Medicine, Hyogo, Japan.
authors.forename: Yoshitoshi
authors.initials: Y
authors.lastname: Ohtsuka
authors.affiliation: Department of Pediatrics and Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Nishikomori
authors.affiliation: Department of Clinical Immunology and Allergology, Western National Medical Center, Guadalajara, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Torres-Lozano
authors.affiliation: Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Juliana T L
authors.initials: JT
authors.lastname: Mazzucchelli
authors.affiliation: Department of Pediatrics, Center for Investigation in Pediatrics-CIPED, University of Campinas Medical School-Unicamp, Campinas, SP, Brazil.
authors.forename: Maria M S
authors.initials: MM
authors.lastname: Vilela
authors.affiliation: Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Fabiola S
authors.initials: FS
authors.lastname: Tavares
authors.affiliation: Federal University of Minas Gerais, Minas Gerais, Brazil.
authors.forename: Luciana
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authors.lastname: Cunha
authors.affiliation: Federal University of Minas Gerais, Minas Gerais, Brazil.
authors.forename: Jorge A
authors.initials: JA
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authors.affiliation: National Institute of Pediatrics, Mexico City Federal District, Mexico City, Mexico.
authors.forename: Sara E
authors.initials: SE
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authors.affiliation: National Institute of Pediatrics, Mexico City Federal District, Mexico City, Mexico.
authors.forename: Leticia
authors.initials: L
authors.lastname: Hernandez-Nieto
authors.affiliation: Department of Pediatric Allergy and Immunology, Children's Hospital, Ain Shams University, Cairo, Egypt.
authors.forename: Reem A
authors.initials: RA
authors.lastname: Elfeky
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.affiliation: Department of Pediatrics, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Heike
authors.initials: H
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authors.affiliation: Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey.
authors.forename: Figen
authors.initials: F
authors.lastname: Dogu
authors.affiliation: Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey.
authors.forename: Funda
authors.initials: F
authors.lastname: Cipe
authors.affiliation: Charles University, and University Hospital Motol, Prague, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Formankova
authors.affiliation: Department of Clinical Immunology and Allergology, Western National Medical Center, Guadalajara, Mexico.
authors.forename: M Enriqueta
authors.initials: ME
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authors.affiliation: Immunology Unit, Children's Hospital Ricardo Gutierrez, Buenos Aires, Argentina.
authors.forename: Liliana
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authors.lastname: Bezrodnik
authors.affiliation: Primary Immunodeficiency Center, Lisbon Academic Center, Santa María Hospital, Lisbon, Portugal.
authors.forename: Jose Gonçalo
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authors.affiliation: Division of Allergy and Clinical Immunology, Santísima Trinidad Children's Hospital, Córdoba, Argentina.
authors.forename: María I
authors.initials: MI
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authors.affiliation: Division of Allergy and Clinical Immunology, Santísima Trinidad Children's Hospital, Córdoba, Argentina.
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authors.affiliation: Paediatric Immunology Department, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary A
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authors.affiliation: Paediatric Immunology Department, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Zohreh
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authors.lastname: Nademi
authors.affiliation: Department of Clinical Immunology and Transplantology, Children's University Hospital, Krakow, Poland.
authors.forename: Danuta
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authors.lastname: Kowalczyk
authors.affiliation: Immunology Service, DLM, CC, National Institutes of Health, Bethesda, Md.
authors.forename: Thomas A
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authors.lastname: Fleisher
authors.affiliation: Immunology Department, Great Ormond Street Hospital for Children, London, United Kingdom.
authors.forename: Graham
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authors.affiliation: Immunology-Hematology and Rheumatology Service, Necker Hospital, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Neven
authors.affiliation: Primary Immunodeficiency Clinic and Infectious Diseases Susceptibility Unit, LHD, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: srosenzweig@cc.nih.gov.
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mesh_terms: D001500:BCG Vaccine / Q000009:adverse effects* / Q000276:immunology; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D012306:Risk; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D014611:Vaccination / Q000009:adverse effects / Q000331:legislation & jurisprudence
chemical_list: D001500:BCG Vaccine
keywords: BCG; Primary immunodeficiency; hematopoietic stem cell transplant; immune reconstitution syndrome; mycobacteria; newborn screening; severe combined immunodeficiency; vaccine