Thomas Nørrelykke Nissen1, Nina Marie Birk2, Jesper Kjærgaard3, Lisbeth Marianne Thøstesen4, Gitte Thybo Pihl5, Thomas Hoffmann6, Dorthe Lisbeth Jeppesen7, Poul-Erik Kofoed8, Gorm Greisen9, Christine Stabell Benn10, Peter Aaby11, Ole Pryds12, Lone Graff Stensballe13. 1. Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: thomas.nissen@dadlnet.dk. 2. Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: ninabirk@dadlnet.dk. 3. The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Jesper.Kjaergaard@regionh.dk. 4. Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark. Electronic address: lmje@dadlnet.dk. 5. Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark. Electronic address: Gitte.Thybo.Pihl@rsyd.dk. 6. Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: thoffmann@dadlnet.dk. 7. Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: Dorthe.Lisbeth.Jeppesen@regionh.dk. 8. Department of Pediatrics, Kolding Hospital, Skovvangen 2-8, DK-6000 Kolding, Denmark. Electronic address: Poul.Erik.Kofoed@rsyd.dk. 9. The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Gorm.Greisen@regionh.dk. 10. Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: cb@ssi.dk. 11. Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. Electronic address: p.aaby@bandim.org. 12. Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: pryds@dadlnet.dk. 13. The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Lone.graff.stensballe@regionh.dk.
Abstract
OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age. SETTING:Pediatric and maternity wards at three Danish university hospitals. PARTICIPANTS: All women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 toBCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions. MAIN OUTCOME AND MEASURE: Trial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. RESULTS: Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value <0.001). CONCLUSIONS AND RELEVANCE: BCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications. TRIAL REGISTRATION: Trial registration number NCT01694108 at www.clinicaltrials.gov.
RCT Entities:
OBJECTIVE: To evaluate adverse reactions of the Bacillus Calmette-Guérin (BCG) Statens Serum Institut (SSI) (Danish strain 1331) used as intervention in a randomized clinical trial. DESIGN: A randomized clinical multicenter trial, The Danish Calmette Study, randomizing newborns to BCG or no intervention. Follow-up until 13 months of age. SETTING: Pediatric and maternity wards at three Danish university hospitals. PARTICIPANTS: All women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred and eighty four families consented to participate and 4262 children, gestational age 32 weeks and above, were randomized: 2129 to BCG vaccine and 2133 to no vaccine. None of the participants withdrew because of adverse reactions. MAIN OUTCOME AND MEASURE: Trial-registered adverse reactions after BCG vaccination at birth. Follow-up at 3 and 13 months by telephone interviews and clinical examinations. RESULTS: Among the 2118 BCG-vaccinated children we registered no cases of severe unexpected adverse reaction related to BCG vaccination and no cases of disseminated BCG disease. Two cases of regional lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value <0.001). CONCLUSIONS AND RELEVANCE: BCG vaccination was associated with only mild morbidity and no mortality. A higher incidence of suppurative lymphadenitis than expected was observed. All children were treated conservatively without sequelae or complications. TRIAL REGISTRATION: Trial registration number NCT01694108 at www.clinicaltrials.gov.
Authors: Katia Abarca; Emma Rey-Jurado; Natalia Muñoz-Durango; Yaneisi Vázquez; Jorge A Soto; Nicolás M S Gálvez; Javier Valdés-Ferrada; Carolina Iturriaga; Marcela Urzúa; Arturo Borzutzky; Jaime Cerda; Luis Villarroel; Victoria Madrid; Pablo A González; José V González-Aramundiz; Susan M Bueno; Alexis M Kalergis Journal: EClinicalMedicine Date: 2020-10-06
Authors: T N Nissen; N M Birk; B A Blok; R J W Arts; A Andersen; J Kjærgaard; L M Thøstesen; T Hoffmann; D L Jeppesen; S D Nielsen; P-E Kofoed; L G Stensballe; P Aaby; M Ruhwald; M G Netea; C S Benn; O Pryds Journal: Eur J Clin Microbiol Infect Dis Date: 2017-09-10 Impact factor: 3.267
Authors: Nina Marie Birk; Thomas Nørrelykke Nissen; Jesper Kjærgaard; Hans Jacob Hartling; Lisbeth Marianne Thøstesen; Poul-Erik Kofoed; Lone Graff Stensballe; Andreas Andersen; Ole Pryds; Mihai G Netea; Christine Stabell Benn; Susanne Dam Nielsen; Dorthe Lisbeth Jeppesen Journal: Sci Rep Date: 2017-09-29 Impact factor: 4.379