title: Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau.
abstract: BACKGROUND
  Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar negative effects.
  
  
  METHODS
  In 2007-2011, we conducted a randomised placebo-controlled trial of vitamin A at routine vaccination contacts among children aged 6-23 months in urban and rural Guinea-Bissau. In the present study, we included 2331 children randomised to placebo who received live vaccines only (MV or MV+YF) or a combination of live and inactivated vaccines (MV+DTP or MV+YF+pentavalent). Mortality was compared in Cox proportional hazards models stratified for urban/rural enrolment adjusted for age and unevenly distributed baseline factors.
  
  
  RESULTS
  While DTP was still used 685 children received MV only and 358 MV+DTP; following the change in programme, 940 received MV+YF only and 348 MV+YF+pentavalent. During 6 months of follow-up, the adjusted mortality rate ratio (MRR) for co-administered live and inactivated vaccines compared with live vaccines only was 3.24 (1.20-8.73). For MV+YF+pentavalent compared with MV+YF only, the adjusted MRR was 7.73 (1.79-33.4).
  
  
  CONCLUSIONS
  In line with previous studies of DTP, the present results indicate that pentavalent vaccine co-administered with MV and YF is associated with increased mortality.
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Electronic address: a.fisker@bandim.org.
authors: Ane Bærent
authors: AB
authors: Fisker
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Electronic address: hjn@ssi.dk.
authors: Henrik
authors: H
authors: Ravn
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: a.rodrigues@bandim.org.
authors: Amabelia
authors: A
authors: Rodrigues
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: mariedrivsholm@gmail.com.
authors: Marie Drivsholm
authors: MD
authors: Østergaard
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: c.bale@bandim.org.
authors: Carlito
authors: C
authors: Bale
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Electronic address: cb@ssi.dk.
authors: Christine Stabell
authors: CS
authors: Benn
authors: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau; Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Electronic address: p.aaby@bandim.org.
authors: Peter
authors: P
authors: Aaby
mesh_terms: D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006169:Guinea-Bissau; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D008458:Measles Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D009026:Mortality; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects; D014801:Vitamin A / Q000008:administration & dosage; D022341:Yellow Fever Vaccine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; C524361:DtwP-HepB-Hib vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D008458:Measles Vaccine; D015164:Vaccines, Inactivated; D022341:Yellow Fever Vaccine; D014801:Vitamin A
keywords: BCG; BHP; Bacillus Calmette–Guérin vaccine; Bandim Health Project; Child mortality; DTP; Diphtheria–tetanus–pertussis vaccine; EPI; Expanded Programme on Immunisations; HDSS; MRR; MV; Measles vaccine; OPV; Pentavalent vaccine; YF; Yellow fever vaccine; diphtheria–tetanus–pertussis vaccine; health and demographic surveillance system; measles vaccine; mortality rate ratio; oral polio vaccine; yellow fever vaccine