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

Vaccine. 2014 Jan 23;32(5):598-605. doi: 10.1016/j.vaccine.2013.11.074. Epub 2013 Dec 8.


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).

Conclusion: 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.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage*
  • Diphtheria-Tetanus-Pertussis Vaccine / adverse effects
  • Female
  • Guinea-Bissau
  • Haemophilus Vaccines / administration & dosage*
  • Haemophilus Vaccines / adverse effects
  • Hepatitis B Vaccines / administration & dosage*
  • Hepatitis B Vaccines / adverse effects
  • Humans
  • Immunization Schedule
  • Infant
  • Male
  • Measles Vaccine / administration & dosage*
  • Measles Vaccine / adverse effects
  • Mortality*
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Vaccination
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / adverse effects
  • Vitamin A / administration & dosage
  • Yellow Fever Vaccine / administration & dosage*
  • Yellow Fever Vaccine / adverse effects


  • Diphtheria-Tetanus-Pertussis Vaccine
  • DtwP-HepB-Hib vaccine
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Measles Vaccine
  • Vaccines, Inactivated
  • Yellow Fever Vaccine
  • Vitamin A