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.

Ane Bærent Fisker, Henrik Ravn, Amabelia Rodrigues, Marie Drivsholm Østergaard, Carlito Bale, Christine Stabell Benn, Peter Aaby

Journal: Vaccine 2014;32(5):598-605

PMID: 24325827

Full Text on Elsevier Science View on PubMed

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).

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.

Address: 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: [email protected].; 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: [email protected].; Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: [email protected].; Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: [email protected].; Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: [email protected].; 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: [email protected].; 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: [email protected].

DOI: 10.1016/j.vaccine.2013.11.074

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MeSH Terms: Diphtheria-Tetanus-Pertussis Vaccine, Female, Guinea-Bissau, Haemophilus Vaccines, Hepatitis B Vaccines, Humans, Immunization Schedule, Infant, Male, Measles Vaccine, Mortality, Proportional Hazards Models, Randomized Controlled Trials as Topic, Vaccination, Vaccines, Inactivated, Vitamin A, Yellow Fever Vaccine