Vaccine 32 (2014) 598–605 Contents lists available at ScienceDirect Vaccine j our nal homep ag e: www.elsevier.com/locate/vaccine 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 a,b,∗ , Henrik Ravn a,b , Amabelia Rodrigues a , Marie Drivsholm Østergaard a , Carlito Bale a , Christine Stabell Benn a,b , Peter Aaby a,b a Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau b Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark a r t i c l e i n f o Article history: Received 6 June 2013 Received in revised form 11 November 2013 Accepted 21 November 2013 Available online 8 December 2013 Keywords: Diphtheria–tetanus–pertussis vaccine Pentavalent vaccine Measles vaccine Yellow fever vaccine Child mortality a b s t r a c t 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. © 2013 Elsevier Ltd. All rights reserved. 1. Introduction The vaccination schedule in many low-income countries com- prises Bacillus Calmette–Guérin (BCG) and oral polio vaccine (OPV) Abbreviations: BCG, Bacillus Calmette–Guérin vaccine; BHP, Bandim Health Project; DTP, diphtheria–tetanus–pertussis vaccine; EPI, Expanded Programme on Immunisations; HDSS, health and demographic surveillance system; MRR, mortality rate ratio; MV, measles vaccine; OPV, oral polio vaccine; YF, yellow fever vaccine. ∗ Corresponding author at: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark. Tel.: +45 32 68 31 62; fax: +45 32 68 31 65. E-mail addresses: a.fisker@bandim.org (A.B. Fisker), hjn@ssi.dk (H. Ravn), a.rodrigues@bandim.org (A. Rodrigues), mariedrivsholm@gmail.com (M.D. Østergaard), c.bale@bandim.org (C. Bale), cb@ssi.dk (C.S. Benn), p.aaby@bandim.org (P. Aaby). at birth, 3 doses of whole-cell diphtheria–tetanus–pertussis (DTP) and OPV at 6, 10 and 14 weeks of age and measles vaccine (MV) at 9 months of age [1]. Vaccination coverage is normally assessed at 12 months of age [2]. The coverage for the third dose of DTP (DTP- 3) is the primary indicator of the performance of the vaccination programme [3,4]. Both observational studies [5,6] and randomised trials [7,8] indicate that the live BCG and MV are associated with much lower mortality than can be explained by prevention of tuber- culosis and measles infection; these vaccines reduce susceptibility to diseases unrelated to the targeted infection. In contrast, the inac- tivated DTP vaccine has been associated with increased mortality in areas with herd immunity to pertussis [9]. These effects beyond target disease protection have been called “non-specific effects”. According to the recommended vaccine schedule, DTP-3 is pro- vided more than 5 months before MV. However, vaccines are often given with delay and DTP is often co-administered with 0264-410X/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.vaccine.2013.11.074