title: Contrasting female-male mortality ratios after routine vaccinations with pentavalent vaccine versus measles and yellow fever vaccine. A cohort study from urban Guinea-Bissau.
abstract: In addition to protection against the target diseases, vaccines may have non-specific effects (NSEs). Measles vaccine (MV) has beneficial NSEs, providing protection against non-measles deaths, most so for girls. By contrast, though protecting against diphtheria, tetanus and pertussis, DTP vaccine is associated with increased female mortality relative to male mortality. In 2008, Guinea-Bissau replaced DTP with the DTP-containing pentavalent vaccine (Penta; DTP-H. influenza type B-Hepatitis B) at 6, 10 and 14weeks and yellow fever vaccine (YF) was to be given with MV. We investigated possible sex-differential mortality rates following Penta and MV+YF vaccination.
  
  
  
  Bandim Health Project (BHP) registers vaccines given by the three government health centres in the study area and vital status through demographic surveillance. We assessed the association between sex and mortality by vaccination status in Cox proportional hazards models with age as underlying timescale. Follow-up was censored at a subsequent vaccination contact or after 6months of follow-up.
  
  
  
  Between September 2008 and April 2011, we registered 23,448 vaccination contacts for children aged 42-365days; 17,313 were for Penta and 3028 for MV (2907 co-administered with YF). During follow-up 112 children died. The female/male mortality rate ratio was 1.73 (1.11-2.70) following Penta and 0.38 (0.12-1.19) after MV (p=0.02 for same effect). Adjusting for maternal education or weight-for-age at the time of vaccination did not change the estimates.
  
  
  
  Penta appears to have the same negative effects on mortality as those seen for DTP. Assessing post-vaccination mortality for boys and girls is necessary to improve the vaccination programme.
authors.affiliation: 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; OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, 5000 Odense C, Denmark. Electronic address: a.fisker@bandim.org.
authors.forename: Ane B
authors.initials: AB
authors.lastname: Fisker
authors.affiliation: 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: s.biering@bandim.org.
authors.forename: Sofie
authors.initials: S
authors.lastname: Biering-Sørensen
authors.affiliation: 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: najaaraq.lund@gmail.com.
authors.forename: Najaaraq
authors.initials: N
authors.lastname: Lund
authors.affiliation: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: q.djana@gmail.com.
authors.forename: Queba
authors.initials: Q
authors.lastname: Djana
authors.affiliation: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: a.rodrigues@bandim.org.
authors.forename: Amabelia
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: Bandim Health Project, INDEPTH Network, Apartado 861, Bissau, Guinea-Bissau. Electronic address: c.martins@bandim.org.
authors.forename: Cesario L
authors.initials: CL
authors.lastname: Martins
authors.affiliation: Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark; OPEN, Institute of Clinical Research, University of Southern Denmark/Odense University Hospital, 5000 Odense C, Denmark. Electronic address: cb@ssi.dk.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Benn
mesh_terms: D002648:Child; D046688:Child Mortality; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006169:Guinea-Bissau / Q000453:epidemiology; D018073:Haemophilus Vaccines / Q000009:adverse effects* / Q000627:therapeutic use; D017325:Hepatitis B Vaccines / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D017589:Immunization Programs; D007223:Infant; D008297:Male; D008458:Measles Vaccine / Q000009:adverse effects* / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011897:Random Allocation; D012737:Sex Factors; D012744:Sex Ratio; D016019:Survival Analysis; D022341:Yellow Fever Vaccine / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D008458:Measles Vaccine; D022341:Yellow Fever Vaccine; C122182:diphtheria-tetanus-acellular pertussis-Hib-hepatitis B vaccine
keywords: Measles vaccine; Mortality; Non-specific/heterologous effects of vaccines; Pentavalent vaccine; Sex-difference