Do Pentavalent (DTwP-Hib-HBV) vaccines have sex-differential nonspecific effects? An observational study

Hum Vaccin Immunother. 2023 Dec 15;19(3):2288297. doi: 10.1080/21645515.2023.2288297. Epub 2023 Dec 6.

Abstract

Vaccines may alter the ability to combat infections unrelated to the target disease, i.e. have "nonspecific effects." The non-live Diphtheria-Tetanus-Pertussis vaccine (DTP) has been associated with increased child mortality, especially for females. In 2008, the DTP-containing Pentavalent vaccine replaced DTP vaccine in Guinea-Bissau. We investigate female relative to male mortality after Penta vaccination. In Guinea-Bissau, Bandim Health Project (BHP) registered children's vaccination and vital status at biannual village visits and provided vaccines. Among children Penta-vaccinated by BHP, we compared mortality of males and females in Cox proportional hazards models. Children aged 6 weeks to 8 months entered the analysis at the date of vaccination and were followed for up to 6 months. Between September 2008 and December 2017, 33,989 children aged 6 weeks to 8 months were under surveillance. Of these 12,753 (females: 6,363; males: 6,390) received Penta by the BHP and entered the study contributing with 19,667 observations. The mortality rate following Penta vaccination was 25.2 per 1,000 person years for females and 26.6 for males, resulting in an adjusted Female/Male mortality rate ratio of (F/M aMRR) 1.01 (0.82-1.25). The association between sex and mortality differed by timeliness of vaccination, F/M aMRR: 0.62 (0.41-0.93) for children vaccinated below median age, and F/M aMRR: 1.38 (0.90-2.13) for children vaccinated above median age. We did not find higher overall mortality in females than males after Penta vaccination. Our findings suggest that mortality differences between males and females following Penta vaccination may depend on timeliness of Penta vaccination.

Keywords: Pentavalent vaccines; child mortality; nonspecific effects; sex-differential effects; vaccines.

Publication types

  • Observational Study

MeSH terms

  • Child Mortality
  • Diphtheria-Tetanus-Pertussis Vaccine* / adverse effects
  • Female
  • Haemophilus Vaccines* / adverse effects
  • Hepatitis B Vaccines* / adverse effects
  • Humans
  • Infant
  • Male
  • Sex Factors
  • Vaccination
  • Vaccines, Combined / adverse effects

Substances

  • Diphtheria-Tetanus-Pertussis Vaccine
  • Haemophilus Vaccines
  • Hepatitis B Vaccines
  • Vaccines, Combined

Grants and funding

This work was supported by the Independent Research Council Denmark (Grant no: 845-00083B), Aase og Ejnar Danielsens Fond (Grant no: N/A), Fonden til Lægevidenskabens Fremme (Grant no: N/A), Handelsgartner Ove William Buhl Olesen og ægtefælle fru Edith Buhl Olesens Mindelegat (Grant no: N/A), Else og Mogens Wedell Wedellsborg Fond (Grant no: N/A), Kong Christian IX og Dronning Louises Jubilæums Legat (Grant no: N/A). The Bandim Health Project HDSS received funding from University of Southern Denmark (Grant no: N/A), the Danish National Research Foundation (Grant no: DNRF108), and Karen Elise Jensens Fond (Grant no: N/A). ABFs research is supported through a Sapere Aude: DFF-Research leader grant from Independent Research Fund Denmark (Grant no: 9060-00018B) and an Ascending Investigator grant from Lundbeck Foundation (Grant no: R313-2019-635). SMT is funded by a grant from Region Hovedstadens Forskningsfond (Grant no: A7131). The funders had no role in study design, data collection, data analysis, or paper writing.