Penta is associated with an increased female-male mortality ratio: cohort study from Bangladesh

ABSTRACT

Diphtheria-tetanus-pertussis (DTP) vaccine may be associated with excess female deaths. There are few studies of possible nonspecific effects of the DTP-containing vaccine Penta (DTP-hepatitis B-Haemophilus influenzae type b). We therefore investigated whether Penta vaccinations were associated with excess female deaths in rural Bangladesh. Between June 29, 2011 and April 20, 2016, we examined the mortality rates of 7644 children followed between 6 weeks and 9 months of age. We analyzed mortality using crude mortality rate ratio (MRR) and age-adjusted MRR (aMRR) from a Cox proportional hazards model. Mortality was analyzed according to sex, number of doses of Penta, and the order in which BCG and Penta were administered. During follow-up, 43 children died. For children who were only BCG vaccinated (BCG-only), the adjusted F/M MRR was 0.47 (0.09–2.48). However, among children who had Penta as their most recent vaccination, the adjusted F/M MRR was 9.91 (1.16–84.44). Hence, the adjusted F/M MRR differed significantly for BCG-only and for Penta as the most recent administered vaccination. Although the mortality rate was low in rural Bangladesh, there was a marked difference between adjusted F/M MRR’s for children vaccinated with BCG-only compared with children where Penta was the most recent administered vaccination. Although usually ascribed to differential treatment and access to care, DTP-containing vaccines may be part of the explanation for the excessive female mortality reported in some regions.

KEYWORDS:

• Nonspecific/heterologous effects of vaccines
• mortality
• sex-differential effects
• BCG
• penta

Acknowledgments

icddr,b acknowledges with gratitude the commitment of the INDEPTH Network to its research efforts. icddr,b is also grateful to the Government of Bangladesh, Canada, Sweden, and the UK for providing core/unrestricted support. The authors are grateful to the villagers for their cooperation in providing invaluable information. The untiring efforts of the team members of the Chakaria HDSS in maintaining the surveillance system are gratefully acknowledged.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Author contributions

MAH, PA, and AB conceived and designed the study and are the guarantors of the study. MAH, SBS, and AKGJ analyzed the data. PA and AB supervised the data analysis. MAH wrote the first draft of the manuscript. All authors contributed to the final version of the manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis.

Data sharing

No additional data available

Transparency declaration

The first author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted and that any discrepancies from the study as planned have been explained.

Ethical approval

Ethical Review Committee of International Centre of Diarrhoeal Disease Research, Bangladesh provided approval for the study.

Additional information

Funding

This research protocol/activity/study was funded by International Network for the Demographic Evaluation of Populations and their Health (INDEPTH Network) (Grant number: IND/002/2013) through a grant from DANIDA.