Consistent, Excess Viral Meningitis Incidence Rates in Young Males: A Multi-country, Multi-year, Meta-analysis of National Data. The Importance of Sex as a Biological Variable

Victoria Peer, Naama Schwartz, Manfred S. Green

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sex can be an important biological variable in the immune response to infections and the response to vaccines. The magnitude and consistency in age-specific sex differences in the incidence of viral infections remain unclear. Methods: We obtained data from national official agencies on cases of viral meningitis by sex and age group over a period of 6–16 years from five countries: Canada, Czech Republic, Germany, Israel, and Poland. Male to female incidence rate ratios (RR) were computed for each year, by country, and age group. For each age group, we used meta-analysis methodology to combine the incidence RRs. Meta-regression was conducted to the estimate the effects of age, country, and time period on the RR. Findings: In the age groups < 1, 1–4, 5–9, 10–14, there were consistently higher incidence rates in males, over countries and time. The pooled incidence RRs (with 95% CI) were 1.38 (1.30–1.47), 1.94 (1.85–2.03), 1.98 (1.88–2.07), and 1.58 (1.47–1.71) respectively. In young and middle-age adults there were no differences with pooled incidence RRs of 1.00 (0.97–1.03), and 0.97 (0.94–1.00), respectively. Sensitivity analysis confirms that the results are stable and robust. Meta-regression showed that almost all the variations in the incidence RRs were contributed by age group. Interpretation: The higher incidence rates from viral meningitis in males under the age of 15 are remarkably consistent across countries and time-periods. These findings emphasize the importance of sex as a biological variable in infectious diseases. This could provide keys to the mechanisms of infection and lead to more personalized treatment and vaccine doses and schedules. Funding: There was no funding source for this article.

Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalEClinicalMedicine
Volume15
DOIs
StatePublished - Oct 2019

Bibliographical note

Funding Information:
We would like to thank all the official institutions of all countries (Canada, Czech Republic, Germany, Israel, and Poland) for the publication of their national data on viral meningitis incidence and their willingness to share them with the world. VP participated in the conception and design of the study, acquisition of data, analysis and interpretation of the data and writing the manuscript. NS assisted in the data analysis and reviewed the manuscript. MSG designed and supervised the study, interpreted the data, helped in drafting the and revising the manuscript for important intellectual content. All authors approved the final version submitted. We declare no competing interests. There was no funding source for this study. Victoria Peer carried out this study as part of the requirements for the degree Doctor of Philosophy in the University of Haifa.

Publisher Copyright:
© 2018

Keywords

  • Incidence rates
  • Male excess
  • Metaanalysis
  • Sex differences
  • Viral meningitis

ASJC Scopus subject areas

  • Medicine (all)

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