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

Abstract

BackgroundSex 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. MethodsWe obtained data from national official agencies on cases of viral meningitis by sex and age group over a period of 6–16years 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. FindingsIn 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. InterpretationThe 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. FundingThere was no funding source for this article.