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

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.

A multi-country, multi-year, meta-analytic evaluation of the sex differences in age-specific pertussis incidence rates

“…The meta-regression results revealed that among the variables, age group contributed almost all the variation in the incidence RRs. The results of this study contrast with the perception that males suffer more than females from infectious diseases [13,31].…”

Sex differences in campylobacteriosis incidence rates at different ages - a seven country, multi-year, meta-analysis. A potential mechanism for the infection.

“…Our ndings considerably extend those from population-based studies in multiple or single countries (10)(11)(12) and provide age-speci c pooled estimates of the male to female IRR, while controlling for country and different timeperiods. We have used the same meta-analytic methods to combine data from various countries and time periods for other diseases and demonstrated a male predominance in viral meningitis and shigellosis in young children (13,14). On the other hand, the incidence rates for pertussis were higher in females at all ages (29).…”

Sex differences in campylobacteriosis incidence rates at different ages - a seven country, multi-year, meta-analysis. A potential mechanism for the infection.

“…Our findings considerably extend those from population-based studies in multiple or single countries (9,10,25,26), by producing age-specific pooled estimates of the incidence rate ratio accounting for country and time-period. A male predominance has been reported in the incidence of certain other infectious diseases, mainly in children (27,28).…”