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

Background Pertussis is frequently reported to be more common in females than in males. However, the variability of the sources of these observations makes it difficult to estimate the magnitude and consistency of the sex differences by age. To address this question, we used meta-analytic methods to analyze pertussis national incidence rates by sex and age group from nine countries between the years 1990 and 2017. Methods For each age group, we used meta-analytic methods to combine the female to male incidence rate ratios (RRs) by country and year. Meta-regression was performed to assess the relative contributions of age, country and time-period to the variation in the incidence RRs. Results The pooled female to male incidence RRs (with 95% CI) for ages 0-1, 1-4, 5-9 and 10-14, were 1.03 (1.01-1.06), 1.16 (1.14-1.17), 1.18 (1.15-1.22), 1.15 (1.11-1.18) respectively. For the ages 15-44, 45-64 and 65+ they were 1.65 (1.58-1.72), 1.59 (1.53-1.66), 1.20 (1.16-1.24), respectively. While there were some differences between the countries, the directions were consistent. When including age, country and time in meta-regression analyses, almost all the variation could be attributed to the differences between the age groups. Conclusions The consistency of the excess pertussis incidence rates in females, particularly in infants and very young children, is unlikely to be due to differences in exposure. Other factors that impact on the immune system, including chromosomal differences and hormones, should be further investigated to explain these sex differences. Future studies should consider sex for better understanding the mechanisms affecting disease incidence, with possible implications for management and vaccine development.