Sex differences in bacterial meningitis and associations with socioeconomic indicators: a systematic review and meta-analysis with metaregression.

Introduction We aimed to describe global sex-specific proportions and case fatality ratios of bacterial meningitis and to explore their associations with the Human Development Index (HDI) and Gender Inequality Index (GII). Methods Google Scholar and MEDLINE (via PubMed.gov) were searched in January 2022 using the terms "bacterial meningitis" and "mortality". Studies with a mean observation period after the year 1940 and reporting ≥10 patients with community-acquired bacterial meningitis and their survival status were included, irrespective of the participants' age. Studies that selected participants by specific risk factors, reported specific pathogens only, or had >10% missing outcomes were disregarded. Data were extracted by one researcher and validated by a second researcher. The main outcomes, sex-specific proportions and case fatality ratios, were analysed using random-effects models. Associations with HDI and GII were explored using metaregression. Results In this meta-analysis with metaregression, from 371 studies with 157 656 meningitis episodes, 217 (58%) reported the patients' sex and 41 (11%) reported sex-specific outcomes. Proportion of males was 58% (95% CI 57%-59%, prediction interval (PI) 45%-71%). Case fatality ratios were slightly higher in females (male-to-female fatality ratio, 0.89, 95% CI 0.78 to 1.01, PI 0.53-1.49). The size of the male proportion was strongly associated with HDI (per index point, -0.64, 95% CI -0.88 to -0.40; R2 16%; p<0.001) and GII (per index point, 0.61, 95% CI 0.39 to 0.83; R2 19%; p<0.001). Sex-specific case fatality ratios were weakly associated with HDI (per index point, 0.53, 95% CI -0.19 to 1.25; R2 2%; p=0.15) and GII (per index point, -0.58, 95% CI -1.55 to 0.39; R2 7%; p=0.24). Conclusion Based on worldwide reporting from the last 80 years, we show that indicators of human development and gender inequality are associated with sex-based disparities and case fatality ratios in bacterial meningitis.