Sex-based differences in clearance of chronic Plasmodium falciparum infection

Abstract

Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a malaria endemic area of eastern Uganda and estimated both force of infection (FOI) and rate of clearance using amplicon deep-sequencing. We found no evidence of differences in behavioral risk factors, incidence of malaria, or FOI by sex. In contrast, females cleared asymptomatic infections at a faster rate than males (hazard ratio [HR]=1.82, 95% CI 1.20 to 2.75 by clone and HR = 2.07, 95% CI 1.24 to 3.47 by infection event) in multivariate models adjusted for age, timing of infection onset, and parasite density. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.

Trial registration: ClinicalTrials.gov NCT02909218 NCT03789448.

Keywords: P. falciparum; amplicon deep sequencing; asymptomatic malaria infection; duration of infection; epidemiology; global health; infectious disease; microbiology; molecular epidemiology; sex-based differences.

Figure 1.. Study design.

Figure 2.. Estimates of duration of infection from sex- and age-adjusted model.

Estimated duration of infection in days, calculated by adjusting the point estimate of the baseline hazard by the coefficients of the sex- and age-adjusted model. Error bars represent standard errors of duration obtained from variance in the model coefficients. Point estimates of duration are labeled (*).