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.
Highlights
Malaria, a protozoan infection of the red blood cells, remains one of the greatest global health challenges (World malaria report, 2019)
We show that females cleared their asymptomatic infections more rapidly than males, implicating biological sex-based differences as important in the host response to this globally important pathogen
Antimalarial use outside the study clinic was reported only four times (3 females and one male, all under the age of 5). In this region receiving regular rounds of indoor residual spraying (IRS), the incidence of symptomatic malaria was low in all age categories, and there was no evidence of a difference in incidence of symptomatic malaria by sex overall
Summary
A protozoan infection of the red blood cells, remains one of the greatest global health challenges (World malaria report, 2019). It is well established that chronic asymptomatic infection with Plasmodium falciparum, the most common and fatal malaria parasite, can lead to morbidity for those infected and contribute to ongoing transmission (Bousema et al, 2014; Okell et al, 2012; Tadesse et al, 2018; Slater et al, 2019). Characterization of these asymptomatic infections is paramount as they represent a major obstacle for malaria elimination efforts. While age-specific immunity to malaria in hyperendemic areas is well-
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