Sex-based differences in clearance of chronicPlasmodium falciparuminfection

Abstract

Background: Multiple studies have reported a higher prevalence of malaria infection in males compared to females. However, it remains unknown whether this is due to differences in behavioral factors or biological sex playing a direct role in the host response to the malaria parasite. Methods and Findings: To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed a cohort of individuals living in a malaria endemic area of eastern Uganda. By performing frequent sampling, ultrasensitive quantitative PCR (qPCR), and amplicon deep sequencing, we followed P. falciparum infections over time to estimate both force of infection (FOI) and rate of clearance by sex. Prevalence of malaria infection by qPCR was 14.4% in males versus 9.2% in females (difference 5.2%, 95% confidence interval [CI] 3.8% to 6.5%). There was 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. Conclusions: In this study, differences in P. falciparum prevalence between males and females observed in endemic settings were driven by faster clearance rates in females and not by increased infection rates in males. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.

Decreasing Trend of Plasmodium Falciparum and Vivax Transmission in Mojo Health Center, East Shoa Oromia Region, Ethiopia: a Retrospective Study

“…Moreover, hormonal differences might play the role in such a way that testosterone was associated with decreased adaptive immunity against malaria [53]. Briggs and the colleagues have also thought that females cleared their infections at a faster rate than males [54] which might support the lower prevalence of malaria among females in the current study.…”

Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study

“…For each experiment, between 60-80 Anopheles gambiae ss mosquitoes were offered heparinised venous blood (Vacutainer Lithium Heparin Tube 4 mL; BD Biosciences, Plymouth, UK) via two glass feeders filled with 0•5 mL of blood each. 18 10 days after feeding, mosquitoes were dissected in 0•5% mercurochrome using a stereo microscope, and examined for the presence of oocysts on the mosquito midgut under an optic microscope by two microscopists (JO and AM); P falciparum DNA (18S) was detected in infected guts by nested PCR. To assess parasite diversity over the entire follow-up period, DNA from study participants and infected mosquito midguts was analysed by amplicon deep sequencing of the apical membrane antigen 1 (AMA-1) gene, as described previously.…”

Spotlight on Three Rs Progress

“…A cohort study that followed individuals in a malaria endemic region has suggested that females clear asymptomatic malaria infections faster than males, and this could have an impact on approaches to eliminate the disease. 1…”

“…A better understanding of host–parasite interactions, and how sex influences them, particularly in terms of the immune responses that result in asymptomatic infection, could help to optimise malaria eradication measures. Briggs et al 1 studied a population of 477 individuals (233 males and 244 females), living in malaria endemic regions. To detect the onset of new infections and track infections over time, frequent sampling was combined with molecular techniques (ultrasensitive quantitative PCR (qPCR) and amplicon deep-sequencing) to genotype parasite clones.…”