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.

Five-Year Trend of Malaria Prevalence in Mojo Town, Central Ethiopia: Shifting Burden of the Disease and Its Implication for Malaria Elimination: A Retrospective Study

“…48 Moreover, hormonal differences might play the role in such a way that testosterone was associated with decreased adaptive immunity against malaria. 49 Briggs et al had thought that females cleared their infections at a faster rate than males, 50 which might support the lower prevalence of malaria among females in the current study.…”

Hyper-prevalence of submicroscopic Plasmodium falciparum infections in a rural area of western Kenya with declining malaria cases

“…With an odds ratio of 1:8 for detecting submicroscopic infection in males versus females, these observations were slightly higher than previously reported ratio of 1:4 in patients from low transmission zones within Belaga district of Malaysia [ 24 ]. The high levels of submicroscopic infections in female patients support findings that females have a higher rate of asexual stage parasite clearance than males [ 44 ]. Although few in numbers, children < 5 years had the highest percentage of submicroscopic infections than the rest of age groups.…”

Clustering of subpatent infections in households with asymptomatic rapid diagnostic test-positive cases in Bioko Island, Equatorial Guinea independent of travel to regions of higher malaria endemicity: a cross-sectional study

“…These factors may increase their cumulative exposure to malaria, which increases the likelihood they have built up a sufficient antibody response to control recent infections and keep parasite densities low [ 34 ]. Interestingly, a recent prospective analysis of P. falciparum infections in Uganda challenged this theory by showing that females cleared subpatent chronic infections twice as quickly as males [ 35 ]. Given that most data that compare subpatent and patent infections, including this study, come from cross-sectional studies, if there is a true difference in the rate of parasite clearance between males and females, it is possible that the increased risk reflects length-biased sampling instead of changes to the immune response.…”

“…While this measure has been used to evaluate imported infections in other settings [ 36 ], there are several limitations that should be considered. First, given that a P. falciparum infection, on average, takes 12 days to be detected in blood in malaria-exposed populations [ 37 ], and the average time to naturally clear an infection is estimated between 87 and 200 + days [ 35 ], recent travellers could experience either higher or lower density infections, depending on date of their return and the date they acquired the infection in relation to the time of the survey. In an attempt to account for this possibility, recent travel of the RDT(−) individuals was controlled for, but it is still possible that some imported infections were missed.…”