Sex-based differences in clearance of chronic Plasmodium falciparum infection

Jessica Briggs, Noam Teyssier, Joaniter I Nankabirwa, John Rek, Prasanna Jagannathan, Emmanuel Arinaitwe, Teun Bousema, Chris Drakeley, Margaret Murray, Emily Crawford, Nicholas Hathaway, Sarah G Staedke, David Smith, Phillip J Rosenthal, Moses Kamya, Grant Dorsey, Isabel Rodriguez-Barraquer, Bryan Greenhouse, Jessica Briggs, Noam Teyssier, Joaniter I Nankabirwa, John Rek, Prasanna Jagannathan, Emmanuel Arinaitwe, Teun Bousema, Chris Drakeley, Margaret Murray, Emily Crawford, Nicholas Hathaway, Sarah G Staedke, David Smith, Phillip J Rosenthal, Moses Kamya, Grant Dorsey, Isabel Rodriguez-Barraquer, Bryan Greenhouse

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.

Conflict of interest statement

JB, NT, JN, JR, PJ, EA, TB, CD, MM, EC, NH, SS, DS, PR, MK, GD, BG No competing interests declared, IR Reviewing editor, eLife

© 2020, Briggs et al.

Figures

Figure 1.. Study design.
Figure 1.. Study design.
Figure 2.. Estimates of duration of infection…
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 (*).

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