Sex-based differences in clearance of chronic Plasmodium falciparum infection

Elife. 2020 Oct 27:9:e59872. doi: 10.7554/eLife.59872.


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: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Chronic Disease / epidemiology
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Malaria, Falciparum / epidemiology*
  • Malaria, Falciparum / parasitology*
  • Male
  • Middle Aged
  • Plasmodium falciparum / physiology*
  • Prevalence
  • Sex Factors
  • Uganda / epidemiology
  • Young Adult

Associated data