Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study

Malar J. 2020 Jan 15;19(1):21. doi: 10.1186/s12936-020-3105-3.

Abstract

Background: Multiple red blood cell (RBC) variants appear to offer protection against the most severe forms of Plasmodium falciparum malaria. Associations between these variants and uncomplicated malaria are less clear.

Methods: Data from a longitudinal cohort study conducted in 3 sub-counties in Uganda was used to quantify associations between three red blood cell variants Hb [AA, AS, S (rs334)], alpha thalassaemia 3.7 kb deletion, and glucose-6-phosphate dehydrogenase deficiency A-(G6PD 202A genotype) and malaria incidence, parasite prevalence, parasite density (a measure of anti-parasite immunity) and body temperature adjusted for parasite density (a measure of anti-disease immunity). All analyses were adjusted for age, average household entomological inoculation rate, and study site. Results for all variants were compared to those for wild type genotypes.

Results: In children, HbAS was associated, compared to wild type, with a lower incidence of malaria (IRR = 0.78, 95% CI 0.66-0.92, p = 0.003), lower parasite density upon infection (PR = 0.66, 95% CI 0.51-0.85, p = 0.001), and lower body temperature for any given parasite density (- 0.13 ℃, 95% CI - 0.21, - 0.05, p = 0.002). In children, HbSS was associated with a lower incidence of malaria (IRR = 0.17, 95% CI 0.04-0.71, p = 0.02) and lower parasite density upon infection (PR = 0.31, 95% CI 0.18-0.54, p < 0.001). α-/αα thalassaemia, was associated with higher parasite prevalence in both children and adults (RR = 1.23, 95% CI 1.06-1.43, p = 0.008 and RR = 1.52, 95% CI 1.04-2.23, p = 0.03, respectively). G6PD deficiency was associated with lower body temperature for any given parasite density only among male hemizygote children (- 0.19 ℃, 95% CI - 0.31, - 0.06, p = 0.003).

Conclusion: RBC variants were associated with non-severe malaria outcomes. Elucidation of the mechanisms by which they confer protection will improve understanding of genetic protection against malaria.

Keywords: Erythrocyte; Malaria; Plasmodium; Red blood cell variants; Sickle hemoglobin; Thalassemia.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Binomial Distribution
  • Caregivers
  • Child
  • Child, Preschool
  • Cohort Studies
  • Erythrocytes / chemistry
  • Erythrocytes / classification
  • Erythrocytes / cytology*
  • Female
  • Humans
  • Incidence
  • Infant
  • Longitudinal Studies
  • Malaria / blood*
  • Malaria / epidemiology
  • Malaria / genetics
  • Malaria / parasitology
  • Male
  • Parasitemia / blood
  • Parasitemia / epidemiology
  • Parasitemia / genetics
  • Parasitemia / parasitology
  • Prevalence
  • Prospective Studies
  • Sex Factors
  • Uganda / epidemiology
  • Young Adult