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

  • Kakande, Elijah1
  • Greenhouse, Bryan2
  • Bajunirwe, Francis3
  • Drakeley, Chris4
  • Nankabirwa, Joaniter I.1
  • Walakira, Andrew1
  • Nsobya, Samuel L.1
  • Katureebe, Agaba1
  • Rek, John1
  • Arinaitwe, Emmanuel1
  • Rosenthal, Philip J.2
  • Kamya, Moses R.1
  • Dorsey, Grant2
  • Rodriguez-Barraquer, Isabel2
  • 1 Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, Kampala, Uganda , Kampala (Uganda)
  • 2 University of California, San Francisco, CA, 94110, USA , San Francisco (United States)
  • 3 Mbarara University of Science and Technology, Mbarara, Uganda , Mbarara (Uganda)
  • 4 London School of Hygiene & Tropical Medicine, Keppel Street, London, WC1E 7HT, UK , London (United Kingdom)
Published Article
Malaria Journal
Springer (Biomed Central Ltd.)
Publication Date
Jan 15, 2020
DOI: 10.1186/s12936-020-3105-3
Springer Nature


BackgroundMultiple 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.MethodsData 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.ResultsIn 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).ConclusionRBC 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.

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