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dc.contributor.authorKakande, Elijah
dc.contributor.authorGreenhouse, Bryan
dc.contributor.authorBajunirwe, Francis
dc.contributor.authorDrakeley, Chris
dc.contributor.authorNankabirwa, Joaniter I.
dc.contributor.authorWalakira, Andrew
dc.contributor.authorNsobya, Samuel L.
dc.contributor.authorKatureebe, Agaba
dc.contributor.authorRek, John
dc.contributor.authorArinaitwe, Emmanuel
dc.contributor.authorRosenthal, Philip J.
dc.contributor.authorKamya, Moses R.
dc.contributor.authorDorsey, Grant
dc.contributor.authorBarraquer, Isabel Rodriguez
dc.identifier.citationKakande, E., Greenhouse, B., Bajunirwe, F., Drakeley, C., Nankabirwa, J. I., Walakira, A., ... & Rodriguez-Barraquer, I. (2020). Associations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort study. Malaria journal, 19(1), 1-9.en_US
dc.description.abstractBackground: 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.en_US
dc.description.sponsorshipNational Institute of Allergy and Infectious Diseases of the National Institute of Health as part of the International Centers of Excellence in Malaria Research (ICEMR) program (Grant Number: U19AI089674).en_US
dc.publisherMalaria Journalen_US
dc.subjectRed blood cell variantsen_US
dc.subjectSickle hemoglobinen_US
dc.titleAssociations between red blood cell variants and malaria among children and adults from three areas of Uganda: a prospective cohort studyen_US

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