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

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.

Association Between Haematological Parameters and Sickle Cell Genotypes in Children With Plasmodium Falciparum Malaria Residents in Kisumu County in Western Kenya

“…However, we did not nd any signi cant association between both HbAS and HbSS with P. falciparum infection. A study in Uganda involving both children and adults revealed that both HbAS and HbSS were associated with reduced non-severe malaria outcomes (28). The difference in our results in reference to other studies could be attributed to the fact that we only used children (1-192 months) strati ed into infected and non-infected groups.…”

“…It is therefore imperative to determine the association between the haematological parameters and sickle cell genotypes in Plasmodium falciparum malaria infection because these haematological parameters determine the occurrence of various sickle cell crises as demonstrated by vaso-occlusion (3,27). However, few studies in East Africa and none in Kenya has been undertaken to elucidate the association of these haematological parameters and sickle cell genotypes in P. falciparum infection (28). Recently, a retrospective study involving patients with severe malaria in Cameroon did not nd any signi cant association between these parameters and SCD (29), however, leucocytosis and thrombocytosis have been previously reported to drive sickle cell crises (27,30).…”

Association between haematological parameters and sickle cell genotypes in children with Plasmodium falciparum malaria residents in Kisumu County in western Kenya

“…However, we did not nd any signi cant association between both HbAS and HbSS with P. falciparum infection. A study in Uganda involving both children and adults revealed that both HbAS and HbSS were associated with reduced non-severe malaria outcomes (28). The difference in our results in reference to other studies could be attributed to the fact that we only used children (1-192 months) strati ed into infected and noninfected groups.…”

A novel population of memory‐activated natural killer cells associated with low parasitaemia in Plasmodium falciparum‐exposed sickle‐cell trait children

“…Whereas the homodimerisation of mutated HbS is responsible for the sickle‐cell disease, which is characterised by a chronic haemolytic anaemia, no severe conditions are associated with the sickle‐cell trait phenotype (HbAS). On the contrary, it is well established that individuals carrying the heterozygous form HbAS are relatively protected from malaria 1,2 . Specifically, HbAS individuals display a reduced mortality to Plasmodium falciparum ( Pf ) infection, 3 a reduced parasitaemia during symptomatic malaria 1,4‐8 and a delayed onset of malaria, 8,9 as compared with HbAA individuals.…”