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

Abstract

Background: Sickle cell disease (SCD) is a monogenic disorder due to point mutation in the β-globin gene resulting in substitution of Valine for Glutamic acid. The SCD is prevalent in P. falciparum endemic regions such as western Kenya. Carriage of different sickle cell genotypes may influence haematological parameter during malaria. Children resident in malaria holoendemic regions suffer more from malaria-related complications and this is moderated by the presence of the SCD. In the current study, we determined the association between sickle cell genotypes and haematological parameters in children with P. falciparum malaria resident in Kisumu County in Western Kenya.Methodology: Children (n=217, aged 1-192 months) with acute febrile condition were recruited at Jaramogi Oginga Odinga Teaching and Referral Hospital. Chi-square (c2) analysis was used to determine differences between proportions. Differences in haematological parameters were compared across groups using Kruskal Wallis test and between groups using Mann Whitney U test. Multivariate logistic regression analysis controlling for infection status was used to determine the association between sickle cell genotypes and haematological parameters. Results: Using HbAA as the reference group, multivariate logistic regression analysis revealed that carriage of HbSS was associated with reduced haemoglobin [OR=0.310, 95% CI=0.101-0.956, P=0.041], reduced haematocrit [OR=0.318, 95% CI=0.128-0.793, P=0.014], reduced RBC count [OR=0.124, 95% CI=0.045-0.337, P=0.001], reduced MCHC [OR=0.325, 95% CI=0.118-0.892, P=0.029], increased leucocytosis [OR=9.283, 95% CI=3.167-27.210, P=0.001] and reduced monocytosis [OR=0.319, 95% CI=0.123-0.830, P=0.019]. However, carriage of HbAS was only associated with increased micro-platelets [OR=3.629, 95% CI=1.291-8.276, P=0.012]. Conclusion: Results show that carriage of HbSS in children influence the levels of haemoglobin, haematocrit, RBC, MCHC, WBC and Monocytes. Therefore prior knowledge of HbSS should be considered to improve clinical management of haematological alterations during malaria in children.

Decreased in vitro dihydroartemisinin sensitivity in malaria parasites infecting sickle cell disease patients

“…The participants included in the study were divided into four groups according to their sickle cell phenotypes (HbSS, HbSC, HbAS, HbAC and HbAA), and no significant difference in mean age was found, underlining the efficacy of the clinical management of children with SCD at the YUH (13, 50–54). As already reported, parasitaemia and haemoglobin levels at inclusion were lower in sickle cell patients with major forms than in patients with normal phenotype (55–58). This low parasite density could be an element explaining a protective effect against severe malaria.…”

Haematological Abnormalities in Children With Sickle Cell Disease and Non-severe Malaria Infection in Western Kenya

“…Haematological changes or abnormalities are some of the most common complications in malaria and they play a major role in malaria pathogenesis [27,28]. Previous studies have reported that haematological parameters are affected by P. falciparum infection and mutations in the HBB gene [19,29,30]. The presence of the sickle cell mutation has been shown to in uence malaria outcome in populations where the infection is endemic [31] such as western Kenya.…”

“…The sample size was calculated based on prevalence of sickle cell trait in the study area [20] using Cochran's formula [21]. The details of the study population are described in details in our previous publication [19].…”

“…The details of the laboratory procedures such as haematological measurements, microscopy for demonstration of any asexual form of P. falciparum, DNA extraction and quanti cation are described in details in our previous publication [19]. HBB rs334 genotyping: Genotyping of the HBB rs334 SNP was performed using TaqMan® SNP Genotyping Assay in accordance with manufacturer's protocols (Life Technologies, Grand Island, NY).…”

“…HBB rs334 genotyping: Genotyping of the HBB rs334 SNP was performed using TaqMan® SNP Genotyping Assay in accordance with manufacturer's protocols (Life Technologies, Grand Island, NY). Identi cation of haemoglobin S was from biallellic discrimination (missense change) [Glu6VAL] in the single nucleotide polymorphism rs334 by the following custom primer and probe sequences: Forward-TCAAACAGACACCATGGTGCAT, Reverse-CCCCACAGGGCAGTAACG, VIC-CTGACTCCTGAGGAGAA-MGB, 6FAM-CTGACTCCTGTGGAGAA-MGB, respectively and as per our previous work [19]. For quality assurance, a triplicate of control sample for genotype HbAA, HbAS and HbSS were also run.…”