Analysis of clinical presentation, hematological factors, self-reported bed net usage, and malaria burden in sickle cell disease patients

Abstract

Background: Sickle cell anemia (SCA) is a severe monogenic disorder, caused by single nucleotide mutations in the hemoglobin (Hb) gene, that is prevalent in malaria endemic regions of the world. Sickle cell trait (SCT) individuals carry only one of the mutated alleles and were shown to be protected against malaria. However, defining the relative contribution of hematological, clinical, and environmental factors to the overall burden of malaria in individuals with hemoglobinopathies such as SCA has been challenging. Methods: We hypothesized that hematological differences, clinical presentations, and self-reported bed net usage among Plasmodium-infected and uninfected individuals may govern overall malaria burden in individuals with sickle cell disease (SCD). We conducted a cross-sectional study in Ghana from 2014 to 2019 and described clinical presentations, hematological characteristics, and bed net use based on a comprehensive questionnaire. Hematological characteristics were compared using a parametric or nonparametric ANOVA, pending if data passed D'Agostino & Pearson normality test. When comparing only two Hb genotypes hematological characteristics a MannÀWhitney U-test were used. Logistic regressions and Chi-squared tests were used to compare questionnaire responses between Hb genotypes. All statistical significance was set at p < 0.05. Findings: Multiple hematological parameters were significantly (p < 0.05) altered depending on sickle cell genotype and/or malaria status. When compared to other Hb genotypes, SCA individuals with or without malaria had significantly (p < 0.05) higher WBC and platelets counts and lower Hb levels. While the sickle cell genotype may affect malaria severity, SCT and SCA participants were found to significantly (p < 0.007) use bet nets more than HbAA participants. Interpretations: Our findings can be utilized to enhance national guidelines for reducing the incidence of malaria especially among individuals with SCD, SCT protection and health disparities among hemoglobinopathies.

MicroRNAs miR-451a and Let-7i-5p Profiles in Circulating Exosomes Vary among Individuals with Different Sickle Hemoglobin Genotypes and Malaria

“…A total of 183 participant samples were randomly selected out of a cohort of 923 participants from each genotype (HbAA, HbAS, HbAC, HbSC, HbSS, and HbCC) with (+) and without (−) malaria (Table 1). The hematological characteristics and clinical data of the original cohort of 923 participants were compared in previous publication [33]. Results from the miRNA RT-qPCR were analyzed by ∆∆Ct analysis.…”

“…The samples used for this study were selected from a larger cohort, which compared hematological parameters between HbAA, HbAS, HbAC, HbSC, HbSS, and HbCC with and without malaria [33]. The study determined that Hb genotypes and malaria status changed an individual's hematological parameters.…”

“…The study determined that Hb genotypes and malaria status changed an individual's hematological parameters. For example, SCA individuals, regardless of malaria status, had increased WBC and platelet counts and lower Hb levels compared to other Hb genotypes [33]. Additionally, the same pool of samples was also used previously to measure cytokine and chemokine levels [81].…”

MiR-451a and let-7i-5p loaded extracellular vesicles attenuate heme-induced inflammation in hiPSC-derived endothelial cells

“…In contrast, people with sickle cell anemia (SCA), homozygous HbSS, are more likely to die of malaria than those with wildtype (normal) Hb (homozygous HbAA) or those with SCT ( 10 ). Furthermore, SCA patients are more likely to develop severe malaria symptoms compared to non-SCA patients ( 9 , 11 ). Patients with SCA often have more severe malaria due to their shorter RBC lifespan, as well as the parasite rupturing them, releasing higher levels of toxic heme into the body ( 12 – 14 ).…”

Simultaneous adjunctive treatment of malaria and its co-evolved genetic disorder sickle cell anaemia

“…This co-evolution has occurred because a single copy of the HBB mutation leads to sickle trait (HbAS), which confers substantial protection against severe malaria and death due to malaria 15 . However individuals who inherit two copies have SCA (HbSS) show lower levels of parasite infection those with normal hemoglobin 16 17 but are potentially more susceptible to infection-induced severe anemia and disease [17][18][19] .…”