Abstract
BackgroundIn Plasmodium falciparum infection, clinical conditions such as anaemia, thrombocytopenia and leukocytosis are common. Mutation in haemoglobin sub-unit beta gene (HBB) may be a genetic factor responsible for these haematological changes during infection. However, the contributions of the carriage of different HBB genotypes on these changes remain largely unknown.MethodologyIn this cross-sectional study, we evaluated haematological abnormalities in P. falciparum-infected children (n = 217, aged 1–192 months) with different haemoglobin sub-unit beta (HBB) genotypes (HbAA, HbAS and HbSS). Children with acute febrile conditions were recruited at Jaramogi Oginga Odinga Teaching and Referral Hospital at the outpatient clinic. Haematological parameters were determined using Beckman Coulter counter ACTdiff2™ while HBB genotyping was done using TaqMan® SNP genotyping assay. Chi-square (χ2) 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. Partial correlation test was used to determine correlation between haematological parameters and sickle cell genotypes while controlling for age and sex.ResultsHaemoglobin (Hb), [median (IQR); 7.3 (1.3), P = 0.001], haematocrit (HCT), [median (IQR); 26.4 (4.4), P = 0.009], red blood cells (RBC), [median (IQR); 3.2 (1.7), P = 0.048] were markedly reduced in HbSS, however, red cell distribution with (RDW) [median (IQR); 14.9 (3.3), P = 0.030] was increased in malaria infected children with HbSS. Severe anaemia was highest in HbSS (23.1%) followed by HbAA (8.6%) and HbAS (7.1%). There were no differences in platelet count (P = 0.399) hence no severe thrombocytopeania across the genotypes. Leukocytosis was highest in HbSS (69.2%), 42% in HbAS and 31% in HbAA. The RBC, HCT and Hb had negative correlation with RDW in HbSS in malarial-infected children (r = − 0.725, P = 0.008), (r = − 0.718, P = 0.009) and (r = − 0.792, P = 0.002), respectively.ConclusionOur study reveals that anaemia is the most common abnormality in malaria-infected children with carriage of HbSS. The RBC, HCT and Hb concentration decrease with increase in RDW levels in infected children with carriage of HbSS compared to other HBB genotypes. Therefore, carriage of HbSS genotype is correlated with severity of haematological abnormalities.
Highlights
In Plasmodium falciparum infection, clinical conditions such as anaemia, thrombocytopenia and leukocytosis are common
The red blood cells (RBC), HCT and Hb concentration decrease with increase in red cell distribution with (RDW) levels in infected children with carriage of HbSS compared to other haemoglobin beta sub-unit gene (HBB) genotypes
Haematological abnormalities in carriage of different sickle cell genotypes in P. falciparum infection To determine whether carriage of different sickle cell genotypes have effect on the severity of haematological abnormalities once an individual is infected, we evaluated their severity in children with P. falciparum infection and carriage of different sickle cell genotypes
Summary
In Plasmodium falciparum infection, clinical conditions such as anaemia, thrombocytopenia and leukocytosis are common. Mutation in haemoglobin sub-unit beta gene (HBB) may be a genetic factor responsible for these haematological changes during infection. Several studies in Africa especially in Nigeria [8] and Kenya [9] demonstrated that platelet count is significantly reduced in severe malaria infection and recommended the inclusion of thrombocytopenia in case definition of severe malaria. The above study did not consider different haemoglobin beta sub-unit (HBB) genotypes more so sickle cell gene mutation (6GAG > 6GTG). Whether malaria is severe or non-severe, it is important to note that the overlapping interactions between haemoglobinopathy especially in the haemoglobin beta sub-unit gene (HBB) and malaria, remains a complex biological conundrum that is not well understood [13]
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