Haematological abnormalities in children with sickle cell disease and non-severe malaria infection in western Kenya.

BACKGROUND: 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. However, the contributions of the carriage of different HBB genotypes on these changes remain largely unknown. METHODOLOGY: In 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. RESULTS: Haemoglobin (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. CONCLUSION: Our 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.

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

BACKGROUND: Sickle cell disease (SCD) is a monogenic disorder due to point mutation in the ß-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 (χ2) 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.