Distinct pattern and prevalence of Plasmodium falciparum dihydropteroate synthase gene mutations in children with sickle cell anaemia and haemoglobin AA in Benin City, Nigeria: the impact of HbAA

Abstract

Introduction: specific mutations on the Plasmodium falciparum dihydropteroate synthase (Pfdhps) gene mediate sulphadoxine/pyrimethamine (SP) resistance and thus, pose a threat to the efficacy of SPIntermittent Preventive Therapy (SP-IPT) in malaria chemoprevention in children, including those with sickle cell anaemia (SCA). This study determined the distinct pattern and prevalence of Pfdhps mutations in children with SCA and in those with homozygous haemoglobin A (HbAA) in Benin City, Nigeria; showing the impact of haemoglobin phenotype. Methods: this was a cross-sectional study involving children with SCA and HbAA. Those with successfully amplified Pfdhps genes were included in the study. Point mutations and mutant haplotypes of the Pfdhps gene were identified. Parasite density (PD) was determined by estimating the parasite numbers/μl of blood from the thick film. Descriptive, univariable and multivariable analysis were used appropriately. Results: a total of 146 children: 71 with SCA and 75 with HbAA were recruited, with a mean age of 46.6 ± 13.0 and 36.4 ± 17.6 respectively; proportion of males were 45(63.4%) and 43(57.3%) respectively. I431V, S436A, A437G, A581G, and A613G mutations were present; but the K540E mutation was absent. ISGKAA 41(28.1%) and VAGKGS 61(41.8%) were the most prevalent mutant haplotypes in this study. The prevalence of VAGKGS haplotype 43(57.3%) was significantly higher in HbAA group compared to that 18(25.4%) in the SCA group (p < 0.001). The prevalence of ISGKAA in SCA group 25(35.2%) was significantly higher than that 16(21.3%) in the HbAA group (p=0.032). HbAA phenotype was the only significant predictor for the presence of the VAGKGS mutant haplotype (aOR: 3.0, 95%CI: 1.375 to 6.499; p=0.006). Conclusion: the HbAA phenotype was a significant predictor for the occurrence of the quintuple mutant haplotype (VAGKGS). The K540E mutation was absent; thus, SP-IPT can be explored in children younger than five years with SCA.