Abstract
BackgroundPlasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection.MethodsA total of 771 blood donors were selected from five districts in the Greater Accra Region, Ghana. Each donor sample was screened with malaria rapid diagnostic test (RDT) kit and parasitaemia quantified microscopically. Dried blood spots from malaria positive samples were genotyped for P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum multi-drug resistance (Pfmdr1), P. falciparum dihydropteroate-synthetase (Pfdhps), P. falciparum dihydrofolate-reductase (Pfdhfr) and Kelch 13 propeller domain on chromosome 13 (Kelch 13) genes.ResultsOf the 771 blood donors, 91 (11.8%) were positive by RDT. Analysis of sequence reads indicated successful genotyping of Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes in 84.6, 81.3, 86.8, 86.9 and 92.3% of the isolates respectively. Overall, 21 different mutant haplotypes were identified in 69 isolates (75.8%). In Pfcrt, CVIET haplotype was observed in 11.6% samples while in Pfmdr1, triple mutation (resulting in YFN haplotype) was detected in 8.1% of isolates. In Pfdhfr gene, triple mutation resulting in IRNI haplotype and in Pfdhps gene, quintuple mutation resulting in AGESS haplotype was identified in 17.7% parasite isolates. Finally, five non-synonymous Kelch 13 alleles were detected; C580Y (3.6%), P615L (4.8%), A578S (4.8%), I543V (2.4%) and A676S (1.2%) were detected.ConclusionResults obtained in this study indicated various frequencies of mutant alleles in Pfcrt, Pfmdr1, Pfdhfr, Pfdhps and Kelch 13 genes from P. falciparum infected blood donors. These alleles could reduce the efficacy of standard malaria treatment in transfusion-transmitted malaria cases. Incorporating malaria screening into donor screening protocol to defer infected donors is therefore recommended.
Highlights
Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas
Donor malaria parasitaemia did not associate past malaria episode within past year (x2 = 3.6, p = 0.059), number of blood donations (x2 = 8.2, p = 0.08) and gender (x2 = 2.3, p = 0.13)
Analysis of genomic data obtained in this study indicated 24.0% triple mutations in the P. falciparum dihydrofolate-reductase (Pfdhfr) gene (N51I, C59R, S108N resulting in IRNI haplotype) and 17.7% double mutations in P. falciparum dihydropteroate-synthetase (Pfdhps) gene (A437G, K540E resulting in AGESS haplotype)
Summary
Plasmodium falciparum parasites, which could harbour anti-malaria drug resistance genes, are commonly detected in blood donors in malaria-endemic areas. Notwithstanding, anti-malaria drug resistant biomarkers have not been characterized in blood donors with asymptomatic P. falciparum infection. In blood recipients with no or reduced immunity to malaria, TTM can be fatal, if infections are not detected and treated quickly [6]. Blood donors with semi-immunity could harbor low levels of the Plasmodium parasites, which are mostly below the detection threshold of currently available assays. This will cause malaria parasites to persist for several years in infected blood recipients [7, 9]. Most reported cases of TTM were either through whole blood or red blood cell concentrates, with a few cases of TTM occurring after platelets and leukocytes transfusions [12]
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