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Effects of Sub-Optimal Dihydroartemisinin Drug Concentration on Development of Antimalarial Drug Resistance Markers Among Malaria Patients in Kisumu County, Western Kenya

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dc.contributor.author CHERUIYOT, Agnes C
dc.date.accessioned 2021-05-07T08:22:28Z
dc.date.available 2021-05-07T08:22:28Z
dc.date.issued 2017
dc.identifier.uri https://repository.maseno.ac.ke/handle/123456789/3697
dc.description.abstract The fight against malaria has been hindered by emergence of drug resistance to current antimalarial drugs. Mutations in Plasmodium faleiparum chloroquine transporter gene (Pfert) and Plasmodium faleiparum multi-drug resistance gene 1 (Pfmdr 1) confer selective survival advantage in the presence of some antimalarial drugs. Malaria treatment failure has been linked to sub-optimal antimalarial drug levels. However, there is limited know ledge on the potential role of sub-optimal drug in the emergence and spread of artemisinin resistance. Dihydroartemisinin (DRA) is the active metabolite of artemisinin the current treatment regime. An in vitro (DHA) sub optimal exposure on Plasmodium faleiparum samples would allow the evaluation of drug resistance markers and genetic diversity without host confounding factors. This study sought to evaluate effects of DRA sub-optimal concentration on development of antimalarial drug resistance markers and genetic diversity among malaria patients in Kisumu County. The specific objectives of this study were: to determine polymorphisms in Pfert codon 76 and Pfmdr 1gene in both DRA exposed and unexposed samples at 24 and 72 hours in culture; to determine the difference in genetic diversity in DRA exposed and unexposed samples at the two-time points; and to compare parasite polymorphisms and genetic diversity in DRA exposed and unexposed samples at the two-time points. The study adopted a cross-sectional study design where 54 whole blood samples from individuals presenting with uncomplicated malaria at Kisumu sub County hospitals were analyzed in three sub sets (day 0 samples, day 0 samples subsets, samples exposed to DRA 70nM and 700nM). Aliquots of 200llL were made at the two-time points. Genotypes in Pfcrt and Pfmdrl genes were obtained using Mass ARRA Y®technique and analyzed as proportions. Twelve microsatellites genotyping was done by nested PCR and run on an ABI3500XI Genetic Analyzer. The heterozygosity and genetic differentiation were obtained using GenAIEx v.6.5®. Further analysis was done using Kruskal-Wallis test and Mann Whitney test. Pfmdr1 codon 86 and codon 1246 were predominantly wild type in DRA exposed and unexposed samples at both time points. Codon 1034 and 1042 did not have any polymorphic variants and this observation was similar to Pfert codon 76. Heterozygosity in DRA exposed and unexposed samples were comparable at the two-time points (p=0.:3852). All sample sets revealed high genetic diversity with low genetic differentiation. In this study, no loci selection was observed. The findings may guide antimalarial treatment in the study area to control re-infections. en_US
dc.publisher Maseno University en_US
dc.title Effects of Sub-Optimal Dihydroartemisinin Drug Concentration on Development of Antimalarial Drug Resistance Markers Among Malaria Patients in Kisumu County, Western Kenya en_US
dc.type Article en_US


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