Abstract
BackgroundPlasmodium falciparum resistance to chloroquine (CQ) denied healthcare providers access to a cheap and effective anti-malarial drug. Resistance has been proven to be due to point mutations on the parasite’s pfcrt gene, particularly on codon 76, resulting in an amino acid change from lysine to threonine. This study sought to determine the prevalence of the pfcrt K76T mutation 13 years after CQ cessation in Msambweni, Kenya.MethodsFinger-prick whole blood was collected on 3MM Whatman® filter paper from 99 falciparum malaria patients. Parasite DNA was extracted via the Chelex method from individual blood spots and used as template in nested PCR amplification of pfcrt. Apo1 restriction enzyme was used to digest the amplified DNA to identify the samples as wild type or sensitive at codon 76. Prevalence figures of the mutant pfcrt 76T gene were calculated by dividing the number of samples bearing the mutant gene with the total number of samples multiplied by 100 %. Chi square tests were used to test the significance of the findings against previous prevalence figures.ResultsOut of 99 clinical samples collected in 2013, prevalence of the mutant pfcrt 76T gene stood at 41 %.ConclusionThe results indicate a significant [χ2 test, P ≤ 0.05 (2006 vs 2013)] reversal to sensitivity by the P. falciparum population in the study site compared to the situation reported in 2006 at the same study site. This could primarily be driven by diminished use of CQ in the study area in line with the official policy. Studies to establish prevalence of the pfcrt 76T gene could be expanded countrywide to establish the CQ sensitivity status and predict a date when CQ may be re-introduced as part of malaria chemotherapy.
Highlights
Plasmodium falciparum resistance to chloroquine (CQ) denied healthcare providers access to a cheap and effective anti-malarial drug
CQ targets the parasite haematin detoxification pathway in the parasite digestive vacuole (DV) in a two-pronged attack where it adsorbs onto growing hemozoin polymers and binds to toxic haematin molecules generated as the parasite digests host haemoglobin resulting in accumulation of toxic haematin in the DV [16, 17]
The current study has identified an encouraging increase in the prevalence of CQS parasites in the said study area. This could be attributed to a number of factors, chief among which is the reduction or absence of drug pressure to sustain CQR P. falciparum strains
Summary
Plasmodium falciparum resistance to chloroquine (CQ) denied healthcare providers access to a cheap and effective anti-malarial drug. To counter CQ, P. falciparum is believed to primarily employ a mutant pfcrt product to increase efflux of CQ from the DV [20] This phenotype is the result of complex genetic changes involving point mutations on ten or more codons of the pfcrt gene [18, 21, 22]. Numerous studies have identified the K76T mutation as the central factor in CQR development [18, 21, 23] This mutation is present in all CQR laboratory lines and field isolates from various malaria-endemic regions and can reliably be used as a CQR marker alone [23] or in concert with other pfcrt mutations.
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