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Single Nucleotide Polymorphisms (SNPs) in the  Pfmdr1,  and  Pfcrt,  genes  of Plasmodium falciparum  may confer resistance to a number of anti-malaria drugs.  Pfmdr1  86Y and haplotypes at  Pfcrt  72-76 have been linked to chloroquine (CQ) as well as amodiaquine (AQ) resistance. mefloquine (MQ) and lumefantrine (LU) sensitivities are linked to  Pfmdr1  86Y. Additionally,  Pfcrt  K76 allele carrying parasites have shown tolerance to LU. We investigated the association between  Pfmdr1  86/ Pfcrt  72-76 and  P. falciparum  resistance to CQ, AQ, MQ and LU using field samples collected during 2008–2011 from malaria endemic sites in western Kenya. Genomic DNA from these samples was genotyped to examine SNPs and haplotypes in  Pfmdr1  and  Pfcrt  respectively. Additionally, immediate  ex vivo  and  in vitro  drug sensitivity profiles were assessed using the malaria SYBR Green I fluorescence-based assay. We observed a rapid but steady percent increase in wild-type parasites with regard to both  Pfmdr1  and  Pfcrt  between 2008 and 2011 (p<0.0001). Equally, a significant reciprocate decrease in AQ and CQ median IC 50  values occurred (p<0.0001) during the same period. Thus, the data in this study point to a significantly rapid change in parasite response to AQ and CQ in the study period. This may be due to releasing of drug pressure on the parasite from reduced use of AQ in the face of increased Artemisinin (ART) Combination Therapy (ACT) administration following the intervention of the Global Fund in 2008. LU has been shown to select for 76K genotypes, thus the observed increase in 76K genotypes coupled with significant cross resistance between LU and MQ, may herald emergence of tolerance against both drugs in future.

plos one

The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008–2011