The mechanism of chloroquine (CQ) resistance in Plasmodium falciparum is not clearly understood. However, CQ resistance has been shown to be associated with point mutations in Pfcrt and Pfmdr1. These genes encode for digestive vacuole transmembrane proteins Pfcrt and Pgh1, respectively. The present study was carried out to analyze the association of Pfcrt-K76T and Pfmdr1-N86Y mutations with CQ resistance in Northeast Indian P. falciparum isolates. 115 P. falciparum isolates were subjected to in vitro CQ sensitivity testing and PCR-RFLP analysis for the Pfmdr1-N86Y and Pfcrt-K76T mutations. 100 isolates of P. falciparum were found to be resistant to CQ by the in vitro susceptibility test (geometric mean EC50 2.21 µM/L blood) while 15 were found to be CQ sensitive (geometric mean EC50 0.32 µM/L blood). All the CQ resistant isolates showed the presence of Pfmdr1 and Pfcrt mutations. CQ sensitive isolates were negative for these mutations. Strong linkage disequilibrium was observed between the alleles at these two loci (Pfmdr1-N86Y and Pfcrt-K76T). The results indicate that Pfmdr1-N86Y and Pfcrt-K76T mutations can be used as molecular markers to identify CQ resistance in P. falciparum. The result necessitates the evaluation of CQ in vivo therapeutic efficacy in endemic areas for more effective malaria control strategies.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126653PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103848PLOS

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Article Synopsis
  • The study investigated the prevalence of mutations associated with chloroquine resistance in malaria-causing *Plasmodium falciparum* strains in Nyala, Sudan, following the shift to using artesunate and sulfadoxine/pyrimethamine as first-line treatments in 2004.
  • Using techniques like polymerase chain reaction (PCR) and gel electrophoresis, researchers analyzed DNA from 75 isolates and found that significant frequencies of both the K76T and N86Y mutations were present, indicating ongoing chloroquine resistance.
  • Results showed that K76T mutations were found in 65.3% of isolates, and N86Y mutations in 45.3%, suggesting that chloroquine resistance markers continue
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