Molecular epidemiology of drug resistance markers of Plasmodium falciparum in Yunnan Province, China

• Published in: Malaria Journal
• Main Authors: Huang Fang, Tang Linhua, Yang Henglin, Zhou Shuisen, Liu Hui, Li Junwei, Guo Shaohua
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2012
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-11-243; https://doaj.org/article/3b2f6b2fe0d746b7991ef58ef5e5ee8a

Abstract Background The mutations in Plasmodium falciparum chloroquine resistance transporter ( pfcrt ), multidrug resistance 1 ( pfmdr1 ), dihydrofolate reductase ( pfdhfr ), dihydropteroate synthase ( pfdhps ) and ATPase ( pfatp6 ) genes were associated with anti-malaria drug resistance. The aim of this study was to investigate the prevalence of polymorphisms in pfcrt , pfmdr1 , pfdhfr , pfdhps and pfatp6 in Yunnan Province. Finger-prick blood samples were collected from malaria-positive patients from Yunnan Province in 2009-2010. Single-nucleotide polymorphisms (SNPs) in the resistance-related genes were analysed by various PCR-based methods. Results A total of 108 blood samples were collected. Although chloroquine has not been used to treat falciparum malaria for nearly 30 years, 95.3% of the parasites still carried the pfcrt K76T mutation, whereas the majority of isolates displayed the wild-type pfmdr1 N86 and D1246 sequences. The molecular level of sulphadoxine–pyrimethamine resistance in P. falciparum was high. The most prevalent mutation was pfdhfr C59R (95.9%), whereas the frequencies of the quadruple, triple and double mutants were 22.7% (N51I/C59R/S108N/I164L), 51.5% (N51I/C59R/S108N, N51I/C59R/I164L and C59R/S108N/ I164L) and 21.6% (N51I/ C59R, C59R/S108N and C59R/I164L), respectively. A437G (n = 77) and K540E (n = 71) were the most prevalent mutations in pfdhps , and 52.7% of the samples were double mutants, among which A437G/K540E was the most common double mutation (37/49). Quadruple mutants were found in 28.0% (26/93) of samples. A total of 8.6% of isolates (8/93) carried the S436A/A437G/A581G triple mutation. No mutations were found in pfatp6 codons 623 or 769, but another two mutations (N683K and R756K) were found in 4.6% (3/97) and 9.2% (6/97) of parasite isolates, respectively. Conclusions This study identified a high frequency of mutations in pfcrt , pfdhfr and pfdhps associated with CQ and SP resistance in P. falciparum and no mutations linked to artemisinin resistance ( pfatp6 ). Molecular ...