| Objective:The polymorphisms of Plasmodium falciparum(P.falciparum)genes including P.falciparum chloroquine resistance transporter gene(Pfcrt),Multidrug resistance gene 1 of P.falciparum(Pfmdr1),P.falciparum dihydrofolate reductase gene(Pfdhfr),P.falciparum dihydroponic synthase gene(Pfdhps)and Kelch 13-propeller 3)were identified to analyze the dynamic drug resistance status and regional difference.This could provide scientific basis for the local formulation of effective treatment strategies and measures for P.falciparum in China-Myanmar border areas including Xishuangbanna(BN)Prefecture of Yunnan Province,Lazan(LZ)City of Kachin State and Mengmao(MM)County,the Second Special Zone of Shan State in Myanmar.Methods:P.falciparum samples(n=175)from BN,LZ and MM were collected along the China-Myanmar border.The polymorphism of Pfcrt,Pfmdrl,Pfdhf,Pfdhps and PfK13 genes were detected by Nested PCR.Results:Pfcrt.The prevelence of C72S,M74I and N75E was significantly different in BN,LZ and MM(P<0.05),and the main mutation type was triple mutation(CVIET).In 2001,wild-type strains collected from BN,were accounted for 20%(6/30),and the proportion of triple mutation(CVIET)was 76.7%(23/30).But 100%(25/25)strains were totally triple mutation(CVIET)by 2006.In LZ,the triple mutation(CVIET)was increased from 75%(15/20)in 2001 to 77.5%(31/40)in 2012.Additionally,a small number of triple mutation(CVIDT)were still existed in 2007 and 2012,and were both 5%(1/20)and 5%(2/40).In MM,the proportion of triple mutation(CVIET)was 67.5%(27/40),and double mutation(SVMNT)was 30%(12/40)in 2009.Pfmdr1.Mutation rates of N86Y and F1226Y was significantly different in these regions(P<0.05).In 2001,the wild type strains in BN was 36.7%(11/30),and the N86Y and Y1 84F mutation rates was 20%(6/30).F1226Y mutation rate was 16.7%(5/30).However,F1226Y was predominant mutation,which was accounted for 40%(10/25)in BN,and double mutation(N86Y/F1226Y and Y184F/F1226Y)were also detected,with the proportion of 8%(2/25)in 2006.In LZ,the proportion of wild-type strains was decreased from 2001 to 2012.The mutation was Y184F,which was increased from 25%(5/20)in 2001 to 35%(7/20)in 2007 and 37.5%(15/40)in 2012.The proportion of wild-type strains decreased,while Y184F mutation was mainly accounted for 37.5%during 2001 and 2012 in LZ.The wild-type was a higher proportion of wild-type,which was accounting for 47.5%(19/40),and Y184F mutation rate was 27.5%(1 1/40)in MM.Pfdhfr.The mutation rates of N511,C59R and S108N were remarkably different among the regions(P<0.001).In BN,the propertion of wild-type was 23.3%(7/30)in 2001,and was dominated by quadruple mutantion(IRNL),with the prevelence of 26.7%(8/30)in 2001.By 2006,mutations were occurred in BN,and dominated by double mutation(NRNI)which was accounted for 44%(11/25).However,in LZ,the proportion of quadruple mutation(IRNL)was increased from 35%(7/20)in 2001 to 60%(24/40)in 2012.Interestingly,wild type was the highest proportion with the prevelence of 45%(18/40)in 2009,and quadruple mutation(IRNL)was 40%(16/40)in MM.Pfdhps.The prevelence of S436A/F,A437G and K540N were significantly different in above regions(P<0.05).In BN,double mutation(SAEG)was dominated in 2001,which was accounted for 53.3%(16/30).But 40%(10/25)of single mutation S436A was identified in 2006 in BN.In LZ,5%of wild type strains were existed from 2001 to 2012,and triple mutation(FAEG)was increased from 5%(1/20)in 2001 to 37.5%(15/40)in 2012.However,wild type was not detected,while double mutation(AAEA and FGKA)and triple mutation(FAEG)were dominantly accounted for 50%(20/40)and 27.5%(11/40)in MM.PfK13.The F446I mutation rate was significantly different among the regions(P<0.001).In BN,there was only one sample carried F4461 in 2001 and no mutation was occurred in 2006.In MM,no mutation was found in 2009.However,there was a higher mutation rate in LZ,while the mutation rate of F446I was decreased from 45%(9/20)in 2001 to 40%(8/20)in 2007 and 25%(10/40)in 2012.Conclusion:The Pfcrt mutation was dominated by triple mutation(CVIET)among three regions of China-Myanmar border,which means that Chloroquine resistance rate was generally higher.Pfmdrl F1226Y mutation was mainly occurred in BN.The Y184F mutation was mainly occurred in LZ but with a downward trend.In MM,Y184F and N86Y were the main mutation.Except that Pfdhfr was dominated by double mutation(NRNI)in BN,quadruple mutation(IRNL)was both detected in LZ and MM.The main mutation type of Pfdhps was double mutation(AAEA and FGKA)or triple mutation(FAEG)among three China-Myanmar border regions,which was suggested the resistance of Sulfadoxine-Pyrimethamine drugs was still high.The mutation rate of PfK13 in BN was extremely low.No mutation was not found in MM in 2009.In LZ,F446I mutation was dominated,and in 2001,Artemisinin resistance was appeared,while the trend was decreased from 2001 to 2012.The above research results suggest that relevant departments should further strengthen drug resistance monitoring of P.falciparum in China-Myanmar border. |
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