Amplification of pfmdr1, pfcrt, pvmdr1, and K13 Propeller Polymorphisms Associated with Plasmodium falciparum and Plasmodium vivax Isolates from the China-Myanmar Border

ABSTRACT Malaria in the China-Myanmar border region is still severe; local transmission of both falciparum and vivax malaria persists, and there is a risk of geographically expanding antimalarial resistance. In this research, the pfmdr1, pfcrt, pvmdr1, and K13-propeller genotypes were determined in 26 Plasmodium falciparum and 64 Plasmodium vivax isolates from Yingjiang county of Yunnan province. The pfmdr1 (11.5%), pfcrt (34.6%), and pvmdr1 (3.1%) mutations were prevalent at the China-Myanmar border. The indigenous samples exhibited prevalences of 14.3%, 28.6%, and 14.3% for pfmdr1 N86Y, pfcrt K76T, and pfcrt M74I, respectively, whereas the samples from Myanmar showed prevalences of 10.5%, 21.1%, and 5.3%, respectively. The most prevalent genotypes of pfmdr1 and pfcrt were Y86Y184 and M74N75T76, respectively. No pvmdr1 mutation occurred in the indigenous samples but was observed in two cases coming from Myanmar. In addition, we are the first to report on 10 patients (38.5%) with five different K13 point mutations. The F446I allele is predominant (19.2%), and its prevalence was 28.6% in the indigenous samples of Yingjiang county and 15.8% in samples from Myanmar. The present data might be helpful for enrichment of the molecular surveillance of antimalarial resistance and useful for developing and updating guidance for the use of antimalarials in this region.

[1]  Fangli Lu,et al.  Molecular surveillance of pvdhfr, pvdhps, and pvmdr-1 mutations in Plasmodium vivax isolates from Yunnan and Anhui provinces of China , 2014, Malaria Journal.

[2]  D. Kwiatkowski,et al.  Spread of artemisinin resistance in Plasmodium falciparum malaria. , 2014, The New England journal of medicine.

[3]  Guofa Zhou,et al.  Clinical Malaria along the China–Myanmar Border, Yunnan Province, China, January 2011–August 2012 , 2014, Emerging infectious diseases.

[4]  B. Genton,et al.  A molecular marker of artemisinin-resistant Plasmodium falciparum malaria , 2013, Nature.

[5]  K. Na-Bangchang,et al.  Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along the Thai-Myanmar border. , 2013, Asian Pacific journal of tropical biomedicine.

[6]  F. Nosten,et al.  Malaria Burden and Artemisinin Resistance in the Mobile and Migrant Population on the Thai–Myanmar Border, 1999–2011: An Observational Study , 2013, PLoS medicine.

[7]  J. Sattabongkot,et al.  Prevalence of Drug Resistance-Associated Gene Mutations in Plasmodium vivax in Central China , 2012, The Korean journal of parasitology.

[8]  C. Beyrer,et al.  Molecular surveillance for drug-resistant Plasmodium falciparum in clinical and subclinical populations from three border regions of Burma/Myanmar: cross-sectional data and a systematic review of resistance studies , 2012, Malaria Journal.

[9]  Fang Huang,et al.  Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border , 2012, Malaria Journal.

[10]  L. Cui,et al.  In Vitro Sensitivity of Plasmodium falciparum from China-Myanmar Border Area to Major ACT Drugs and Polymorphisms in Potential Target Genes , 2012, PloS one.

[11]  F. Nosten,et al.  Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study , 2012, The Lancet.

[12]  Y. Guan,et al.  Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in China , 2009, Tropical medicine & international health : TM & IH.

[13]  K. Silamut,et al.  Artemisinin resistance in Plasmodium falciparum malaria. , 2009, The New England journal of medicine.

[14]  K. Thimasarn,et al.  Malaria trends and challenges in the Greater Mekong Subregion. , 2009, The Southeast Asian journal of tropical medicine and public health.

[15]  Xiao-dong Sun,et al.  [Sensitivity of Plasmodium vivax to chloroquine in Laza City, Myanmar]. , 2009, Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases.

[16]  S. Meshnick,et al.  Pfmdr1 copy number and arteminisin derivatives combination therapy failure in falciparum malaria in Cambodia , 2009, Malaria Journal.

[17]  R. Price,et al.  Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. , 2008, The Journal of infectious diseases.

[18]  Y. Guan,et al.  No PfATPase6 S769N mutation found in Plasmodium falciparum isolates from China , 2008, Malaria Journal.

[19]  S. Meshnick,et al.  Declining Artesunate-Mefloquine Efficacy against Falciparum Malaria on the Cambodia–Thailand Border , 2008, Emerging infectious diseases.

[20]  P. Newton,et al.  Gene Amplification of the Multidrug Resistance 1 Gene of Plasmodium vivax Isolates from Thailand, Laos, and Myanmar , 2008, Antimicrobial Agents and Chemotherapy.

[21]  F. Nosten,et al.  Plasmodium vivax resistance to chloroquine in Dawei, southern Myanmar , 2008, Tropical medicine & international health : TM & IH.

[22]  D. Fidock,et al.  Decreasing pfmdr1 copy number in plasmodium falciparum malaria heightens susceptibility to mefloquine, lumefantrine, halofantrine, quinine, and artemisinin. , 2006, The Journal of infectious diseases.

[23]  L. Gradoni,et al.  Identification of the Plasmodium vivax mdr-like gene (pvmdr1) and analysis of single-nucleotide polymorphisms among isolates from different areas of endemicity. , 2005, The Journal of infectious diseases.

[24]  L. Hua Investigation into an outbreak of malaria in Lincang profecture on China - Myanmar border and the neighboring area outside China. , 2005 .

[25]  D. Ying The prevalence of malaria and control situation in Jiangcheng County of Yunnan Province. , 2005 .

[26]  I. Hastings The origins of antimalarial drug resistance. , 2004, Trends in parasitology.

[27]  F. Smithuis,et al.  Comparison of chloroquine, sulfadoxine/pyrimethamine, mefloquine and mefloquine‐artesunate for the treatment of falciparum malaria in Kachin State, North Myanmar , 2004, Tropical medicine & international health : TM & IH.

[28]  B. Sharp,et al.  Intercontinental Spread of Pyrimethamine-Resistant Malaria , 2004, Science.

[29]  Momiao Xiong,et al.  Multiple transporters associated with malaria parasite responses to chloroquine and quinine , 2003, Molecular microbiology.

[30]  Purnomo,et al.  Very high risk of therapeutic failure with chloroquine for uncomplicated Plasmodium falciparum and P. vivax malaria in Indonesian Papua. , 2003, The American journal of tropical medicine and hygiene.

[31]  L. Dequan,et al.  Changes in susceptibility of Plasmodium falciparum to artesunate in vitro in Yunnan Province, China. , 2003 .

[32]  Heng-lin Yang,et al.  Changes in susceptibility of Plasmodium falciparum to artesunate in vitro in Yunnan Province, China. , 2003, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[33]  H. Q. Le,et al.  Artemisinin or chloroquine for blood stage Plasmodium vivax malaria in Vietnam * , 2002, Tropical medicine & international health : TM & IH.

[34]  C. Wongsrichanalai,et al.  In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs. , 2001, The American journal of tropical medicine and hygiene.

[35]  H. Babiker,et al.  High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1. , 2001, The Journal of infectious diseases.

[36]  X. Su,et al.  A molecular marker for chloroquine-resistant falciparum malaria. , 2001, The New England journal of medicine.

[37]  M. Duraisingh,et al.  The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin. , 2000, Molecular and biochemical parasitology.

[38]  Yang Hl,et al.  [Comparison of sensitivity of artesunate-sensitive and artesunate-resistant Plasmodium falciparum to chloroquine and amodiaquine]. , 1999 .

[39]  H. Yang,et al.  [Comparison of sensitivity of artesunate-sensitive and artesunate-resistant Plasmodium falciparum to chloroquine and amodiaquine]. , 1999, Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases.

[40]  Guoqiao Li,et al.  Clinical trials of artemisinin and its derivatives in the treatment of malaria in China. , 1994, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[41]  P. Rees Chloroquine resistant malaria. , 1984, East African medical journal.