title: Historical survey of the kdr mutations in the populations of Anopheles sinensis in China in 1996-2014.
abstract: BACKGROUND
  Anopheles sinensis has become an important malaria vector in China. The long-term extensive utilization of pyrethroids for ITNs and IRS for mosquito control in the last three decades has resulted in the occurrence of resistant An. sinensis populations in many regions. Knockdown resistance (kdr), caused by point mutations in the VGSC gene, is one of the mechanisms that confer resistance to DDT and pyrethroids. Recently, several investigations revealed the kdr occurrence in some An. sinensis populations, however, no kdr data were available earlier than 2009. A survey tracking the dynamics of the kdr mutations in past decades would provide invaluable information to understand how the kdr alleles spread in mosquito populations temporally and spatially.
  
  
  METHODS
  A survey was conducted on the kdr alleles at condon 1014 of the VGSC gene and their distributions in 733 specimens of An. sinensis and 232 specimens of the other eight member species of the Anopheles hyrcanus group that were collected from 17 provinces in China in 1996-2014.
  
  
  RESULTS
  A total of three kdr alleles, TTT (F), TTG (F) and TGT (C) were detected, and TGT (C) and TTT (F) were already present in the specimens from Jiangsu and Shandong as early as 1997. The TTT (F) was the most frequent mutant allele, and largely distributed in central China, namely Shandong, Jiangsu, Anhui, Henan, Shanghai, Jiangxi and Hubei. When data were analysed in three time intervals, 1996-2001, 2005-2009, 2010-2014, the prevalence of kdr alleles increased progressively over time in the populations in central China. In contrast, the kdr alleles were less frequent in the samples from other regions, especially in Yunnan and Hainan, despite the documented presence of pyrethroid resistant populations in those regions. Interestingly, no mutant alleles were detected in all 232 specimens of eight other species in the An. hyrcanus group.
  
  
  CONCLUSIONS
  The survey revealed that the kdr occurrence and accumulation in the An. sinensis populations were more frequent in central China than in the other regions, suggesting that the kdr mutations may contribute significantly to the pyrethroid resistance in the mosquitoes in central China.
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, 200433, China. wang1yu2yan@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biology, Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. ivyyu@nmsu.edu.
authors.forename: Wanqin
authors.initials: W
authors.lastname: Yu
authors.affiliation: Center for Disease Control and Prevention of P. L.A., Beijing, 100071, China. placdc@139.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Shi
authors.affiliation: Center for Disease Control and Prevention of P. L.A., Beijing, 100071, China. pcochina@hotmail.com.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Biology, Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA. jxu@nmsu.edu.
authors.forename: Jiannong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Tropical Infectious Diseases, Second Military Medical University, Shanghai, 200433, China. yajun_ma@163.com.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000378:metabolism; D002681:China; D005787:Gene Frequency / Q000235:genetics; D019476:Insect Proteins / Q000235:genetics* / Q000378:metabolism; D007305:Insecticide Resistance / Q000235:genetics*; D007306:Insecticides / Q000494:pharmacology*; D011722:Pyrethrins / Q000494:pharmacology*
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D011722:Pyrethrins