title: Emerging polymorphisms in falciparum Kelch 13 gene in Northeastern region of India.
abstract: BACKGROUND
  Recent reports of emergence and spread of artemisinin resistance in the Southeast Asia region, including Myanmar, pose a greater threat to malaria control and elimination in India. Whole genome sequencing studies have associated mutations in the K13 propeller gene (k13), PF3D7_1343700 with artemisinin resistance both in vitro and in vivo. The aim of the present study was to find the k13 gene polymorphisms in Plasmodium falciparum parasites from the three sites in the Northeast region of India, bordering Bangladesh and Myanmar.
  
  
  METHODS
  A total of 254 samples collected during 2014-2015 from Tripura, Mizoram and Arunachal Pradesh states in the Northeast region of India were used to obtain the full-length k13 gene sequences.
  
  
  RESULTS
  Three non-synonymous (NS) mutations: two in the propeller region, namely at codon 446 and 578, were observed besides one at codon 189 in the non-propeller region. The treatment outcome was not affected by these mutations at any of the sites. In addition, microsatellite variation in the N-terminus of the k13 protein was observed at all the study sites.
  
  
  CONCLUSIONS
  This is the first study to document the presence of F446I NS mutation in the k13 propeller region from Changlang district, Arunachal Pradesh, a site adjoining the Indo-Myanmar border region, where this mutation is highly prevalent. In addition, NS mutation A578S has been observed only at Lunglei district, Mizoram, a site bordering Bangladesh and K189T mutation with relatively higher frequency in Mizoram and Tripura states. The presence of F446I mutation in a region close to the Myanmar border is notable. Considering the spread of anti-malarial drug resistance from Southeast Asia to the Northeast region of India in the past, there is an urgent need to undertake systematic mapping studies to ascertain the role and extent of this mutation in artemisinin resistance in this region of country.
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Neelima
authors.initials: N
authors.lastname: Mishra
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Ram Suresh
authors.initials: RS
authors.lastname: Bharti
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Mallick
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Om Prakash
authors.initials: OP
authors.lastname: Singh
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Bina
authors.initials: B
authors.lastname: Srivastava
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Roma
authors.initials: R
authors.lastname: Rana
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Sobhan
authors.initials: S
authors.lastname: Phookan
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India.
authors.forename: Hardev Prasad
authors.initials: HP
authors.lastname: Gupta
authors.affiliation: Global Malaria Programme, Geneva, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Ringwald
authors.affiliation: National Institute of Malaria Research, Sector 8, Dwarka, New Delhi, 110 077, India. neenavalecha@gmail.com.
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
mesh_terms: D004351:Drug Resistance; D006801:Humans; D007194:India / Q000453:epidemiology; D016778:Malaria, Falciparum / Q000469:parasitology*; D017720:Molecular Epidemiology; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D015800:Protozoan Proteins
keywords: Artemisinin resistance; K13 gene; Malaria; PF3D7_1343700; Plasmodium falciparum