title: Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009-2013).
abstract: BACKGROUND
  Bangladesh is a malaria hypo-endemic country sharing borders with India and Myanmar. Artemisinin combination therapy (ACT) remains successful in Bangladesh. An increase of artemisinin-resistant malaria parasites on the Thai-Cambodia and Thai-Myanmar borders is worrisome. K13 propeller gene (PF3D7_1343700 or PF13_0238) mutations have been linked to both in vitro artemisinin resistance and in vivo slow parasite clearance rates. This group undertook to evaluate if mutations seen in Cambodia have emerged in Bangladesh where ACT use is now standard for a decade.
  
  
  METHODS
  Samples were obtained from Plasmodium falciparum-infected malaria patients from Upazila health complexes (UHC) between 2009 and 2013 in seven endemic districts of Bangladesh. These districts included Khagrachari (Matiranga UHC), Rangamati (Rajasthali UHC), Cox's Bazar (Ramu and Ukhia UHC), Bandarban (Lama UHC), Mymensingh (Haluaghat UHC), Netrokona (Durgapur and Kalmakanda UHC), and Moulvibazar (Sreemangal and Kamalganj UHC).
  
  
  RESULTS
  Out of 296 microscopically positive P. falciparum samples, 271 (91.6%) were confirmed as mono-infections by both real-time PCR and nested PCR. The K13 propeller gene from 253 (93.4%) samples was sequenced bi-directionally. One non-synonymous mutation (A578S) was found in Bangladeshi clinical isolates. The A578S mutation was confirmed and lies adjacent to the C580Y mutation, the major mutation causing delayed parasite clearance in Cambodia. Based on computational modeling A578S should have a significant effect on tertiary structure of the protein.
  
  
  CONCLUSIONS
  The data suggest that P. falciparum in Bangladesh remains free of the C580Y mutation linked to delayed parasite clearance. However, the mutation A578S is present and based on structural analysis could affect K13 gene function. Further in vivo clinical studies are required to validate the effect of this mutation.
authors.forename: Abu Naser
authors.initials: AN
authors.lastname: Mohon
authors.forename: Mohammad Shafiul
authors.initials: MS
authors.lastname: Alam
authors.forename: Abebe Genetu
authors.initials: AG
authors.lastname: Bayih
authors.forename: Asongna
authors.initials: A
authors.lastname: Folefoc
authors.forename: Dea
authors.initials: D
authors.lastname: Shahinas
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, Faculty of Medicine, University of Calgary, Diagnostic and Scientific Centre, Room 1 W-416, 9-3535 Research Road NW, Calgary, AB T2L 2 K8, Canada. drpillai@ucalgary.ca.
authors.forename: Dylan R
authors.initials: DR
authors.lastname: Pillai
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001459:Bangladesh; D002648:Child; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000469:parasitology; D008297:Male; D008958:Models, Molecular; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000235:genetics* / Q000302:isolation & purification; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D016054:DNA, Protozoan; D015800:Protozoan Proteins