title: Distribution of Plasmodium vivax pvdhfr and pvdhps alleles and their association with sulfadoxine-pyrimethamine treatment outcomes in Indonesia.
abstract: BACKGROUND
  Sympatric existence of Plasmodium falciparum and Plasmodium vivax, and the practice of malaria treatment without microscopic confirmation suggest that the accidental treatment of vivax malaria with sulfadoxine-pyrimethamine (SP) is common.
  
  
  METHODS
  In this study, the frequency distribution of alleles associated with SP resistance were analysed among the P. vivax infections from malariometric surveys and its association with SP treatment failure in clinical studies in Indonesia. The dhfr and dhps alleles were detected using PCR-RFLP method.
  
  
  RESULTS
  Analysis of 159 P. vivax isolates from malariometric surveys and 69 samples from in vivo SP efficacy study revealed various the existence of various alleles of the pvdhfr and pfdhps genes including 57L/I, 58R, 61M, and 117N/T. Allele 13L of the dhfr gene and 553G of the dhps gene were not detected in any isolates examined in both studies. In the dhfr gene, tandem repeat type-A was the major tandem repeat observed in any isolates analysed. In the dhps gene, only the 383G allele was observed. Isolates carrying double, triple and quadruple mutants of dhfr gene were found in Lampung, Purworejo, Sumba, and Papua. Although this study revealed a wide distribution of dhfr and dhps alleles among the P. vivax isolates across a broad geographic regions in Indonesia, impact on SP efficacy was not observed in Sumba.
  
  
  CONCLUSIONS
  With proper malaria diagnosis, SP may still be used as a rational anti-malarial drug either as a single prescription or in combination with artemisinin.
authors.affiliation: Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. puji@eijkman.go.id.
authors.forename: Puji B S
authors.initials: PB
authors.lastname: Asih
authors.affiliation: Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. sylvia@eijkman.go.id.
authors.forename: Sylvia S
authors.initials: SS
authors.lastname: Marantina
authors.affiliation: Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. rodiah.nababan@yahoo.com.
authors.forename: Rodiah
authors.initials: R
authors.lastname: Nababan
authors.affiliation: Eck Institute for Global Health, University of Notre Dame, Notre Dame, IN, USA. nlobo@nd.edu.
authors.forename: Neil F
authors.initials: NF
authors.lastname: Lobo
authors.affiliation: Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. eko@eijkman.go.id.
authors.forename: Ismail E
authors.initials: IE
authors.lastname: Rozi
authors.affiliation: Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. wajiyo03@gmail.com.
authors.forename: Wajio
authors.initials: W
authors.lastname: Sumarto
authors.affiliation: Department of Biomedicine and Pharmacology, National Institute for Health Research and Development, Jakarta, Indonesia. rmdewi@gmail.com.
authors.forename: Rita M
authors.initials: RM
authors.lastname: Dewi
authors.affiliation: Department of Biomedicine and Pharmacology, National Institute for Health Research and Development, Jakarta, Indonesia. sekartuti@yahoo.com.
authors.forename: Sekar
authors.initials: S
authors.lastname: Tuti
authors.affiliation: Immunobiology Laboratory, School of Medicine, University of Mataram, Mataram, Indonesia. taufik.unram@gmail.com.
authors.forename: Ahmad S
authors.initials: AS
authors.lastname: Taufik
authors.affiliation: West Nusa Tenggara Hepatitis Laboratory, Mataram, Indonesia. mulyanto205@gmail.com.
authors.lastname: Mulyanto
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. r.sauerwein@mmb.umcn.nl.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Eijkman Institute for Molecular Biology, Jalan Diponegoro 69, Jakarta, 10430, Indonesia. din@eijkman.go.id.|Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makasar, Indonesia. din@eijkman.go.id.
authors.forename: Din
authors.initials: D
authors.lastname: Syafruddin
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics*; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000201:enzymology* / Q000235:genetics; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine