title: Quinine treatment selects the pfnhe-1 ms4760-1 polymorphism in Malian patients with Falciparum malaria.
abstract: BACKGROUND
  The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13.
  
  
  METHODS
  We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing.
  
  
  RESULTS
  Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment.
  
  
  CONCLUSIONS
  This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy, and Odonto-Stomatology,  University of Science, Techniques and Technology, Bamako,  Mali.
authors.forename: Aminatou
authors.initials: A
authors.lastname: Kone
authors.forename: Jianbing
authors.initials: J
authors.lastname: Mu
authors.forename: Hamma
authors.initials: H
authors.lastname: Maiga
authors.forename: Abdoul H
authors.initials: AH
authors.lastname: Beavogui
authors.forename: Omar
authors.initials: O
authors.lastname: Yattara
authors.forename: Issaka
authors.initials: I
authors.lastname: Sagara
authors.forename: Mamadou M
authors.initials: MM
authors.lastname: Tekete
authors.forename: Oumar B
authors.initials: OB
authors.lastname: Traore
authors.forename: Antoine
authors.initials: A
authors.lastname: Dara
authors.forename: Souleymane
authors.initials: S
authors.lastname: Dama
authors.forename: Nouhoum
authors.initials: N
authors.lastname: Diallo
authors.forename: Aly
authors.initials: A
authors.lastname: Kodio
authors.forename: Aliou
authors.initials: A
authors.lastname: Traoré
authors.forename: Anders
authors.initials: A
authors.lastname: Björkman
authors.forename: Jose P
authors.initials: JP
authors.lastname: Gil
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wellems
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimde
mesh_terms: D000595:Amino Acid Sequence; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance / Q000235:genetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008302:Mali; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011803:Quinine / Q000494:pharmacology / Q000627:therapeutic use*; D016415:Sequence Alignment; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics*
chemical_list: D000962:Antimalarials; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D011803:Quinine