title: In vivo susceptibility of Plasmodium falciparum to artesunate in Binh Phuoc Province, Vietnam.
abstract: BACKGROUND
  By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam.
  
  
  METHODS
  From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS) (2mg/kg/day versus 4 mg/kg/day for three days) followed by dihydroartemisinin-piperaquine (DHA-PPQ) and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time.
  
  
  RESULTS
  166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2.72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4%) and late clinical failure occurred in one (2%) of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR) rates in the three groups were 94%, 100%, and 100% (p=0.04).
  
  
  CONCLUSIONS
  This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but slower clearance in comparison with historical data from Vietnam. Further studies to determine whether this represents the emergence of artemisinin resistance in this area are needed. Currently, the therapeutic response to DHA-PPQ remains satisfactory in southern Vietnam.
  
  
  BACKGROUND
  NTC01165372.
authors.affiliation: Wellcome Trust Major Overseas Programme (MOP), Oxford University Clinical Research Unit (OUCRU), Ho Chi Minh City, Vietnam. hientt@oucru.org
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Thuy-Nhien
authors.forename: Nguyen Hoan
authors.initials: NH
authors.lastname: Phu
authors.forename: Maciej F
authors.initials: MF
authors.lastname: Boni
authors.forename: Ngo Viet
authors.initials: NV
authors.lastname: Thanh
authors.forename: Nguyen Thuy
authors.initials: NT
authors.lastname: Nha-Ca
authors.forename: Le Hong
authors.initials: le H
authors.lastname: Thai
authors.forename: Cao Quang
authors.initials: CQ
authors.lastname: Thai
authors.forename: Pham Van
authors.initials: PV
authors.lastname: Toi
authors.forename: Phung Duc
authors.initials: PD
authors.lastname: Thuan
authors.forename: Le Thanh
authors.initials: le T
authors.lastname: Long
authors.forename: Le Thanh
authors.initials: le T
authors.lastname: Dong
authors.forename: Laura
authors.initials: L
authors.lastname: Merson
authors.forename: Christiane
authors.initials: C
authors.lastname: Dolecek
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Pascal
authors.initials: P
authors.lastname: Ringwald
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Jeremy
authors.initials: J
authors.lastname: Farrar
authors.forename: Marcel
authors.initials: M
authors.lastname: Wolbers
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002648:Child; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D011804:Quinolines / Q000008:administration & dosage; D016896:Treatment Outcome; D014744:Vietnam; D055815:Young Adult; D010879:Piperazines
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines