title: In vivo parasitological measures of artemisinin susceptibility.
abstract: Parasite clearance data from 18,699 patients with falciparum malaria treated with an artemisinin derivative in areas of low (n=14,539), moderate (n=2077), and high (n=2083) levels of malaria transmission across the world were analyzed to determine the factors that affect clearance rates and identify a simple in vivo screening measure for artemisinin resistance. The main factor affecting parasite clearance time was parasite density on admission. Clearance rates were faster in high-transmission settings and with more effective partner drugs in artemisinin-based combination treatments (ACTs). The result of the malaria blood smear on day 3 (72 h) was a good predictor of subsequent treatment failure and provides a simple screening measure for artemisinin resistance. Artemisinin resistance is highly unlikely if the proportion of patients with parasite densities of <100,000 parasites/microL given the currently recommended 3-day ACT who have a positive smear result on day 3 is <3%; that is, for n patients the observed number with a positive smear result on day 3 does not exceed (n + 60)/24.
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand. kasia@tropmedres.ac
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ashley
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Nicholas
authors.initials: N
authors.lastname: Anstey
authors.forename: Karen I
authors.initials: KI
authors.lastname: Barnes
authors.forename: Tran Quang
authors.initials: TQ
authors.lastname: Binh
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Peter J
authors.initials: PJ
authors.lastname: de Vries
authors.forename: Grant
authors.initials: G
authors.lastname: Dorsey
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Guthmann
authors.forename: Mayfong
authors.initials: M
authors.lastname: Mayxay
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Piero
authors.initials: P
authors.lastname: Olliaro
authors.forename: Lyda
authors.initials: L
authors.lastname: Osorio
authors.forename: Ric N
authors.initials: RN
authors.lastname: Price
authors.forename: Mark
authors.initials: M
authors.lastname: Rowland
authors.forename: Frank
authors.initials: F
authors.lastname: Smithuis
authors.forename: Walter R J
authors.initials: WR
authors.lastname: Taylor
authors.forename: François
authors.initials: F
authors.lastname: Nosten
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D019353:Endemic Diseases; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology* / Q000635:transmission; D008875:Middle Aged; D018512:Parasitemia / Q000188:drug therapy / Q000453:epidemiology / Q000469:parasitology* / Q000635:transmission; D010963:Plasmodium falciparum / Q000187:drug effects*; D012008:Recurrence
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin