In vivo parasitological measures of artemisinin susceptibility.
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.
Stepniewska
Kasia
K
Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand. kasia@tropmedres.ac
Ashley
Elizabeth
E
Lee
Sue J
SJ
Anstey
Nicholas
N
Barnes
Karen I
KI
Binh
Tran Quang
TQ
D'Alessandro
Umberto
U
Day
Nicholas P J
NP
de Vries
Peter J
PJ
Dorsey
Grant
G
Guthmann
Jean-Paul
JP
Mayxay
Mayfong
M
Newton
Paul N
PN
Olliaro
Piero
P
Osorio
Lyda
L
Price
Ric N
RN
Rowland
Mark
M
Smithuis
Frank
F
Taylor
Walter R J
WR
Nosten
François
F
White
Nicholas J
NJ
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
D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin