Randomized, controlled dose-optimization studies of dihydroartemisinin-piperaquine for the treatment of uncomplicated multidrug-resistant falciparum malaria in Thailand.
BACKGROUND
Dihydroartemisinin-piperaquine (DP) is a new and relatively inexpensive artemisinin-containing fixed-combination antimalarial treatment. An adult treatment course contained 6.4 mg/kg dihydroartemisinin (DHA), which is >40% lower than the level in most artemisinin-containing combinations. This raised the possibility that the efficacy of the current coformulation may not be optimal in the treatment of multidrug-resistant falciparum malaria.


METHODS
In 2 large randomized, controlled studies in Thailand, the recommended dose of DP was compared with a regimen with additional artemisinin derivative (12 mg/kg; DP+) and with mefloquine plus artesunate (MAS3).


RESULTS
A total of 731 patients were included: 201 in a hospital-based study and 530 in a community study. Day-28 cure rates in the hospital-based study were 100% (95% confidence interval [CI], 93.9%-100%) in the MAS3 and DP+ groups and 98.3% (95% CI, 91%-99.7%) in the DP group, with a single recrudescence on day 21. In the community study, polymerase chain reaction genotyping-adjusted cure rates on day 63 were 96.1% (95% CI, 92.6%-99.7%) in the DP group, 98.3% (95% CI, 96.1%-100%) in the DP+ group, and 94.9% (95% CI, 91.2%-98.6%) in the MAS3 group (P=.2). Adverse events were few, with an excess of mild abdominal pain in the DP group.


CONCLUSIONS
The current dosage of DP (6.4 mg/kg DHA and 51.2 mg/kg piperaquine phosphate) given over the course of 48 h is highly effective, safe, and well tolerated for the treatment of multidrug-resistant falciparum malaria, and its efficacy is not improved by the addition of more DHA.
Ashley
Elizabeth A
EA
Shoklo Malaria Research Unit, Mae Sot, and Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Krudsood
Srivicha
S
Phaiphun
Lucy
L
Srivilairit
Siripan
S
McGready
Rose
R
Leowattana
Wattana
W
Hutagalung
Robert
R
Wilairatana
Polrat
P
Brockman
Alan
A
Looareesuwan
Sornchai
S
Nosten
Francois
F
White
Nicholas J
NJ
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D011804:Quinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013785:Thailand; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D004338:Drug Combinations; D015767:Mefloquine; D011804:Quinolines; D012717:Sesquiterpenes; C039060:artenimol; C034759:piperaquine; D010879:Piperazines