Dihydroartemisinin-piperaquine against multidrug-resistant Plasmodium falciparum malaria in Vietnam: randomised clinical trial.
BACKGROUND
Southeast Asia has the most resistant malaria parasites in the world, which severely limits treatment options. There is general acceptance that to combat resistance, combinations of antimalarial drugs that include an artemisinin derivative should be used, and, if possible, these should be formulated in a single tablet.


METHODS
We did a pilot randomised study in a tertiary referral hospital in Vietnam to compare the efficacy of 3-day regimens of dihydroartemisinin-trimethoprim-piperaquine (DHA-TP total dose 4.8/13.6/48 mg/kg, respectively) with the standard antimalarial regimen in Vietnam, artesunate-mefloquine (A3M total dose 12/25 mg/kg, respectively) in non-immune patients with uncomplicated Plasmodium falciparum malaria. 114 patients were randomised, 76 to DHA-TP and 38 to A3M. The subsequent open randomised trial at a Provincial Health Station compared DHA-TP, dihydroartemisinin-piperaquine, and A3M in 400 patients. In both studies all patients received directly observed therapy and were followed up for 56 days. The primary endpoint was reappearance of P falciparum malaria within 56 days of treatment. Analysis was by intention to treat.


RESULTS
The 56-day cure rate in the pilot study, adjusted for reinfections identified by PCR genotyping, was 97.4% (74/76) in the DHA-TP group and 100% (38/38) in the A3M group. In the second study, cure rates were similar in the three groups; DHA-TP 97.4% (153/157), dihydroartemisinin-piperaquine 98.7% (164/166), and A3M 98.7% (76/77). The DHA-TP and dihydroartemisinin-piperaquine regimens were well tolerated; fewer than 3% of patients had side-effects that might have been related to treatment, compared with 16% of A3M patients (p<0.001). No patients were lost to follow-up.


CONCLUSIONS
Dihydroartemisinin-piperaquine is an inexpensive, safe, highly efficacious fixed-dose antimalarial combination treatment that could make an important contribution to the control of multidrug-resistant falciparum malaria.
Tran
Tinh Hien
TH
Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam.
Dolecek
Christiane
C
Pham
Phuong Mai
PM
Nguyen
Thi Dung
TD
Nguyen
Thanh Truong
TT
Le
Hong Thai
HT
Dong
Thi Hoai An
TH
Tran
Tan Thanh
TT
Stepniewska
Kasia
K
White
Nicholas J
NJ
Farrar
Jeremy
J
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology / Q000517:prevention & control; D008297:Male; D010865:Pilot Projects; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D011804:Quinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014295:Trimethoprim / Q000008:administration & dosage / Q000627:therapeutic use; D014744:Vietnam; D010879:Piperazines
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011804:Quinolines; D012717:Sesquiterpenes; D014295:Trimethoprim; C039060:artenimol; C034759:piperaquine; D010879:Piperazines