A randomized comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine combined with primaquine for radical treatment of vivax malaria in Sumatera, Indonesia.
BACKGROUND
A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established.


METHODS
We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year.


RESULTS
Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%-18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%-3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%-15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ.


CONCLUSIONS
In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated.


BACKGROUND
NCT01288820.
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Ayodhia Pitaloka
AP
Pasaribu
Watcharee
W
Chokejindachai
Chukiat
C
Sirivichayakul
Naowarat
N
Tanomsing
Irwin
I
Chavez
Emiliana
E
Tjitra
Syahril
S
Pasaribu
Mallika
M
Imwong
Nicholas J
NJ
White
Arjen M
AM
Dondorp
D000293:Adolescent; D000328:Adult; D000368:Aged; D000655:Amodiaquine / Q000009:adverse effects / Q000627:therapeutic use*; D000962:Antimalarials / Q000009:adverse effects / Q000627:therapeutic use*; D037621:Artemisinins / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007214:Indonesia; D053208:Kaplan-Meier Estimate; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D010966:Plasmodium vivax / Q000187:drug effects; D011319:Primaquine / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D011804:Quinolines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D010879:Piperazines
D000655:Amodiaquine; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D011319:Primaquine; D011804:Quinolines; C515299:amodiaquine, artesunate drug combination; C039060:artenimol; C034759:piperaquine; D010879:Piperazines
Indonesia; Plasmodium vivax; primaquine; radical cure