Treatment of uncomplicated falciparum malaria in southern Vietnam: can chloroquine or sulfadoxine-pyrimethamine be reintroduced in combination with artesunate?
The effectiveness of chloroquine or sulfadoxine-pyrimethamine administered with artesunate for treating uncomplicated falciparum malaria was assessed in 2 Vietnamese provinces where the sensitivity of parasites in vitro to conventional therapies had increased with the removal of drug pressure. In the province of Dac Lac, where potential malaria exposure begins at birth, 57 subjects (mean age, 9.6 years) were randomized to receive artesunate-chloroquine (group 1) or artesunate-sulfadoxine-pyrimethamine (group 2). In the province of Binh Phuoc, 66 nonimmune workers and their relatives (mean age, 24.2 years) were similarly randomized. By day 28 of follow-up, >96% of Dac Lac patients and <52% of Binh Phuoc patients in group 1 and group 2 had an in vivo response that demonstrated sensitivity to therapy. PCR-confirmed cure rates paralleled in vivo results among patients in Binh Phuoc, but PCR results identified 9 (15.7%) of the Dac Lac patients as having experienced asymptomatic, submicroscopic recrudescences. In Dac Lac, pfcrt K76T was near fixation, but infection with parasites with this mutation predicted recrudescence among group 1 patients in Binh Phuoc. Common pfdhfr mutations did not predict outcome in group 2. The successful reintroduction of conventional therapies in combination with artesunate depends on epidemiological and/or parasitological factors.
Nguyen
Mai Huong
MH
National Institute of Malariology, Parasitology and Entomology, Ministry of Health, Hanoi, Vietnam. (tdavis@cyllene.uwa.edu.au)
Davis
Timothy M E
TM
Cox-Singh
Janet
J
Hewitt
Sean
S
Tran
Quoc Toan
QT
Tran
Bach Kim
BK
Nguyen
Thi Hanh
TH
Vo
Nhu Phuong
NP
Doan
Hanh Nhan
HN
Le
Dinh Cong
DC
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002738:Chloroquine / Q000627:therapeutic use*; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D011739:Pyrimethamine / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014744:Vietnam
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine