Artemisinin-derivative combination
therapies (ACT) are highly efficacious against multidrug-resistant
Plasmodium falciparum malaria. Few efficacy data, however, are available for
vivax malaria. With high rates of
chloroquine (CQ) resistance in both vivax and
falciparum malaria in Papua Province, Indonesia, new combination
therapies are required for both species. We recently found
artesunate plus
sulfadoxine-pyrimethamine (ART-SP) to be highly effective (96%) in the treatment of
falciparum malaria in Papua Province. Following a preliminary study of CQ plus
sulfadoxine-pyrimethamine (CQ-SP) for the treatment of Plasmodium vivax
infection, we used modified World Health Organization criteria to evaluate the efficacy of ART-SP for the treatment of
vivax malaria in Papua. Nineteen of 22 patients treated with ART-SP could be evaluated on day 28, with no early treatment failures. Adequate clinical and parasitological responses were found by day 14 in all 20 (100%) of the patients able to be evaluated and by day 28 in 17 patients (89.5%).
Fever and parasite clearance times were short, with hematological improvement observed in 70.6% of the patients. Double (at positions 58 and 117) and quadruple (at positions 57, 58, 61, and 117) mutations in the P. vivax
dihydrofolate reductase (PvDHFR) were common in Papuan P. vivax isolates (46 and 18%, respectively). Treatment failure with SP-containing regimens was significantly higher with isolates with this PvDHFR quadruple mutation, which included a novel T-->M mutation at residue 61 linked to an S-->T (but not an S-->N) mutation at residue 117. ART-SP ACT resulted in a high cure rate for both major Plasmodium species in Papua, though progression of DHFR mutations in both species due to the continued use of SP monotherapy for clinically diagnosed
malaria threatens the future utility of this combination.