Sulfadoxine-Pyrimethamine for the Treatment of Acute Malaria in Children in Papua New Guinea

Darlow, Brian A; Jolley, Damien; Gibney, Sean; Stace, John; Alpers, Michael P.; H, Vrbova

doi:10.4269/ajtmh.1982.31.10

Cited by 20 publications

(13 citation statements)

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“…These mutations are associated with lower 48-h parasite reduction ratios following monotherapy of P. vivax infection with SP than are isolates with double mutations (at positions 58 and 117); however, no differences in cure rates have been demonstrated (16). Even when P. vivax is sensitive to pyrimethamine, SP therapy of vivax malaria results in slow clearance of parasites and fever (9). Therefore, SP is not recommended as monotherapy for P. vivax in Indonesia (13).…”

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confidence: 97%

Therapeutic Efficacies of Artesunate-Sulfadoxine-Pyrimethamine and Chloroquine-Sulfadoxine-Pyrimethamine in Vivax Malaria Pilot Studies: Relationship to Plasmodium vivax dhfr Mutations

Tjitra

Baker²,

Suprianto

et al. 2002

Antimicrob Agents Chemother

115

132

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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 T3M mutation at residue 61 linked to an S3T (but not an S3N) 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.High rates of chloroquine (CQ) resistance and CQ treatment failure have been found in both vivax and falciparum malaria in Papua Province (formerly Irian Jaya), Indonesia (2,3,5,21,28,38), and new combination therapies are required for each species. Artemisinin-derivative combination therapies (ACT) are being used increasingly for the treatment of multidrug-resistant Plasmodium falciparum malaria (29) because of their excellent efficacy (23,31,39,41), their ability to slow or reverse the emergence of resistance (24, 30), and their ability to reduce malaria transmission (24, 30). Despite the coexistence of falciparum and vivax malaria in many parts of the world where malaria treatment is usually based on clinical diagnosis, there have been few studies assessing the efficacy of artemisinin derivatives in treating vivax malaria and none in the area of CQ-resistant P. vivax. Studies of artesunate (ART) monotherapy for P. vivax infection have demonstrated rapid clearance of fever and parasites (1,6,33,43). However, with its very short half-life, no ART remains by the time of the first relapse of P. vivax infection, approximately 3 weeks after treatment begins, resulting in a high frequency of...

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confidence: 97%

Therapeutic Efficacies of Artesunate-Sulfadoxine-Pyrimethamine and Chloroquine-Sulfadoxine-Pyrimethamine in Vivax Malaria Pilot Studies: Relationship to Plasmodium vivax dhfr Mutations

Tjitra

Baker²,

Suprianto

et al. 2002

Antimicrob Agents Chemother

115

132

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“…Most commonly used antimalarial drugs are also active against the asexual stages of P. vivax, the exception being the antifolates, which act slowly, 40 and are vulnerable to the rapid development of drug resistance. 41,42 Mefloquine, 43 atovaquone + proguanil, 44 halofantrine, 45 piperaquine, 46 artesunate, 47,48 and pyronaridine, 49 all show good efficacy against chloroquine-resistant (CQR) P. vivax in clinical trials.…”

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confidence: 99%

Diagnosis and Treatment of Plasmodium vivax Malaria

Baird

Maguire

Price

2012

Advances in Parasitology

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“…Since the two species cannot be differentiated on clinical grounds, malaria infections, whether due to P. falciparum or P. vivax, are treated with S-P. Unfortunately, S-P is less effective in clearing fever and parasites in patients infected with P. vivax than in those infected with P. falciparum (9,11). Earlier studies had already shown that sulfa drugs are less active against P. vivax than against P. falciparum (16,18,20).…”

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Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

Korsinczky

Fischer

Chen³

et al. 2004

Antimicrob Agents Chemother

109

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Sulfadoxine is predominantly used in combination with pyrimethamine, commonly known as Fansidar, for the treatment of Plasmodium falciparum. This combination is usually less effective against Plasmodium vivax, probably due to the innate refractoriness of parasites to the sulfadoxine component. To investigate this mechanism of resistance by P. vivax to sulfadoxine, we cloned and sequenced the P. vivax dhps (pvdhps) gene. The protein sequence was determined, and three-dimensional homology models of dihydropteroate synthase (DHPS) from P. vivax as well as P. falciparum were created. The docking of sulfadoxine to the two DHPS models allowed us to compare contact residues in the putative sulfadoxine-binding site in both species. The predicted sulfadoxine-binding sites between the species differ by one residue, V585 in P. vivax, equivalent to A613 in P. falciparum. V585 in P. vivax is predicted by energy minimization to cause a reduction in binding of sulfadoxine to DHPS in P. vivax compared to P. falciparum. Sequencing dhps genes from a limited set of geographically different P. vivax isolates revealed that V585 was present in all of the samples, suggesting that V585 may be responsible for innate resistance of P. vivax to sulfadoxine. Additionally, amino acid mutations were observed in some P. vivax isolates in positions known to cause resistance in P. falciparum, suggesting that, as in P. falciparum, these mutations are responsible for acquired increases in resistance of P. vivax to sulfadoxine.

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Sulfadoxine-Pyrimethamine for the Treatment of Acute Malaria in Children in Papua New Guinea

Cited by 20 publications

References 0 publications

Therapeutic Efficacies of Artesunate-Sulfadoxine-Pyrimethamine and Chloroquine-Sulfadoxine-Pyrimethamine in Vivax Malaria Pilot Studies: Relationship to Plasmodium vivax dhfr Mutations

Therapeutic Efficacies of Artesunate-Sulfadoxine-Pyrimethamine and Chloroquine-Sulfadoxine-Pyrimethamine in Vivax Malaria Pilot Studies: Relationship to Plasmodium vivax dhfr Mutations

Diagnosis and Treatment of Plasmodium vivax Malaria

Sulfadoxine Resistance in Plasmodium vivax Is Associated with a Specific Amino Acid in Dihydropteroate Synthase at the Putative Sulfadoxine-Binding Site

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