Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: KEGG:D02448 (Fansidar)
 243 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination of pyrimethamine and sulfadoxine (PSD or Fansidar) represents one of the most important chemotherapeutic agents currently used to treat falciparum malaria. To investigate the molecular basis of resistance to PSD, reliable in vitro drug assays are required to permit correlation of resistance levels with different genotypes. We describe here protocols that permit accurate evaluation of IC50 values for sulfadoxine (SDX) inhibition of Plasmodium falciparum. Historically, tests for this drug have suffered from poor reproducibility and extreme variability in reported values. We have examined a series of variables, including serum-containing versus serum-free media, erythrocyte source, pre-test growth conditions, test components and post-test processing. We define conditions which better control the levels of the drug antagonists folate and p-aminobenzoate, yielding reproducible differences between lines of P. falciparum with differing alleles of the dihydropteroatic synthetase gene, which encodes the target enzyme of SDX. We also use this assay to demonstrate a marked difference in the response of different parasite lines to antagonism of SDX inhibition by exogenous folate. The ability to measure reliable IC50 values for SDX inhibition should greatly facilitate further experiments to explore the molecular basis of Fansidar resistance.
 ...
PMID:A modified in vitro sulfadoxine susceptibility assay for Plasmodium falciparum suitable for investigating Fansidar resistance. 930 Apr 59

As part of a study to assess the infectivity of gametocytes after treatment with four antimalarial regimens, the efficacy of each treatment was also determined. From September to December 1998, 598 children with uncomplicated malaria were treated; 135 received chloroquine (CQ) alone, 276 received pyrimethamine/sulfadoxine (Fansidar, PSD) alone, 113 received PSD with a single dose of artesunate (PSD + 1ART) and 74 received PSD combined with three doses of artesunate (PSD + 3ART). On day 28 19/63 (30.2%; 95% C.I. 19.2% to 43.1%) of children treated with CQ alone, 5/134 (3.7%; 95% C.I. 1.2% to 8.5%) treated with PSD alone, 1/71 (1.4%, 95% C.I. 0.0% to 7.9%) treated with PSD + 1ART and 0/45 (0.0%; 95% C.I. 0.0% to 7.9%) treated with PSD + 3ART were parasitaemic. The proportion of children with gametocytes on day 7 after treatment with CQ alone was 16/89 (18.0%; 95% C.I. 10.6% to 27.6%), 98/174 (56.3%; 95% C.I. 48.6% to 63.8%) after treatment with PSD alone, 8/70 (11.4%; 95% C.I. 5.1% to 21.3%) after treatment with PSD + 1ART and 4/46 (8.7%; 95% C.I., 2.4% to 20.8%) after treatment with PSD + 3ART. CQ thus has a lower efficacy than PSD or either of the PSD and artesunate combinations. Use of PSD alone as an alternative first line treatment results in a very high post-treatment gametocyte prevalence that is likely to enhance transmission. There would be greater and more sustainable benefits from using PSD and artesunate combinations.
 ...
PMID:Parasitaemia and gametocytaemia after treatment with chloroquine, pyrimethamine/sulfadoxine, and pyrimethamine/sulfadoxine combined with artesunate in young Gambians with uncomplicated malaria. 1125 3