Abstract
In 1982, 2 of 14 Plasmodium falciparum infections acquired in East Africa and diagnosed in Copenhagen were resistant to treatment with sulfadoxine plus pyrimethamine (Fansidar), while in 1983, 6 of 18 were so. The in vivo tests were supplemented by determinations of drug concentrations in serum, and 4 isolates from in vivo-sensitive cases and 6 from in vivo-resistant cases were selected for in vivo tests. These were performed in ordinary RPMI 1640 medium and in a medium with physiological p-aminobenzoic acid and folic acid concentrations. Pharmacokinetic aberrations were found to be of possible importance in only 2 of the in vivo-resistant cases. In vitro susceptibility to sulfadoxine was found to be uniformly low in all isolates. Testing with a combination of sulfadoxine and pyrimethamine in the medium with physiological concentrations of cofactors probably reflects the in vivo situation most accurately, but in all but 1 of the isolates studied in vitro the in vivo susceptibility to Fansidar would be predicted by in vitro susceptibility to pyrimethamine in either medium. The concentration of p-aminobenzoic acid in serum, quantitated by high performance liquid chromatography, was found to be subject to wide variation, and this may have implications for in vitro testing.
| Original language | English |
|---|---|
| Journal | American Journal of Tropical Medicine and Hygiene |
| Volume | 35 |
| Issue number | 2 |
| Pages (from-to) | 239-45 |
| Number of pages | 7 |
| ISSN | 0002-9637 |
| Publication status | Published - 1 Mar 1986 |
Keywords
- Adult
- Antimalarials
- Drug Combinations
- Drug Resistance, Microbial
- Humans
- Malaria
- Microbial Sensitivity Tests
- Plasmodium falciparum
- Pyrimethamine
- Sulfadoxine
- Sulfanilamides
