Short report: effects of pyronaridine on gametocytes in patients with acute uncomplicated falciparum malaria.

The effects of pyronaridine and chloroquine on mature Plasmodium falciparum gametocytes were compared in 161 patients treated with chloroquine or pyronaridine. Neither pyronaridine nor chloroquine showed gametocytocidal activity. The relative risks of post-treatment gametocytemia after pyronaridine and chloroquine treatment in the presence of chloroquine-resistant isolates were 1.25 and 11.5, respectively, suggesting that the use of chloroquine was associated with a high risk of favoring post-therapeutic gametocytemia in chloroquine-resistant infections.

In vitro culture and drug sensitivity assay of Plasmodium falciparum with nonserum substitute and acute-phase sera.

The short-term in vitro growth of Plasmodium falciparum parasites in the asexual erythrocytic stage and the in vitro activities of eight standard antimalarial drugs were assessed and compared by using RPMI 1640 medium supplemented with 10% nonimmune human serum, 10% autologous or homologous acute-phase serum, or 0.5% Albumax I (lipid-enriched bovine serum albumin). In general, parasite growth was maximal with autologous (or homologous) serum, followed by Albumax I and nonimmune serum. The 50% inhibitory concentrations (IC50s) varied widely, depending on the serum or serum substitute. The comparison of IC50s between assays with autologous and nonimmune sera showed that monodesethylamodiaquine, halofantrine, pyrimethamine, and cycloguanil had similar IC50s. Although the IC50s of chloroquine, monodesethylamodiaquine, and dihydroartemisinin were similar with Albumax I and autologous sera, the IC50s of all test compounds obtained with Albumax I differed considerably from the corresponding values obtained with nonimmune serum. Our results suggest that Albumax I and autologous and homologous sera from symptomatic, malaria-infected patients may be useful alternative sources of serum for in vitro culture of P. falciparum isolates in the field. However, autologous sera and Albumax I do not seem to be suitable for the standardization of isotopic in vitro assays for all antimalarial drugs.

In vitro activities of DU-1102, a new trioxaquine derivative, against Plasmodium falciparum isolates.

The antimalarial trioxaquine derivative DU-1102, synthesized by covalent linkage between aminoquinoline and trioxane moieties, was highly active against Cameroonian isolates (mean 50% inhibitory concentration of 43 nmol/liter) of Plasmodium falciparum. There was no correlation between the responses to DU-1102 and chloroquine and only a low correlation between the responses to DU-1102 and pyrimethamine, suggesting an independent mode of action of the trioxaquine against the parasites.