[In vitro sensitivity of Plasmodium falciparum isolates from Gabon to chloroquine and cycloguanil]. / Sensibilité in vitro d'isolats gabonais de Plasmodium falciparum vis-à-vis de la chloroquine et du cycloguanil.

The in vitro susceptibility of 91 Plasmodium falciparum isolates obtained from malaria-infected children living near Libreville (Gabon) was evaluated against chloroquine and cycloguanil (biologically active metabolite of proguanil), using an isotopic micro-drug susceptibility test. In vitro resistance to chloroquine and cycloguanil was observed in 83% (35/42) and in 38% (30/78) of the patients, respectively. Our data showed that 41% (16/39) of Gabonese field isolates were resistant both to chloroquine and cycloguanil. These findings are of great importance because they might indicate imminent chloroquine-proguanil failure, and there are not many affordable antimalarial drugs to replace chloroquine-proguanil combination.

In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.

In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine.

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 34.8 nM (mean IC50 5.0 nM) and the 95% confidence interval (CI95%) was 3.6-6.3 nM. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2 = 0.45, P < 0.001), artemether and chloroquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.31, P < 0.001), and artemether and halofantrine (r2 = 0.19, P < 0.01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.