In vitro sensitivity of Plasmodium falciparum and clinical response to lumefantrine (benflumetol) and artemether.

AIMS: To assess the sensitivity of 103 Plasmodium falciparum isolates to a combination of lumefantrine (benflumetol) and artemether (CGP 56697), with the objective of determining a correlation between in vitro drug sensitivity and therapeutic outcome. METHODS: Patients suffered from uncomplicated falciparum malaria and came from areas of Thailand affected by multidrug resistance. CGP 56697 was given in the form of tablets containing 20 mg artemether and 120 mg lumefantrine. The standard dose regimen, 4 doses of 4 tablets over 48 h, was compared with two lower dose regimens (4 x 2 tablets and 3 x 4 tablets). RESULTS: The parasites showed high resistance to chloroquine, fairly advanced resistance to mefloquine and compromised sensitivity to quinine. Sensitivity to artemisinin and lumefantrine prior to treatment was similar in all treatment groups. The 4 x 4 tablet regimen was more effective than the other regimens in coping with infections with relatively low sensitivity to artemisinin and/or lumefantrine. The EC90 for artemisinin is an important determinant of treatment success. Parasite density at the start of treatment was identified as another critical predictor of treatment outcome. CONCLUSIONS: The results indicate that parasite exposure to the drugs may have been inadequate and/or too short in the cases of treatment failure, particularly marked in the lower dose regimens. This could probably be remedied by expanding the dose regimen in areas affected by multidrug resistance and in the case of relatively high parasitaemia.

Decrease in susceptibility of Plasmodium falciparum to mefloquine in continuous culture.

Chloroquine-resistant P. falciparum, line FCK from Thailand, was tested for susceptibility to mefloquine in continuous culture. The drug resulted in 50% schizont inhibition at the level of 8.0 nmol/ml of culture when tested for the first time. After three months of discontinuous exposure to mefloquine at increasing levels, the sensitivity of the parasite decreased. A concentration as high as 128 nmol/ml eventually was required for 50% inhibition of growth.