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Plasmodium falciparum in Kisumu, Kenya: Differences in Sensitivity to Amodiaquine and Chloroquine in Vitro

Harrison C. Spencer, T. Kipingor, Richard Agure, D. Koech, Jeffrey D. Chulay

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Abstract

Sensitivity to amodiaquine and chloroquine was examined in 11 Plasmodium falciparum isolates from Kisumu, Kenya, and three chloroquine-resistant parasites. All 11 Kisumu isolates were sensitive to amodiaquine in vivo. Six of 10 Kisumu isolates successfully tested were more sensitive to amodiaquine in a microtest (minimal inhibitory concentration [MIC], less than or equal to 114 nM for amodiaquine vs 160 nM for chloroquine) and/or 48-hr in vitro tests (MIC, 60 nM for amodiaquine vs 100 nM for chloroquine). All nine successfully cultured Kisumu isolates had a lower 50% inhibitory dose (ID50) for amodiaquine (9.0-18.2 nM) than for chloroquine (24.9-75.4 nM) in a radioisotopic assay. Five were also more sensitive when retested in the 48-hr test. The chloroquine-resistant parasites had reduced in vitro sensitivity to chloroquine (ID50, greater than or equal to 103 nM; MIC, 300 nM) but not to amodiaquine (ID50, less than or equal to 22 nM; MIC, less than or equal to 100 nM). These data indicate that amodiaquine is more potent than chloroquine and should be evaluated for efficacy against P falciparum in areas where RI and RII chloroquine resistance occurs.

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What this paper is about

Sensitivity to amodiaquine and chloroquine was examined in 11 Plasmodium falciparum isolates from Kisumu, Kenya, and three chloroquine-resistant parasites. All 11 Kisumu isolates were sensitive to amodiaquine in vivo. Six of 10 Kisumu isolates successfully tested were more sensitive to amodiaquine in a microtest (minimal inhibitory concentration [MIC], less than or equal to 114 nM for amodiaquine vs 160 nM for chloroquine) and/or 48-hr in vitro tests (MIC, 60 nM for amodiaquine vs 100 nM for chloroquine). All nine successfully cultured Kisumu isolates had a lower 50% inhibitory dose (ID50) for amodiaquine (9.0-18.2 nM) than for chloroquine (24.9-75.4 nM) in a radioisotopic assay. Five were also more sensitive when retested in the 48-hr test. The chloroquine-resistant parasites had reduced in vitro sensitivity to chloroquine (ID50, greater than or equal to 103 nM; MIC, 300 nM) but not to amodiaquine (ID50, less than or equal to 22 nM; MIC, less than or equal to 100 nM). These data indicate that amodiaquine is more potent than chloroquine and should be evaluated for efficacy against P falciparum in areas where RI and RII chloroquine resistance occurs.

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Available abstract

Sensitivity to amodiaquine and chloroquine was examined in 11 Plasmodium falciparum isolates from Kisumu, Kenya, and three chloroquine-resistant parasites. All 11 Kisumu isolates were sensitive to amodiaquine in vivo. Six of 10 Kisumu isolates successfully tested were more sensitive to amodiaquine in a microtest (minimal inhibitory concentration [MIC], less than or equal to 114 nM for amodiaquine vs 160 nM for chloroquine) and/or 48-hr in vitro tests (MIC, 60 nM for amodiaquine vs 100 nM for chloroquine). All nine successfully cultured Kisumu isolates had a lower 50% inhibitory dose (ID50) for amodiaquine (9.0-18.2 nM) than for chloroquine (24.9-75.4 nM) in a radioisotopic assay. Five were also more sensitive when retested in the 48-hr test. The chloroquine-resistant parasites had reduced in vitro sensitivity to chloroquine (ID50, greater than or equal to 103 nM; MIC, 300 nM) but not to amodiaquine (ID50, less than or equal to 22 nM; MIC, less than or equal to 100 nM). These data indicate that amodiaquine is more potent than chloroquine and should be evaluated for efficacy against P falciparum in areas where RI and RII chloroquine resistance occurs.

Key concepts: Amodiaquine, Chloroquine, Plasmodium falciparum, Malaria, In vitro, Virology, Medicine, Biology

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