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In Vitro Response of Plasmodium falciparum to Atovaquone and Correlation with other Antimalarials: Comparison between African and Asian Strains
Frederick Gay
Frederick Gay
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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Dorina Bustos
Dorina Bustos
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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Boubacar Traore
Boubacar Traore
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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Catherine Jardinel
Catherine Jardinel
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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Manivanh Southammavong
Manivanh Southammavong
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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Liliane Ciceron
Liliane Ciceron
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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M. Martin Danis
M. Martin Danis
Laboratoire d'Epidemiologie et de Chimioresistance du Paludisme, Departement de Medecine Tropicale, Groupe Hospitalier Pitie-Salpetriere, Research Institute for Tropical Medicine, Department of Health, Paris, France
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Atovaquone (dihydroxynaphthoquinone 566C80) is a broad-spectrum antiprotozoal compound demonstrating potent antimalarial activity against multidrug-resistant malaria. We present the results of in vitro drug sensitivity tests of 142 Plasmodium falciparum isolates, 108 from 14 countries of West and Central Africa, 32 from the Philippines, and one each from Laos and Myanmar. These were tested in vitro against nine drugs: the classic antimalarials chloroquine, quinine, mefloquine and halofantrine, the four qinghaosu derivatives, artemisinin, artemether, artesunate, and arteether, and the new compound atovaquone. Results showed the Asian strains have a higher median 50% inhibitory concentration (IC50) to almost all drugs compared with those from Africa. This was significantly different for chloroquine, halofantrine, and artemisinin. We used three different approaches to estimate the threshold for resistance of atovaquone to be approximately 5–7 nmol/L. The global median of 96 pooled strains is 1.4 nmol/L and the 90th percentile is 5.5 nmol/L for atovaquone. There were no correlations of atovaquone with the eight other antimalarials among African strains, but significant correlations, except for halofantrine, were observed among Asian strains. The absence of a correlation between atovaquone and the other available drugs indicates the potential of atovaquone as an alternative antimalarial in Africa. The correlation observed among Asian strains, however, suggests that atovaquone has to be used cautiously in Asia. Nevertheless, the association with proguanil in recently concluded clinical trials in Europe, South America, Asia, and Africa has demonstrated its antimalarial efficacy.
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| Past two years | Past Year | Past 30 Days | |
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