IN-VITRO RESPONSE OF PLASMODIUM-FALCIPARUM TO ATOVAQUONE AND CORRELATION WITH OTHER ANTIMALARIALS - COMPARISON BETWEEN AFRICAN AND ASIAN STRAINS

Atovaquone (dihydroxynaphthoquinone 566C80) is a broad-spectrum antipr otozoal compound demonstrating potent antimalarial activity against mu ltidrug-resistant malaria. We present the results of in vitro drug sen sitivity tests of 142 Plasmodium falciparum isolates, 108 from 14 coun tries of West and Central Africa, 32 from the Philippines, and one eac h from Laos and Myanmar. These were tested in vitro against nine drugs : the classic antimalarials chloroquine, quinine, mefloquine and halof antrine, the four qinghaosu derivatives, artemisinin, artemether, arte sunate, 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 si gnificantly different for chloroquine, halofantrine, and artemisinin. We used three different approaches to estimate the threshold for resis tance 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 e ight other antimalarials among African strains, but significant correl ations, except for halofantrine, were observed among Asian strains. Th e absence of a correlation between atovaquone and the other available drugs indicates the potential of atovaquone as an alternative antimala rial in Africa. The correlation observed among Asian strains, however, suggests that atovaquone has to be used cautiously in Asia. Neverthel ess, the association with proguanil in recently concluded clinical tri als in Europe, South America, Asia, and Africa has demonstrated its an timalarial efficacy.