Susceptibility of Plasmodium falciparum to the drugs used to treat severe malaria (quinine) and to prevent malaria (mefloquine, cycloguanil) in Comoros Union and Madagascar

Abstract

Objectives: To monitor the sensitivity of Plasmodium falciparum to the drugs used to treat severe malaria and to prevent malaria in Comoros and Madagascar.

Design: We used the in vitro isotopic method to test the sensitivity of P. falciparum to quinine, mefloquine and cycloguanil.

Results: We tested fresh isolates of P. falciparum, collected from patients living in urban, suburban and rural areas and suffering from uncomplicated malaria in 2001, against at least one of the antimalarials cited above. In both countries all of the successfully tested isolates were sensitive to quinine (N = 243) and to cycloguanil (N = 67). The mean IC50 ranged from 85.7 to 133.7 nM for quinine. For cycloguanil, the mean IC50 ranged from 1.4 to 20.2 nM and the highest IC50 value (102.5 nM) was recorded in Comoros. Only 0.9% (1/110) of the informative isolates from Madagascar were mefloquine-resistant (0/18 in Comoros). The mefloquine mean IC50s were 8.2 nM, 14.1 nM and 11.6 nM respectively in the rural, suburban and urban areas of Madagascar, and 5.9 nM in Comoros. A positive correlation was found between quinine and mefloquine IC50s (N = 127, r = 0.48, p < 10(-6)), but in vitro mefloquine was 6-16 times more potent than quinine. No correlation was noticed between the activities of quinine and cycloguanil or between the activities of mefloquine and cycloguanil.

Conclusion: We therefore advocate the use of a full-course regimen of quinine, as recommended by the World Health Organisation (WHO), to treat above all severe malaria in Madagascar and Comoros. Our results also demonstrate that the use of mefloquine- and cycloguanil-based antimalarials is still justified to prevent malaria in both countries, mainly in the case of travellers.