In-vitro sensitivity of Plasmodium falciparum to chloroquine, halofantrine, mefloquine and quinine in Madagascar.

To determine how sensitive Plasmodium falciparum is to the major antimalarial drugs in Madagascar. Assessment of Plasmodium falciparum isolates sensitivity to antimalarials, by use of the in-vitro radioisotope method. Ankazobe and Saharevo in the foothill areas; and Toamasina and Tolagnaro in the coastal areas (between January 1998 and November 1999). Primary Plasmodium falciparum isolates from patients with uncomplicated malaria attack. Between January 1998 and November 1999, of the 293 in-vitro tests done with at least one antimalarial, 70% (205/293) were interpretable. As there was no significant difference between results from the four study sites, the data have been expressed as a whole. All of the successfully tested isolates were sensitive to halofantrine (n = 56) and to quinine (n = 199), 5.8% (12/205) of the isolates were resistant to chloroquine and 2% (4/199) to mefloquine. The geometric mean IC50 was 0.3 microg/L for halofantrine (95% CI = 0.1-0.4 microg/L); 9.4 microg/L for chloroquine (95% CI = 7.3-10.8 microg/L); 3.8 microg/L for mefloquine (95% CI = 3.3-4.3 microg/L); and 26.8 microg/L for quinine (95% CI = 24.3-29.4 microg/L). The low positive correlation found between halofantrine and chloroquine IC50s (n = 56; r = 0.41, P = 0.002) suggests a risk of cross-resistance between these two drugs. The degree and frequency of chloroquine resistance in-vitro is stationary in Madagascar compared to previous results during the last decade. The in-vitro sensitivity of P. falciparum to quinine, mefloquine and halofantrine encourages the use of these drugs as alternative in case of chloroquine treatment failure. Nevertheless, it is important to maintain and to extend malaria and drug sensitivity surveillance in Madagascar.