Amodiaquine as the first-line treatment of malaria in Yaoundé, Cameroon: presumptive evidence from activity in vitro and cross-resistance patterns.

The spread of chloroquine-resistant Plasmodium falciparum in most counmes in sub-saharan Africa has raised an urgent need to determine what alternative antimalarial drug should replace chloroquine for the first-line oral treatment of acute uncomplicated falciparum malaria. The drug must satisfy the following requirements to be a viable option in Africa: high and rapid clinical efficacy, short treatment course, good tolerance, safety, and low cost. Two well-known antimalarial drugs satisfy these criteria: pyrimethaminehlfadoxine and amodiaquine. Of these 2 candidates, the Cameroonian Ministry of Health has chosen amodiaquine as an immediate successor for chloroquine, keeping pyrimethamine/sulfadoxine as a second-line drug. Although the World Health Organization (WHO) has officially recommended the suspension of clinical use of amodiaquine, both for chemoprophylaxis and treatment, recent meta-analysis of amodiaquine treatment seems to suggest that WHO is currently re-evaluating its past recommendations in the light of newer experience (WHO, 1990a; O m o et al., 1996). To evaluate whether amodiaquine still retains its activity ill vitro and in vivo against chloroquine-resistant P. fakiparum in Central Africa, we analysed our recent in vitro data, together with clinical observations of amodiaquine-treated patients in Yaoundé, Cameroon, where previous studies have established that 50-60% of patients fail to respond favourably to chloroquine, with RI resistance in most cases (LOUIS et al., 1992; RINGWALD et al., 1996a). Between 1994 and 1997, 135 clinical isolates of P. falciparum were obtained fkom symptomatic Cameroonian adults and children attending Nlongkak Catholic missionary dispensary (where amodiaquine was initiated as the first-line treatment in 1992) to determine the activity in vitro of chloroquine and monodesethylamodiaquine, a major biologically active human metabolite of amodiaquine, using the isotopic semi-microtest or microtest (DESJARDINS et al., 1979; RINGWALD et al., 1996b). This study was approved by the Cameroonian national ethics committee. The results obtained from individual isolates were expressed as 50% inhibitory concentration (IC50). IC,, values obtained by the semimicrotest and the microtest are concordant (BICKII et al., in press). Based on our previous studies, the threshold IC50 values for chloroquine resistance and monodesethylamodiaquine resistance were fixed at 1 O0 nM and 60 nM, respectively (BASCO & LE BRAS,