PROGRESSIVE INCREASE OF RESISTANCE OF PLA SMODIUM-FALCIPARUM TO AMINO-4-QUINOLEINS IN THE HIGHLANDS OF MADAGASCAR

Malaria in Madagascar is one of the first causes of death and hospital ization and remains a real public health problem. Recent research prov es that the resistance of the R III type, which is very widespread not ably in Central Africa does not yet exist on the Island, even though a decrease in sensitivity of the Malgasy strains of Plasmodium falcipar um has been reported. A surveillance of the sensitivity to the amino-4 -quinoleins has been carried out since 1988 by the malaria laboratory of the Pasteur institute of Madagascar. Until recent years, the level of resistance had maintained itself at from 10 to 15 % of In vitro res istance (Ankazobe region) and from 10 to 35 % of parasitological failu re on the seventh day of observation (simplified WHO test). The increa se in value of the Cl90 in vitro of chloroquine was however alarming, although the clinical efficiency of chloroquine was constant. During t he 1995-1996 period of transmission, a new set of tests was carried ou t in the region of Ankazobe and Moramanga. in both geographically sepa rated zones of stable malaria, 92 isolates of Plasmodium falciparum we re tested for their sensitivity in vitro to Chloroquine (CQ) using the method of the isotopic microtest based on the inhibition of the incor poration of tritium marked hypoxanthine. Out of the 85 isolates which matured well, 57 % were sensitive CQS (CI50<80nM); 25 % CQSR (80nM<CI5 0<120nM); and the remaining were classified as resistant. increased va lue of Cl50 was noted relatively to those registered over the last 5 y ears. The in vitro tests carried out in parallel did however show that all the isolates were sensitive to quinine and mefloquine. These stra ins came from 92 patients aged from 2 to 78 years, who had been admini stered, under medical observation, the standard dose of 25mg/kg of CQ base for three days. The parasitaemia was followed up by pap screen an d drops for seven days according to the simplified standard protocol o f the WHO. At the end of this study sixty-four therapeutic successes ( or 70 %), ten parasitological failures and four clinical failures were recorded. For fourteen subjects, the observation could not be carried out to the seventh day When the results of the in vitro and in vivo t ests are compared, four CQS and CSR strains have characteristics of R1 resistance and nine of R2 resistance. Out of the fourteen CQR strains , four had characteristics of R2 resistance, two of R1, and eight were sensitive in vivo. In the course of the study, the decrease in sensit ivity of the Plasmodium falciparum to CQ was frequently noticed among children under 6 years of age who are subject to repeated bouts of mal aria. It is thus necessary to keep up the surveillance of chimiosensit ivity and to foresee immediately relay strategies to amino-4-quinolein s.