DRUG-RESISTANCE DEVELOPMENT OF PLASMODIUM -FALCIPARUM IN MADAGASCAR FROM 1982 TO 1993 AND ITS OPERATIONAL IMPACT

Madagascar was one of the first African countries with reported chloro quine drug resistance of p. falciparum. Suspected as early as 1975, it was confirmed in 1981. Hereafter regular tests in vivo and in vitro h ave been performed and allow for a study of drug resistance developmen t. In 742 standard in vivo tests at the dose of 25 mg/kg of chloroquin e that were executed between 1983 and 1993, R I resistance levels coul d be found in 8,5 % of cases, R II was found in 8,2 %. No resistance a t R III levels was detected. The overall situation for in vitro is equ ally favorable. In 406 tests 78 % of samples proved sensitive. The inv estigations undertaken by the Pasteur Institute of Madagascar, by the Institute for Tropical Medicine and Epidemiology in Paris and by the U nit of Epidemiological Surveillance within the Malagasy Ministry of He alth raise a number of questions: Taking to account the various causes for imprecision in measurement and in evaluation (variations in paras ite density, microscopic detection levels, bio-availability of the dru g) of the groups of R I and R II how significant are the variations ob served in numbers and proportions of resistance levels R I and R II? H ow important are the effects of auto-medication? Can they be correctly evaluated by Bergquist's test? How explain the low level of drug resi stance in a country close to East Africa, in which chemoprophylaxis ha s been widely practiced and in which insufficient dosage for treatment is common?The absence of R III resistance in vivo permit for chloroqu ine to remain the first line treatment for malaria in Madagascar. It h as become necessary, however, to develop an adapted surveillance syste m for drug resistance in areas with unstable malaria and to concentrat e mainly on treatment failures.