Chemoresistance of Plasmodium falciparum in urban Yaounde (Cameroon). PartOne: Monitoring in vitro and in vivo of Plasmodium falciparum resistance to chloroquine between 1994 and 1999 in Yaounde (Cameroon)

Chloroquine is indicated for the first-line treatment of uncomplicated mala ria in most African countries. However, the spread of chloroquine-resistant Plasmodium falciparum requires periodic monitoring. Between 1994 and 1999, we studied the evolution of chloroquine resistance in adults (aged > 15 ye ars) and children aged 5-15 years by using tests of therapeutic efficacy an d in vitro assays. Responses to the 14-day in vivo test were classified acc ording to the new criteria established by the World Health Organization. Th e results of the semi-microtest and the microtest were expressed as the 50% inhibitory concentration (IC50), and the threshold level of resistance was set at IC50 > 100 nM. The overall percentages of clinical and parasitologi cal failures were 39.7% (31.3% - 48.1%) and 48.8% (40.2% - 57.4%), respecti vely. Similarly, the percentage of isolates that were resistant in vitro wa s 52.5%. During the study, IC50 geometric mean varied between 84,6 nM and 1 49,8 nM. The results of the in vitro assays agreed with those of tests of t herapeutic efficacy (kappa coefficient = 0.69). The patients' chloroquine p lasma levels were measured on day 0, day 3, day 7, and day 14. Drug measure ment showed wide inter-individual variations and higher plasma levels in ad ults than in children. Some cases of therapeutic failure were associated wi th inadequate plasma levels of chloroquine. Our results confirm the high le vel of chloroquine resistance in Yaounde and suggest that the use of an alt ernative antimalarial drug for the first-line treatment of uncomplicated ma laria is warranted.