Chemoresistance of P. falciparum in an urban area of Yaounde, Cameroon. Part 1: In vitro and in vivo surveillance of chloroquine resistance in Plasmodium falciparum between 1994 and 1999 in Yaounde, Cameroon

Chloroquine is indicated for the first-line treatment of uncomplicated malaria 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 years) and children aged 5-15 ) years by using rests of therapeutic efficacy and in vitro assays. Responses to the 14-day in vivo test were classified according to the new criteria established by the World Health Organization. The result 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 parasitological failures were 39.7% (31.3% -48.1%) and 48.8% (40.2% - 57.4%), respectively. Similarly, the percentage of isolates that were resistant in vitro was 52.5%. During the study, IC50 geometric mean varied between 84,6 nM and 149,8 nM. The results of the in vitro assays agreed with those of tests of therapeutic efficacy (kappa coefficient = 0.69). The patients' chloroquine plasma levels were measured on day 0, day 3, day 7, and day 14. Drug measurement showed ,vide inter-individual variations and higher plasma levels in adults than in children. Some cases of therapeutic failure were associated with inadequate plasma levels of chloroquine. Our results confirm the high level of chloroquine resistance in Yaounde and suggest that the use of all alternative antimalarial drug for the first-line treatment of uncomplicated malaria is warranted.