Ringwald P, Same Ekobo A, Keundjian A, Kedy Mangamba D, Basco L K
Laboratoire de Recherche sur le Paludisme, Laboratoire Associé Francophone 302, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Yaoundé, Cameroun.
Trop Med Int Health. 2000 Sep;5(9):612-9. doi: 10.1046/j.1365-3156.2000.00613.x.
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 tests 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 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 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 wide 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 Yaoundé and suggest that the use of an alternative antimalarial drug for the first-line treatment of uncomplicated malaria is warranted.
在大多数非洲国家,氯喹被用于非复杂性疟疾的一线治疗。然而,耐氯喹恶性疟原虫的传播需要定期监测。1994年至1999年期间,我们通过治疗效果测试和体外试验研究了15岁以上成年人及5至15岁儿童氯喹耐药性的演变。根据世界卫生组织制定的新标准对14天体内试验的反应进行分类。半微量试验和微量试验的结果以50%抑制浓度(IC50)表示,耐药阈值设定为IC50>100 nM。临床和寄生虫学治疗失败的总体百分比分别为39.7%(31.3%-48.1%)和48.8%(40.2%-57.4%)。同样,体外耐药分离株的百分比为52.5%。在研究期间,IC50几何平均值在84.6 nM至149.8 nM之间变化。体外试验结果与治疗效果测试结果一致(kappa系数=0.69)。在第0天、第3天、第7天和第14天测量患者的氯喹血浆水平。药物测量显示个体间差异很大,成年人的血浆水平高于儿童。一些治疗失败的病例与氯喹血浆水平不足有关。我们的结果证实了雅温得氯喹耐药性的高水平,并表明有必要使用替代抗疟药物进行非复杂性疟疾的一线治疗。