Nosten F, ter Kuile F, Chongsuphajaisiddhi T, Luxemburger C, Webster H K, Edstein M, Phaipun L, Thew K L, White N J
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Lancet. 1991 May 11;337(8750):1140-3. doi: 10.1016/0140-6736(91)92798-7.
Mefloquine is the treatment of choice for uncomplicated multiresistant falciparum malaria, and in combination with sulphadoxine and pyrimethamine (MSP) at a single dose of 15/30/1.5 mg/kg, respectively, has been used in Thailand for the past 6 years. In 1985-86, MSP cured over 98% of 5192 patients with falciparum malaria on the Thai-Burmese border. 4 years later we studied the efficacy of MSP in 395 patients at the same location. The cure rate at 28 days was 70.8% (95% Cl 67-77.2%). The proportion of early treatment failures (in whom parasitaemia did not clear) had risen from 0.27 to 3.7% (p less than 0.0001). Failure rates were 50% in children under 6 years old, 29% in the 6-15 age group, and 19% in adults (p less than 0.001). Patients with early treatment failure were retreated with 25 mg/kg mefloquine, but 27% had a further recrudescence of infection within 28 days. The mean (95% Cl) serum mefloquine concentration at the time of first recrudescence was 638 (546-730) ng/ml, a value previously associated with successful treatment. Mefloquine concentrations were no lower in those with recrudescent infections than in age-matched successfully treated patients, suggesting that pharmacokinetic factors were not responsible for the high treatment-failure rate. Plasmodium falciparum has developed resistance to mefloquine rapidly, despite the addition of sulphadoxine and pyrimethamine and strict control of drug administration. The MSP combination should now be abandoned.
甲氟喹是单纯性多重耐药恶性疟的首选治疗药物，在泰国过去6年中，一直将其与周效磺胺和乙胺嘧啶（MSP）联合使用，剂量分别为15/30/1.5mg/kg。1985 - 1986年，MSP治愈了泰缅边境5192例恶性疟患者中的98%以上。4年后，我们在同一地点对395例患者研究了MSP的疗效。28天的治愈率为70.8%（95%可信区间67 - 77.2%）。早期治疗失败（寄生虫血症未清除）的比例从0.27%上升至3.7%（p<0.0001）。6岁以下儿童的失败率为50%，6 - 15岁年龄组为29%，成人组为19%（p<0.001）。早期治疗失败的患者用25mg/kg甲氟喹进行了再治疗，但27%的患者在28天内再次出现感染复发。首次复发时的平均（95%可信区间）血清甲氟喹浓度为638（546 - 730）ng/ml，该值此前与治疗成功相关。复发感染患者的甲氟喹浓度并不低于年龄匹配的治疗成功患者，这表明药代动力学因素并非导致高治疗失败率的原因。尽管添加了周效磺胺和乙胺嘧啶并严格控制药物使用，但恶性疟原虫对甲氟喹的耐药性仍迅速产生。现在应放弃MSP联合用药。
