Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Clin Infect Dis. 2010 Dec 1;51(11):e82-9. doi: 10.1086/657120. Epub 2010 Oct 28.
Increasing rates of failure of artemisinin-based combination therapy have highlighted the possibility of emerging artemisinin resistance along the Thai-Cambodian border. We used an integrated in vivo-in vitro approach to assess the presence of artemisinin resistance in western Cambodia. This article provides additional data from a clinical trial that has been published in The New England Journal of Medicine.
Ninety-four adult patients from Battambang Province, western Cambodia, who presented with uncomplicated falciparum malaria were randomized to receive high-dose artesunate therapy (4 mg/kg/day orally for 7 days) or quinine-tetracycline. Plasma concentrations of dihydroartemisinin, in vitro drug susceptibility, and molecular markers were analyzed. Cases meeting all the following criteria were classified as artemisinin resistant: failure to clear parasites within 7 days of treatment or reemergence of parasites within 28 days of follow-up; adequate plasma concentrations of dihydroartemisinin; prolonged parasite clearance; and increased in vitro drug susceptibility levels for dihydroartemisinin.
Two (3.3%) of 60 artesunate-treated patients were classified as artemisinin resistant. Their parasite clearance times were prolonged (133 and 95 h, compared with a median of 52.2 h in patients who were cured). These patients had 50% inhibitory concentrations of dihydroartemisinin that were almost 10 times higher than the reference clone W2. Resistance did not appear to be mediated by the pfmdr1 copy number or selected PfATPase6 polymorphisms previously proposed to confer artemisinin resistance.
Artemisinin resistance has emerged along the Thai-Cambodian border. The potentially devastating implications of spreading resistance to a drug that currently has no successor call for further studies of this emerging problem.
ClinicalTrials.gov identifier NCT00479206.
青蒿素类复方疗法失败率不断上升，这凸显出在泰柬边境可能出现青蒿素耐药的情况。我们采用体内-体外相结合的方法，评估柬埔寨西部是否存在青蒿素耐药性。本文提供了一项已在《新英格兰医学杂志》上发表的临床试验的补充数据。
94 名来自柬埔寨西部班迭棉吉省的成人疟疾病人，患有无并发症的恶性疟，他们被随机分配接受高剂量青蒿琥酯治疗（4 mg/kg/天，口服 7 天）或奎宁-四环素。分析了患者的血浆中二氢青蒿素浓度、体外药敏性和分子标志物。符合以下所有标准的病例被归类为青蒿素耐药：治疗后 7 天内未能清除寄生虫或随访 28 天内寄生虫再次出现；有足够的血浆中二氢青蒿素浓度；寄生虫清除时间延长；以及体外二氢青蒿素敏感性水平增加。
60 名接受青蒿琥酯治疗的患者中有 2 名（3.3%）被归类为青蒿素耐药。他们的寄生虫清除时间延长（133 和 95 小时，而治愈的患者中位数为 52.2 小时）。这些患者的二氢青蒿素 50%抑制浓度几乎是参考克隆 W2 的 10 倍。耐药性似乎不是由先前提出的 pfmdr1 拷贝数或选定的 PfATPase6 多态性介导的，这些多态性被认为与青蒿素耐药性有关。
青蒿素耐药性已在泰柬边境出现。由于目前尚无后继药物，耐药性传播可能带来毁灭性影响，因此需要进一步研究这一新兴问题。
ClinicalTrials.gov 标识符 NCT00479206。
