Clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among Afghan refugees in Pakistan
Clinical trial of extended-dose chloroquine for treatment of resistant falciparum malaria among Afghan refugees in Pakistan
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DOI：
10.1186/1475-2875-10-171
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发表时间：
2011-06-23
期刊：
影响因子：
3
通讯作者：
Rowland, Mark
中科院分区：
文献类型：
--
作者：
Howard, Natasha;Durrani, Naeem;Rowland, Mark
背景：恶性疟疾是巴基斯坦境内阿富汗难民面临的一个重大问题。难民治疗指南建议对首次发作进行标准的三天氯喹治疗（25毫克/公斤），并根据五天疗程更有可能治愈的假设，对复发感染进行延长的五天治疗（40毫克/公斤）。在患有无并发症恶性疟疾的难民中进行了一项体内随机对照试验，以确定5天治疗（CQ40）是否比标准治疗（CQ25）更有效。方法：将142例恶性疟患者纳入CQ25或CQ40治疗组，随访60 d，定期进行血涂片检查。主要结果为寄生虫学治愈无复发。治疗失败用CQ40治疗。对来自同一地点和附近地点的270份样本进行PCR基因分型，以支持对结果的解释。结果：随访期间，84%的CQ25患者和51%的CQ40患者出现寄生虫复发（校正优势比0.17,95%CI 0.08-0.38）。CQ40显著提高了治愈率，尤其是在成人中。两组治疗后发热清除率、寄生虫清除率及配子体发生比例相似。二线CQ40治疗失败率高于一线CQ40治疗。所有菌株均检测到cq抗性标记pfcrt 76T， pfmdr186y和184Y分别检测到18%和37%的菌株。结论：CQ不适合阿富汗难民社区的一线恶性疟治疗。大剂量CQ方案可克服39%的标准方案下复发的耐药感染，但直接观察治疗后的高失败率表明其不适合使用。
Background: Falciparum malaria is a significant problem for Afghan refugees in Pakistan. Refugee treatment guidelines recommended standard three-day chloroquine treatment (25 mg/kg) for first episodes and extended five-day treatment (40 mg/kg) for recrudescent infections, based on the assumption that a five-day course would more likely achieve a cure. An in-vivo randomized controlled trial was conducted among refugees with uncomplicated falciparum malaria to determine whether five-day treatment (CQ40) was more effective than standard treatment (CQ25).Methods: 142 falciparum patients were recruited into CQ25 or CQ40 treatment arms and followed up to 60 days with regular blood smears. The primary outcome was parasitological cure without recrudescence. Treatment failures were retreated with CQ40. PCR genotyping of 270 samples, from the same and nearby sites, was used to support interpretation of outcomes.Results: 84% of CQ25 versus 51% of CQ40 patients experienced parasite recrudescence during follow-up (adjusted odds ratio 0.17, 95%CI 0.08-0.38). Cure rates were significantly improved with CQ40, particularly among adults. Fever clearance time, parasite clearance time, and proportions gametocytaemic post-treatment were similar between treatment groups. Second-line CQ40 treatment resulted in higher failure rates than first-line CQ40 treatment. CQ-resistance marker pfcrt 76T was found in all isolates analysed, while pfmdr1 86Y and 184Y were found in 18% and 37% of isolates respectively.Conclusions: CQ is not suitable for first-line falciparum treatment in Afghan refugee communities. The extended-dose CQ regimen can overcome 39% of resistant infections that would recrudesce under the standard regimen, but the high failure rate after directly observed treatment demonstrates its use is inappropriate.