London School of Hygiene and Tropical Medicine, London, UK.
Malar J. 2011 Jun 23;10:171. doi: 10.1186/1475-2875-10-171.
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).
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.
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.
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.
恶性疟原虫疟疾是巴基斯坦阿富汗难民面临的重大问题。难民治疗指南建议，对于初次发作，采用标准的三天氯喹治疗（25mg/kg），对于复发性感染，采用延长的五天治疗（40mg/kg），这是基于五天疗程更有可能治愈的假设。在无并发症的恶性疟原虫疟疾难民中进行了一项体内随机对照试验，以确定五天治疗（CQ40）是否比标准治疗（CQ25）更有效。
142 例恶性疟原虫患者被招募到 CQ25 或 CQ40 治疗组，并进行了长达 60 天的定期血涂片随访。主要结局是无复发性寄生虫学治愈。治疗失败的患者用 CQ40 进行再次治疗。从相同和附近地点采集的 270 个样本的 PCR 基因分型用于支持结果的解释。
84%的 CQ25 患者与 51%的 CQ40 患者在随访期间出现寄生虫复发（调整后的优势比 0.17，95%CI 0.08-0.38）。CQ40 治疗显著提高了治愈率，尤其是在成人中。两组间退热时间、寄生虫清除时间和治疗后配子体血症比例相似。二线 CQ40 治疗的失败率高于一线 CQ40 治疗。所有分析的分离株均发现 CQ 耐药标记物 pfcrt 76T，而 pfmdr1 86Y 和 184Y 分别在 18%和 37%的分离株中发现。
CQ 不适合阿富汗难民社区的一线恶性疟原虫治疗。延长剂量的 CQ 方案可以克服标准方案下复发的 39%的耐药感染，但直接观察治疗后的高失败率表明其使用是不合适的。
