吡喹酮-青蒿琥酯治疗间日疟原虫、卵形疟原虫和混合疟原虫感染的疗效：CANTAM-Pyramax 试验的事后分析。
Effectiveness of pyronaridine-artesunate against Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections: a post-hoc analysis of the CANTAM-Pyramax trial.
机构信息
Institut für Tropenmedizin, University of Tubingen, Tubingen, Germany; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, and Department of Internal Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Unité de Pharmacologie Clinique et Pharmacovigilance, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
出版信息
Lancet Microbe. 2022 Aug;3(8):e598-e605. doi: 10.1016/S2666-5247(22)00092-1. Epub 2022 May 30.
BACKGROUND
High-quality evidence for the therapeutic efficacy and effectiveness of antimalarials for infections caused by Plasmodium malariae, Plasmodium ovale spp, and mixed-Plasmodium infections is scarce. In this study, we aimed to analyse the efficacy of pyronaridine-artesunate for the treatment of non-falciparum and mixed-species Plasmodium infections from a large phase 3b/4 clinical trial in central Africa.
METHODS
This post-hoc analysis was done in a random subset of samples from two sites (in the Democratic Republic of the Congo and in Gabon) of the CANTAM-Pyramax trial assessing pyronaridine-artesunate therapy. We randomly selected paired dried blood spot samples from day 0 and day 28 (or unforeseen visit) and analysed them by quantitative PCR for mixed Plasmodium infections or non-falciparum mono-infections. Day 28 (or unforeseen visit) samples positive for non-falciparum malaria were re-assessed by microscopy to identify microscopic versus submicroscopic infections. Analyses were done on two sample sets: a per-protocol set and an intention-to-treat set.
FINDINGS
Among 1502 randomly selected samples, 192 (12·8%) showed mixed-Plasmodium infections or non-falciparum mono-infections. We did not detect P vivax in the samples. For both the per-protocol and intention-to-treat sets, the overall day 28 cure rates for P malariae, P ovale curtisi, and P ovale wallikeri were 96·3% or higher (95% CIs from 81·0-99·9 to 95·7-100). Cure rates were consistently high in P malariae (99·2%, 95·7-100) and P ovale spp (97·9%, 88·7-99·9, for P ovale curtisi and 96·3%, 81·0-99·9, for P ovale wallikeri) infections.
INTERPRETATION
This post-hoc analysis provides important evidence supporting the high efficacy of pyronaridine-artesunate against mono-infections with P malariae, P ovale curtisi, or P ovale wallikeri and mixed-Plasmodium infections in a real-world setting.
FUNDING
Medicines for Malaria Venture.
背景
对于由疟原虫疟疾病原体、卵形疟原虫和混合疟原虫引起的感染，抗疟药物的治疗效果和有效性的高质量证据很少。在这项研究中，我们旨在分析吡喹酮-青蒿琥酯治疗中非恶性疟原虫和混合物种疟原虫感染的疗效，该研究来自中非的一项大型 3b/4 期临床试验。
方法
这是一项在评估吡喹酮-青蒿琥酯治疗效果的 CANTAM-Pyramax 试验的两个地点（刚果民主共和国和加蓬）的随机亚组样本中的事后分析。我们随机选择了来自第 0 天和第 28 天（或意外就诊）的配对干血斑样本，并通过定量 PCR 分析混合疟原虫感染或非恶性疟原虫单感染。第 28 天（或意外就诊）的非恶性疟原虫阳性样本通过显微镜重新评估，以确定显微镜下和亚显微镜下的感染。分析在两个样本集上进行：一个是符合方案集，另一个是意向治疗集。
结果
在 1502 个随机选择的样本中，192 个（12.8%）显示出混合疟原虫感染或非恶性疟原虫单感染。我们在样本中未检测到间日疟原虫。对于符合方案集和意向治疗集，疟原虫、卵形疟原虫 curtisi 和卵形疟原虫 wallikeri 的第 28 天总体治愈率均为 96.3%或更高（95%CI 为 81.0-99.9 至 95.7-100）。疟原虫感染的治愈率一直很高（99.2%，95.7-100），卵形疟原虫 spp 的治愈率也很高（卵形疟原虫 curtisi 为 97.9%，88.7-99.9，卵形疟原虫 wallikeri 为 96.3%，81.0-99.9）。
解释
这项事后分析提供了重要证据，支持吡喹酮-青蒿琥酯在真实环境中对疟原虫、卵形疟原虫 curtisi 或卵形疟原虫 wallikeri 单感染和混合疟原虫感染的高疗效。
资助
疟疾药物基金会。
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