Schnyder Jenny L, Vos-van der Meer Marloes, van Hest Reinier M, Mathot Ron, Schlagenhauf Patricia, de Jong Hanna K, Grobusch Martin P
Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
Department of Hospital Pharmacy & Clinical Pharmacology, Amsterdam UMC, Location University of Amsterdam, Amsterdam, Netherlands.
New Microbes New Infect. 2025 Jul 29;67:101617. doi: 10.1016/j.nmni.2025.101617. eCollection 2025 Oct.
Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria, with cure rates exceeding 95 %. However, recrudescence occurs in 2-14 % of cases, often linked to inadequate lumefantrine exposure. Retrospective assessment of drug exposure in recrudescence cases is challenging, as lumefantrine levels are undetectable in blood after several weeks. Hair analysis may offer an alternative method to assess drug exposure over time. The objective of this proof-of-concept study was to assess whether artemether and lumefantrine, and their respective metabolites dihydroartemisinin and desbutyl-lumefantrine, could be detected and quantified in hair of falciparum malaria patients who completed an AL treatment course.
Hair samples were collected from six patients with falciparum malaria at Amsterdam UMC, four weeks after treatment initiation. Samples were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Lumefantrine and its metabolite desbutyl-lumefantrine were detected in all hair samples, with quantifiable levels in five cases. Artemether and its active metabolite dihydroartemisinin were undetectable. No study participants developed recrudescence.
This study demonstrates that lumefantrine and its metabolite can be detected in hair weeks after treatment, suggesting hair analysis may serve as a retrospective tool to assess drug exposure in recrudescent malaria cases. The absence of artemether and dihydroartemisinin was likely due to their short half-lives, preventing incorporation into hair. A larger study is warranted to evaluate correlations between lumefantrine hair and plasma concentrations. If validated, this approach could aid in distinguishing inadequate drug exposure from reduced parasite susceptibility to AL, optimizing malaria treatment strategies.
蒿甲醚-本芴醇（AL）是无并发症疟疾的一线治疗药物，治愈率超过95%。然而，2%-14%的病例会复发，这通常与本芴醇暴露不足有关。由于数周后血液中无法检测到本芴醇水平，对复发病例的药物暴露进行回顾性评估具有挑战性。毛发分析可能提供一种评估一段时间内药物暴露的替代方法。本概念验证研究的目的是评估在完成AL治疗疗程的恶性疟患者的毛发中是否能够检测到并定量分析蒿甲醚和本芴醇及其各自的代谢产物双氢青蒿素和去丁基本芴醇。
在阿姆斯特丹大学医学中心，于治疗开始四周后从六名恶性疟患者收集毛发样本。使用液相色谱-串联质谱法（LC-MS/MS）对样本进行分析。
在所有毛发样本中均检测到本芴醇及其代谢产物去丁基本芴醇，其中五例可定量。未检测到蒿甲醚及其活性代谢产物双氢青蒿素。没有研究参与者出现复发。
本研究表明，治疗数周后毛发中可检测到本芴醇及其代谢产物，这表明毛发分析可能作为一种回顾性工具来评估复发性疟疾病例的药物暴露。未检测到蒿甲醚和双氢青蒿素可能是由于它们的半衰期较短，无法掺入毛发中。有必要开展更大规模的研究来评估本芴醇毛发浓度与血浆浓度之间的相关性。如果得到验证，这种方法有助于区分药物暴露不足与寄生虫对AL敏感性降低，从而优化疟疾治疗策略。
