Ambroise-Thomas P
Département de Parasitologie-Mycologie Médicale et Moléculaire, Faculté de Médecine, Université Joseph Fourier Grenoble UPRES-A CNRS 5082, La Tronche.
Bull Acad Natl Med. 1999;183(4):797-80; discussion 810-3.
Artemisinin or Qinghaosu (QHS) and its derivatives (mainly artemether and artesunate) are novel and the most rapidly acting antimalarial drugs, effective in adults and children against all the Plasmodium of humans, including multi-drug resistant Plasmodium falciparum. Resistance to these drugs has not been identified so far. QHS derivatives are very well tolerated and there is no evidence of serious clinical toxicity in man. The neurotoxicity seen in animals after high doses of certain compounds has not been reported in humans. In the treatment of severe malaria, QHS administered by either the intramuscular (artemether and artesunate) or intravenous (artesunate) route, are at least as effective as quinine, and are simpler to use. Intramuscular artemether appears to be an excellent alternative to intravenous quinine, which is specially important since quinine resistance is common in Asia and a decrease of sensitivity to quinine has been reported in Africa. For the treatment of uncomplicated malaria, the use of QHS must be highly selective. Treatment by QHS is only totally justifiable in areas where multi-drug resistant strains are prevalent and always concurrently with an other effective, longer-acting, antimalarial drug (mefloquine, preferably). This combination approach is associated with an accelerated antimalarial response. It avoids or limits the risk of recrudescences, and protects both drugs from the development of resistance. Artemether and artesunate have also been administered by the rectal route with highly promising results for treatment of severe malaria. This route eliminates several disadvantages or risks associated with injections. The best indication for rectal administration will be probably a rescue treatment of severe malaria in rural and poorly equipped dispensaries before transfer to hospital for treatment using conventional modalities. All QHS derivatives should not be used for chemophophylaxis.
青蒿素或青蒿琥酯(QHS)及其衍生物(主要是蒿甲醚和青蒿琥酯)是新型且起效最快的抗疟药物,对成人和儿童的所有人类疟原虫均有效,包括耐多药的恶性疟原虫。目前尚未发现对这些药物的耐药性。QHS衍生物耐受性良好,尚无人体严重临床毒性的证据。高剂量某些化合物在动物身上出现的神经毒性在人类中尚未有报道。在治疗重症疟疾时,通过肌肉注射(蒿甲醚和青蒿琥酯)或静脉注射(青蒿琥酯)途径给药的QHS至少与奎宁一样有效,且使用更简便。肌肉注射蒿甲醚似乎是静脉注射奎宁的极佳替代品,这一点尤为重要,因为奎宁耐药性在亚洲很常见,且非洲也有对奎宁敏感性降低的报道。对于治疗非重症疟疾,QHS的使用必须高度选择性。仅在耐多药菌株流行的地区,且始终与另一种有效、长效的抗疟药物(最好是甲氟喹)同时使用时,QHS治疗才完全合理。这种联合用药方法可加快抗疟反应。它避免或限制了复发的风险,并保护两种药物不产生耐药性。蒿甲醚和青蒿琥酯也已通过直肠途径给药,在治疗重症疟疾方面取得了非常有前景的结果。该途径消除了与注射相关的几个缺点或风险。直肠给药的最佳适应证可能是在农村和设备简陋的诊所对重症疟疾进行抢救治疗,然后再转至医院采用传统方式治疗。所有QHS衍生物均不应用于化学预防。