Carrara Verena I, Phyo Aung P, Nwee Paw, Soe Ma, Htoo Hsar, Arunkamomkiri Jaruwan, Singhasivanon Pratap, Nosten François
Shoklo Malaria Research Unit, Mae Sot, Thailand.
Malar J. 2008 Nov 6;7:233. doi: 10.1186/1475-2875-7-233.
The use of artemisinin derivatives has increased exponentially with the deployment of artemisinin combination therapy (ACT) in all malarious areas. They are highly effective and are considered safe, but in animal studies artemisinin derivatives produce neurotoxicity targeting mainly the auditory and vestibular pathways. The debate remains as to whether artemisinin derivatives induce similar toxicity in humans.
This prospective study assessed the effects on auditory function of a standard 3-day oral dose of artesunate (4 mg/kg/day) combined with mefloquine (25 mg/kg) in patients with acute uncomplicated falciparum malaria treated at the Shoklo Malaria Research Unit, on the Thai-Burmese border. A complete auditory evaluation with tympanometry, audiometry and auditory brainstem responses (ABR) was performed before the first dose and seven days after initiation of the antimalarial treatment.
Complete auditory tests at day 0 (D0) and day 7 (D7) were obtained for 93 patients. Hearing loss (threshold > 25 dB) on admission was common (57%) and associated with age only. No patient had a threshold change exceeding 10 dB between D0 and D7 at any tested frequency. No patient showed a shift in Wave III peak latency of more than 0.30 msec between baseline and D7.
Neither audiometric or the ABR tests showed clinical evidence of auditory toxicity seven days after receiving oral artesunate and mefloquine.
随着青蒿素联合疗法(ACT)在所有疟疾流行地区的推广,青蒿素衍生物的使用呈指数级增长。它们高效且被认为安全,但在动物研究中,青蒿素衍生物会产生主要针对听觉和前庭通路的神经毒性。关于青蒿素衍生物是否会在人类中诱发类似毒性的争论仍在继续。
这项前瞻性研究评估了在泰缅边境的Shoklo疟疾研究单位接受治疗的急性非复杂性恶性疟患者中,标准的3日口服青蒿琥酯(4毫克/千克/天)联合甲氟喹(25毫克/千克)剂量对听觉功能的影响。在首次给药前以及抗疟治疗开始7天后,进行了包括鼓室图、听力测定和听觉脑干反应(ABR)的完整听觉评估。
93名患者在第0天(D0)和第7天(D7)完成了完整的听觉测试。入院时听力损失(阈值>25分贝)很常见(57%),且仅与年龄相关。在任何测试频率下,没有患者在D0和D7之间的阈值变化超过10分贝。没有患者在基线和D7之间的波III峰潜伏期变化超过0.30毫秒。
在接受口服青蒿琥酯和甲氟喹7天后,听力测定或ABR测试均未显示出听觉毒性的临床证据。