Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Malar J. 2009 Dec 3;8:277. doi: 10.1186/1475-2875-8-277.
A 20 year-old healthy female volunteer participated in a clinical Phase I and IIa safety and efficacy trial with candidate malaria vaccine PfLSA-3-rec adjuvanted with aluminium hydroxide. Eleven weeks after the third and last immunization she was experimentally infected by bites of Plasmodium falciparum-infected mosquitoes. When the thick blood smear became positive, at day 11, she was treated with artemether/lumefantrine according to protocol. On day 16 post-infection i.e. two days after completion of treatment, she woke up with retrosternal chest pain. She was diagnosed as acute coronary syndrome and treated accordingly. She recovered quickly and her follow-up was uneventful. Whether the event was related to the study procedures such as the preceding vaccinations, malaria infection or antimalarial drugs remains elusive. However, the relation in time with the experimental malaria infection and apparent absence of an underlying condition makes the infection the most probable trigger. This is in striking contrast, however, with the millions of malaria cases each year and the fact that such complication has never been reported in the literature. The rare occurrence of cardiac events with any of the preceding study procedures may even support a coincidental finding. Apart from acute coronary syndrome, myocarditis can be considered as a final diagnosis, but the true nature and patho-physiological explanation of the event remain unclear.
一位 20 岁健康的女性志愿者参与了一项候选疟疾疫苗 PfLSA-3-rec 联合氢氧化铝的 I 期和 IIa 期安全性和疗效临床试验。第三次也是最后一次免疫接种 11 周后,她被感染了疟原虫的蚊子叮咬,进行了实验性感染。当厚血涂片呈阳性时,即在感染后第 11 天,根据方案用青蒿琥酯/咯萘啶进行治疗。感染后第 16 天,即治疗完成后两天,她醒来时出现胸骨后胸痛。她被诊断为急性冠脉综合征,并进行了相应的治疗。她很快恢复,随访无异常。该事件是否与研究程序有关,如先前的疫苗接种、疟疾感染或抗疟药物,仍不清楚。然而,与实验性疟疾感染的时间关系以及明显没有潜在疾病,使得感染成为最可能的诱因。然而,每年有数百万人感染疟疾,而文献中从未报告过这种并发症,这形成了鲜明的对比。在任何先前的研究程序中,心脏事件的罕见发生甚至可能支持巧合的发现。除了急性冠脉综合征,心肌炎也可以作为最终诊断,但事件的真正性质和病理生理解释仍不清楚。