In 2011, the World Health Organization recommended injectable artesunate as the first-line therapy for severe malaria (SM) due to its superiority in reducing mortality compared to quinine. There are limited data on long-term clinical and neurobehavioral outcomes after artemisinin use for treatment of SM. From 2008 to 2013, 502 Ugandan children with two common forms of SM, cerebral malaria and severe malarial anemia, were enrolled in a prospective observational study assessing long-term neurobehavioral and cognitive outcomes following SM. Children were evaluated a week after hospital discharge, and 6, 12, and 24 months of follow-up, and returned to hospital for any illness. In this study, we evaluated the impact of artemisinin derivatives on survival, post-discharge hospital readmission or death, and neurocognitive and behavioral outcomes over 2 years of follow-up. 346 children received quinine and 156 received parenteral artemisinin therapy (artemether or artesunate). After adjustment for disease severity, artemisinin derivatives were associated with a 78% reduction in in-hospital mortality (adjusted odds ratio, 0.22; 95% CI, 0.07–0.67). Among cerebral malaria survivors, children treated with artemisinin derivatives also had reduced neurologic deficits at discharge (quinine, 41.7%; artemisinin derivatives, 23.7%, p=0.007). Over a 2-year follow-up, artemisinin derivatives as compared to quinine were associated with better adjusted scores (negative scores better) in internalizing behavior and executive function in children irrespective of the age at severe malaria episode. After adjusting for multiple comparisons, artemisinin derivatives were associated with better adjusted scores in behavior and executive function in children <6 years of age at severe malaria exposure following adjustment for child age, sex, socioeconomic status, enrichment in the home environment, and the incidence of hospitalizations over follow-up. Children receiving artesunate had the greatest reduction in mortality and benefit in behavioral outcomes and had reduced inflammation at 1-month follow-up compared to children treated with quinine. Treatment of severe malaria with artemisinin derivatives, particularly artesunate, results in reduced in-hospital mortality and neurologic deficits in children of all ages, reduced inflammation following recovery, and better long-term behavioral outcomes. These findings suggest artesunate has long-term beneficial effects in children surviving severe malaria.

中文翻译：

---

肠外青蒿素与严重疟疾儿童的死亡率和神经功能缺损降低以及长期行为结果的改善有关

2011 年，世界卫生组织推荐青蒿琥酯注射液作为重症疟疾 (SM) 的一线治疗药物，因为与奎宁相比，青蒿琥酯在降低死亡率方面具有优势。关于使用青蒿素治疗 SM 后的长期临床和神经行为结果的数据有限。从 2008 年到 2013 年，502 名患有两种常见 SM（脑型疟疾和严重疟疾性贫血）的乌干达儿童参加了一项前瞻性观察研究，该研究评估了 SM 后的长期神经行为和认知结果。出院后一周、随访 6、12 和 24 个月对儿童进行评估，并在出现任何疾病时返回医院。在这项研究中，我们评估了青蒿素衍生物对生存、出院后再入院或死亡的影响，以及 2 年随访期间的神经认知和行为结果。346 名儿童接受奎宁治疗，156 名儿童接受肠外青蒿素治疗（蒿甲醚或青蒿琥酯）。调整疾病严重程度后，青蒿素衍生物与院内死亡率降低 78% 相关（调整后的比值比，0.22；95% CI，0.07–0.67）。在脑型疟疾幸存者中，接受青蒿素衍生物治疗的儿童出院时神经功能缺损也有所减少（奎宁，41.7%；青蒿素衍生物，23.7%，p=0.007）。在 2 年的随访中，与奎宁相比，青蒿素衍生物在儿童的内化行为和执行功能方面具有更好的调整分数（负分数更好），而与严重疟疾发作的年龄无关。多重比较调整后，在对儿童年龄、性别、社会经济地位、家庭环境的丰富度以及随访期间的住院发生率进行调整后，青蒿素衍生物与严重疟疾暴露的 6 岁以下儿童的行为和执行功能的调整得分更好相关. 与接受奎宁治疗的儿童相比，接受青蒿琥酯治疗的儿童在死亡率和行为结果方面的获益最大，并且在 1 个月的随访中炎症减少。用青蒿素衍生物，特别是青蒿琥酯治疗严重疟疾，可降低所有年龄段儿童的住院死亡率和神经功能缺损，减少康复后的炎症，并改善长期行为结果。