Department of Medical Microbiology, College of Health Sciences, Makerere University, Kampala, Uganda.
Department of Psychiatry, College of Health Sciences, Makerere University, Kampala, Uganda.
Malar J. 2021 Jan 6;20(1):17. doi: 10.1186/s12936-020-03545-6.
Elevated angiopoietin-2 (Angpt-2) concentrations are associated with worse overall neurocognitive function in severe malaria survivors, but the specific domains affected have not been elucidated.
Ugandan children with severe malaria underwent neurocognitive evaluation a week after hospital discharge and at 6, 12 and 24 months follow-up. The relationship between Angpt-2 concentrations and age-adjusted, cognitive sub-scale z-scores over time were evaluated using linear mixed effects models, adjusting for disease severity (coma, acute kidney injury, number of seizures in hospital) and sociodemographic factors (age, gender, height-for-age z-score, socio-economic status, enrichment in the home environment, parental education, and any preschool education of the child). The Mullen Scales of Early Learning was used in children < 5 years and the Kaufman Assessment Battery for Children 2nd edition was used in children ≥ 5 years of age. Angpt-2 levels were measured on admission plasma samples by enzyme-linked immunosorbent assay. Adjustment for multiple comparisons was conducted using the Benjamini-Hochberg Procedure of False Discovery Rate.
Increased admission Angpt-2 concentration was associated with worse outcomes in all domains (fine and gross motor, visual reception, receptive and expressive language) in children < 5 years of age at the time of severe malaria episode, and worse simultaneous processing and learning in children < 5 years of age at the time of severe malaria who were tested when ≥ 5 years of age. No association was seen between Angpt-2 levels and cognitive outcomes in children ≥ 5 years at the time of severe malaria episode, but numbers of children and testing time points were lower for children ≥ 5 years at the time of severe malaria episode.
Elevated Angpt-2 concentration in children with severe malaria is associated with worse outcomes in multiple neurocognitive domains. The relationship between Angpt-2 and worse cognition is evident in children < 5 years of age at the time of severe malaria presentation and in selected domains in older years.
血管生成素-2（Angpt-2）浓度升高与重症疟疾幸存者的整体神经认知功能下降有关，但具体受影响的领域尚未阐明。
乌干达患有重症疟疾的儿童在出院后一周以及 6、12 和 24 个月的随访时进行神经认知评估。使用线性混合效应模型评估 Angpt-2 浓度与随时间变化的年龄调整认知子量表 z 分数之间的关系，调整疾病严重程度（昏迷、急性肾损伤、住院期间癫痫发作次数）和社会人口因素（年龄、性别、身高年龄 z 分数、社会经济地位、家庭环境丰富度、父母教育程度以及儿童的任何学前教育）。5 岁以下儿童使用 Mullen 早期学习量表，5 岁及以上儿童使用 Kaufman 儿童评估量表第二版。入院时通过酶联免疫吸附试验测定血浆样本中的 Angpt-2 水平。使用 Benjamini-Hochberg 假发现率程序进行多重比较调整。
入院时 Angpt-2 浓度升高与所有领域（精细和粗大运动、视觉接受、接受性和表达性语言）的结局较差相关在患有重症疟疾的 5 岁以下儿童中，并且在患有重症疟疾的 5 岁以下儿童中同时进行处理和学习时，结果较差当≥5 岁时接受测试。在患有重症疟疾的 5 岁及以上儿童中，未发现 Angpt-2 水平与认知结局之间存在关联，但患有重症疟疾的 5 岁及以上儿童的数量和测试时间点较少。
重症疟疾患儿 Angpt-2 浓度升高与多个神经认知领域的结局较差有关。在患有重症疟疾的 5 岁以下儿童中，Angpt-2 与认知能力下降之间的关系明显，并且在年龄较大的儿童中在某些领域也存在这种关系。
