Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina.
Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina.
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DOI：
10.7554/elife.32208
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发表时间：
2018-03-26
期刊：
影响因子：
7.7
通讯作者：
Harding SP
中科院分区：
文献类型：
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作者：
Barrera V;MacCormick IJC;Czanner G;Hiscott PS;White VA;Craig AG;Beare NAV;Culshaw LH;Zheng Y;Biddolph SC;Milner DA;Kamiza S;Molyneux ME;Taylor TE;Harding SP
恶性脑型疟疾患儿在常规眼科检查中可直接观察到视网膜血管改变和视网膜白化，这是疟疾视网膜病变的显著特征。我们通过相关的临床、临床病理和图像分析研究来研究它们的临床意义和潜在机制。黄斑血管和黄斑中心凹严重白化(临床检查，95%CI：2.9，1.96~4.3；3.4，1.8~6.3，P均为0.001)和血管内充盈缺陷性小动脉受累(血管造影图像分析，n=260，2.81，1.17~6.72，P<；0.02)与死亡密切相关。橙色血管致密隔离晚期寄生红细胞(组织病理学29例，敏感性0.97，特异性0.89)，累及360°管腔周长，血视网膜屏障细胞蛋白表达改变，周细胞明显丢失/破坏。视网膜白化在地形图上与组织对缺氧的反应有关。严重的神经血管隔离在床边可见，是对诊断和治疗有用的严重疾病的标志。
Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with P. falciparum cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.90, 1.96–4.30; 3.4, 1.8–6.3, both p<0.001), and arteriolar involvement by intravascular filling defects (angiographic image analysis, n = 260, 2.81, 1.17–6.72, p<0.02) were strongly associated with death. Orange vessels had dense sequestration of late stage parasitised red cells (histopathology, n = 29; sensitivity 0.97, specificity 0.89) involving 360° of the lumen circumference, with altered protein expression in blood-retinal barrier cells and marked loss/disruption of pericytes. Retinal whitening was topographically associated with tissue response to hypoxia. Severe neurovascular sequestration is visible at the bedside, and is a marker of severe disease useful for diagnosis and management.