ArticleThe Journal of infectious diseases2022
How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria?
Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Retinal imaging technologies in cerebral malaria: a systematic review.Malaria journal · 2023Pooled it
- Intravenous Fluid Bolus Resuscitation Increases Mortality Risk in Malawian Children with Cerebral Malaria.The American journal of tropical medicine and hygiene · 2025Article
- Unveiling new perspectives about the onset of neurological and cognitive deficits in cerebral malaria: exploring cellular and neurochemical mechanisms.Frontiers in cellular and infection microbiology · 2025Review
- Severity of Vessel Color Changes and Macular and Peripheral Whitening in Malarial Retinopathy Are Associated with Higher Total Body and Sequestered Parasite Burdens.Tropical medicine and infectious disease · 2024Article
- Exploring the hidden mental health consequences of malaria beyond the fever.Frontiers in human neuroscience · 2024Review
- Review
- Cerebral malaria-using the retina to study the brain.Eye (London, England) · 2023Review
- Clinical aspects of malarial retinopathy: a critical review.Pathogens and global health · 2023Review
- Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria.Infectious diseases of poverty · 2023Article
- Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis.Frontiers in human neuroscience · 2023Article
- Predicting Acute and Post-Recovery Outcomes in Cerebral Malaria and Other Comas by Optical Coherence Tomography (OCT in CM) - A protocol for an observational cohort study of Malawian children.Wellcome open research · 2023Article
- A proposed theoretical framework for retinal biomarkers.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria.Scientific reports · 2021Article
- Plasma angiopoietin-2 is associated with age-related deficits in cognitive sub-scales in Ugandan children following severe malaria.Malaria journal · 2021Article
- Localised release of matrix metallopeptidase 8 in fatal cerebral malaria.Clinical & translational immunology · 2021Article
- Retinoic acid signaling in mouse retina endothelial cells is required for early angiogenic growth.Differentiation; research in biological diversityArticle
- Automated malarial retinopathy detection using transfer learning and multi-camera retinal images.Biocybernetics and biomedical engineeringArticle
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundIn cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling, and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling.
methodsWe used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain magnatic resonance imaging (MRI), and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria.
resultsThree types of retinal leakage were seen: large focal leak (LFL), punctate leak (PL), and vessel leak. The LFL and PL were associated with death (odds ratio [OR] = 13.20, 95% confidence interval [CI] = 5.21-33.78 and OR = 8.58, 95% CI = 2.56-29.08, respectively) and brain swelling (P < .05). Vessel leak and macular nonperfusion were associated with neurological disability (OR = 3.71, 95% CI = 1.26-11.02 and OR = 9.06, 95% CI = 1.79-45.90). Large focal leak was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages.
conclusionsBlood-retina barrier breakdown occurs in 3 patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak, from barrier dysfunction, and nonperfusion were not associated with severe brain swelling but with neurological deficits, suggesting hypoxic injury in survivors.
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