Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina
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, clinicop...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/32208 |
| _version_ | 1811235907782574080 |
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| author | Valentina Barrera Ian James Callum MacCormick Gabriela Czanner Paul Stephenson Hiscott Valerie Ann White Alister Gordon Craig Nicholas Alexander Venton Beare Lucy Hazel Culshaw Yalin Zheng Simon Charles Biddolph Danny Arnold Milner Steve Kamiza Malcolm Edward Molyneux Terrie Ellen Taylor Simon Peter Harding |
| author_facet | Valentina Barrera Ian James Callum MacCormick Gabriela Czanner Paul Stephenson Hiscott Valerie Ann White Alister Gordon Craig Nicholas Alexander Venton Beare Lucy Hazel Culshaw Yalin Zheng Simon Charles Biddolph Danny Arnold Milner Steve Kamiza Malcolm Edward Molyneux Terrie Ellen Taylor Simon Peter Harding |
| author_sort | Valentina Barrera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T11:59:53Z |
| format | Article |
| id | doaj.art-0eb7b948e8ed4879a96cb014e6bfaf6b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:59:53Z |
| publishDate | 2018-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0eb7b948e8ed4879a96cb014e6bfaf6b2022-12-22T03:33:53ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.32208Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retinaValentina Barrera0https://orcid.org/0000-0003-0515-5901Ian James Callum MacCormick1Gabriela Czanner2Paul Stephenson Hiscott3Valerie Ann White4Alister Gordon Craig5Nicholas Alexander Venton Beare6Lucy Hazel Culshaw7Yalin Zheng8Simon Charles Biddolph9Danny Arnold Milner10Steve Kamiza11Malcolm Edward Molyneux12Terrie Ellen Taylor13Simon Peter Harding14https://orcid.org/0000-0003-4676-1158Department of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United KingdomDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom; Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, MalawiDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom; Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, United KingdomDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United KingdomDepartment of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, Canada; Department of Ophthalmology and Visual Science, University of British Columbia and Vancouver General Hospital, Vancouver, CanadaLiverpool School of Tropical Medicine, Liverpool, United KingdomDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom; St Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, United KingdomDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United KingdomDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United KingdomNational Specialist Ophthalmic Pathology Service, Royal Liverpool University Hospital, Liverpool, United KingdomCenter for Global Health, American Society for Clinical Pathology, Chicago, United StatesDepartment of Histopathology, College of Medicine, University of Malawi, Blantyre, MalawiMalawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, Blantyre, Malawi; Liverpool School of Tropical Medicine, Liverpool, United KingdomBlantyre Malaria Project, College of Medicine, University of Malawi, Blantyre, Malawi; Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, United StatesDepartment of Eye and Vision Science, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, United Kingdom; St Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, United KingdomRetinal 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.https://elifesciences.org/articles/32208plasmodium falciparum cerebral malariasequestrationpaediatric comaneurovasculatureblood-retinal barriermalarial retinopathy |
| spellingShingle | Valentina Barrera Ian James Callum MacCormick Gabriela Czanner Paul Stephenson Hiscott Valerie Ann White Alister Gordon Craig Nicholas Alexander Venton Beare Lucy Hazel Culshaw Yalin Zheng Simon Charles Biddolph Danny Arnold Milner Steve Kamiza Malcolm Edward Molyneux Terrie Ellen Taylor Simon Peter Harding Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina eLife plasmodium falciparum cerebral malaria sequestration paediatric coma neurovasculature blood-retinal barrier malarial retinopathy |
| title | Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina |
| title_full | Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina |
| title_fullStr | Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina |
| title_full_unstemmed | Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina |
| title_short | Neurovascular sequestration in paediatric P. falciparum malaria is visible clinically in the retina |
| title_sort | neurovascular sequestration in paediatric p falciparum malaria is visible clinically in the retina |
| topic | plasmodium falciparum cerebral malaria sequestration paediatric coma neurovasculature blood-retinal barrier malarial retinopathy |
| url | https://elifesciences.org/articles/32208 |
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