Novel Retinal Lesion in Ebola Survivors, Sierra Leone, 2016

Steptoe, Paul J.; Scott, Janet T.; Baxter, Julia; Parkes, Craig; Dwivedi, Rahul; Czanner, Gabriela; Vandy, Matthew Jusu; Momorie, Fayiah; Fornah, Alimamy D; Komba, Patrick; Richards, Jade; Sahr, Foday; Beare, Nicholas A. V.; Semple, Malcolm G

doi:10.3201/eid2307.161608

Cited by 33 publications

(41 citation statements)

References 26 publications

(46 reference statements)

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“…The seroprevalence of T gondii IgG was 73% within our cohort, in keeping with uveitis secondary to T gondii being common in West Africa. 8 Retinal lesions suggestive of toxoplasmosis chorioretinitis were also present in 18.2% and 19% of survivors of EVD and local control individuals, respectively, in our previous study. 5 Therefore, a differential diagnosis for cataracts within survivors of EVD must include alternative etiologies that are common in the West African population.…”

Section: Cataractssupporting

confidence: 51%

Evolving Longitudinal Retinal Observations in a Cohort of Survivors of Ebola Virus Disease

et al. 2020

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IMPORTANCE The 2-year ophthalmic sequelae of Ebola virus disease (EVD) in survivors of the 2013 to 2016 epidemic is unknown and may have public health implications for future outbreaks. OBJECTIVE To assess the potential for uveitis recurrence, the behavior of dark without pressure, and visual outcomes in a cohort of Sierra Leonean survivors of EVD 2 years following the 2013 to 2016 Ebola epidemic.

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Section: Cataractssupporting

confidence: 51%

Evolving Longitudinal Retinal Observations in a Cohort of Survivors of Ebola Virus Disease

et al. 2020

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“…Fourteen Ebola survivors met the eligibility criteria of at least one identified Ebola retinal lesions on UWF retinal imaging in keeping with the findings of our previous study 1. All fourteen were recalled and attended the clinic for examination including OCT of accessible Ebola retinal lesions.…”

Section: Methodsmentioning

confidence: 82%

Multimodal Imaging and Spatial Analysis of Ebola Retinal Lesions in 14 Survivors of Ebola Virus Disease

et al. 2018

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Importance Differentiation between Ebola retinal lesions and other retinal pathologies in West Africa is important and the pathogenesis of Ebola retinal disease remains poorly understood. Objective To describe the appearance of Ebola virus disease (EVD) retinal lesions using multimodal imaging to enable inferences regarding potential pathogenesis. Design Consecutive, prospectively identified, cohort study Setting 34 Military Hospital, Freetown, Sierra Leone Participants Fourteen EVD survivors of Sierra Leonean origin with identified Ebola virus retinal lesions. Mean age 37years (SD 8.8years) 43% Female. Exposures Ebola virus disease. Main Outcomes and measures Multimodal imaging findings including ultra-widefield (UWF) scanning laser ophthalmoscopy, fundus autofluorescence, swept source optical coherence tomography (OCT), Humphrey visual field analysis, and spatial analysis. Results 141 Ebola virus retinal lesions were observed in 22 of 27 eyes of fourteen survivors on UWF imaging. 41 lesions were accessible to OCT imaging. Retinal lesions are predominantly non-pigmented with a pale grey appearance. Peripapillary lesions exhibit variable curvatures in keeping with the retinal nerve fiber layer projections. All lesions respect the horizontal raphe and spare the fovea. OCT demonstrates a ‘V’ shaped hyperreflectivity of the outer nuclear layer overlying discontinuities of the ellipsoid zone and interdigitation zone in the smaller lesions. Larger lesions cause a collapse of the retinal layers and loss of retinal thickness. Lesion shapes are variable but sharp angulations are characteristic. Perilesional areas of dark-without-pressure (thinned ellipsoid zone hyporeflectivity) of variable extent, accompany 89% of lesions. Conclusions and relevance We demonstrate OCT evidence of localized pathological changes seen at the level of the photoreceptors in small lesions. The relevance of associated areas of dark-without-pressure remains undetermined.

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“…The demonstration of infectious virus in the CSF of patients is a clear indication that the virus is capable of entering and replicating within the immunoprivileged locale of the CNS (8, 15, 21). The demonstration of viral persistence in other immunoprivileged sites, such as the eye and testes, also raises the question of viral persistence in the CNS (23, 26, 50, 51).…”

Section: Discussionmentioning

confidence: 99%

“…However, a number of studies have demonstrated the presence of infectious virus within the cerebrospinal fluid (CSF) of Ebola survivors, months after initial discharge from hospital (8, 15, 21). In addition, there have been numerous reports of ocular involvement following Ebola virus disease, leading to persistent infection (22–26). Taken together, these observations demonstrate that Ebola virus is capable of crossing both the blood-ocular and blood-brain barriers to gain entry to otherwise immune-privileged sites.…”

Section: Introductionmentioning

confidence: 99%

“…The exact mechanisms responsible for the neurological signs and symptoms observed during and following Ebola and Marburg infections are poorly understood but are likely to involve direct infection of human neurons and/or immunopathology due to infection-associated immune responses. Direct infection of neurons by Ebola and Marburg viruses remains a controversial topic, due to the lack of direct experimental evidence, although some groups have suggested that infection of the optic nerve could account for the subsequent generation of retinal lesions (26).…”

Section: Introductionmentioning

confidence: 99%

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Filoviruses Can Efficiently Infect Human Neuron-Like Cells Without Genetic Adaptation

McAuley

Tachedjian

Marsh

2019

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7 Recent large-scale Ebola outbreaks, combined with improved follow-up of survivors, has 8 permitted the observation of common long-term neurological sequelae in patients that have 9 survived Ebola virus infection. To date there have been few studies into neurological 10 infections by Ebola or related filoviruses, however, recent studies have isolated infectious 11 virus from patients' cerebrospinal fluid months after being discharged from the treatment 12 facility. 13 14 In order to determine whether different filoviruses were capable of infecting human 15 neurons, the human neuroblastoma cell lines, SH-SY5Y and M17, were chemically-16 differentiated into more neuron-like cells using established protocols. The neuron-like 17 profiles of the differentiated cells were confirmed by the determination of expression of a 18 range of neuron-specific markers. Zaire ebolavirus, Reston ebolavirus, and Marburg virus 19 were serially-passaged in both cell lines to determine permissiveness of the cells, as well as 20 permit the acquisition of adaptive mutations in the viral genomes. Whilst Marburg virus 21 grew to high titres in both cell lines, Zaire ebolavirus only grew in SH-SY5Y cells, and Reston 22 ebolavirus rapidly died out in both cell lines. Whole-genome sequencing of the passaged 23 viruses revealed two consensus-level non-coding mutations in the SH-SY5Y-passaged 24 Marburg virus. Viral growth kinetics were determined for pre-and post-passaging Zaire 25 ebolavirus and Marburg virus in both human neuronal cell lines, as well as the human 26 hepatocyte cell line, Huh7. Growth kinetics were similar for both the pre-and post-passaged 27 viruses, suggesting that adaptive mutations were not required for efficient growth in these 28 cells.29 30 This study is the first to demonstrate that filoviruses are capable of infecting human neuron-31 like cells in a species-specific manner. Marburg virus-infected cells remained alive up to Day 32 21 post-infection, suggesting that long-term neurological sequelae following filovirus 33 infection may be a result of direct neuronal infection, and that infection of neurons might 34 contribute to viral persistence in survivors. 3536 Author Summary 37 Filoviruses, including Ebola and Marburg viruses, have been traditionally considered 38 "haemorrhagic fever" viruses, with infections causing bleeding and frequently death. Recent 39 large-scale outbreaks in Africa have challenged these assumptions due to a significant 40 number of patients reporting neurological symptoms sometimes months after infection. In 41 many of these patients, virus was present at detectable levels in the fluid surrounding the 42 brain. There has been significant debate about the ability of Ebola and Marburg viruses to 43 infect and grow in human neurons (brain cells), and evidence has been lacking due to the 44 lack of feasibility in taking brain samples. Our study demonstrates that both Zaire ebolavirus 3 45 and Marburg virus are capable of infecting cells derived from human brains without needing 46 to change, and...

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Novel Retinal Lesion in Ebola Survivors, Sierra Leone, 2016

Abstract: A lesion specific to Ebola virus disease showed an anatomical distribution suggesting neuronal transmission.

Cited by 33 publications

References 26 publications

Evolving Longitudinal Retinal Observations in a Cohort of Survivors of Ebola Virus Disease

Evolving Longitudinal Retinal Observations in a Cohort of Survivors of Ebola Virus Disease

Multimodal Imaging and Spatial Analysis of Ebola Retinal Lesions in 14 Survivors of Ebola Virus Disease

Filoviruses Can Efficiently Infect Human Neuron-Like Cells Without Genetic Adaptation

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