Understanding the Pathogenesis of Uveitis in Ebola Virus Disease Survivors: An Observational Cohort and Cross-Sectional Study Protocol for Clinical, Molecular Virologic and Immunologic Characterisation

Authors

• Caleb D. Hartley, University of Nebraska Medical Center
• Susanne Linderman, Emory University
• Tolulope Fashina, University of Nebraska Medical CenterFollow
• Laura Ward, Emory University
• Carolyn Drews-Botsch, George Mason University
• Catherine Pratt, Biosurv International
• Sanjana Kuthyar, Emory University
• Alcides Filho Fernandes, Emory University
• Ye Huang, University of Illinois at Chicago
• Charlene Choo, University of Nebraska Medical CenterFollow
• Nam Nguyen, University of Nebraska Medical CenterFollow
• Jessica Carag, Emory University
• Jill Morgan, Emory University
• Colleen S. Kraft, Emory University
• Angela L. Hewlett, University of Nebraska Medical CenterFollow
• David Brett-Major, University of Nebraska Medical CenterFollow
• John S. Schieffelin, Tulane University
• Robert F. Garry, Tulane University
• Donald Grant, Kenema Government Hospital Lassa Hemorrhagic Fever Lab
• Grant A. Justin, Walter Reed Army Medical Centre
• Christopher D. Conrady, University of Nebraska Medical Center
• Justine R. Smith, Flinders University
• Brent R. Hayek, University of Nebraska Medical Center
• Shiama Balendra, University College London
• Nisha Acharya, University of California, San Francisco
• Thuy Doan, University of California, San Francisco
• Anais Legand, World Health Organization
• Pierre Formenty, World Health Organization
• Xiankun Zeng, US Army Medical Research Institute of Infectious Diseases
• Ibrahim Conteh, Ministry of Health
• Matthew Jusu Vandy, Ministry of Health
• Lloyd Harrison-Williams, Ministry of Health
• Jalikatu Mustapha, Ministry of Health
• Zikan Koroma, Ministry of Health
• Michael R. Wiley, University of Nebraska Medical CenterFollow
• Ian Crozier, Frederick National Laboratory for Cancer Research
• Jean-Claude Mwanza, The University of North Carolina at Chapel Hill
• Jessica G. Shantha, University of California, San Francisco
• Rafi Ahmed, Emory University
• Steven Yeh, University of Nebraska Medical CenterFollow
• SMILE and EVICT-VR Investigator Study Groups

Document Type

Article

Journal Title

BMJ Open

Publication Date

2025

Volume

15

Abstract

INTRODUCTION: The 2013-2016 Western African outbreak of the Ebola virus disease (EVD), the largest recorded outbreak since the discovery of Ebola virus (EBOV) in 1976, destabilised local health systems and left thousands of survivors at risk for postacute sequelae, including vision-threatening uveitis. In an EVD survivor with severe panuveitis, the detection of persistent EBOV in the aqueous humour, long after clearance of acute viremia, focused clinical and research attention on the host-EBOV interaction in the unique terrain of ocular immune privilege. Despite the recognition that uveitis is common and consequential in EVD survivors, our understanding of pathogenesis is extremely limited, including the contributions of viral persistence and ocular-specific and systemic immune responses to disease expression. In this study protocol, we outline a multifaceted approach to characterise EVD-associated intraocular inflammation, including the clinical phenotype and complications; the presence of EBOV (or EBOV RNA/antigen) in ocular fluids and tissues; and associated local ocular-specific and peripheral immune responses.

METHODS AND ANALYSIS: We use an observational cohort design, which includes EVD survivors and close contacts of EVD survivors (ie, no documented history of EVD), and we propose disease (clinical examination and imaging), as well as molecular, virologic and immunologic characterisation, to meet research objectives.

ETHICS AND DISSEMINATION: This study has received Institutional Review Board approval from University of Nebraska Medical Centre, Emory University and Sierra Leone Ministry of Health. Findings will be disseminated through peer-reviewed publications.

MeSH Headings

Humans, Hemorrhagic Fever, Ebola, Uveitis, Survivors, Ebolavirus, Cross-Sectional Studies, Aqueous Humor, Cohort Studies, Observational Studies as Topic

DOI Link

10.1136/bmjopen-2025-104843

ISSN

2044-6055

Rights

This is an open access article distributed under the terms of the Creative Commons Attribution IGO License (CC BY 3.0 IGO), which permits use, distribution,and reproduction in any medium, provided the original work is properly cited. In any reproduction of this article there should not be any suggestion that WHO or this article endorse any specific organization or products. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL. https://doi.org/10.1136/bmjopen-2025-104843

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

Recommended Citation

Hartley, Caleb D.; Linderman, Susanne; Fashina, Tolulope; Ward, Laura; Drews-Botsch, Carolyn; Pratt, Catherine; Kuthyar, Sanjana; Fernandes, Alcides Filho; Huang, Ye; Choo, Charlene; Nguyen, Nam; Carag, Jessica; Morgan, Jill; Kraft, Colleen S.; Hewlett, Angela L.; Brett-Major, David; Schieffelin, John S.; Garry, Robert F.; Grant, Donald; Justin, Grant A.; Conrady, Christopher D.; Smith, Justine R.; Hayek, Brent R.; Balendra, Shiama; Acharya, Nisha; Doan, Thuy; Legand, Anais; Formenty, Pierre; Zeng, Xiankun; Conteh, Ibrahim; Vandy, Matthew Jusu; Harrison-Williams, Lloyd; Mustapha, Jalikatu; Koroma, Zikan; Wiley, Michael R.; Crozier, Ian; Mwanza, Jean-Claude; Shantha, Jessica G.; Ahmed, Rafi; Yeh, Steven; and SMILE and EVICT-VR Investigator Study Groups, "Understanding the Pathogenesis of Uveitis in Ebola Virus Disease Survivors: An Observational Cohort and Cross-Sectional Study Protocol for Clinical, Molecular Virologic and Immunologic Characterisation" (2025). Journal Articles: Epidemiology. 227.
https://digitalcommons.unmc.edu/coph_epidem_articles/227