Emerging infectious diseases can lead to devastating epidemics and pose a threat to global health security. The World Health Organization has identified pathogens that are likely to cause severe and imminent outbreaks, which include Ebolavirus (EBOV) and Lassa fever virus, all of which require urgent attention in research. The West African Ebola virus disease (EVD) outbreak of 2013-2016 is the most devasting EBOV outbreak in history with over 28,600 infected and 11,300 deaths. To date there continue to be isolated outbreaks with significant morbidity and mortality. There are approximately 17,000 EVD survivors who are at-risk for Post-Ebolavirus Disease Syndrome, a recently described entity, which includes systemic conditions, ocular disease, and viral persistence in immune privileged sites (aqueous humor, semen, and central nervous system). Viral persistence is of public health importance, given its initiation of EBOV transmission events and its association with end-organ damage. Uveitis, a potentially blinding inflammatory eye disease, is the most common ocular complication, occurring in approximately 13-34% of EVD survivors in West Africa. We have described vision loss due to ocular complications in retrospective cohorts in both Sierra Leone and Liberia. Specifically, within Liberian EVD survivors with uveitis developed vision impairment was noted in 60% and blindness (vision worse than 20/400) in approximately 40% of EVD survivors. Currently, we have insufficient knowledge about the disease course of EVD-associated uveitis, long-term visual acuity outcomes, and appropriate treatment for this sight-threatening disease. Besides our recent studies related to clinical uveitis in EVD survivors, our recent investigation of EBOV persistence raises questions about the potential for the eye to serve as a novel tissue site for infectious disease surveillance, particularly in a viral hemorrhagic fever zone endemic for other emerging pathogens of public health significance. The objectives of this study are to 1. Determine the prevalence of uveitis, incident vision loss over time, and risk factors for uveitis development in EVD survivors 2. Explore ophthalmic manifestation in Lassa fever virus survivors 3. Validate ocular fluid sampling as method for detection for surveillance of infectious diseases in collaboration with the Child Health and Mortality Prevention Surveillance study. The career development aims for this K-23 proposal are to 1. Obtain methodological skills in disease surveillance systems 2. Gain competency in molecular diagnostics of ocular fluid in the diagnosis of infectious pathogens 3. Continue to develop skills in clinical research in international settings 4. Further my training in statistical and epidemiology methods necessary for success in clinical studies. To accomplish these goals, I have designed a training plan that includes coursework, mentorship with international leaders, attendance and presentation at local and national research meetings/conferences, and directed, hands-on training. This K23 mentored career development award will be the foundation for the skills necessary to become a successful independent clinician scientist.

Public Health Relevance

Significant gaps exist in our understanding of ocular complications associated with emerging infectious diseases including Ebola virus disease and Lassa fever, as well as the potential for vision loss. The detection of novel emerging pathogens in the eye, an immune privileged organ, have raised additional questions related to infectious disease surveillance utilizing ocular fluid and tissues. This proposal with further define the ocular complications in Ebola virus disease survivors, explore eye disease in Lassa fever virus survivors, and validate the eye as a model of infectious disease surveillance in under-5 mortality in collaboration with the Child Health and Mortality Prevention Surveillance network to impact clinical care, inform public health policy, and assist with guideline development for ophthalmic care.

National Institute of Health (NIH)
National Eye Institute (NEI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZEY1)
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Agarwal, Neeraj
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Emory University
Schools of Medicine
United States
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