A large number of Ebola virus infections may have been unrecognized during the 2013-2016 West African outbreak, both undiagnosed Ebola virus disease (EVD) as well as mildly symptomatic and asymptomatic infection. The epidemiology and natural history of infection in this unrecognized population, which is defined by positive Ebola serology and a history of exposure, are poorly understood. For instance, it is unknown if individuals with unrecognized infection have similar clinical and psychosocial sequelae as recognized cases, such as uveitis, depression, and work-related disability. Understanding the extent to which post-infectious sequelae occur and the predictors of unrecognized infection will bolster efforts to screen and link unrecognized, infected individuals - both symptomatic and asymptomatic - to survivor services and to better identify this population in future outbreaks. I will study a well characterized cohort of individuals with serological evidence of past, unrecognized, Ebola virus infection. I will utilize an existing cohort of close contacts of EVD survivors developed by the National Institute of Allergy and Infectious Diseases' Partnership for Research on Ebola Virus in Liberia (PREVAIL). The PREVAIL program began a natural history study of EVD survivors and their close contacts in June 2015. Over 1,100 EVD survivors have been enrolled with the aim of characterizing their post-EVD clinical sequelae, viral persistence, and durability of antibody response. Over 2,300 close contacts have also been enrolled as the comparison population. A total of 230 (10%) close contacts of EVD survivors were found to be seropositive by the quantitative FANG Ebola EIA and had not been reported as having had EVD. At study baseline, 57% of this population reported having had symptoms in the three-week period after exposure to Ebola virus, and 43% did not. This will be the first systematic, longitudinal study of unrecognized survivors of Ebola virus infection. This K23 proposal aims to: (1) identify the clinical sequelae of unrecognized, symptomatic Ebola virus infection, (2) identify the predictors and clinical sequelae of unrecognized, asymptomatic Ebola virus infection, and (3) identify psychosocial sequelae among unrecognized, symptomatic EVD survivors. My career development aims involve: (1) design of observational studies, (2) advanced biostatistics, and (3) field epidemiology in low-resource settings. This plan will be carried out with coursework, directed study, and the guidance of an international team of mentors. In addition to future study of longer-term sequelae of EVD, I will apply these skills and expertise to an R01 application in which I study the epidemiology and natural history of other viral hemorrhagic fever and emerging infectious diseases such as Marburg virus and monkeypox.
The epidemiology and natural history of unrecognized Ebola virus infection ? both individuals with classic symptoms who were not reported and those with milder or asymptomatic infection ? are poorly understood. These individuals may have post-infectious clinical and psychosocial sequelae that are similar to diagnosed survivors of Ebola virus disease. This proposal aims to improve the care of unrecognized Ebola virus-infected individuals by identifying the predictors and post-infectious sequelae of the first systematically studied, longitudinal cohort of individuals with serological evidence of unrecognized Ebola virus infection from the 2013- 2016 West African outbreak.