UCLA

Background: The rise of zoonotic diseases is attributed to human-induced factors such as urbanization, deforestation, and climate change, amplifying disease transmission globally1. Particularly, low-income countries like the Democratic Republic of the Congo (DRC) face heightened challenges, with Ebola virus disease (EVD) emerging as a significant threat. Concurrent outbreaks of multiple diseases further strain the country's resources, leading to extensive morbidity and mortality. To combat the escalating menace of EVD, the DRC implements various surveillance and prevention measures, including the Integrated Disease Surveillance and Response (IDSR) system, the single-dose ERVEBO® vaccine by Merck, and awareness of known risk factors and behaviors linked to Ebola virus (EBOV) infection. However, knowledge gaps persist regarding the efficacy of these tools within the DRC context: 1) Limited examinations have been conducted on the IDSR system's capacity to detect EVD early since its inception in 2000, necessitating quasi-experimental methodologies for comprehensive assessment. 2) EVD risk factors are seldom explored among survivors, and simultaneous assessment of EVD case exposures and animal-related behaviors is scarce, highlighting the need for integrated research approaches. 3)Data on the long-term durability of the ERVEBO® vaccine beyond a two-year period remains scarce, underscoring the necessity for extended studies to inform vaccination strategies effectively. Methods: This dissertation utilizes data from the Integrated Disease Surveillance and Response (IDSR) reporting system and recent Ebola virus disease (EVD) serology studies to evaluate critical aspects of these tools. An interrupted time series analysis is employed to scrutinize the IDSR system, aiming to ascertain changes in the rate of reported diseases that mimic the clinical symptoms of EVD (differential diagnoses) and their correlation with laboratory confirmed EVD outbreaks. Furthermore, a matched case-control risk factor analysis explores the association between specific behaviors and Ebola virus (EBOV) infection among EVD survivors and various control groups. Lastly, a descriptive analysis of antibody titers is conducted to discern patterns in immunogenicity and elucidate the durability of the vaccine-induced antibody response. Results: The interrupted time series analysis conducted on the Integrated Disease Surveillance and Response (IDSR) data revealed significant changes in the rate of reporting for differential diagnoses following confirmed EVD outbreaks. In the risk factor analysis, notable associations were observed between EBOV infection and participants involved in herding, hunting, and slaughtering animals, as well as those who consumed non-human primates or bushmeat, or had contact with human remains. Conversely, higher levels of education were inversely correlated with the risk of infection. Regarding vaccine durability, the study found that 95.7% of participants exhibited seroreactive antibody titers, with 86.3% showing seroconversion at or before 21 days and 83.6% demonstrating antibody persistence. Additionally, the vaccine generated stable titer across follow-up visits. Conclusion: The findings of this dissertation underscore the critical role played by the tools deployed by the DRC in mitigating EVD. Through these analyses, the effectiveness of the surveillance and prevention mechanisms is illuminated, emphasizing the ongoing need for evaluation and investment. Sustaining and enhancing these resources is imperative to uphold the quality of data and the protective measures they afford.