Meta-analysis of predictive symptoms for Ebola virus disease

Introduction: One of the leading challenges in the 2013–2016 West African Ebola virus disease (EVD) outbreak was how best to quickly identify patients with EVD, separating them from those without the disease, in order to maximise limited isolation bed capacity and keep health systems functioning. Methodology: We performed a systematic literature review to identify all published data on EVD clinical symptoms in adult patients. Data was dual extracted, and random effects meta-analysis performed for each symptom to identify symptoms with the greatest risk for EVD infection. Results: Symptoms usually presenting late in illness that were more than twice as likely to predict a diagnosis of Ebola, were confusion (pOR 3.04, 95% CI 2.18–4.23), conjunctivitis (2.90, 1.92–4.38), dysphagia (1.95, 1.13–3.35) and jaundice (1.86, 1.20–2.88). Early non-specific symptoms of diarrhoea (2.99, 2.00–4.48), fatigue (2.77, 1.59–4.81), vomiting (2.69, 1.76–4.10), fever (1.97, 1.10–4.52), muscle pain (1.65, 1.04–2.61), and cough (1.63, 1.24–2.14), were also strongly associated with EVD diagnosis. Conclusions: The existing literature fails to provide a unified position on the symptoms most predictive of EVD, but highlights some early and late stage symptoms that in combination will be useful for future risk stratification. Confirmation of these findings across datasets (or ideally an aggregation of all individual patient data) will aid effective future clinical assessment, risk stratification tools and emergency epidemic response planning. Author summary: Ebola is a rare but deadly virus, found mainly in sub-Saharan Africa. People can get it through direct contact with an infected animal (bat or nonhuman primate) or a sick or dead person infected with Ebola virus. The virus can cause a host of different symptoms that overlap with many other diseases, making diagnosis a challenge for doctors, particularly with a lack of available rapid diagnostic tests or laboratory facilities.