Differential symptomatology of possible and confirmed infection with Ebola virus disease in the Democratic Republic of the Congo: a retrospective cohort study

Background

In its early stages, the rapid onset, high fever, and gastrointestinal symptoms of Ebola virus disease are largely indistinguishable from other infectious diseases. Our objective was to characterize the clinical indicators associated with Ebola virus disease in order to improve the response to epidemics.

Methods

In this retrospective analysis, we assessed routinely collected data from people with suspected Ebola virus disease attending 30 Ebola health facilities in two provinces of the Democratic Republic of the Congo between August 1, 2018 and August 28, 2019. We used logistic regression analysis to model the probability of Ebola infection across 34 clinical variables and four types of possible exposure to Ebola virus disease: contact with someone known to have Ebola virus disease, presence at a funeral, consultation in a health facility or consultation with an informal health professional.

Results

Data from 24,666 people were included. If a patient presented to care in the early symptomatic phase (i.e., days 0–2), Ebola virus disease positivity was most associated with prior exposure to someone with Ebola virus disease. Ebola virus disease (odds ratio [OR]
11 9, 95% CI 9 1–15 8), attendance at funeral (2 1, 1 6–2 7), or visits to a health facility (2 1, 1 6– 2 8), rather than clinical parameters. If presentation occurred on day 3 or later (after onset of symptoms), injection site bleeding (OR 33 9, 95% CI 12 7–101 3), bleeding gums (7 5, 3 7–15 4), conjunctivitis (2 4, 1 7–3 4), asthenia (1 9, 1 5–2 3), sore throat (1 8, 1 3–2 4), dysphagia (1 8, 1 4–2 3) and diarrhea (1 6, 1 3–1 9) were other strong predictors of disease to Ebola virus. Some signs specific to Ebola virus disease were less frequent in vaccinated persons positive for Ebola virus disease than in non-vaccinated persons, such as dysphagia (–47%, p=0 0024), hematemesis (– 90%, p=0 0131) and bleeding gums (–100%, p=0 0035).

Interpretation

Establishing the exact time at which an individual presented their first symptoms is essential to assess their risk of infection. An individual’s exposure history remains of paramount importance, particularly in the early phase. Vaccination against Ebola virus disease reduces the severity of symptoms and should also be considered when assessing the likelihood of infection. These findings on symptomatology need to be translated into practice during triage and should inform testing and quarantine procedures.

Funding

Médecins Sans Frontières and its research subsidiary Epicenter.