Zoonotic risk factors associated with seroprevalence of Ebola virus GP antibodies in the absence of diagnosed Ebola virus disease in the Democratic Republic of Congo

Abstract

Background: Ebola virus (EBOV) is a zoonotic filovirus spread through exposure to infected bodily fluids of a human or animal. Though EBOV is capable of causing severe disease, referred to as Ebola Virus Disease (EVD), individuals who have never been diagnosed with confirmed, probable or suspected EVD can have detectable EBOV antigen-specific antibodies in their blood. This study aims to identify risk factors associated with detectable antibody levels in the absence of an EVD diagnosis.

Methodology: Data was collected from September 2015 to August 2017 from 1,366 consenting individuals across four study sites in the DRC (Boende, Kabondo-Dianda, Kikwit, and Yambuku). Seroreactivity was determined to EBOV GP IgG using Zaire Ebola Virus Glycoprotein (EBOV GP antigen) ELISA kits (Alpha Diagnostic International, Inc.) in Kinshasa, DRC; any result above 4.7 units/mL was considered seroreactive. Among the respondents, 113 (8.3%) were considered seroreactive. Several zoonotic exposures were associated with EBOV seroreactivity after controlling for age, sex, healthcare worker status, location, and history of contact with an EVD case, namely: ever having contact with bats, ever having contact with rodents, and ever eating non-human primate meat. Contact with monkeys or non-human primates was not associated with seroreactivity.

Conclusions: This analysis suggests that some zoonotic exposures that have been linked to EVD outbreaks can also be associated with EBOV GP seroreactivity in the absence of diagnosed EVD. Future investigations should seek to clarify the relationships between zoonotic exposures, seroreactivity, asymptomatic infection, and EVD.

Fig 1. Map of the Democratic Republic of the Congo with health zones of study sites highlighted in red.

Base layer from https://www.arcgis.com/home/item.html?id=10df2279f9684e4a9f6a7f08febac2a9.

Fig 2. Directed Acyclic Graph (DAG) depicting hypothesized causal structure of zoonotic exposure and Ebola virus seroreactivity among individuals with no history of Ebola Virus Disease.

Age and location are assumed to be simple confounders, influencing both presence of zoonotic exposures and Ebola virus (EBOV) seroreactivity. Sex is assumed to influence both zoonotic exposure and seroreactivity, and to be associated with healthcare worker status, as women were more likely to be healthcare workers in our sample. Being a healthcare worker is assumed to influence EBOV seroreactivity, due to potential for unknown exposures to Ebola Virus Disease (EVD) cases, and zoonotic exposure, due to relatively low contact with animals and forest when compared to non-healthcare workers. Working in healthcare is assumed to raise an individual’s risk of having known contact with an EVD case, which in turn is assumed to increase an individual’s risk of EBOV seroreactivity. Our DAG includes a residual confounding path through an unknown ancestor of zoonotic exposure and contact with an EVD case. In the analysis we controlled for contact with an EVD case as a proxy for this unknown confounder, which led to a more conservative analysis.