Pan-ebolavirus serology study of healthcare workers in the Mbandaka Health Region, Democratic Republic of the Congo

Abstract

Although multiple antigenically distinct ebolavirus species can cause human disease, previous serosurveys focused on only Zaire ebolavirus (EBOV). Thus, the extent of reactivity or exposure to other ebolaviruses, and which sociodemographic factors are linked to this seroreactivity, are unclear. We conducted a serosurvey of 539 healthcare workers (HCW) in Mbandaka, Democratic Republic of the Congo, using ELISA-based analysis of serum IgG against EBOV, Sudan ebolavirus (SUDV) and Bundibugyo ebolavirus (BDBV) glycoproteins (GP). We compared seroreactivity to risk factors for viral exposure using univariate and multivariable logistic regression. Seroreactivity against different GPs ranged from 2.2-4.6%. Samples from six individuals reacted to all three species of ebolavirus and 27 samples showed a species-specific IgG response. We find that community health volunteers are more likely to be seroreactive against each antigen than nurses, and in general, that HCWs with indirect patient contact have higher anti-EBOV GP IgG levels than those with direct contact. Seroreactivity against ebolavirus GP may be associated with positions that offer less occupational training and access to PPE. Those individuals with broadly reactive responses may have had multiple ebolavirus exposures or developed cross-reactive antibodies. In contrast, those individuals with species-specific BDBV or SUDV GP seroreactivity may have been exposed to an ebolavirus not previously known to circulate in the region.

Fig 1. Filovirus Outbreaks in Central Africa.

Mbandaka was the site of two EBOV outbreaks: 2018 (54 cases) and 2020 (130 cases). Other outbreaks in the northwestern DRC occurred in: Yambuku (1976; 318 cases; 540 km from Mbandaka), Tandala (1977; 1 case; 350 km), Boende (2014; 69 cases; 300 km) and Likati (2017; 8 cases; 725 km from Mbandaka). The surrounding countries of Angola and Uganda experienced outbreaks of marburgviruses while Gabon, Republic of the Congo, Uganda and present-day South Sudan have experienced numerous outbreaks of multiple ebolaviruses [3]. Within the DRC, most confirmed outbreaks have been due to EBOV infections. In two instances, cases of MARV and RAVV were documented simultaneously, and numerous filoviruses likely co-circulate due to their close geography [6,10]. Map adapted from USGS. (https://ngmdb.usgs.gov/topoview/viewer/#5/-0.931/21.904). Abbreviations: EBOV = Zaire ebolavirus, BDBV = Bundibugyo ebolavirus, SUDV = Sudan ebolavirus, MARV = Marburg marburgvirus, RAVV = Ravn Marburgvirus.

Fig 2. Patient Seroreactivity by Antigen.

The breadth of participant seroreactivity against ebolaviruses in the 36 reactive samples is illustrated. None of these individuals reported exposure to confirmed or probable EVD cases. The samples were characterized by the interpolation of the IgG concentration (Titer) divided by the EC₅₀ of Adimab-15878 for the plate. They were further classified into separate groups by the level of the Titer/EC₅₀ ratio: 1<2 for Weak Reactivity, 2≤10 for Moderate Reactivity, and 10+ for Strong Reactivity. Four samples were strongly reactive: 3 EBOV GPe (Titer/EC₅₀: 86 (HCW 49), 16 (HCW 168), 16 (HCW 229)) and 1 SUDV GPΔMuc (Titer/EC₅₀: 30 (HCW 29)).