Ebola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease

Abstract

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).

Figure 1

Timeline of the first and second EVD episodes.

Figure 2

Phylogenetic and epidemiological analysis of the relapse patient and linked cases A) Maximum clade credibility tree with a two-rate clock model where branches indicating persistent infection were allowed to have a different rate of evolution from the rest of the tree. The tree was estimated using sequenced isolates with >95% coverage from the current Nord Kivu EBOV outbreak in DRC (n=297), colored by health zone. Branch colors indicate the evolutionary rate as indicated in substitutions/site/year. Internal nodes of the tree with a posterior probability > 50% are marked with black circles. B) Zoomed-in view of the time tree showing the first (Sample d1) and second EVD episodes (Sample d171) of the relapse patient, as well as 61 viral genomes sampled from epidemiologically linked cases. The 95% highest posterior density of the estimated time to most recent common ancestor (TMRCA) for the relapse clade is indicated in gray, and shown in full in the top left corner. The median TMRCA was estimated to be November 7th, 2019 (95% HPD: 15 Oct 2019 - 24 Nov 2019). The evolutionary rate between samples d1 and d7 is 4-fold reduced compared to the overall outbreak (see Figure S2). Data taken from https://nextstrain.org/community/inrb-drc/ebola-nord-kivu and released on NCBI GenBank database. C) Haplotype network of the relapse case patient and 72 epidemiology linked cases across five different health zones in DRC. Circle sizes represent the number of cases.