Late Ebola virus relapse causing meningoencephalitis: a case report

Michael Jacobs, Alison Rodger, David J Bell, Sanjay Bhagani, Ian Cropley, Ana Filipe, Robert J Gifford, Susan Hopkins, Joseph Hughes, Farrah Jabeen, Ingolfur Johannessen, Drosos Karageorgopoulos, Angie Lackenby, Rebecca Lester, Rebecca S N Liu, Alisdair MacConnachie, Tabitha Mahungu, Daniel Martin, Neal Marshall, Stephen Mepham, Richard Orton, Massimo Palmarini, Monika Patel, Colin Perry, S Erica Peters, Duncan Porter, David Ritchie, Neil D Ritchie, R Andrew Seaton, Vattipally B Sreenu, Kate Templeton, Simon Warren, Gavin S Wilkie, Maria Zambon, Robin Gopal, Emma C Thomson, Michael Jacobs, Alison Rodger, David J Bell, Sanjay Bhagani, Ian Cropley, Ana Filipe, Robert J Gifford, Susan Hopkins, Joseph Hughes, Farrah Jabeen, Ingolfur Johannessen, Drosos Karageorgopoulos, Angie Lackenby, Rebecca Lester, Rebecca S N Liu, Alisdair MacConnachie, Tabitha Mahungu, Daniel Martin, Neal Marshall, Stephen Mepham, Richard Orton, Massimo Palmarini, Monika Patel, Colin Perry, S Erica Peters, Duncan Porter, David Ritchie, Neil D Ritchie, R Andrew Seaton, Vattipally B Sreenu, Kate Templeton, Simon Warren, Gavin S Wilkie, Maria Zambon, Robin Gopal, Emma C Thomson

Abstract

Background: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2).

Methods: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach.

Findings: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus.

Interpretation: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern.

Funding: Royal Free London NHS Foundation Trust.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Clinical laboratory findings over the course of Ebola virus relapse RT-PCR=reverse transcriptase PCR.
Figure 2
Figure 2
Contrast-enhanced MRI of the head and spine Gadolinium-enhanced, fat-suppressed, 3 mm axial T1-weighted images of the brain showing: abnormal area of enhancement within the left cerebellar hemisphere (black arrow) and abnormal enhancement of the left cochlea basal turn (red arrow; A); and abnormal enhancement within the left cerebellar hemisphere (black arrow), right cochlea basal turn (red arrow), anterior genu of the tympanic segment of the left facial nerve (blue arrow), and focus of enhancement within the left internal auditory canal (orange arrow; B). Gadolinium-enhanced 4 mm sagittal T1-weighted image of the lumbar spine showing enhancement involving the surface of conus and along the cauda equina (green arrow; C).

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