Journal Article

Late Ebola virus relapse causing meningoencephalitis: a case report

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

2016

Overview

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). 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. 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. 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. Royal Free London NHS Foundation Trust.

• Publisher: Elsevier Ltd,Elsevier B.V,Elsevier Limited,Elsevier
• Subject: Acute Disease / Adenosine Monophosphate - analogs & derivatives / Adult / Alanine - analogs & derivatives / Alanine - therapeutic use / Ankle / Antiviral agents / Antiviral Agents - therapeutic use / Biological products industry / Blood / Case reports / Catheters / Cerebrospinal fluid / Consciousness / Corticoids / Corticosteroids / Cranial Nerve Diseases - virology / Disease Outbreaks / Drug dosages / Drugs, Investigational - therapeutic use / Ebola virus / Ebola virus infections / Ebolavirus / Ebolavirus - genetics / Ebolavirus - isolation & purification / Encephalitis / Epidemics / Female / Genome, Viral / Genomes / Genomics / Glycoproteins / Health services / Hemorrhagic Fever, Ebola - diagnosis / Hemorrhagic Fever, Ebola - drug therapy / Humans / Illnesses / Immune privilege / Internal Medicine / Meningitis / Meningoencephalitis / Meningoencephalitis - complications / Meningoencephalitis - diagnosis / Meningoencephalitis - drug therapy / Meningoencephalitis - virology / Metagenomics / Monoclonal antibodies / Non-coding RNA / Nurses / Pain / Pathology / Patients / Peak load / Peripheral blood / Peripheral neuropathy / Plasma / Public health / Radiculopathy - virology / Recurrence / Ribonucleic acid / Ribonucleotides - therapeutic use / RNA / RNA viruses / RNA, Viral - blood / RNA, Viral - cerebrospinal fluid / RNA, Viral - isolation & purification / RNA-directed DNA polymerase / Scotland / Sierra Leone / Signs and symptoms / Streptococcus infections / Survival / Thyroid gland / Ultrasonic imaging / Vigilance / Viral diseases / Viral infections / Viral Load - drug effects / Virus diseases