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.
Bibliographical noteFunding Information:
The work was funded by the Royal Free London NHS Foundation Trust, without external grants. The pharmaceutical companies Beijing MabWorks Biotech (China) and Gilead Sciences provided investigational medicines free of charge. These companies had no input into patient selection or clinical management, or this Article. Sequencing and bioinformatics analyses were funded by the Medical Research Council. ECT is funded by the Wellcome Trust (grant number 102789/Z/13/Z). We thank Pauline Cafferkey for consenting to publication of her case, and for her suggestions for the manuscript. We also thank Gary Kobinger (National Microbiology Laboratory of the Public Health Agency of Canada); Erin Quirk (Gilead Sciences); Breda Athan and staff of the high-level isolation unit; Stephen Powis, Steve Shaw, and staff of the intensive-care, patient-at-risk, high-level isolation unit laboratory and pharmacy teams at Royal Free London NHS Foundation Trust, London, UK; Liz Hughes and her nursing team at the Queen Elizabeth University Hospital, Glasgow, UK; Gillian Mulholland and her nursing team at Gartnavel General Hospital, Glasgow, UK; the Royal Air Force Air Transportable Isolator Teams; and staff of the Virus Reference Department and Rare and Imported Pathogens Laboratory, Pubic Health England.
© 2016 Elsevier Ltd