Late Ebola virus relapse causing meningoencephalitis: a case report

Abstract

SummaryBackgroundThere 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).MethodsA 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.FindingsOn 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.InterpretationOur 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.FundingRoyal Free London NHS Foundation Trust.

Post-exposure treatments for Ebola and Marburg virus infections

“…Complications collectively referred to as 'post-Ebola syndrome' , including musculoskeletal pain, headache and ocular problems, have been noted in a number of survivors of filovirus infection [24][25][26][27][28][29] . In rare cases, encephalitis has also been noted [30][31][32][33] . Filoviruses have also been detected by PCR and/or virus isolation in the breast milk 34,35 and semen [36][37][38][39] of survivors.…”

“…GS-5734 was used in a relapsed patient with meningoencephalitis who had been repatriated to Europe and had previously been treated with other experimental therapies 32 . This relapsed patient received GS-5734 and advanced supportive care, including high-dose cortico steroids, and recovered.…”

“…Nonetheless, brincidofovir was used most famously to treat an individual with EBOV haemorrhagic fever in Dallas, Texas, who did not survive 183 . Brincidofovir was also used in other repatriated patients in the USA and Europe who also received other experimental drugs and advanced supportive care 32,125,148 . A single-arm phase II trial of brincidofovir was initiated in Liberia in January 2015 (REF.…”

“…In 1976, during the original EBOV (Mayinga strain) outbreak, a single patient was also treated with heparin but did not survive 202 . Heparin was used in two instances during the 2013-2016 EBOV epidemic 32,149 . Both patients in these reports survived, but they also received antiviral drugs and advanced supportive care; therefore, the role of heparin is unknown.…”

“…ZMapp was subsequently used on at least four additional patients evacuated from West Africa to Europe and the USA [146][147][148] . ZMAb was also used in at least two cases 32,149 , as was MIL77 (REFS 32,150). The role of ZMapp, ZMAb or MIL77 in patient survival is impossible to discern as all the patients were repatriated to developed countries and received advanced supportive care; most also received other experimental therapies.…”