There
are thous
ands of survivors of the 2014 Ebol
a outbre
ak in west Afric
a. Ebol
a virus c
an persist in survivors for
months in i
mmune-privileged sites; however, vir
al rel
apse c
ausing life-thre
atening
and potenti
ally tr
ans
missible dise
ase h
as not been described. We report
a c
ase of l
ate rel
apse in
a p
atient who h
ad been tre
ated for severe Ebol
a virus dise
ase with high vir
al lo
ad (pe
ak cycle threshold v
alue 13&
middot;2).
absSec_2">Methods
ara60">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.
absSec_3">Findings
ara70">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.
absSec_4">Interpretation
ara80">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.
absSec_5">Funding
ara90">Royal Free London NHS Foundation Trust.