@article{fdi:010092037,
  title = {{F}atal meningoencephalitis associated with {E}bola virus persistence in two survivors of {E}bola virus disease in the {D}emocratic {R}epublic of the {C}ongo : a case report study},
  author = {{M}ukadi-{B}amuleka, {D}. and {E}didi-{A}tani, {F}. and {M}orales-{B}etoulle, {M}. {E}. and {L}egand, {A}. and {N}kuba-{N}daye, {A}. and {B}ulabula-{P}enge, {J}. and {M}bala-{K}ingebeni, {P}. and {C}rozier, {I}. and {M}ambu-{M}bika, {F}. and {W}hitmer, {S}. and {M}baya, {O}. {T}. and {H}ensley, {L}. {E}. and {K}itenge-{O}masumbu, {R}. and {D}avey, {R}. and {M}ulangu, {S}. and {F}onjungo, {P}. {N}. and {W}iley, {M}. {R}. and {K}lena, {J}. and {P}eeters, {M}artine and {D}elaporte, {E}. and van {G}riensven, {J}. and {A}rien, {K}. {K}. and {P}ratt, {C}. and {M}ontgomery, {J}. {M}. and {F}ormenty, {P}. and {M}uyembe-{T}amfum, {J}. {J}. and {A}huka-{M}undeke, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {D}uring the 2018-20 {E}bola virus disease outbreak in the {D}emocratic {R}epublic of the {C}ongo, thousands of patients received unprecedented vaccination, monoclonal antibody (m{A}b) therapy, or both, leading to a large number of survivors. {W}e aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and m{A}b-treated survivors of {E}bola virus disease in the {D}emocratic {R}epublic of the {C}ongo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence. {M}ethods {I}n this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent {E}bola virus disease and subsequent fatal meningoencephalitis. {W}e obtained data from epidemiological databases, {E}bola treatment units, survivor programme databases, laboratory datasets, and hospital records. {F}ollowing national protocols established during the 2018-20 outbreak in the {D}emocratic {R}epublic of the {C}ongo, blood, plasma, and cerebrospinal fuid ({CSF}) samples were collected during the first and second episodes of {E}bola virus disease from both individuals and were analysed by molecular (quantitative {RT}-{PCR} and next-generation sequencing) and serological ({I}g{G} and {I}g{M} {ELISA} and {L}uminex assays) techniques. {F}indings {T}he total time between the end of the fi rst {E}bola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. {I}n both patients, {E}bola virus {RNA} was detected in blood and {CSF} samples during the second episode of disease. {C}omplete genomes from {CSF} samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of {E}bola virus. {S}erological analysis showed an antigen-specific humoral response with typical {I}g{M} and {I}g{G} kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2. {I}nterpretation {W}e report the fi rst two cases of fatal meningoencephalitis associated with {E}bola virus persistence in two survivors of {E}bola virus disease who had received vaccination and m{A}b-based treatment in the {D}emocratic {R}epublic of the {C}ongo. {O}ur fi ndings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of {E}bola virus persistence. {F}unding {M}inistry of {H}ealth of the {D}emocratic {R}epublic of the {C}ongo, {I}nstitut {N}ational de {R}echerche {B}iom & eacute;dicale, {I}nfectious {D}isease {R}apid {R}esponse {R}eserve {F}und, {US} {C}enters for {D}isease {C}ontrol and {P}revention, {US} {N}ational {C}ancer {I}nstitute ({N}ational {I}nstitutes of {H}ealth), {F}rench {N}ational {R}esearch {I}nstitute for {D}evelopment, and {WHO}.},
  keywords = {{AFRIQUE} {CENTRALE} ; {REPUBLIQUE} {DEMOCRATIQUE} {DU} {CONGO}},
  booktitle = {},
  journal = {{L}ancet {M}icrobe},
  volume = {5},
  numero = {10},
  pages = {100905 [10 ]},
  year = {2024},
  DOI = {10.1016/s2666-5247(24)00137-x},
  URL = {https://www.documentation.ird.fr/hor/fdi:010092037},
}