International external quality assessment study for detection of monkeypox virus by PCR supporting laboratory preparedness during the 2022-2023 mpox outbreak and beyond.
Diagnostic capabilities and correspondent External Quality Assessments (EQA) are key for outbreak preparedness. To support diagnostic facilities with a quality assessment of newly established monkeypox virus (MPXV) molecular diagnostic workflows, Quality Control for Molecular Diagnostics (QCMD) and the Bundeswehr Institute of Microbiology (IMB) piloted an international EQA study conducting four challenges from autumn 2022 to summer 2023 during the global mpox outbreak.
To assess the performance (sensitivity/specificity) of molecular assays used by diagnostic laboratories.
Inactivated EQA panels were prepared and distributed containing seven samples of clade Ia and clade IIb MPXV strains at different viral concentrations, two specificity controls with other zoonotic orthopoxviruses (vaccinia and cowpox virus) and a negative control. Assessment was based on reported qualitative testing results.
In this outbreak-related EQA study, a total of 192 laboratories from 37 countries reported 346 qualitative datasets. Overall, core samples were correctly detected by approximately 92 % of participants in all four challenges. While sensitivity performance was acceptable in at least 90 % of datasets correctly reported even for educational MPXV-positive samples with low viral concentration [102 genome equivalents (GE)/mL], several laboratories reported the educational specificity controls as false positives or were unable to differentiate MPXV from related orthopoxviruses.
Mpox is now a globally occurring infection with a demand for quality-assured diagnostic capabilities. The newly established EQA scheme presented here, offers a multi-purpose panel for orthopoxviruses with a focus on MPXV which will continue to ensure diagnostic quality in clinical settings with up-to-date sample panels.
Ehmann R
，Donoso Mantke O
，McCulloch E
，Yousef A
，Ricketts A
，Staines H
，Bugert JJ
，Wölfel R
，Niesters HGM
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Fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease in the Democratic Republic of the Congo: a case report study.
During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence.
In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques.
The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete 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 Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2.
We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings 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 Ebola virus persistence.
Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, US National Cancer Institute (National Institutes of Health), French National Research Institute for Development, and WHO.
Mukadi-Bamuleka D
，Edidi-Atani F
，Morales-Betoulle ME
，Legand A
，Nkuba-Ndaye A
，Bulabula-Penge J
，Mbala-Kingebeni P
，Crozier I
，Mambu-Mbika F
，Whitmer S
，Tshiani Mbaya O
，Hensley LE
，Kitenge-Omasumbu R
，Davey R
，Mulangu S
，Fonjungo PN
，Wiley MR
，Klena JD
，Peeters M
，Delaporte E
，van Griensven J
，Ariën KK
，Pratt C
，Montgomery JM
，Formenty P
，Muyembe-Tamfum JJ
，Ahuka-Mundeke S
，EBOV Persistence Study Group
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《Lancet Microbe》
ResearchGate
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