• Clinical and epidemiological performance of WHO Ebola case definitions: a systematic review and meta-analysis

      Caleo, G; Theocharaki, F; Lokuge, K; Weiss, HA; Inamdar, L; Grandesso, F; Danis, K; Pedalino, B; Kobinger, G; Sprecher, A; et al. (Elsevier, 2020-06-25)
      Background Ebola virus disease case definition is a crucial surveillance tool to detect suspected cases for referral and as a screening tool for clinicians to support admission and laboratory testing decisions at Ebola health facilities. We aimed to assess the performance of the WHO Ebola virus disease case definitions and other screening scores. Methods In this systematic review and meta-analysis, we searched PubMed, Scopus, Embase, and Web of Science for studies published in English between June 13, 1978, and Jan 14, 2020. We included studies that estimated the sensitivity and specificity of WHO Ebola virus disease case definitions, clinical and epidemiological characteristics (symptoms at admission and contact history), and predictive risk scores against the reference standard (laboratory-confirmed Ebola virus disease). Summary estimates of sensitivity and specificity were calculated using bivariate and hierarchical summary receiver operating characteristic (when four or more studies provided data) or random-effects meta-analysis (fewer than four studies provided data). Findings We identified 2493 publications, of which 14 studies from four countries (Sierra Leone, Guinea, Liberia, and Angola) were included in the analysis. 12 021 people with suspected disease were included, of whom 4874 were confirmed as positive for Ebola virus infection. Six studies explored the performance of WHO case definitions in non-paediatric populations, and in all of these studies, suspected and probable cases were combined and could not be disaggregated for analysis. The pooled sensitivity of the WHO Ebola virus disease case definitions from these studies was 81·5% (95% CI 74·1–87·2) and pooled specificity was 35·7% (28·5–43·6). History of contact or epidemiological link was a key predictor for the WHO case definitions (seven studies) and for risk scores (six studies). The most sensitive symptom was intense fatigue (79·0% [95% CI 74·4–83·0]), assessed in seven studies, and the least sensitive symptom was pain behind the eyes (1·0% [0·0–7·0]), assessed in three studies. The performance of fever as a symptom varied depending on the cutoff used to define fever. Interpretation WHO Ebola virus disease case definitions perform suboptimally to identify cases at both community level and during triage at Ebola health facilities. Inclusion of intense fatigue as a key symptom and contact history could improve the performance of case definitions, but implementation of these changes will require effective collaboration with, and trust of, affected communities.
    • Clinical and epidemiological performance of WHO Ebola case definitions: a systematic review and meta-analysis

      Caleo, G; Theocharaki, F; Lokuge, K; Weiss, HA; Inamdar, L; Grandesso, F; Danis, K; Pedalino, B; Kobinger, G; Sprecher, A; et al. (Elsevier, 2020-11-01)
      Background Ebola virus disease case definition is a crucial surveillance tool to detect suspected cases for referral and as a screening tool for clinicians to support admission and laboratory testing decisions at Ebola health facilities. We aimed to assess the performance of the WHO Ebola virus disease case definitions and other screening scores. Methods In this systematic review and meta-analysis, we searched PubMed, Scopus, Embase, and Web of Science for studies published in English between June 13, 1978, and Jan 14, 2020. We included studies that estimated the sensitivity and specificity of WHO Ebola virus disease case definitions, clinical and epidemiological characteristics (symptoms at admission and contact history), and predictive risk scores against the reference standard (laboratory-confirmed Ebola virus disease). Summary estimates of sensitivity and specificity were calculated using bivariate and hierarchical summary receiver operating characteristic (when four or more studies provided data) or random-effects meta-analysis (fewer than four studies provided data). Findings We identified 2493 publications, of which 14 studies from four countries (Sierra Leone, Guinea, Liberia, and Angola) were included in the analysis. 12 021 people with suspected disease were included, of whom 4874 were confirmed as positive for Ebola virus infection. Six studies explored the performance of WHO case definitions in non-paediatric populations, and in all of these studies, suspected and probable cases were combined and could not be disaggregated for analysis. The pooled sensitivity of the WHO Ebola virus disease case definitions from these studies was 81·5% (95% CI 74·1–87·2) and pooled specificity was 35·7% (28·5–43·6). History of contact or epidemiological link was a key predictor for the WHO case definitions (seven studies) and for risk scores (six studies). The most sensitive symptom was intense fatigue (79·0% [95% CI 74·4–83·0]), assessed in seven studies, and the least sensitive symptom was pain behind the eyes (1·0% [0·0–7·0]), assessed in three studies. The performance of fever as a symptom varied depending on the cutoff used to define fever. Interpretation WHO Ebola virus disease case definitions perform suboptimally to identify cases at both community level and during triage at Ebola health facilities. Inclusion of intense fatigue as a key symptom and contact history could improve the performance of case definitions, but implementation of these changes will require effective collaboration with, and trust of, affected communities.
    • Ebola

      Feldmann, H; Sprecher, A; Geisbert, TW (Massachusetts Medical Society, 2020-05-07)
    • New filovirus disease classification and nomenclature

      Kuhn, JH; Adachi, T; Adhikari, NKJ; Arribas, JR; Bah, IE; Bausch, DG; Bhadelia, N; Borchert, M; Brantsæter, AB; Brett-Major, DM; et al. (Nature Research, 2019-03-29)
      The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision.
    • Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment

      Cross, RW; Bornholdt, ZA; Prasad, AN; Geisbert, JB; Borisevich, V; Agans, KN; Deer, DJ; Melody, K; Fenton, KA; Feldmann, H; et al. (Nature Research, 2020-07-27)
      A replication-competent vesicular stomatitis virus vaccine expressing the Ebola virus (EBOV) glycoprotein (GP) (rVSV-ZEBOV) was successfully used during the 2013-16 EBOV epidemic. Additionally, chimeric and human monoclonal antibodies (mAb) against the EBOV GP have shown promise in animals and humans when administered therapeutically. Uncertainty exists regarding the efficacy of postexposure antibody treatments in the event of a known exposure of a recent rVSV-ZEBOV vaccinee. Here, we model a worst-case scenario using rhesus monkeys vaccinated or unvaccinated with the rVSV-ZEBOV vaccine. We demonstrate that animals challenged with a uniformly lethal dose of EBOV one day following vaccination, and then treated with the anti-EBOV GP mAb MIL77 starting 3 days postexposure show no evidence of clinical illness and survive challenge. In contrast, animals receiving only vaccination or only mAb-based therapy become ill, with decreased survival compared to animals vaccinated and subsequently treated with MIL77. These results suggest that rVSV-ZEBOV augments immunotherapy.