• 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-negative neonates born to Ebola-infected mothers after monoclonal antibody therapy: a case series

      Ottoni, MP; Ricciardone, JD; Nadimpalli, A; Singh, S; Katsomya, AM; Pokoso, LM; Petrucci, R (Elsevier, 2020-12-01)
      Background Few fetuses survive childbirth when the mother is positive for Ebola virus, with almost all being miscarried or stillborn, or dying shortly after birth. Before 2019, only two infants had been reported surviving past 28 days, of whom one tested positive for Ebola virus and subsequently received experimental therapies. Little is understood regarding the care of surviving neonates born to Ebola virus-positive mothers in the postnatal period and how novel anti-Ebola virus therapies might affect neonatal outcomes. Methods In this case series, we report on two neonates liveborn during the 2018–20 North Kivu Ebola epidemic in the Democratic Republic of the Congo who, along with their Ebola virus-positive mothers, received investigational monoclonal antibody treatment (mAB114 or REGN-EB3) as part of a randomised controlled trial (NCT03719586). Findings Both infants were born Ebola-negative and progressed well while in the Ebola Treatment Centre. Neither neonate developed evidence of Ebola virus disease during the course of the admission, and both were Ebola-negative at 21 days and remained healthy at discharge. Interpretation To our knowledge these neonates are the first documented as Ebola virus-negative at birth after being born to Ebola virus-positive mothers, and only the third and fourth neonates ever documented to have survived into infancy. Although no conclusions can be drawn from this small case series, and further research is required to investigate the neonatal effects of antibody therapies, these cases warrant review regarding whether post-delivery antibody therapy should be considered for all liveborn neonates of Ebola virus-positive mothers. In the context of a low resource setting, where survival of low-birthweight infants is poor, these cases also highlight the importance of adequate neonatal care.
    • Humoral and cellular immune response induced by rVSVΔG-ZEBOV-GP vaccine among frontline workers during the 2013-2016 West Africa Ebola outbreak in Guinea

      Boum, Y; Juan-Giner, A; Hitchings, M; Soumah, A; Strecker, T; Sadjo, M; Cuthbertson, H; Hayes, P; Tchaton, M; Jemmy, JP; et al. (Elsevier, 2020-06-26)
      Background As part of a Phase III trial with the Ebola vaccine rVSVΔG-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine. Methods We conducted an open‐label, non‐randomized, single-arm immunogenicity evaluation of one dose of rVSVΔG-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein–specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response. Results A total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1–88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0–95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0–3.8) at 28 days and 5.4% (95% CI 2.1–13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ≥ 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180. Conclusions We found one dose of rVSVΔG-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.
    • The power of touch

      Dahl, EH (Elsevier, 2020-04-04)