• Ensuring On-site Ebola Patient Monitoring and Follow-up: Development of a Laboratory Structure Embedded in an Ebola Treatment Center.

      Williams, A; Amand, M; Van den Bergh, R; De Clerck, H; Antierens, A; Chaillet, P (Cambridge University Press, 2019-12-01)
      The capacity to rapidly distinguish Ebola virus disease from other infectious diseases and to monitor biochemistry and viremia levels is crucial to the clinical management of suspected Ebola virus disease cases. This article describes the design and practical considerations of a laboratory straddling the high- and low-risk zones of an Ebola treatment center to produce timely diagnostic and clinical results for informed case management of Ebola virus disease in real-life conditions. This innovation may be of relevance for actors requiring flexible laboratory implementation in contexts of high-communicability, high-lethality disease outbreaks.
    • A meta-analysis of clinical studies conducted during the West Africa Ebola virus disease outbreak confirms the need for randomized control groups

      Dodd, L; Follman, D; Proschan, M; Wang, J; Malvy, D; Horby, P; Gouel-Cheron, A; Ciglenecki, I; Davey, R; Lane, C; et al. (American Association for the Advancement of Science, 2019-11-27)
      Recent Ebola virus disease outbreaks affirm the dire need for treatments with proven efficacy. Randomized controlled clinical trials remain the gold standard but, during disease outbreaks, may be difficult to conduct due to ethical concerns and challenging field conditions. In the absence of a randomized control group, statistical modeling to create a control group could be a possibility. Such a model-based reference control would only be credible if it had the same mortality risk as that of the experimental group in the absence of treatment. One way to test this counterfactual assumption is to evaluate whether reasonable similarity exists across nonrandomized control groups from different clinical studies, which might suggest that a future control group would be similarly homogeneous. We evaluated similarity across six clinical studies conducted during the 2013-2016 West Africa outbreak of Ebola virus disease. These studies evaluated favipiravir, the biologic ZMapp, the antimalarial drug amodiaquine, or administration of convalescent plasma or convalescent whole blood. We compared the nonrandomized control groups of these six studies comprising 1147 individuals infected with Ebola virus. We found considerable heterogeneity, which did not disappear after statistical modeling to adjust for prognostic variables. Mortality risk varied widely (31 to 66%) across the nonrandomized control arms of these six studies. Models adjusting for baseline covariates (age, sex, and cycle threshold, a proxy for viral load) failed to sufficiently recalibrate these studies and showed that heterogeneity remained. Our findings highlight concerns about making invalid conclusions when comparing nonrandomized control groups to cohorts receiving experimental treatments.
    • 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.
    • The power of touch

      Dahl, EH (Elsevier, 2020-04-04)
    • A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

      Mulangu, S; Grais, R; Dodd, L; Follmann, D; Proschan, M; Davey, R; Mukadi, D; Lusakibanza, M (2019-12-12)
      BACKGROUND Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial. METHODS We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days. RESULTS A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P = 0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P = 0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs. CONCLUSIONS Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586.)
    • What can be learnt from Ebola about the dangers of the global health security approach?

      Roper, S (Transactions of the Royal Society, 2019-12-01)
      The current outbreak of Ebola that has been raging out of control for over 1 y in the Democratic Republic of Congo (DRC) has brought back painful memories from West Africa about the dangers of the global health security approach. Drawing on the author’s personal experience of working as a medic in both outbreaks, this article reflects on the challenges of responding to the disease inside a global health security framework. Insights and recommendations are made as to how the global health community can contribute towards gaining better control of Ebola both now and in the future.