Produire de la science en situation de crise. Les traitements médicamenteux spécifiques de la maladie à virus Ebola en 2016 : leçons et perspectives

Science in a crisis. Medical countermeasures in Ebola virus disease, 2016: lessons learned and perspectives


Au cours de l’épidémie de maladie à virus Ebola qui a affecté l’Afrique de l’Ouest en 2014–2016, la mise en place d’essais cliniques en vue de l’évaluation de stratégies thérapeutiques et de vaccins prometteurs mais non homologués est apparue comme une composante emblématique de la réponse globale à l’épidémie. La recherche clinique en situation épidémique causée par un agent infectieux hautement pathogène est un enjeu complexe en contexte de ressources limitées. En situation sanitaire extrême, priorité de soins et impératif d’interventions construites dans la perspective de l’évidence scientifique sont conciliables par une approche pragmatique et évolutive guidée par l’intégration de la recherche dans la démarche de soins et l’adaptation réactive aux critères contextuels. Ces enjeux sont portés aux scénarios à construire et anticiper au cours de la phase interépidémique inaugurée en 2016.


In 2013, the world began to witness an unprecedented Ebola epidemic in West Africa that was smoldering by early 2016. Under this urgent circumstance, the global scientific community organized and made progress in identifying potential preventive countermeasures and therapeutics and accelerated the development of those promising interventions. Trials of experimental interventions soon emerged as a key component of the global response. Hence, an interdisciplinary issue ensued concerning how best to assess clinical safety and effectiveness of potential interventions prior to or concurrent with their broad use in humans. Key issues rely on the close collaboration between research and clinical teams involved in care in the field. Indeed, it is of prime importance to consider cultural dimensions when aiming to build trust within communities and flexibility to adapt trial procedures to field constraints. Trials implemented during the outbreak crisis illustrates challenging inputs for producing scientific and ethical gains for the benefits of vulnerable populations in the context of an international emerging or re-emerging infectious disease event. This includes rapid implementation of clinical research studies from the early phase of the next global outbreak on the basis of practical and ready-to-apply innovative methodological framework built during interepidemic periods.


  1. 1.

    Adebamowo C, Bah-Sow O, Binka F, et al (2014) Randomised controlled trials for Ebola: practical and ethical issues. Lancet 384:1423–4

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Bai CQ, Mu JS, Kargbo D, et al (2016) Clinical and virological characteristics of Ebola virus disease patients treated with favipiravir (T-705), Sierra Leone, 2014. Clin Inf Dis (accessible en ligne, 23 août 2016)

    Google Scholar 

  3. 3.

    Beavogui AH, Delamou A, Yansane ML, et al (2016) Clinical research during the Ebola virus disease outbreak in Guinea: lessons learned and ways forward. Clin Trials 1–6, doi: 10.1177/1740774515619877

    Google Scholar 

  4. 4.

    Bellissant E, Benichou J, Chastang C (1990) Application of the triangular test to phase II cancer clinical trials. Stat Med 9(8):907–917

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Bouazza N, Treluyer JM, Foissac F, et al (2015) Favipiravir for children with Ebola. Lancet 385:603–4

    Article  PubMed  Google Scholar 

  6. 6.

    Chimerix. An open-label, multicenter study of the safety and antiviral activity of brincidofovir (BCV, CMX001) for Ebola virus disease. 2014 Oct 7 [cited 15 Aug 2016].

  7. 7.

    Chow SC, Chang M (2008) Adaptive design methods in clinical trials: a review. Orphanet J Rate Dis 3:11, doi101186/1750-1172-3-11

    Article  Google Scholar 

  8. 8.

    Cooper BS, Boni MF, Pan-Ngum W, et al (2015) Evaluating clinical trial designs for investigational treatments of Ebola virus disease. PLoS Med 12:e100181

    Article  Google Scholar 

  9. 9.

    Davey RT, Dodd L, Proschan MA, et al (2016) PREVAIL II: a multicenter RCT of Zmapp™ in Ebola virus infection. N Engl J Med 375:1448–56.

    Article  Google Scholar 

  10. 10.

    Diallo B, Sissoko D, Loman NJ, et al (2016) Resurgence of Ebola virus disease in Guinea linked to a survivor with virus persistence in seminal fluid for more than 500 days. Clin Infect Dis pii:ciw601 (accessible en ligne, 1er septembre 2016)

    Google Scholar 

  11. 11.

    Dodd LE, Proschan MA, Neuhaus J, et al (2016) Design of a Randomized Controlled Trial for Ebola Virus Disease Medical Countermeasures: PREVAIL II, the Ebola MCM Study. J Infect Dis 213(12):1906–13

    Article  PubMed  Google Scholar 

  12. 12.

    Dunning J, Sahr F, Rojek A, et al (2016) Experimental treatment of Ebola virus disease with TKM-130803: a single-arm phase 2 clinical trial. PLoS Med 13:e1001997

    Article  Google Scholar 

  13. 13.

    Dunning J, Kennedy SB, Antierens A, et al (2016) Experimental treatment of Ebola virus disease with brincidofovir. PLoS One 11:e0162199

    Article  Google Scholar 

  14. 14.

    Henao-Restrepo AM, Longini IM, Egger M, et al (2015) Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet 386:857–66

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Institut National de la Santé et de la Recherche Médicale, France. Efficacy of favipiravir against Ebola (JIKI). 2014 Dec 16 [cited 15 Aug 2016].

  16. 16.

    Institut National de la Santé et de la Recherche Médicale, France. Tolerance and activity evaluation of high doses of favipiravir against Ebola virus in the semen (FORCE). 2016 Fev 24 [cited 15 Aug 2016].

  17. 17.

    Institute of Tropical Medicine, Belgium. Emergency evaluation of convalescent plasma for Ebola viral disease (EVD) in Guinea (Ebola-Tx). 2015 Jan 15 [cited 15 Aug 2016].

  18. 18.

    Jacobs M, Aarons E, Bhagani S, et al (2015) Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers. Lancet Infect Dis 15:1300–4

    Article  PubMed  Google Scholar 

  19. 19.

    Lanini S, Zumla A, Ioannidis JPA, et al (2015) Are adaptive randomised trials or non-randomised trails studies the best way to address the Ebola outbreak in West Africa? Lancet Infect Dis 15:738–45

    Article  PubMed  Google Scholar 

  20. 20.

    London AJ (2015) Research in a public health crisis: the integrative approach to managing the moral tensions. In: Jennings B, et al (eds) Emergency ethics: public health preparedness and response. Oxford University Press, New York, NY

    Google Scholar 

  21. 21.

    Madelain V, Nguyen TH, Olivo A, et al (2016) Ebola virus infection: review of the pharmacokinetic and pharmacodynamics properties of drugs considered for testing in human efficacy trials. Clin Pharmacokinet 55:907–23

    CAS  Article  PubMed  Google Scholar 

  22. 23.

    Malvy D, le groupe d’étude JIKI (2014) Évaluation des antiviraux dans la maladie à virus Ebola, 2014–2015: enjeux et perspectives. Bull Acad Natle Med 198:1515–27

    Google Scholar 

  23. 23.

    Mentre F, Taburet AM, Guedj J, et al (2014) Dose regimen of favipiravir for Ebola virus disease. Lancet Infect Dis 15:150–1

    Article  PubMed  Google Scholar 

  24. 24.

    National Institute of Allergy and Infectious Diseases. Putative investigational therapeutics in the treatment of patients with known Ebola infection. 2015 Feb 13 [cited 15 Aug 2015].

  25. 25.

    National Institute of Allergy and Infectious Diseases. GS-5734 to assess the antiviral activity, longer-term clearance of Ebola virus, and safety in male Ebola survivors with evidence of Ebola virus persistence in semen. 2016 Jun 28 [cited 15 Aug 2015].

  26. 26.

    Palich R, Gala JL, Petitjean F, et al (2016) A 6-year old child with severe Ebola virus disease: laboratory-guided clinical care in an Ebola treatment center in Guinea. PLoS Negl Trop Dis 10:e0004393

    Article  Google Scholar 

  27. 27.

    Piot P, Muyembe JJ, Edmunds WJ (2014) Ebola in West Africa: from disease outbreak to humanitarian crisis. Lancet Infect Dis 14:1034–5

    Article  PubMed  Google Scholar 

  28. 28.

    Schieffelin JS, Shaffer JG, Goba A, et al (2014) Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med 371:2092–100

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sissoko D, Laouénan C, Folkesson E, et al (2016) Experimental treatment of favipiravir for Ebola virus disease (the JIKI trial): a historically-controlled, single arm proof-of concept trial in Guinea. PLoS Med 13:e1001967

    Article  Google Scholar 

  30. 30.

    University of Oxford. Open-label, single arm trial to investigate the efficacy of TKM-130803 with a concurrent observational study of Ebola virus disease in an outbreak setting in West Africa. 2015 Jan 16 [cited 15 Aug 2016].

  31. 31.

    Uyeki TM, Mehta AK, Davey RT Jr, et al (2016) Clinical management of Ebola virus disease in the United States and Europe. N Engl J Med 374:636–46

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    van Griensven J, Edwards T, de Lamballerie X, et al (2016) Evaluation of convalescent plasma for Ebola virus disease in Guinea. N Engl J Med 374:33–42

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Whitehead J (1997) The Design and Analysis of Sequential Clinical Trials, Revised, 2nd Edition. Chichester, UK: John Wiley & Sons Ltd. 328p.

    Google Scholar 

  34. 34.

    World Health Organization (2014) Categorization and prioritization of drugs for consideration for testing or use in patients infected with Ebola (consulté le 15 août 2016).

    Google Scholar 

  35. 35.

    World Health Organization (2016) Clinical Management of Patients with Viral Haemorrhagic Fever: A Pocket Guide for front-line health workers. Second updated version. Geneva, CH: WHO. 203p.

    Google Scholar 

  36. 36.

    Yazdanpanah Y, Arribas JR, Malvy D (2015) Treatment of Ebola virus disease. Intensive Care Med 41:115–117

    Article  PubMed  Google Scholar 

  37. 37.

    Yazdanpanah Y, Horby P, van Griensven J, et al (2015) Drug assessment in the Ebola virus disease epidemic in West Africa. Lancet Infect Dis 15:1258

    Article  Google Scholar 

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Correspondence to D. Malvy.

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Malvy, D. Produire de la science en situation de crise. Les traitements médicamenteux spécifiques de la maladie à virus Ebola en 2016 : leçons et perspectives. Bull. Soc. Pathol. Exot. 109, 262–271 (2016).

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Mots clés

  • Fièvre hémorragique à virus Ebola
  • Stratégies thérapeutiques


  • Hemorrhagic fever
  • Ebola
  • Therapeutic strategies