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Developments in the Containment of Ebola—Commentary

Commentary
09/25/19 Thomas M. Yuill, PhD, University of Wisconsin-Madison;

Containment of Ebola virus disease in the Democratic Republic of the Congo (DRC) is proving to be extraordinarily difficult but there is a recent development in antiviral therapy that may be helpful.

 The Ebola outbreak was first recognized in August of last year in North Kivu and Ituri provinces. It has subsequently spread to Goma, a city of over 1 million people and recently to South Kivu province. Since the beginning of the epidemic, as of September 8, 2019, the cumulative number of cases is 3,081, of which 2970 are confirmed, 111 are probable, and 403 suspected. There were a total of 2,064 deaths and 922 people recovered. The case fatality rate is 69% (1). Because this is an area of over 1 million displaced people and borders on Uganda, South Sudan, and Rwanda, there is concern about local and international spread in this socially unstable population.

 Treatment centers have been set up and surveillance implemented that includes case finding with contact identification, monitoring and ring vaccination (ie, of contacts and contacts of contacts). The rVSV-ZEBOV-GP vaccine, shown to be effective on a limited scale in the West African Ebola virus outbreak, is being used in the current DRC outbreak (2, 3).  Even with these measures in place, containment of the outbreak has not been successful for a variety of reasons. The main obstacle is distrust by local people of the effectiveness of DRC and foreign care givers and the care centers where they work and doubt that Ebola disease really exists.  This environment is complicated by the presence of many armed insurgent groups that have attacked Ebola care centers and field personnel.

 The very recent development of an effective treatment may help to foster the confidence and trust that is urgently needed. In November 20, 2018, a randomized, controlled trial began in the DRC of four investigational agents for the treatment of patients with Ebola virus disease. The study included two previously used drugs, ZMapp and remdesivir, and two newer agents, the monoclonal antibodies mAb114 and REGN-EB3. As of August 9, 2019, the trial had enrolled 681 patients toward an enrollment target of 725 at four Ebola Treatment Centers (ETCs) in Ebola disease hotspots. The study was overseen by staff from the Institut National de Recherche Biomédicale (INRB); the DRC Ministry of Health; and three medical humanitarian organizations: the Alliance for International Medical Action (ALIMA), the International Medical Corps (IMC), and Médecins Sans Frontières (MSF).

 The preliminary results in 499 study participants indicated that those individuals receiving REGN-EB3 or mAb114 had overall mortality of 29% and 34%, respectively, and if treated early in the course of the disease, had about a 90 percent chance of survival. This was compared to 49% and 53% mortality among participants in the other two arms. The independent monitoring board overseeing the trial recommended early termination because of the superior efficacy of the newer drugs (4, 5).

 One hope is that these monoclonal antibody cocktails will demonstrate that the treatment centers can save lives, boost confidence in the centers and their staffs so that infected individuals will come in early in the course of their infections. This will not solve all the barriers to containment of the outbreak, but it will help. These monoclonals will also be an effective treatment should infected individuals travel to large urban centers like Kinshasa or internationally. 

References

1. Tuite AR, Watts AG, Khan K, Bogoch II: Ebola virus outbreak in North Kivu and Ituri provinces, Democratic Republic of Congo, and the potential for further transmission through commercial air travel. J Travel Med Aug 15. pii: taz063, 2019. doi: 10.1093/jtm/taz063 

2. Heppner DG Jr, Kemp TL, Martin BK, et  alSafety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. Lancet Infect Dis 17:854–866, 2017. doi: 10.1016/S1473-3099(17)30313-4

3. Regules JA, Beigel JH, Paolino KM, et al: A recombinant vesicular stomatitis virus Ebola vaccine. N Engl J Med 376:330–341, 2017. doi: 10.1056/NEJMoa1414216

4. Dyer OTwo Ebola treatments halve deaths in trial in DRC outbreakBMJ 366:l5140, 2019. doi: 10.1136/bmj.l5140

5. Maxmen A: Two Ebola drugs show promise amid ongoing outbreak. Nature August 12, 2019. doi: 10.1038/d41586-010-02442-6

      

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