Recurrent Ebolavirus disease in the Democratic Republic of Congo: update and challenges

Joseph Inungu; Kechi Iheduru-Anderson; Ossam J Odio; Joseph Inungu; Kechi Iheduru-Anderson; Ossam J Odio

doi:10.3934/publichealth.2019.4.502

AIMS Public Health

2019, Volume 6, Issue 4: 502-513. doi: 10.3934/publichealth.2019.4.502

Previous Article Next Article

Perspective

Recurrent Ebolavirus disease in the Democratic Republic of Congo: update and challenges

1.
Master of Public Health Program, College of Health Professions, Central Michigan University, Michigan, United States
2.
Nursing Program, Central Michigan University, Michigan, United States
3.
Department of Internal Medicine, Medical School Hospital, University of Kinshasa, Kinshasa, Congo

Received: 30 August 2019 Accepted: 18 November 2019 Published: 20 November 2019

The current Ebolavirus disease (EVD) outbreak in the provinces of North Kivu and Ituri is the tenth outbreak affecting the Democratic Republic of Congo (DRC); the first outbreak occurring in a war context, and the second most deadly Ebolavirus outbreak on record following the 2014 outbreak in West Africa. The DRC government’s response consisted of applying a package of interventions including detection and rapid isolation of cases, contact tracing, population mapping, and identification of high-risk areas to inform a coordinated effort. The coordinated effort was to screen, ring vaccinate, and conduct laboratory diagnoses using GeneXpert (Cepheid) polymerase chain reaction. The effort also included ensuring safe and dignified burials and promoting risk communication, community engagement, and social mobilization. Following the adoption of the “Monitored Emergency Use of Unregistered Products Protocol,” a randomized controlled trial of four investigational treatments (mAb114, ZMapp, and REGN-EB3 and Remdesivir) was carried out with all consenting patients with laboratory-confirmed EVD. REGN-EB3 and mAb114 showed promise as treatments for EVD. In addition, one investigational vaccine (rVSV-ZEBOV-GP) was used first, followed by a second prophylactic vaccine (Ad26.ZEBOV/MVA-BN-Filo) to reinforce the prevention. Although the provision of clinical supportive care remains the cornerstone of EVD outbreak management, the DRC response faced daunting challenges including general insecurity, violence and community resistance, appalling poverty, and entrenched distrust of authority. Ebolavirus remains a public health threat. A fully curative treatment is unlikely to be a game-changer given the settings of transmission, zoonotic nature, limits of effectiveness of any therapeutic intervention, and timing of presentation.
- Ebola outbreak,
- hemorrhagic fever,
- epidemiology,
- treatment,
- prevention
Citation: Joseph Inungu, Kechi Iheduru-Anderson, Ossam J Odio. Recurrent Ebolavirus disease in the Democratic Republic of Congo: update and challenges[J]. AIMS Public Health, 2019, 6(4): 502-513. doi: 10.3934/publichealth.2019.4.502

Related Papers:

Abstract

The current Ebolavirus disease (EVD) outbreak in the provinces of North Kivu and Ituri is the tenth outbreak affecting the Democratic Republic of Congo (DRC); the first outbreak occurring in a war context, and the second most deadly Ebolavirus outbreak on record following the 2014 outbreak in West Africa. The DRC government’s response consisted of applying a package of interventions including detection and rapid isolation of cases, contact tracing, population mapping, and identification of high-risk areas to inform a coordinated effort. The coordinated effort was to screen, ring vaccinate, and conduct laboratory diagnoses using GeneXpert (Cepheid) polymerase chain reaction. The effort also included ensuring safe and dignified burials and promoting risk communication, community engagement, and social mobilization. Following the adoption of the “Monitored Emergency Use of Unregistered Products Protocol,” a randomized controlled trial of four investigational treatments (mAb114, ZMapp, and REGN-EB3 and Remdesivir) was carried out with all consenting patients with laboratory-confirmed EVD. REGN-EB3 and mAb114 showed promise as treatments for EVD. In addition, one investigational vaccine (rVSV-ZEBOV-GP) was used first, followed by a second prophylactic vaccine (Ad26.ZEBOV/MVA-BN-Filo) to reinforce the prevention. Although the provision of clinical supportive care remains the cornerstone of EVD outbreak management, the DRC response faced daunting challenges including general insecurity, violence and community resistance, appalling poverty, and entrenched distrust of authority. Ebolavirus remains a public health threat. A fully curative treatment is unlikely to be a game-changer given the settings of transmission, zoonotic nature, limits of effectiveness of any therapeutic intervention, and timing of presentation.

Acknowledgments

The authors would like to express their gratitude to Mr. Daryn Papenfuse, MPH, for reviewing, editing, and proofreading this manuscript.

References

[1]	Wannier SR, Worden L, Hoff NA, et al. (2019) Estimating the impact of violent events on transmission in Ebola virus disease outbreak, Democratic Republic of the Congo, 2018–2019. Epidemics 28: 100353. doi: 10.1016/j.epidem.2019.100353
[2]	National Academies of Sciences, Engineering, and Medicine (2016) The Ebola Epidemic in West Africa: Proceedings of a Workshop. National Academies Press.
[3]	Richardson JS, Dekker JD, Croyle MA, et al. (2010) Recent advances in Ebolavirus vaccine development. Hum Vaccines 6: 439–449. doi: 10.4161/hv.6.6.11097
[4]	Maxmen A (2019) Science under fire: Ebola researchers fight to test drugs and vaccines in a war zone. Nat 572: 16–17. doi: 10.1038/d41586-019-02258-4
[5]	World Health Organization (2018) Notes for the record: consultation on Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) for Ebola virus disease (EVD).
[6]	Ilunga Kalenga O, Moeti M, Sparrow A, et al. (2019) The ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018–2019. N Engl J Med.
[7]	Kennedy SB, Bolay F, Kieh M, et al. (2017) Phase 2 placebo-controlled trial of two vaccines to prevent Ebola in Liberia. N Engl J Med 377: 1438–1447. doi: 10.1056/NEJMoa1614067
[8]	Sullivan NJ, Sanchez A, Rollin PE, et al. (2000) Development of a preventive vaccine for Ebola virus infection in primates. Nat 408: 605. doi: 10.1038/35046108
[9]	Geisbert TW, Pushko P, Anderson K, et al. (2002) Evaluation in nonhuman primates of vaccines against Ebola virus. Emerging Infect Dis 8: 503. doi: 10.3201/eid0805.010284
[10]	World Health Organization (2019) Preliminary results on the efficacy of rVSV-ZEBOV- GP Ebola vaccine using the ring vaccination strategy in the control of an Ebola outbreak in the Democratic Republic of the Congo: an example of integration of research into epidemic response. Geneva: Organ.
[11]	Baseler L, Chertow DS, Johnson KM, et al. (2017) The pathogenesis of Ebola virus disease. Annu Rev Pathol: Mech Dis 12: 387–418. doi: 10.1146/annurev-pathol-052016-100506
[12]	World Health Organization (1978) Ebola haemorrhagic fever in Zaire, 1976. Report of an international commission. Bull World Health Organ 56: 271–293.
[13]	Rojek AM, Salam A, Ragotte RJ, et al. (2019) A systematic review and meta-analysis of patient data from the west Africa (2013–16) Ebola virus disease epidemic. Clin Microbiol Infect.
[14]	Benowitz I, Ackelsberg J, Balter SE, et al. (2014) Surveillance and preparedness for Ebola virus disease-New York City, 2014. MMWR Morbidity Mortal Wkly Rep 63: 934.
[15]	Yuan J, Zhang Y, Li J, et al. (2012) Serological evidence of Ebolavirus infection in bats, China. Virol J 9: 236. doi: 10.1186/1743-422X-9-236
[16]	Formenty P, Hatz C, Le Guenno B, et al. (1999) Human infection due to Ebola virus subtype Cote d'Ivoire: clinical and biologic presentation. J Infect Dis 179 (Supplement 1): S48–S53.
[17]	Feldmann H (2014) Ebola-a growing threat? N Engl J Med 371: 1375–1378. doi: 10.1056/NEJMp1405314
[18]	Selvaraj SA, Lee KE, Harrell M, et al. (2018) Infection Rates and Risk Factors for Infection Among Health Workers During Ebola and Marburg Virus Outbreaks: A Systematic Review. J Infect Dis 218: S679–S689. doi: 10.1093/infdis/jiy435
[19]	Martínez MJ, Salim AM, Hurtado JC, et al. (2015) Ebola virus infection: overview and update on prevention and treatment. Infect Dis Ther 4: 365–390. doi: 10.1007/s40121-015-0079-5
[20]	Kaushik A, Tiwari S, Jayant RD, et al. (2016) Towards detection and diagnosis of Ebola virus disease at point-of-care. Biosens Bioelectron 75: 254–272. doi: 10.1016/j.bios.2015.08.040
[21]	Roddy P, Howard N, Van Kerkhove MD, et al. (2012) Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007–2008. PloS One 7: e52986. doi: 10.1371/journal.pone.0052986
[22]	Iwen PC, Smith PW, Hewlett AL, et al. (2015) Safety considerations in the laboratory testing of specimens suspected or known to contain Ebola virus.
[23]	Yang M, Ke Y, Liu C, et al. (2015) Diagnosis of Ebola virus disease: progress and prospects. Infect Dis Transl Med 1: 73–79.
[24]	Saijo M, Niikura M, Morikawa S, et al. (2001) Immunofluorescence method for detection of Ebola virus immunoglobulin G, using HeLa cells which express recombinant nucleoprotein. J Clin Microbiol 39: 776–778. doi: 10.1128/JCM.39.2.776-778.2001
[25]	Li Y, Cu Y, Luo D (2005) Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes. Nat Biotechnol 23: 885. doi: 10.1038/nbt1106
[26]	Fenner F, Henderson DA, Arita I, et al. (1988) Smallpox and its eradication: World Health Organization Geneva. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2491071/pdf/bullwho00076-0026.pdf.
[27]	World Health Organization (2014) Contact tracing during an outbreak of Ebola virus disease.
[28]	World Health Organization (2015) The ring vaccination trial: a novel cluster randomised controlled trial design to evaluate vaccine efficacy and effectiveness during outbreaks, with special reference to Ebola. BMJ Br Med J 351: h3740.
[29]	World Health Organization (2019) Ebola Virus Disease. Democratic Republic of the Congo External Situation Report 39. Available from: http://newsletters.afro.who.int/icfiles/1/46425/184054/6134450/97816cb57ede15249d4eb5b5/sit rep_evd_d%20rc_20190430-eng.pdf?ua=1,%20accessed%207%20May%202019.
[30]	Kadanali A, Karagoz G (2015) An overview of Ebola virus disease. North Clin Istanbul 2: 81.
[31]	Marzi A, Robertson SJ, Haddock E, et al. (2015) VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Sci 349: 739–742. doi: 10.1126/science.aab3920
[32]	Marzi A, Engelmann F, Feldmann F, et al. (2013) Antibodies are necessary for rVSV/ZEBOV-GP–mediated protection against lethal Ebola virus challenge in nonhuman primates. Proc Natl Acad Sci 110: 1893–1898. doi: 10.1073/pnas.1209591110
[33]	Pavot V (2016) Ebola virus vaccines: Where do we stand? Clin Immunol 173: 44–49. doi: 10.1016/j.clim.2016.10.016
[34]	Geisbert TW, Feldmann H (2011) Recombinant vesicular stomatitis virus–based vaccines against Ebola and Marburg virus infections. J Infect Dis 204: S1075–S1081. doi: 10.1093/infdis/jir349
[35]	Roberts A, Buonocore L, Price R, et al. (1999) Attenuated vesicular stomatitis viruses as vaccine vectors. J Virol 73: 3723–3732.
[36]	Rose NF, Marx PA, Luckay A, et al. (2001) An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell 106: 539–549. doi: 10.1016/S0092-8674(01)00482-2
[37]	Milligan ID, Gibani MM, Sewell R, et al. (2016) Safety and immunogenicity of novel adenovirus type 26–and modified vaccinia ankara–vectored ebola vaccines: a randomized clinical trial. Jama 315: 1610–1623. doi: 10.1001/jama.2016.4218
[38]	Anywaine Z, Whitworth H, Kaleebu P, et al. (2019) Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania. J Infect Dis 220: 46–56.
[39]	Mutua G, Anzala O, Luhn K, et al. (2019) Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya. J Infect Dis 220: 57–67.
[40]	World Health Organization (2019) Ebola Vaccines Decision framework. Available from: https://www.who.int/blueprint/priority-%20diseases/keyaction/ebola-vaccinecandidates/en/,%20accessed%2007%20May%202019.
[41]	Dhillon RS, Srikrishna D, Kelly JD (2018) Deploying RDTs in the DRC Ebola outbreak. Lancet 391: 2499–2500. doi: 10.1016/S0140-6736(18)31315-1
[42]	Fleck F (2009) The Democratic Republic of the Congo: quantifying the crisis. Bull World Health Organ 87: 6–7. doi: 10.2471/BLT.09.020109
[43]	Vinck P, Pham PN, Bindu KK, et al. (2019) Institutional trust and misinformation in the response to the 2018–19 Ebola outbreak in North Kivu, DR Congo: a population-based survey. Lancet Infect Dis19: 529–536.
[44]	Caron A, Bourgarel M, Cappelle J, et al. (2018) Ebola Virus Maintenance: If Not (Only) Bats, What Else? Viruses 10: 549. doi: 10.3390/v10100549

Reader Comments

Your name:*

Email:*
© 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)