Ebola causes severe illness in humans and has epidemic potential. How to deploy vaccines most effectively is a central policy question since different strategies have implications for ideal vaccine profile. More than one vaccine may be needed. A vaccine optimised for prophylactic vaccination in high-risk areas but when the virus is not actively circulating should be safe, well tolerated, and provide long-lasting protection; a two- or three-dose strategy would be realistic. Conversely, a reactive vaccine deployed in an outbreak context for ring-vaccination strategies should have rapid onset of protection with one dose, but longevity of protection is less important.
In initial cases, before an outbreak is recognised, healthcare workers (HCWs) are at particular risk of acquiring and transmitting infection, thus potentially augmenting early epidemics. We hypothesise that many early outbreak cases could be averted, or epidemics aborted, by prophylactic vaccination of HCWs. This paper explores the potential impact of prophylactic versus reactive vaccination strategies of HCWs in preventing early epidemic transmissions. To do this, we use the limited data available from Ebola epidemics (current and historic) to reconstruct transmission trees and illustrate the theoretical impact of these vaccination strategies. Our data suggest a substantial potential benefit of prophylactic versus reactive vaccination of HCWs in preventing early transmissions. We estimate that prophylactic vaccination with a coverage >99 % and theoretical 100 % efficacy could avert nearly two-thirds of cases studied; 75 % coverage would still confer clear benefit (40 % cases averted), but reactive vaccination would be of less value in the early epidemic.
A prophylactic vaccination campaign for front-line HCWs is not a trivial undertaking; whether to prioritise long-lasting vaccines and provide prophylaxis to HCWs is a live policy question. Prophylactic vaccination is likely to have a greater impact on the mitigation of future epidemics than reactive strategies and, in some cases, might prevent them. However, in a confirmed outbreak, reactive vaccination would be an essential humanitarian priority.
The value of HCW Ebola vaccination is often only seen in terms of personal protection of the HCW workforce. A prophylactic vaccination strategy is likely to bring substantial additional benefit by preventing early transmission and might abort some epidemics. This has implications both for policy and for the optimum product profile for vaccines currently in development.
World Health Organization. Ebola virus disease: Fact sheet. http://www.who.int/mediacentre/factsheets/fs103/en/. Accessed 17 December 2014.
Ebola haemorrhagic fever in Zaire, 1976. Bull World Health Organ. 1978; 56:247-70.
Dowell SF, Mukunu R, Ksiazek TG, Khan AS, Rollin PE, Peters CJ. Transmission of Ebola hemorrhagic fever: a study of risk factors in family members, Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999; 179:S87-91.
World Health Organization. Ebola response roadmap: Situation response. Update (05/07/2015). http://apps.who.int/ebola/ebola-situation-reports. Accessed 11 July 2015.
World Health Organization. Counting health workers: definitions, data, methods and global results. http://www.who.int/hrh/documents/counting_health_workers.pdf. Accessed 20 February 2015.
Khan AS, Kweteming TF, Heymann DL, Le Guenno B, Nabeth P, Kerstiëns B et al.. The reemergence of Ebola hemorrhagic fever, Democratic Republic of the Congo, 1995. Commission de Lutte contre les Epidémies à Kikwit. J Infect Dis. 1999; 179:S76-86.
Casillas AM, Nyamathi AM, Sosa A, Wilder CL, Sands H. A current review of Ebola virus: pathogenesis, clinical presentation and diagnostic assessment. Biol Res Nurs. 2003; 4:268-75.
Tomori O, Bertolli J, Rollin PE, Fleerackers Y, Guimard Y, De Roo A et al.. Serologic survey among hospital and health center workers during the Ebola haemorrhagic fever outbreak in Kikwit, Democratic Republic of the Congo, 1995. J Infect Dis. 1999; 179:S98-S101.
Kilmarx PH, Clarke KR, Dietz PM, Hamel MJ, Husain F, McFadden JD et al.. Centers for Disease Control and Prevention (CDC). Ebola virus disease in health care workers--Sierra Leone, 2014. MMWR Morb Mortal Wkly Rep. 2014; 63:1168-70.
World Health Organizaton. Personal protective equipment in the context of filovirus disease outbreak response. http://apps.who.int/iris/bitstream/10665/137410/1/WHO_EVD_Guidance_PPE_14.1_eng.pdf?ua=1. Accessed 24 February 2015.
Wamala JF, Lukwago L, Malimbo M, Nguku P, Yoti Z, Musenero M et al.. Ebola haemorrhagic fever associated with novel virus strain, Uganda, 2007–2008. Emerg Infect Dis. 2003; 9:1430-7.
Ebola Response Team WHO. Ebola virus disease in West Africa — The first 9 months of the epidemic and forward projections. N Engl J Med. 2014; 371:1481-95.
Faye O, Boelle P, Heleze E, Faye O, Loucoubar C, Magassouba N et al.. Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in 2014: an observational study. Lancet Infect Dis. 2015; 15:320-6.
Merler S, Ajelli M, Fumanelli L, Gomes MF, Piontti AP, Rossi L et al.. Spatiotemporal spread of the 2014 outbreak of Ebola virus disease in Liberia and the effectiveness of non-pharmaceutical interventions: a computational modelling analysis. Lancet Infect Dis. 2015; 15:204-11.
Centers for Disease Control and Prevention. Bioterrorism agents/diseases. http://emergency.cdc.gov/agent/agentlist-category.asp. Accessed 24 February 2015.
Borio L, Inglesby T, Peters CJ, Schmaljohn AL, Hughes JM, Jahrling PB et al.. Working Group on Civilian Biodefense. Hemorrhagic fevers viruses as biological weapons: medical and public health management. JAMA. 2002; 287:2391-405.
Rampling T, Ewer K, Bowyer G, Wright D, Imoukhuede EB, Payne R, et al. A monovalent chimpanzee adenovirus Ebola vaccine – preliminary report. N Engl J Med. 2015. Ahead of print. doi:10.1056/NEJMoa1411627.
Marzi A, Feldmann F, Geisbert TW, Feldmann H, Safronetz D. Vesicular stomatitis virus-based vaccines against Lassa and Ebola viruses. Emerg Infect Dis. 2015; 21:305-7.
LSHTM. Ebola vaccine trail funding announced by the Innovative Medicines Initiative. http://www.lshtm.ac.uk/newsevents/news/2015/ebola_vaccine_trial_funding.html. Accessed 24 February 2015.
Henao-Restrepo AM, Longini IR, Egger M, Dean NE, Edmunds WJ, Camacho A et al.. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein:interim results from the Guinea ring vaccination cluster-randomised trial. Lancet. 2015; 386:857-66.
Jones SM, Feldmann H, Stroher U, Geisbert JB, Fernando L, Grolla A et al.. Live attenuated recombinant vaccine protects non-human primates against Ebola and Marburg viruses. Nat Med. 2005; 11:786-90.
Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N et al.. Emergence of Zaire Ebola Virus Disease in Guinea. N Engl J Med. 2014; 371:1418-25.
Fasina FO, Shittu A, Lazarus D, Tomori O, Simonsen L, Viboud C et al.. Transmission dynamics and control of Ebola virus disease outbreak in Nigeria, July to September 2014. Euro Surveill. 2014; 19:20920.
BBC News. Seven die in Monrovia Ebola outbreak. http://www.bbc.co.uk/news/world-africa-27888363. Accessed 30 January 2015.
Africa Online News. Ebola deaths turn Redemption Hospital into ghost town. http://frontpageafricaonline.com/index.php/health-sci/1987-ebola-deaths-turn-liberia-s-redemption-hospital-into-ghost-town. Accessed 30 January 2015.
All Africa News. Liberia: Ebola kills doctor at Redemption Hospital. http://allafrica.com/stories/201407021024.html. Accessed 30 January 2015.
All Africa News. Liberia: Four nurses in Ebola web at Phebe Hospital. http://allafrica.com/stories/201407211455.html. Accessed 30 January 2015.
Schieffelin JS, Shaffer JG, Goba A, Gbakie M, Gire SK, Colubri A et al.. KGH Lassa Fever Program; Viral Hemorrhagic Fever Consortium; WHO Clinical Response Team Clinical illness and outcomes in patients with Ebola in Sierra Leone. N Engl J Med. 2014; 371:2092-100.
Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L et al.. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014; 345:1369-72.
World Health Organization. Sierra Leone: a traditional healer and a funeral. http://www.who.int/csr/disease/ebola/ebola-6-months/sierra-leone/en/. Accessed 3 July 2015.
World Health Organization. Mali: Details of the additional cases of Ebola virus disease. http://www.who.int/mediacentre/news/ebola/20-november-2014-mali/en/. Accessed 30 January 2015.
Reuters. Mali says has no remaining Ebola cases as last patient recovers. http://www.reuters.com/article/2014/12/11/us-health-ebola-mali-idUSKBN0JP2HG20141211. Accessed 30 January 2015.
Reuters. Doctor who treated source of second Mali Ebola outbreak dies. http://www.reuters.com/article/2014/11/20/health-ebola-mali-idUSL6N0TA62R20141120. Accessed 30 January 2015.
Centers for Disease Control and Prevention. Cases of Ebola diagnosed in the United States. http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html. Accessed 12 January 2015.
WHO. Ebola virus disease – United Kingdom. http://www.who.int/csr/don/30-december-2014-ebola/en/. Accessed 30 January 2015.
BBC News. Ebola outbreak: nurse infected in Spain. http://www.bbc.co.uk/news/world-europe-29514920. Accessed 30 January 2015.
World Health Organization. The outbreak of Ebola virus disease in Senegal is over. http://www.who.int/mediacentre/news/ebola/17-october-2014/en/. Accessed 30 January 2015.
Muyembe T, Kipasa M. Ebola haemorrhagic fever in Kikwit, Zaire. Lancet. 1995; 345:1448.
Hall RC, Hall RC, Chapman M. The 1995 Kikwit Ebola outbreak: lessons hospitals and physicians can apply to future viral epidemics. Gen Hosp Psych. 2008; 30:446-52.
Muyembe-Tamfum JJ, Mulangu S, Masumu J, Kayembe JM, Kemp A, Paweska JT. Ebola virus outbreaks in Africa: Past and Present. Onderst J Vet Res. 2012; 79:451-8.
Reiter P, Turell M, Coleman R. Field investigations of an outbreak of Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: arthropod studies. J Infect Dis. 1999; 179:S148-54.
Ndambi R, Akamituna P, Bonnet M, Tukadila AM, Muyembe-Tamfum JJ, Colebunders R. Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995. J Infect Dis. 1999; 179:S8-S10.
World Health Organization. Global Atlas of the Health Workforce. Global Health Observatory Data Repository. http://apps.who.int/gho/data/node.main.A1444?lang=en&showonly=HWF. Accessed 30 January 2015.
Leroy EM, Baize S, Volchkov VE, Fisher-Hoch SP. Human asymptomatic Ebola infection and strong inflammatory response. Lancet. 2000; 355:2210-5.