Risk of Ebola virus transmission through donated blood and other substances of human origin

Background

Recent epidemics of Ebola virus disease in Africa [1] have increased the potential risk of Ebola virus transmission via donated blood and blood components, cells, tissues and organs (substances of human origin; SoHO), not only locally and regionally in Africa, but also in non-endemic unaffected areas such as Europe due to population movements.

Ebola virus transmissions through donated blood, tissues or organs have not been described yet. However, asymptomatic replicative infections with Ebola virus have already been described [2,3]. Travellers from Ebola virus-affected countries are deferred from blood donation because malaria-risk countries overlap with the current Ebola virus disease-risk countries in Africa [4]. However, there is a need for specific guidelines to maintain the safety of SoHO donation by people who have been exposed to Ebola virus, especially because of the possibility of spread of an Ebola virus disease outbreak to areas with no malaria risk. There are no specific EU regulations related to Ebola virus in the context of the safety of SoHO. ECDC published a technical report on the risk of transmission of Ebola virus through donated blood and other SoHO in the EU/EEA that included guidance for SoHO safety measures [5]. This is an update of the guidance, reflecting the knowledge gathered as of the date of publication.

Risk assessment

The risk of Ebola virus transmission through SoHO is related to the presence of Ebola virus in the donor’s blood, tissues and organs. The presence and concentration of virus in organs, tissues, blood and other bodily fluids change during the course of the infection. Virus concentration peaks when symptoms are most severe. However, viruses can be detected and isolated from breast milk and semen weeks after recovery [6]. Limited data are available on when patients become viraemic and infectious during the incubation period. The assumption is that the rate of virus replication and excretion into bodily fluids is not high enough in the pre-symptomatic phase to result in person-to-person transmission through day-to-day contacts in the community. However, no data are available on when viraemia starts during the incubation period. Ebola virus disease has an acute onset of prominent symptoms that is believed to be temporally related to viraemia. This makes it unlikely that patients in the viraemic phase would be accepted for a donation of SoHO because it would be obvious that they were ill. During the symptomatic phase of Ebola virus disease, the virus is present in high concentrations in all bodily fluids, tissues and organs [1]. When the disease is fatal, the dead body remains highly infectious. After recovery from the acute phase, a patient may continue to excrete infective viruses in body fluids for long periods [6]. Ebola virus has been isolated by cell culture from blood, saliva, urine, aqueous humor, semen and breast milk from convalescent patients days and months after recovery [7]. Due to the severity of the disease and a high likelihood of Ebola virus transmission by infectious SoHO donation, the risk of virus transmission through SoHO is assessed as high.

Recommendations for the safety of SoHO donations

Individuals arriving from Ebola virus disease-affected areas

It is to be expected that a deferral from SoHO donation for two incubation periods will provide a reasonable margin of safety for asymptomatic donors arriving from Ebola virus disease-affected areas. The longest incubation period for Ebola virus disease is estimated at 21 days. However, the authors of a recent study have proposed that the longest possible incubation period should be considered at 25 days [8]. It is therefore suggested to temporarily defer an asymptomatic person from the donation of SoHO an for eight weeks after arriving from areas with community transmission [9].

Donation of blood and blood components

It should be noted that all Ebola virus disease outbreaks to date have occurred in malaria-endemic areas in Africa and that according to EU Directive 2004/33/EC of 22 March 2004 [3], asymptomatic blood donors arriving from malaria risk areas should be deferred from blood donation for at least four months. Such malaria risk deferral mitigates the risk posed by donors arriving from Ebola virus disease-affected areas. However, an Ebola virus disease outbreak may spread to areas with no malaria-risk and it is also the case that donor deferral due to malaria risk is not required when plasma is donated exclusively for fractionation. In light of this, deferral for eight weeks from the donation of whole blood or plasma for fractionation would be a prudent precaution for asymptomatic travellers or residents arriving from areas with community Ebola virus transmission.

Donation of cells, tissues and organs

According to EU directives, the geographic deferral of potential donors of cells, tissues and organs returning from malaria-endemic areas is not mandatory [10,11]. Therefore, an additional prudent precaution would be to defer an asymptomatic person from the donation of cells, tissues and organs for eight weeks after arrival from areas with community Ebola virus transmission. This period may be reduced to 21 days in the case of organ transplantation provided that the risk factors (arrival from areas with widespread transmission or exposure to Ebola virus within 21 days) of all potential donors (living or deceased) are excluded [12].

Individuals monitored after exposure to Ebola virus

Individuals who are monitored due to history of contact with an Ebola virus disease patient or other exposure to Ebola virus are ineligible for donating SoHO for eight weeks from the beginning of the monitoring period.

Individuals with current Ebola virus infection

During the course of acute infection, Ebola virus is present in blood, cells, tissues, organs and other bodily fluids. Individuals with evidence of current Ebola virus infection are not suitable to be donors of SoHO and are excluded from donation both as living or deceased donors.

Individuals recovered from Ebola virus disease

Convalescence from Ebola virus disease is long and often associated with sequelae such as myelitis, recurrent hepatitis, psychosis or uveitis. Data on the post-recovery viraemic period are limited. Shedding of Ebola virus has been reported in semen, breast milk and ocular (eye) and spinal column fluid after the virus has been cleared from blood [6,7].

Donation of blood, cells and tissues

Based on these findings and a theoretical possibility of intermittent low-level viremia after recovery from illness, a permanent deferral from the donation of blood, cells and tissues is suggested for donors who have recovered from Ebola virus disease. As it is not expected that there will be a large number of individuals recovered from Ebola virus disease in the EU/EEA, the impact of this intervention on the blood, cell and tissue donor base is expected to be insignificant.

Organ donation

In order to preserve the organ donor pool, each donation from a deceased or live donor recovered from Ebola virus disease should be evaluated individually by assessing the urgency of recipient need, obtaining the recipient’s informed consent, specific post-transplant monitoring and considering the risk for healthcare workers and the recipient’s family members.

Individuals after having sexual contact with Ebola virus disease convalescent

Viable viruses have been isolated from semen and transmitted through sexual contact [7] and spermatogenic transmission of Marburg virus has been documented [13]. It is therefore advised to defer individuals who have had sexual contact with persons known to have recovered from Ebola virus disease for eight weeks from SoHO donation regardless of the time since recovery.

Individuals vaccinated against Ebola virus

Several Ebola virus vaccine candidates are being evaluated. A phase 3 clinical trial and vaccination campaign results from the 2014 West Africa outbreak have shown a high level of protection against the Zaire ebolavirus species [14].The most advanced are recombinant vaccine candidates based on viral vectors engineered to serve as antigen delivery platforms that encode the full length of the surface glycoprotein of the Ebola virus [15].

Individuals who have received recombinant Ebola virus vaccines can be accepted for blood donation 24 hours after vaccination if they are symptom-free and have not visited  affected areas or not been potentially exposed to Ebola virus within eight week before vaccination. Otherwise, post-exposure vaccinated individuals who have been monitored due to exposure are ineligible to donate SoHO for eight weeks from the beginning of the monitoring period.

Donation of convalescent blood for post-exposure treatment

The above recommendations do not apply to donations of convalescent whole blood and plasma from Ebola virus disease survivors for the preparation of convalescent plasma for post-exposure treatment. WHO has issued guidance on such donations for empirical treatments [16]. Although the treatment was found to be safe, receiving two consecutive units of 200–250 mL convalescent plasma did not significantly improve the overall survival rate [17].

Importation of SoHO to the EU

The importation of SoHO from Ebola virus disease-epidemic or endemic countries to the EU is not recommended due to the increased risk of infection with Ebola virus.

References

1.            World Health Organization. Ebola virus disease [Internet]. Geneva: WHO; 2018 [cited 3 October 2018]. Available from: http://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease

2.            Leroy EM, Baize S, Volchkov VE, Fisher-Hoch SP, Georges-Courbot MC, Lansoud-Soukate J, et al. Human asymptomatic Ebola infection and strong inflammatory response. Lancet. 2000 Jun 24;355(9222):2210-5.

3.            Leroy EM, Baize S, Debre P, Lansoud-Soukate J, Mavoungou E. Early immune responses accompanying human asymptomatic Ebola infections. Clin Exp Immunol. 2001 Jun;124(3):453-60.

4.            European Commission. Commission Directive 2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC of the European Parliament and of the Council as regards certain technical requirements for blood and blood components – (Text with EEA relevance). Off J Eur U. 30 Mar 2004;L(91):25-39-. Available from: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2004:091:0025:0039:EN:PDF

5.            European Centre for Disease Prevention and Control. Risk of transmission of Ebola virus via donated blood and other substances of human origin in the EU. Stockholm: ECDC; 2014. Available from: http://ecdc.europa.eu/publications-data/risk-transmission-ebola-virus-donated-blood-and-other-substances-human-origin-eu

6.            Bausch DG, Towner JS, Dowell SF, Kaducu F, Lukwiya M, Sanchez A, et al. Assessment of the Risk of Ebola Virus Transmission from Bodily Fluids and Fomites. J Infect Dis.
2007 Nov 15;196 Suppl 2:S142-7.

7.            Vetter P, Fischer WA 2nd, Schibler M, Jacobs M, Bausch DG, Kaiser L. Ebola Virus Shedding and Transmission: Review of Current Evidence. J Infect Dis. 2016 Oct 15;214(suppl 3):S177-S184.

8.            Eichner M, Dowell SF, Firese N. Incubation Period of Ebola Hemorrhagic Virus Subtype Zaire. Osong Public Health Res Perspect. 2011 Jun;2(1):3-7.

9.            U.S.  Food and Drug Administration. Recommendations for Assessment of  Blood Donor Eligibility, Donor  Deferral and Blood Product Management in Response to Ebola Virus – Guidance for Industry. Silver Spring: FDA; 2017. Available from: http://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-assessment-blood-donor-eligibility-donor-deferral-and-blood-product-management

10.          European Commission. Directive 2010/45/EU of the European Parliament and of the Council of 7 July 2010 on standards of quality and safety of human organs intended for transplantation. Off J Eur U. 6 Aug 2010;L(207)14. Available from: http://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:32010L0053

11.          European Commission. Commission Directive 2006/17/EC of 8 February 2006 implementing Directive 2004/23/EC of the European Parliament and of the Council as regards certain technical requirements for the donation, procurement and testing of human tissues and cells – (Text with EEA relevance). Off J Eur J. 9 Feb 2006;L(38)40. Available from: http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32006L0017

12.          Kaul DR, Mehta AK, Wolfe CR, Blumberg E, Green M. Ebola Virus Disease: Implications for Solid Organ Transplantation. Am J Transplant. 2015 Jan;15(1):5-6.

13.          Martini GA, Schmidt HA. [Spermatogenic transmission of the "Marburg virus". (Causes of "Marburg simian disease")]. Klin Wochenschr. 1968 Apr 1;46(7):398-400.

14.          Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet. 2017 Feb 4;389(10068):505-18.

15.          Espeland EM, Tsai CW, Larsen J, Disbrow GL. Safeguarding against Ebola: Vaccines and therapeutics to be stockpiled for future outbreaks. PLoS Negl Trop Dis. 2018 Apr 5;12(4):e0006275.

16.          World Health Organization. Use of Convalescent Whole Blood or Plasma Collected from Patients Recovered from Ebola Virus Disease for Transfusion, as an Empirical Treatment during Outbreaks – Interim Guidance for National Health Authorities and Blood Transfusion Services – Version 1.0 September 2014. Geneva: WHO; 2014. Available from: http://www.who.int/csr/resources/publications/ebola/convalescent-treatment

17.          van Griensven J, Gallian P, de Lamballerie X. Convalescent Plasma and the Dose of Ebola Virus Antibodies. N Engl J Med. 2017 Mar 30;376(13):1296-1297.