Advertisement
Letter to the Editor| Volume 62, ISSUE 1, 103528, February 2023

They come in threes: Marburg virus, emerging infectious diseases, and the blood supply

Published:August 26, 2022DOI:https://doi.org/10.1016/j.transci.2022.103528
They come in threes: Marburg virus, emerging infectious diseases, and the blood supply
Previous ArticleIn vitro comparison of CPD whole blood with conventional blood components

      Keywords

      On July 17, in the midst of the ongoing SARS-CoV-2 pandemic and several months into the monkeypox outbreak currently expanding worldwide, the World Health Organization announced that Ghana had declared its first ever outbreak of Marburg virus [

      WHO . Ghana declares first-ever outbreak of Marburg virus disease; 2022. 〈https://www.afro.who.int/countries/ghana/news/ghana-declares-first-ever-outbreak-marburg-virus-disease-0〉, [Accessed 18 July 2022].

      ]. As of July 18, 2 persons have died and almost 100 have been quarantined, raising fears of an impending mass outbreak [

      WHO . Ghana declares first-ever outbreak of Marburg virus disease; 2022. 〈https://www.afro.who.int/countries/ghana/news/ghana-declares-first-ever-outbreak-marburg-virus-disease-0〉, [Accessed 18 July 2022].

      ]. This marks only the second time in history this infectious disease has been identified in western Africa, though previous outbreaks and sporadic cases have been reported in various geographic regions of Africa, particularly the Democratic Republic of the Congo (DRC), Angola, and Uganda, and cases have been imported into Europe and the United States [

      WHO . Ghana declares first-ever outbreak of Marburg virus disease; 2022. 〈https://www.afro.who.int/countries/ghana/news/ghana-declares-first-ever-outbreak-marburg-virus-disease-0〉, [Accessed 18 July 2022].

      ]. While SARS-CoV-2, monkeypox, and Marburg are quite distinct in their epidemiology, pathogenesis, transmissibility, and mortality, these viruses illustrate the potential impact of emerging infectious diseases on both the safety and adequacy of the international blood supply.
      SARS-CoV-2 has influenced numerous misconceptions regarding the safety of blood transfusion from vaccinated blood donors [
      • Jacobs J.W.
      • Bibb L.A.
      • Savani B.N.
      • Booth G.S.
      Refusing blood transfusions from COVID-19-vaccinated donors: are we repeating history?.
      Br J Haematol. 2022; 196: 585-588https://doi.org/10.1111/bjh.17842
      ] and continues to perpetuate unprecedented blood shortages across the US and Europe [
      • Jacobs J.W.
      • Booth G.S.
      Blood shortages and changes to massive transfusion protocols: survey of hospital practices during the COVID-19 pandemic.
      Transfus Apher Sci. 2022; 61103297https://doi.org/10.1016/j.transci.2021.103297
      ,
      • Stanworth S.J.
      • New H.V.
      • Apelseth T.O.
      • et al.
      Effects of the COVID-19 pandemic on supply and use of blood for transfusion.
      Lancet Haematol. 2020; 7: e756-e764https://doi.org/10.1016/S2352-3026(20)30186-1
      ,
      • Pagano M.B.
      • Rajbhandary S.
      • Nunes E.
      • Cohn C.S.
      Transfusion services operations during the COVID-19 pandemic: results from AABB survey.
      Transfusion. 2020; 60: 2760-2762https://doi.org/10.1111/trf.15986
      ]. Monkeypox also threatens to exacerbate these blood shortages due to confusing donor deferral policies for vaccine recipients and infected donors [
      • Jacobs J.W.
      • Filkins L.
      • Booth G.S.
      • Adkins B.D.
      The potential impact of monkeypox infection and vaccination on blood donor deferrals and the blood supply.
      Br J Haematol. 2022; https://doi.org/10.1111/BJH.18388
      ]. This combination poses a potentially significant burden to maintaining an adequate blood supply; thus, one must consider whether Marburg virus may represent the third element in a perfect storm of an impending, infectious disease-mediated, blood supply disaster?
      To understand what, if any threat, Marburg virus may pose to the international blood supply requires an understanding of the virus itself and the nature of prior Marburg virus outbreaks. Marburg virus, similar to Ebola virus, elicits a severe hemorrhagic syndrome, with a case-fatality rate ranging from 20 to > 80 % depending on the outbreak studied [

      Knust B, Schafer IJ, Wamala J, et al. Multidistrict outbreak of marburg virus disease-Uganda, 2012. J Infect Dis, Vol. 212(no. Suppl 2); 2015, p. S119–128. 〈https://doi.org/10.1093/infdis/jiv351〉.

      ].
      Marburg is a viral zoonosis, with the Egyptian fruit bat believed to be its natural animal reservoir; most prior cases were originally suspected to have been acquired in or near caves or mines inhabited by these bats [

      Knust B, Schafer IJ, Wamala J, et al. Multidistrict outbreak of marburg virus disease-Uganda, 2012. J Infect Dis, Vol. 212(no. Suppl 2); 2015, p. S119–128. 〈https://doi.org/10.1093/infdis/jiv351〉.

      ]. The largest recorded outbreak occurred in Angola in 2005, resulting in more than 350 cases and 300 deaths [

      WHO. Marburg virus disease; 2021. 〈https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease〉, [Accessed 18 July 2022].

      ]. Notably, there have been significantly fewer recognized outbreaks of Marburg virus compared to Ebola virus; however, between 1998 and 2000, an outbreak in the DRC was associated with multiple introductions of distinct viral strains independently, resulting in uninterrupted infections for two years [
      • Mehedi M.
      • Groseth A.
      • Feldmann H.
      • Ebihara H.
      Clinical aspects of Marburg hemorrhagic fever.
      Future Virol. 2011; 6: 1091-1106https://doi.org/10.2217/fvl.11.79
      ]. Furthermore, as Mehedi and colleagues illustrated in their clinical review, most Marburg virus cases occurred during two large outbreaks, highlighting its potential as a serious public health threat [
      • Mehedi M.
      • Groseth A.
      • Feldmann H.
      • Ebihara H.
      Clinical aspects of Marburg hemorrhagic fever.
      Future Virol. 2011; 6: 1091-1106https://doi.org/10.2217/fvl.11.79
      ]; however, this also illustrates that with early recognition and extensive public health measures, many outbreaks have been contained to just a few cases and without geographic spread.
      Marburg virus is transmitted among humans via direct contact with blood or infected bodily secretions, most often occurring while caring for infected individuals [
      • Mehedi M.
      • Groseth A.
      • Feldmann H.
      • Ebihara H.
      Clinical aspects of Marburg hemorrhagic fever.
      Future Virol. 2011; 6: 1091-1106https://doi.org/10.2217/fvl.11.79
      ]. Although the risk of aerosol transmission is considered low, studies have demonstrated viral stability in aerosols, and it is both highly infectious and fatal in nonhuman primate studies of aerosol inoculation [
      • Mehedi M.
      • Groseth A.
      • Feldmann H.
      • Ebihara H.
      Clinical aspects of Marburg hemorrhagic fever.
      Future Virol. 2011; 6: 1091-1106https://doi.org/10.2217/fvl.11.79
      ]. Furthermore, as viremia is common during the symptomatic phase, the Association for the Advancement of Blood and Biotherapies (AABB) and the European Centre for Disease Prevention and Control consider this virus a theoretical risk to the blood supply [

      AABB. Marburg virus. 〈https://www.aabb.org/docs/default-source/default-document-library/regulatory/eid/127s.pdf?sfvrsn=98617ad9_2〉, [Accessed 18 July 2022].

      ,

      European Centre for Disease Prevention and Control. Factsheet about Marburg virus disease; 2022. 〈https://www.ecdc.europa.eu/en/all-topics-z/ebola-virus-disease/facts/factsheet-about-marburg-virus-disease#:~:text=The%20presence%20of%20MARV%20in,origin%20has%20not%20been%20reported〉, [Accessed 19 July 2022].

      ]. In a non-human primate model, blood-borne virus was detectable within the first few days of inoculation, the timing of fever onset corresponded with the presence of detectable virus in blood via culture, and peak viremia titers reached 10^8 PFU/ml [
      • Alves D.A.
      • Glynn A.R.
      • Steele K.E.
      • et al.
      Aerosol exposure to the Angola strain of Marburg virus causes lethal viral hemorrhagic fever in cynomolgus macaques.
      Vet Pathol. 2010; 47: 831-851https://doi.org/10.1177/0300985810378597
      ]. Extrapolating to humans, while viremia could certainly pose a risk to the blood supply if collected during infection, symptomatic donors are expected to be deferred through standard questions. However, the duration of viremia in human Marburg virus disease survivors and asymptomatic viremia are not well characterized, and although transfusion-transmission has not been reported, transmission via contact with blood has occurred in clinical cases [

      AABB. Marburg virus. 〈https://www.aabb.org/docs/default-source/default-document-library/regulatory/eid/127s.pdf?sfvrsn=98617ad9_2〉, [Accessed 18 July 2022].

      ,

      European Centre for Disease Prevention and Control. Factsheet about Marburg virus disease; 2022. 〈https://www.ecdc.europa.eu/en/all-topics-z/ebola-virus-disease/facts/factsheet-about-marburg-virus-disease#:~:text=The%20presence%20of%20MARV%20in,origin%20has%20not%20been%20reported〉, [Accessed 19 July 2022].

      ]. Further lending to this hypothetical, but poorly understood risk, Marburg virus can, at minimum, hide in “immune–privileged” sites, such as the testes or intraocular space, in human survivors and transmission through infected fluids (i.e., semen) has been documented up to 7 weeks after recovery [

      WHO. Marburg virus disease; 2021. 〈https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease〉, [Accessed 18 July 2022].

      ]. Additionally, there is currently no FDA-licensed blood donor screening tests, and in the US, disease testing is only available at the US Centers for Disease Control (CDC) or the US Army Research Institute of Infectious Diseases (USAMRIID) [

      AABB. Marburg virus. 〈https://www.aabb.org/docs/default-source/default-document-library/regulatory/eid/127s.pdf?sfvrsn=98617ad9_2〉, [Accessed 18 July 2022].

      ]. Despite this, there are some jurisdictions, such as the California Department of Public Health, that are prepared to inquire about a history of blood transfusion for patients with concern for viral hemorrhagic fevers, including Marburg [

      California Department of Public Health. Viral hemorrhagic fever case report. 〈https://www.cdph.ca.gov/CDPH%20Document%20Library/ControlledForms/cdph8527.pdf〉, [Accessed 20 July 2022].

      ].
      It should be noted that internationally, pathogen-reduced platelets as well as solvent-detergent treated plasma are commonly utilized, with recent increases in implementation within the United States following FDA approval [

      US FDA. Octaplas. 〈https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/octaplas〉, [Accessed 22 July 2022].

      ,

      US FDA. INTERCEPT blood system for platelets. 〈https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/intercept-blood-system-platelets〉, [Accessed 22 July 2022].

      ]. To that end, one of the benefits of utilizing a pathogen-reduced blood product is inactivation of emerging infectious agents. Though clinical trials are ongoing, pathogen-reduced red blood cell products may become available soon [

      Clinnicaltrials.gov. INTERCEPT blood system for RBCs study in regions at potential risk for zika virus transfusion-transmitted infections (RedeS). 〈https://clinicaltrials.gov/ct2/show/NCT03037164?term=Redes〉, [Accessed 22 July 2022].

      ,

      Clinnicaltrials.gov. Study to evaluate the efficacy & safety of the INTERCEPT blood system for RBCs in complex cardiac surgery patients (ReCePI). 〈https://clinicaltrials.gov/ct2/show/NCT03459287〉, [Accessed 22 July 2022].

      ]. The healthcare and societal impact of these technologies cannot be overstated, though they may be inaccessible in resource-limited countries for many years.
      Given these considerations and the small number of individuals infected/quarantined, the threat of the current Marburg virus outbreak in Ghana to the blood supply currently is minimal. However, as most infections result in severe bleeding, disseminated intravascular coagulation, shock, and multiorgan failure, the greater risk might not be from a donor perspective where deferrals or the risk of transfusion-transmission could limit the supply of blood, but instead from increased plasma and cryoprecipitate utilization if the outbreak were to expand. This is particularly important in resource-restricted countries where availability of fibrinogen and factor concentrates is significantly limited; thus, plasma and cryoprecipitate would be the cornerstone of supportive management to attempt to ameliorate the coagulopathies and hemorrhagic diathesis associated with this disease [
      • Levi M.
      • Scully M.
      How I treat disseminated intravascular coagulation.
      Blood. 2018; 131: 845-854https://doi.org/10.1182/blood-2017-10-804096
      ], further reducing an already constrained international blood inventory.
      Though transfusion-transmitted cases have not been described [

      AABB. Marburg virus. 〈https://www.aabb.org/docs/default-source/default-document-library/regulatory/eid/127s.pdf?sfvrsn=98617ad9_2〉, [Accessed 18 July 2022].

      ], there are numerous issues surrounding a theoretical, large-scale Marburg virus outbreak with significant impact on the international blood supply. As recent history demonstrates, early recognition and familiarity with emerging pathogens are necessities for practicing transfusion medicine and microbiology staff.

      Conflicts of Interest

      The authors declare no conflicts of interest related to this manuscript.

      References

      1. WHO . Ghana declares first-ever outbreak of Marburg virus disease; 2022. 〈https://www.afro.who.int/countries/ghana/news/ghana-declares-first-ever-outbreak-marburg-virus-disease-0〉, [Accessed 18 July 2022].

        View in Article
        • Jacobs J.W.
        • Bibb L.A.
        • Savani B.N.
        • Booth G.S.
        Refusing blood transfusions from COVID-19-vaccinated donors: are we repeating history?.
        Br J Haematol. 2022; 196: 585-588https://doi.org/10.1111/bjh.17842
        View in Article
        • Jacobs J.W.
        • Booth G.S.
        Blood shortages and changes to massive transfusion protocols: survey of hospital practices during the COVID-19 pandemic.
        Transfus Apher Sci. 2022; 61103297https://doi.org/10.1016/j.transci.2021.103297
        View in Article
        • Stanworth S.J.
        • New H.V.
        • Apelseth T.O.
        • et al.
        Effects of the COVID-19 pandemic on supply and use of blood for transfusion.
        Lancet Haematol. 2020; 7: e756-e764https://doi.org/10.1016/S2352-3026(20)30186-1
        View in Article
        • Pagano M.B.
        • Rajbhandary S.
        • Nunes E.
        • Cohn C.S.
        Transfusion services operations during the COVID-19 pandemic: results from AABB survey.
        Transfusion. 2020; 60: 2760-2762https://doi.org/10.1111/trf.15986
        View in Article
        • Jacobs J.W.
        • Filkins L.
        • Booth G.S.
        • Adkins B.D.
        The potential impact of monkeypox infection and vaccination on blood donor deferrals and the blood supply.
        Br J Haematol. 2022; https://doi.org/10.1111/BJH.18388
        View in Article

      7. Knust B, Schafer IJ, Wamala J, et al. Multidistrict outbreak of marburg virus disease-Uganda, 2012. J Infect Dis, Vol. 212(no. Suppl 2); 2015, p. S119–128. 〈https://doi.org/10.1093/infdis/jiv351〉.

        View in Article

      8. WHO. Marburg virus disease; 2021. 〈https://www.who.int/news-room/fact-sheets/detail/marburg-virus-disease〉, [Accessed 18 July 2022].

        View in Article
        • Mehedi M.
        • Groseth A.
        • Feldmann H.
        • Ebihara H.
        Clinical aspects of Marburg hemorrhagic fever.
        Future Virol. 2011; 6: 1091-1106https://doi.org/10.2217/fvl.11.79
        View in Article

      10. AABB. Marburg virus. 〈https://www.aabb.org/docs/default-source/default-document-library/regulatory/eid/127s.pdf?sfvrsn=98617ad9_2〉, [Accessed 18 July 2022].

        View in Article

      11. European Centre for Disease Prevention and Control. Factsheet about Marburg virus disease; 2022. 〈https://www.ecdc.europa.eu/en/all-topics-z/ebola-virus-disease/facts/factsheet-about-marburg-virus-disease#:~:text=The%20presence%20of%20MARV%20in,origin%20has%20not%20been%20reported〉, [Accessed 19 July 2022].

        View in Article
        • Alves D.A.
        • Glynn A.R.
        • Steele K.E.
        • et al.
        Aerosol exposure to the Angola strain of Marburg virus causes lethal viral hemorrhagic fever in cynomolgus macaques.
        Vet Pathol. 2010; 47: 831-851https://doi.org/10.1177/0300985810378597
        View in Article

      13. California Department of Public Health. Viral hemorrhagic fever case report. 〈https://www.cdph.ca.gov/CDPH%20Document%20Library/ControlledForms/cdph8527.pdf〉, [Accessed 20 July 2022].

        View in Article

      14. US FDA. Octaplas. 〈https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/octaplas〉, [Accessed 22 July 2022].

        View in Article

      15. US FDA. INTERCEPT blood system for platelets. 〈https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/intercept-blood-system-platelets〉, [Accessed 22 July 2022].

        View in Article

      16. Clinnicaltrials.gov. INTERCEPT blood system for RBCs study in regions at potential risk for zika virus transfusion-transmitted infections (RedeS). 〈https://clinicaltrials.gov/ct2/show/NCT03037164?term=Redes〉, [Accessed 22 July 2022].

        View in Article

      17. Clinnicaltrials.gov. Study to evaluate the efficacy & safety of the INTERCEPT blood system for RBCs in complex cardiac surgery patients (ReCePI). 〈https://clinicaltrials.gov/ct2/show/NCT03459287〉, [Accessed 22 July 2022].

        View in Article
        • Levi M.
        • Scully M.
        How I treat disseminated intravascular coagulation.
        Blood. 2018; 131: 845-854https://doi.org/10.1182/blood-2017-10-804096
        View in Article

      Article info

      Publication history

      Published online: August 26, 2022
      Accepted: August 24, 2022
      Received in revised form: August 10, 2022
      Received: August 6, 2022

      Footnotes

      ☆This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Identification

      DOI: https://doi.org/10.1016/j.transci.2022.103528

      Copyright

      © 2022 Elsevier Ltd. All rights reserved.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX