Effo-CoE_MED gertler webinar June 2024.pptx

HFV

1. High Consequence infectious diseases „Ebola and Marburg“ Maximilian Gertler Institute for international Health EFFO-Project 4 June 2024

2. Filovirus infections (Marburg and Ebola) - update for specialised medical personnel Institute for international Health, M.Gertler , 2024 2 Foto: MSF

3. overview : Repetition HCIDs and health care EVD and MVD reservoir and viruses diagnostics treatment immunisation other new developments 3 Institute for international Health, M.Gertler , 2024

4. HCIDs – relevance for HCWs Definition (UK) 4 Institute for international Health, M.Gertler , 2024

5. HCIDs – relevance for HCWs Definition (UK) 5 Institute for international Health, M.Gertler , 2024 acute infectious typically has a high case-fatality rate may not have effective prophylaxis or treatment often difficult to recognise and detect rapidly ability to spread in the community and within healthcare settings requires an enhanced individual, population and system response to ensure it is managed effectively , efficiently and safely

6. HCIDs – relevance for HCWs Definition (UK) 6 Institute for international Health, M.Gertler , 2024 acute infectious typically has a high case-fatality rate may not have effective prophylaxis or treatment often difficult to recognise and detect rapidly ability to spread in the community and within healthcare settings requires an enhanced individual, population and system response to ensure it is managed effectively , efficiently and safely „ difficult to recognise “  hidden behind unspecific symptoms which may be Malaria, Flu , ARTI, typhoid etc.

7. Relevance for Health Care Workers? 7 Institute for international Health, M.Gertler , 2024 Contact HCIDs Airborne HCIDs Argentine haemorrhagic fever (Junin virus ) Andes virus infection ( hantavirus ) Bolivian haemorrhagic fever (Machupo virus) Avian influenza A H7N9 and H5N1 Crimean Congo haemorrhagic fever (CCHF) Avian influenza A H5N6 and H7N7* Ebola virus disease (EVD) Middle East respiratory syndrome (MERS) Lassa fever Mpox ( monkeypox ) ( Clade I only )** Lujo virus disease Nipah virus infection Marburg virus disease (MVD) Pneumonic plague (Yersinia pestis ) Severe fever with thrombocytopaenia syndrome (SFTS) Severe acute respiratory syndrome (SARS)*** Public health services of UK

8. HCIDs – may always involve Health Care Workers. 8 Institute for international Health, M.Gertler , 2024 Contact HCIDs Airborne  HCIDs Argentine haemorrhagic fever (Junin virus ) Andes virus infection ( hantavirus ) Bolivian haemorrhagic fever (Machupo virus) Avian influenza A H7N9 and H5N1 Crimean Congo haemorrhagic fever (CCHF) Avian influenza A H5N6 and H7N7* Ebola virus disease (EVD) Middle East respiratory syndrome (MERS) Lassa fever Mpox ( monkeypox ) ( Clade I only )** Lujo virus disease Nipah virus infection Marburg virus disease (MVD) Pneumonic plague (Yersinia pestis ) Severe fever with thrombocytopaenia syndrome (SFTS) Severe acute respiratory syndrome (SARS)*** Public health services of UK

9. 9 t he economist , 2016 Institute for international Health, M.Gertler , 2024

10. 10 t he economist , 2016 Institute for international Health, M.Gertler , 2024

11. > 800 HCWs infected > 500 died 11 t he economist , 2016 Institute for international Health, M.Gertler , 2024 EVD in West Africa 2014:

12. 12

13. MARV & EV – geographical occurence 13 Institute for international Health, M.Gertler , 2024 Robert Koch-Institut

14. Marburg and Ebola Viruses and Diseases Institute for international Health, M.Gertler , 2024 14 Foto: WHO

15. Filovirus - reservoir Abir MH, Rahman T, … Hassan MM. Pathogenicity and virulence of Marburg virus . Virulence . 2022 Dec;13(1):609-633.

16. Filovirus - transmission incubation period has ranged between 2–21 days, and the average duration is 5 to 9 days, in humans – some cases in Ghana (2022) are only explained with longer incubation perods (23-26 d) Abir MH, Rahman T, … Hassan MM. Pathogenicity and virulence of Marburg virus . Virulence . 2022 Dec;13(1):609-633.

17. Filovirus enter host & spreads via lymphatic & vascular systems, causes necrosis in many organs, including the liver, spleen, kidneys, gastrointestinal tract, & endocardium . Immunity is suppressed and cytokines/chemokines number is increased , which leads to shock as well as multiorgan failure.   Filovirus Jacob ST, …Kuhn JH. Ebola virus disease . Nat Rev Dis Primers . 2020 Feb 20;6(1):13.

18. Jacob ST, …Kuhn JH. Ebola virus disease . Nat Rev Dis Primers . 2020 Feb 20;6(1 ):13.

19. Filovirus - genetics Kuhn, J.H. (2017). Guide to the Correct Use of Filoviral Nomenclature . In: Mühlberger, E., Hensley , L., Towner , J. ( eds ) Marburg- and Ebolaviruses . Springer

20. Filovirus – clinical picture No clinicallly relevant difference between MV and ED – incubation period may be longer in MV but data limited KA Schneider, M Eichner, Lancet 2022 (Ghana cases )

21. Filovirus – diagnostics Institute for international Health, M.Gertler , 2024 ED - rapid tests (for POC use ) – no satisfying sensitivity yet (?) MD - no rapid test available D Mukadi-Bamuleka et al. Lancet, 2022

22. Immunization Optional: Klinik, Zentrum, Arbeits-/Sonderbereich etc., M.Gertler, 2024 22 Foto: WHO

23. Filovirus Immunization Two possible domains : „ring- vaccinations “ to curb on- going outbreak General population immunisation  would need regular and extremlely wide reaching activity with highly effective antigene 23 Graphic : statnews.com Institute for international Health, M.Gertler , 2024 2019: DRC: 300 000 pers. vaccinated Contacts & contacts of contacts & front-line medical staff

24. Ervebo – Merck WHO: “ Recombinant vesicular stomatitis virus –Zaire Ebola virus ( rVSV -ZEBOV) is effective and safe (in 5000 persons ) – Guinea 2016 „Ebola – ca suffit !“ – study 2016, Guinea, ring- vaccination approach 24 „Ebola, ca suffit “ study – Lancet 2017 Institute for international Health, M.Gertler , 2024

25. Ervebo – Merck Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) – a vector virus 25 Graphic Université de Genève, 2014 Optional: Klinik, Zentrum, Arbeits-/Sonderbereich etc., M.Gertler, 2024

26. Zabdeno & Mvabea – Janssen- Cilag Adenovirus Type 26 and Modified Vaccinia Virus Ankara - JAMA 2017 – Janssen Zabadeno / Mvabea 26 Foto Janssen heterologous primary and booster vaccination :  1.Dose: Adenov . type 26 vector vaccine encod . Zaire EVGP Ad26.ZEBOV) 2.Dose : modified vaccinia Ankara: AGs of Ebola, Sudan, Marburg, Tai Forest WHO: recommendation for regions neigboring outbreak regions “at risk populations ” – HCWs ? Effectivity against Sudan, Marburg unclear Institute for international Health, M.Gertler , 2024

27. Vaccination – questions and limitations 27 Foto WHO How long does the protection last? Variety of filoviruses Sensitivity to cold chain (-80C) breaks ? Provision, store and costs of vaccines on the long -run? Where ? How many ? Institute for international Health, M.Gertler , 2024

28. Ebola Disease - Treatment 28 Foto: WHO Institute for international Health, M.Gertler , 2024

29. Ebola Specific Treatments 29 Mulangu , S., et al., N Engl J Med , 2019. – PALM Study 681 patients were enrolled 2018/19 – then ZMAPP & Remdesivir were stopped ( eth.Cons .) Licensed as : Ansuvimab ; Ebanga ® (mAb114)& Inmazeb ® (REGN-EB3) Survival > 80% patients w / low VL + early treatment CFR also reduced in advanced stages

30. Marburg No Specific treatment yet 30 No . Compound Mechanism of action Experimental validation 1 Estradiol benzoate Inhibition of VP35 protein, disrupting viral replication and immune evasion Necessary for confirming therapeutic efficacy 2 INVEGA ( Paliperidone ) Inhibition of VP35 protein , disrupting viral replication and immune evasion Necessary for confirming therapeutic efficacy 3 Galidesivir Binds to viral RNA polymerase, halting RNA replication Efficacy demonstrated in mouse model 4 Favipiravir (T-705) Acts as a nucleoside analog, inhibiting viral RNA- dependent RNA polymerase Efficacy demonstrated in mouse model 5 Remdesivir Interferes with viral RNA synthesis by inhibiting RNA- dependent RNA polymerase Demonstrated efficacy in non-human primate model 6 Monoclonal Antibodies Bind to virus, preventing infection and neutralizing it Demonstrated efficacy in non-human primate model 7 Tilorone Believed to induce interferon production, enhancing immune response against viral infections Further investigation needed for efficacy and safety 8 Quinacrine Lysosomotropic properties alter cellular pH, potentially disrupting viral replication ; binds to GP protein Further investigation needed for efficacy and safety 9 Small Molecule Inhibitors Direct binding to Marburg virus glycoprotein , lysosome trapping , prevention of virus-host interactions Further investigation needed for efficacy and safety Novel antiviral approaches for Marburg, AC Puhl 2020, Srivastava S, 2024

31. Best supportive care 31 Fotos: ;MSF; Charité; WA Fisher, NEJM; Since 1976: 20.000 to 30.000 cases in West & Central Africa - Minimal medicine , max protection , many patients - CFR 50 to 80% 2. Since 2014: best supportive therapy : incl. intravenous fluids , electrolytes , oxygen , as well as blood & blood product - CFR 35-50% 3. Since 2014 ±50 cases in Europe/USA - ICU-level care, CFR ~ 18.5% 4. Adapted concepts : „ optimized supportive care“ Allowing most intensive care methods

32. 32

33. New developments 33 CDC 2014 Institute for international Health, M.Gertler , 2024 Stronger awareness gobally - numerous recent filovirus outbreaks detected and contained rapidly e.g. in DRC, Uganda, Tanzania New concepts for barrier nursing A first high-level isolation and care unit In Central/East Africa

34. Murakoze Danke! [email protected] 34 Foto: MSF Institute for international Health, M.Gertler , 2024