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A “bottom up” treatment for Ebola that could have been used in West Africa by Dr. David Fedson - January 2017

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  • A “bottom up” treatment for Ebola that could have been used in West Africa by Dr. David Fedson - January 2017

    submitted to FluTrackers by Dr. David Fedson:


    A “bottom up” treatment for Ebola that could have been used in West Africa

    More than 11,000 people died as a result of the Ebola outbreak in West Africa. Aside from conventional supportive care, no specific treatment was available. In most treatment units, more than 50% of the patients died. We now know that many of them could have survived.

    Patients who die of Ebola have elevated plasma levels of pro-inflammatory cytokines. The same thing is seen in patients with sepsis, and in sepsis patients these findings are associated with endothelial dysfunction and the loss of endothelial barrier integrity [1-3]. Careful studies of healthcare workers who were infected with Ebola virus and evacuated from West Africa for medical care showed they had developed massive fluid losses. These losses were due to a dramatic increase in vascular permeability, a direct effect of the loss of endothelial barrier integrity.

    Cardiologists have known for many years that several common drugs, among them statins and angiotensin receptor blockers, have the ability to stabilize or restore endothelial barrier integrity. These drugs are safe when given to patients with acute critical illness, and clinical studies suggest they might improve survival in patients with sepsis, pneumonia and influenza [1, 3]. For these reasons, in November 2014, local physicians in Sierra Leone treated consecutively approximately 100 Ebola patients with a combination of atorvastatin (40 mg orally /day) and irbesartan (150 mg orally/day) [4-7]. Only three inadequately treated patients are known to have died.

    Unfortunately, several months earlier, the idea for treating Ebola patients was rejected by Ebola scientists [2] and WHO staff, and it received no support from national health agencies or major foundations. There was no financial or logistical support to conduct a proper clinical trial in Sierra Leone; treatment was supported only by a modest private donation. Sadly, physicians and health officials in Sierra Leone refused to release information on their treatment experience. Nonetheless, letters and memoranda they exchanged provide good evidence that treatment brought about “remarkable improvement” in Ebola patients (Figure).

    Unlike investigational treatments (antiviral drugs, convalescent plasma) that have been tested in Ebola patients with little success [8], atorvastatin and irbesartan target the host response to the infection, not the virus itself [3-7]. By stabilizing endothelial function and restoring normal fluid balance, combination treatment allows patients to live long enough to develop immune responses of their own and get rid of the virus.

    All physicians who treat patients with cardiovascular diseases are familiar with atorvastatin and irbesartan, and most of them have used these drugs to treat their patients. The drugs are widely available as inexpensive generics in West Africa. A 10-day course of treatment for an individual Ebola patient would cost only a few dollars.

    Details on the Ebola patients who were treated need to be released, and the findings need to be externally reviewed and validated. Ebola scientists and WHO have shown no interest in doing this, perhaps because treating the host response instead of the virus is for them a new idea [9]. If sporadic cases of Ebola continue to occur, combination treatment could be tried in these patients, and if the number of patients increases, a proper clinical trial could be undertaken. In the meantime, physicians should consider the possibility that this combination might be used to treat patients with other diseases, including pandemic influenza [10] and those caused by emerging viruses [11], in which failure to overcome endothelial dysfunction often leads to multi-organ failure and death.

    David S. Fedson, MD dfedson@wanadoo.fr January 2017

    References
    1. Fedson DS, Opal SM. Can statins help treat Ebola? The New York Times, August 15, 2014.
    2. Enserink M. Debate erupts on ‘repurposed’ drugs for Ebola. Science 2014, 345: 718-9.
    3. Fedson DS. A practical treatment for patients with Ebola virus disease. J Infect Dis 2015; 211: 661-2. (Published online on August 25, 2014)
    4. Fedson DS, Jacobson JR, Rordam OM, Opal SM. Treating the host response to Ebola virus disease with generic statins and angiotensin receptor blockers. mBio 2015; 6: e00716-15.
    5. Fedson, DS, Rordam OM. Treating Ebola patients: a “bottom up” approach using generic statins and angiotensin receptor blockers. Int J Infect Dis 2015; 36: 80-4.
    6. Filewod NC, Lee WL. Is strengthening the endothelial barrier a therapeutic strategy for Ebola? Int J Infect Dis 2015; 36: 78-9.
    7. Fedson DS. Immunomodulatory adjunctive treatment options for Ebola virus disease patients: another view. Intensive Care Med 2015; 7: 1383.
    8. Cohen J, Enserink M. As Ebola epidemic draws to a close, a thin scientific harvest. Science 2016; 351: 12-3.
    9. Baddeley M. Herding, social influences and behavioural bias in scientific research. EMBO Rep 2015; 16: 902-5.
    10. Fedson DS. How will physicians confront the next influenza pandemic? Clin Infect Dis 2014; 58: 233-7.
    11. Fedson DS. Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola. Ann Transl Med 2016; 4: 421.


    Figure. Memorandum from a staff physician at the Port Loko Government Hospital in Sierra Leone. It was published on page one of The Times of Sierra Leone on February 3, 2016. Individual patient records document treatment of 15 patients, all of whom survived [5].
    "May the long time sun
    Shine upon you,
    All love surround you,
    And the pure light within you
    Guide your way on."

    "Where your talents and the needs of the world cross, lies your calling."
    Aristotle

    “In a gentle way, you can shake the world.”
    Mohandas Gandhi

    Be the light that is within.

  • #2
    submitted to FluTrackers by Dr. David Fedson:

    Correspondence A Practical Treatment for Patients With Ebola Virus Disease - February 2015

    snip

    Investigators have not developed an effective vaccine against EVD, and postexposure treatments targeting the virus or the host response are in the early stages of development [2].Although these interventions might eventually benefit laboratory and healthcare workers, they will be expensive and in short supply, and it is unclear how they might be used in patient care during an EVD outbreak. Statins, however, are widely available to African physicians as inexpensive generic drugs and are used to treat patients with cardiovascular disease every day. Along with other generic immunomodulatory agents (eg, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers), statins have been proposed for syndromic treatment of the host response in patients with in fluenza, pneumonia, and sepsis [10]. They should also be considered for treating patients with EVD.

    https://oup.silverchair-cdn.com/oup/...CZBIA4LVPAVW3Q
    "May the long time sun
    Shine upon you,
    All love surround you,
    And the pure light within you
    Guide your way on."

    "Where your talents and the needs of the world cross, lies your calling."
    Aristotle

    “In a gentle way, you can shake the world.”
    Mohandas Gandhi

    Be the light that is within.

    Comment


    • #3

      submitted to FluTrackers by Dr. David Fedson:


      Treating the Host Response to Ebola Virus Disease with Generic Statins and Angiotensin Receptor Blockers
      David S. Fedson,a Jeffrey R. Jacobson,b Ole Martin Rordam,c Steven M. Opald Retired Physician, Sergy Haut, Francea ; University of Illinois College of Medicine, Chicago, Illinois, USAb; Practicing Physician, Trondheim, Norwayc ; Alpert Medical School, Brown University, Providence, Rhode Island, USAd

      ABSTRACT Treatments targeting the Ebola virus may eventually be shown to work, but they will not have an impact on overall Ebola mortality in West Africa. Endothelial dysfunction is responsible for the fluid and electrolyte imbalances seen in Ebola patients. Because inexpensive generic statins and angiotensin receptor blockers restore endothelial barrier integrity, they can be used to treat the host response in these patients. In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved.

      http://mbio.asm.org/content/6/3/e00716-15
      "May the long time sun
      Shine upon you,
      All love surround you,
      And the pure light within you
      Guide your way on."

      "Where your talents and the needs of the world cross, lies your calling."
      Aristotle

      “In a gentle way, you can shake the world.”
      Mohandas Gandhi

      Be the light that is within.

      Comment


      • #4

        submitted to FluTrackers by Dr. David Fedson:

        Open Access


        Treating Ebola patients: a ‘bottom up’ approach using generic statins and angiotensin receptor blockers

        David S. FedsonCorrespondence information about the author David S. FedsonEmail the author David S. Fedson
        , Ole Martin Rordam

        DOI: http://dx.doi.org/10.1016/j.ijid.2015.04.019 |



        Article Info
        Article Outline Highlights

        Lessons learned from evacuated healthcare workers. Treating the host response to Ebola virus disease4. A trial of statin and ARB treatment of Ebola virus disease5. Treating the host response with statins and ARBs represents a ‘bottom up’ approach to managing Ebola virus disease6. A need for changeConflict of interestReferences
        • Ebola virus disease in West Africa has a high mortality rate.
        • The loss of endothelial barrier integrity causes massive fluid losses.
        • Atorvastatin and irbesartan reduced Ebola mortality in Sierra Leone.
        • Treatment is safe and restores endothelial barrier integrity.
        • This inexpensive generic treatment is widely available in West Africa.
        Summary

        The international community has responded to the Ebola outbreak in West Africa with a ‘top down’ approach. This has contributed to outbreak control, but has done much less to reduce the high mortality rate in individual patients. Ebola patients experience a breakdown in endothelial barrier integrity that leads to massive fluid losses and vascular collapse. Statins and angiotensin receptor blockers (ARBs) maintain or restore endothelial barrier integrity. Local physicians in Sierra Leone have treated approximately 100 consecutive Ebola patients with atorvastatin and irbesartan, and all but two inadequately treated patients have survived. The results of this experience have not been released and they need to be reviewed and validated. Unlike other treatments that target the Ebola virus itself, this ‘bottom up’ approach to treatment represents a paradigm shift by targeting the host response to infection. Treatment with these safe, inexpensive generic agents could be implemented readily throughout West Africa.




        http://www.ijidonline.com/article/S1...106-X/fulltext
        "May the long time sun
        Shine upon you,
        All love surround you,
        And the pure light within you
        Guide your way on."

        "Where your talents and the needs of the world cross, lies your calling."
        Aristotle

        “In a gentle way, you can shake the world.”
        Mohandas Gandhi

        Be the light that is within.

        Comment


        • #5
          submitted to FluTrackers by Dr. David Fedson:


          Treating the host response to emerging virus diseases: lessons learned from sepsis, pneumonia, influenza and Ebola

          David S. Fedson
          Formerly, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, USA
          Correspondence to: David S. Fedson, MD. 57, chemin du Lavoir, 01630 Sergy Haut, France. Email: dfedson@wanadoo.fr.

          Abstract: There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases. Most scientists work on new drugs that target viruses, and few accept the idea of treating the host response with generic drugs. A great deal of research will be needed to show conclusively that these drugs work, and this will require the support of public agencies and foundations. Investigators in developing countries should take an active role in this research. If the next Public Health Emergency of International Concern is caused by an emerging virus, a “top down” approach to developing specific new drug treatments is unlikely to be effective. However, a “bottom up” approach to treatment that targets the host response to these viruses by using widely available and inexpensive generic drugs could reduce mortality in any country with a basic health care system. In doing so, it would make an immeasurable contribution to global equity and global security.

          Keywords: Emerging viruses; Ebola; influenza; sepsis; statins; angiotensin receptor blockers (ARBs); angiopoietin (Angpt); angiotensin-converting enzyme 2 (ACE2); WHO


          Submitted Sep 23, 2016. Accepted for publication Oct 10, 2016.


          http://atm.amegroups.com/article/view/12396/12861
          "May the long time sun
          Shine upon you,
          All love surround you,
          And the pure light within you
          Guide your way on."

          "Where your talents and the needs of the world cross, lies your calling."
          Aristotle

          “In a gentle way, you can shake the world.”
          Mohandas Gandhi

          Be the light that is within.

          Comment

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