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A "Bottom Up" Treatment for Ebola That Could Have Been Used in West Africa

As sporadic cases of Ebola continue to arise in West Africa, a controversial approach could be utilized to increase survival rates in those who are infected.

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 markers of severe inflammation. The same is seen in patients with sepsis, and in sepsis patients these findings are associated with endothelial dysfunction and the loss of endothelial barrier integrity.

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(The endothelium is the layer of cells lining our blood vessels. It determines what stays in and what gets out.) Careful studies of healthcare workers who were infected with Ebola virus and evacuated from West Africa for medical care showed they had developed massive internal and external 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 (and now generic) drugs, including 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.

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For this reason, in August 2014, the idea of treating Ebola patients with these drugs was presented to Ebola scientists and World Health Organization (WHO) staff, but it was rejected.

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Moreover, it received no support from national health agencies or major foundations.

This lack of interest notwithstanding, in November 2014, local physicians in Sierra Leone treated consecutively approximately 100 Ebola patients with a combination of atorvastatin and irbesartan.

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Only three inadequately treated patients are known to have died. No financial or logistical support was available to conduct a proper clinical trial; treatment was supported only by a modest private donation. Sadly, physicians and health officials in Sierra Leone have 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 (see Figure).

During the Ebola outbreak, several investigational treatments (antiviral drugs, convalescent plasma) were tested in Ebola patients, but they met with little success.

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Unlike these treatments, atorvastatin and irbesartan target the host response to the infection, not the virus itself.

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By stabilizing endothelial function and restoring normal fluid balance, combination treatment allowed 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. Of critical importance, these drugs are available throughout the world as inexpensive generics, and they could have been purchased in local pharmacies in West Africa. A 10-day course of treatment for an individual Ebola patient would have cost only a few dollars.

Unfortunately, none of the “lessons learned” reports that have analysed the failures of the Ebola response has mentioned this approach to treating Ebola patients.

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Details on the Ebola patients who were treated in Sierra Leone need to be released, and the findings should be externally reviewed and validated. Thus far, Ebola scientists and WHO officials have shown no interest in doing this, perhaps because treating the host response instead of targeting the virus is a new idea.

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If sporadic cases of Ebola re-emerge, combination treatment should be tried in these patients, and if the number of patients is large, 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 emerging virus diseases, including pandemic influenza,

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in which failure to overcome endothelial dysfunction often leads to multi-organ failure and death.

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 Submitted by David S. Fedson. August 12, 2016-08-12. dfedson@wanadoo.fr.

Dr. Fedson received his BA in American Studies from Yale University in 1959. He spent the next two years teaching English at New Asia College in Hong Kong under the Yale-China program. He received his medical degree from Yale University in 1965, spent the next year on a fellowship studying smallpox in London and India, and then trained on the Osler Medical Service at The Johns Hopkins Hospital. He served as a Clinical Associate in the Laboratory of Clinical Investigation at the National Institutes of Health and Chief Medical Resident at the University of Chicago.

Dr. Fedson’s research has focused on the epidemiology of influenza and pneumococcal vaccination. In 2001, he was instrumental in establishing the Influenza Vaccine Supply International Task Force which represents major vaccine companies and is concerned with the global vaccine supply for an influenza pandemic. Since retiring in November 2002, he has continued to work on influenza and pneumococcal vaccination. He established and served as Coordinator of the Macroepidemiology of Influenza Vaccination (MIV) Study Group. In recent years he has explored the possibility of using inexpensive, generic anti-inflammatory and immunomodulatory agents for treatment and prophylaxis of seasonal and pandemic influenza.

References

  1. Fedson DS, Opal SM. Can statins help treat ebola? The New York Times website. http://www.nytimes.com/2014/08/16/opinion/can-statins-help-treat-ebola.html?_r=0. Published August 15, 2014. Accessed August 25, 2016.
  2. Enserink M. Infectious diseases. Debate erupts on ‘repurposed’ drugs for ebola. Science. 2014;345(6198):718-9. doi: 10.1126/science.345.6198.718.
  3. Fedson DS. A practical treatment for patients with ebola virus disease. J Infect Dis. 2015;21(4):661-662. doi: 10.1093/infdis/jiu474.
  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(3):e00716-15. doi: 10.1128/mBio.00716-15.
  5. Fedson, DS, Rordam OM. Treating ebola patients: a ‘bottom up’ approach using generic statins and angiotensin receptor blockers. Int J Infect Dis. 2015;36:80-84. doi: 10.1016/j.ijid.2015.04.019.
  6. Filewod NC, Lee WL. Is strengthening the endothelial barrier a therapeutic strategy for ebola? Int J Infect Dis. 2015;36:78-79. doi: 10.1016/j.ijid.2015.05.016.
  7. Fedson DS. Immunomodulatory adjunctive treatment options for ebola virus disease patients: another view. Intensive Care Med. 2015;41(7):1383. doi: 10.1007/s00134-015-3874-2.
  8. Cohen J, Enserink M. Infectious diseases. As ebola epidemic draws to a close, a thin scientific harvest. Science. 2016;351(6268):12-13. doi: 10.1126/science.351.6268.12.
  9. Gostin LO, Tomori O, Wibulpolprasert S, et al. Toward a common secure future: four global commissions in the wake of ebola. PLoS Med. 2016;13(5):e1002042. doi: 10.1371/journal.pmed.1002042.
  10. Baddeley M. Herding, social influences and behavioural bias in scientific research: simple awareness of the hidden pressures and beliefs that influence our thinking can help to preserve objectivity. EMBO Rep. 2015;16(8):902-905. doi: 10.15252/embr.201540637.
  11. Fedson DS. How will physicians confront the next influenza pandemic? Clin Infect Dis. 2014;58(2):233-237. doi: 10.1093/cid/cit695