A “bottom up” treatment for Ebola that could have been used in West Africa
Author: David S.Fedson, MD (firstname.lastname@example.org)
Affiliation: Former Professor of Medicine, University of Virginia School of Medicine
Editor: Motoi Miura, Tetsuya Tanimoto
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  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 , 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 have 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 . 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  and those caused by emerging viruses , in which failure to overcome endothelial dysfunction often leads to multi-organ failure and death.
The manuscript was originally published in the Sierra Leone Telegraph on July 4, 2015, and reproduced for MRIC Global under the author's permission.
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 .