Health Letter, January 2015
By Sarah Sorscher, J.D., M.P.H.
The largest epidemic of Ebola in world history is now stretching into its tenth month. The outbreak has already led to the estimated infection of over 18,000 people and over 6,900 deaths, with nearly all infections occurring in West Africa (primarily in Guinea, Liberia and Sierra Leone). Four patients have been diagnosed with and treated for Ebola in the U.S. One died, and three recovered from the disease.
The key to bringing this epidemic under control is preventing further transmission of the disease. This is currently being accomplished mainly through humanitarian aid to bring adequate staffing, resources and training into the areas most affected by the epidemic. Yet with thousands already suffering worldwide and many more infections likely before the end of this epidemic, there remains a desperate need for better treatment options that can help reduce mortality from this deadly disease.
One of the deadliest diseases
The Ebola virus comes from a family of viruses known as hemorrhagic fever viruses, which also includes the deadly Marburg virus, as well as those that cause yellow fever and dengue fever. Ebola has one of the highest fatality rates of any known disease, and the current outbreak in West Africa involves one of the more deadly strains of the disease: the Zaire strain. In previous large-scale epidemics involving the Zaire strain, anywhere from 44 to 90 percent of infected patients did not survive.
The Ebola virus is composed of ribonucleic acid (RNA), genetic material that forms the core of many viruses, including the common flu virus. The virus is transmitted when the bodily fluid of an infected person (most often blood, feces or vomit) makes contact with an open cut or the mouth, nostrils or eyes of another person. The virus appears to be able to survive for days or weeks on contaminated objects, meaning people can also be infected through contact with an object that has been exposed to the bodily fluid of an infected person, such as a soiled blanket.
Once a person is exposed to the virus, symptoms usually show up in about a week to 10 days but can appear as late as 21 days after exposure. Diagnosis is challenging during the initial phase of the illness, as early symptoms such as fever, chills and headaches are nonspecific and easily can be mistaken for the flu or many common flu-like illnesses. An Ebola diagnosis can be confirmed only through blood tests that detect the virus. The most sensitive of these tests is able to detect the Ebola virus between three and 10 days after the onset of symptoms.
About a week after the onset of initial symptoms, many patients develop a rash on the face and torso. Very late-stage patients experience signs of internal bleeding. They also may bleed from the mouth, nose and eyes and cough up blood.
Most patients who survive an Ebola infection will start to improve six to 11 days after the onset of symptoms, while people with fatal cases often start with much more severe symptoms and die within one or two weeks of their first symptoms.
The desperate search for a cure
No drug or vaccine has been approved as safe and effective to treat or prevent Ebola by the Food and Drug Administration (FDA) or the drug regulatory agency of any other country. Current treatment strategies rely primarily on keeping patients hydrated: A patient with Ebola must take in about one and a half to two and a half gallons of fluid per day to replace what is lost through vomiting, diarrhea and bleeding.
Because Ebola infection has no proven treatments and such high mortality rates, humanitarian groups have begun to press for broader access to unapproved therapies, particularly for patients in the hardest-hit countries in West Africa.
In October 2014, the FDA authorized the use of brincidofovir — an antiviral drug already being tested in late-stage clinical trials for a variety of diseases — for emergency use in Ebola. The FDA also has permitted physicians to give another unapproved drug, TKM-Ebola, to patients through the agency’s “compassionate use” program.
Yet these drugs, along with many others being investigated for use in treating Ebola, are still in very early stages of clinical development for this disease. Until recently, it had affected relatively few patients and therefore was a low priority for drug developers.
Some of these drugs, including brincidofovir and TKM-Ebola, are antiviral medicines being developed to fight other viral infections. Others were identified through more broad-based screening strategies. For example, chloroquine, an old malaria treatment, was found to be effective against Ebola in one screening study that evaluated 1,012 FDA-approved drugs in a laboratory setting.
Deciding how to test and use these unproven drugs in Ebola patients present a challenge for physicians and regulators. While patients are desperate for a drug with any possibility of effectiveness, the available options remain extremely experimental. There is also a chance that some may even do harm. For example, before the current outbreak, clinical trials for TKM-Ebola had been placed on hold by the FDA due to alarming signs of inflammation in healthy patients.
In November 2014, Doctors Without Borders, a humanitarian group on the front lines of the Ebola epidemic, announced it would soon begin human clinical trials for three treatments: favipiravir (an antiviral drug), brincidofovir, and therapy with whole blood and plasma collected from Ebola infection survivors, which contains antibodies against the disease.
Solid data supporting FDA approval of these drugs likely will come too late to help with the current outbreak. This means that for the thousands already suffering from this epidemic in West Africa, as well as those who contract the disease in the coming months, hope lies not in the drug pipeline, but in the ability to access well-resourced hospitals and clinics. Providing immediate aid to these health care facilities to carry out supportive care and contain the disease remains the best current option to fight this deadly outbreak.
 Centers for Disease Control. 2014 Ebola Outbreak in West Africa (Ebola Virus Disease). Updated November 24, 2014. https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/cumulative-cases-graphs.html. Accessed December 10, 2014.
 Centers for Disease Control. 2014 Ebola Outbreak in West Africa – Case Counts. Updated November 18, 2014. https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/case-counts.html. Accessed December 18, 2014.
 Centers for Disease Control. Cases of Ebola Diagnosed in the United States. Updated November 17, 2014. https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/united-states-imported-case.html. Accessed November 26, 2014.
 Faille M. The Ebola Epidemic. National Post. https://www.citizen.org/sites/default/files/ebola_1200.jpg. Accessed November 26, 2014.
 Doctors without Borders. Ebola: MSF urges immediate action on vaccines and treatments for frontline workers. October 24, 2014. https://www.doctorswithoutborders.org/article/ebola-msf-urges-immediate-action-vaccines-and-treatments-frontline-workers. Accessed November 26, 2014.
 Doctors without Borders. First trials for Ebola treatments to start at MSF sites in December. November 13, 2014. https://www.msf.org/article/first-trials-ebola-treatments-start-msf-sites-december. Accessed November 26, 2014.