To date, there have been over 1,050 deaths attributed to Ebola virus infection and disease (Ebola hemorrhagic fever) in the 2014 Western Africa epidemic, and the World Health Organization (WHO) believes these numbers to be underestimated.1 There is no cure for Ebola, and treatment is limited to supportive care consisting of hydration, blood transfusions (if needed) and the use of antibiotics (if secondary infections arise).2 About 50% of infected people survive.

Although there are no drugs or vaccines proven to work against the disease, a number of pharmaceuticals are in the pipeline. The road to U.S. Food and Drug Administration (FDA) approval is a long one, spanning many years; it typically takes over ten years from initial drug concept to market. All candidate medicines are first tested in vitro (think cells in a petri dish), then in animal models, then finally in a series of human trials. Phase I human trials are typically performed on a small number of individuals to test a drug’s safety, to see if it tolerated without severe side effects. Phase II and III trials can employ thousands of individuals to test a drug’s effectiveness (while continuing to monitor for side effects). Prior to the current Ebola outbreak, only one treatment, TKM-Ebola (made by Tekmira Pharmaceuticals-Canada), had begun human safety trials.3 TKM-Ebola is a mixture of small interfering RNAs which works by blocking the production of key viral proteins. Although its phase I trial raised concerns about the drug’s safety, the FDA has ruled to allow studies of TKM-Ebola in people infected with the virus (citing the special circumstance of the current epidemic).4 Before the phase I trial, TKM-Ebola was tested on infected monkeys, where it showed promise.5 However, experiments involving non-human primates contain very small numbers of subjects (in this case, 7 monkeys split into two groups). Clearly, these numbers are not enough to gauge efficacy in monkeys, let alone tell us how it will behave in humans.

A number of vaccines against Ebola are in the works. A vaccine developed by Canadian government scientists will begin phase I trials by summer’s end.3 GlaxoSmithKline is awaiting approval from the FDA to begin a phase I trial of their vaccine, possibly by September.3 Two other potential vaccines won’t begin human trials until late 2015/2016 at the earliest.6

The one experimental treatment that most people have heard about in the news is ZMapp (made by Mapp Biopharmaceutical Inc.–USA). ZMapp consists of anti-Ebola antibodies that help the patient’s immune system identify and destroy the virus. Generation of these antibodies is a long, complicated process;7 that the antibodies must be kept at cold temperatures prior to administration further complicates its use as a treatment option in Africa. Although the drug had never been tested in humans, two doses were given to American health care workers who had contracted Ebola while helping treat infected patients in Africa. A third dose was given to an infected Spanish missionary who became infected also while working with Ebola patients. As of this writing (August 18), the two Americans seem to be recovering, however, the Spaniard passed away three days after receiving ZMapp (August 11).8

In the wake of the administration of ZMapp, the WHO gathered a panel of ethicists to weigh the pros and cons of the use of experimental Ebola drugs in humans. Since we know nothing of the side effects of these potential treatments, giving these drugs to people could cause more harm than the Ebola infection itself. Scarce supplies of these medicines also raise questions about who gets priority treatment. Should health care workers be a priority? They are at the front lines battling this disease and are at greatest risk for contracting it. Also, once treated (and hopefully recovered), they would presumably have immunity to disease and be able to continue treating patients without risk of re-infection. Should those most recently infected have first dibs on these treatments? The sooner these drugs are administered after the time of infection, the better the chance of survival, so making the recently infected a priority would maximize effectiveness. Finally, should patient age be a consideration? The Spanish priest who died after ZMapp treatment was 75 years old. Would this precious aliquot of antibodies have been better served if given to a younger patient whose immune system has a better chance of fighting off the infection? Lastly, because about half of the people infected with Ebola survive with just supportive care, we have no way of knowing if these new drugs have any effect at all. Perhaps it would be best to randomize access to these drugs in order to mimic those conditions found in clinical trials and therefore get information on their effectiveness.9 Over half of all recorded Ebola cases in history (1976-present) have happened in this 2014 outbreak. With so many cases happening right now, there may be no better time to test these treatments on humans. If we wait, it may be years until another Ebola outbreak, and we will still not know how best to treat the disease.

On August 12, the WHO ethical panel endorsed the use of experimental Ebola medicines in humans, although who would be receiving which treatments has not been defined.6 Liberia has confirmed that it has received some of the final doses of ZMapp and it plans to treat two infected doctors, the first Africans to be given the drug.6 As mentioned earlier, the drug TKM-Ebola is also now cleared for use, although how many doses are available is unknown; it takes months to produce.10 As the cases of Ebola continue to rise in Western Africa, it makes the administration of these drugs a difficult decision.


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