Delegates met in Geneva on Sept 4–5 to prioritise experimental therapies and vaccines that could be rapidly used to help curb the present Ebola outbreak in west Africa. John Maurice reports.

“Right now the epidemic is out of control. The situation is drastic and calls for drastic measures.” This statement, by Marie-Paule Kieny, WHO Assistant Director-General for Health Systems and Innovation, encapsulates the mood of a WHO consultation meeting in Geneva, Switzerland, on Sept 4–5, 2014, that brought together more than 150 international experts involved in the current Ebola outbreak in west Africa. Their task was to determine if and how experimental vaccines and therapies for Ebola could be pulled out of the development pipeline and put to work to halt transmission of the virus and alleviate the suffering of its victims.

“This 2-day meeting was in itself a drastic measure”, Kieny told The Lancet. “Delegates came from 29 countries, including the three west African countries severely affected by the outbreak. Just about every sector of the international health community was represented. What impressed me most was the willingness that everyone expressed to take action to curb the epidemic.” The number of people affected by this epidemic certainly calls for action. As of Sept 5, the last day of the meeting, there were, according to a WHO Ebola Response Roadmap Situation Report , 3944 probable, confirmed, and suspected cases of Ebola and 2097 deaths in Guinea, Liberia, and Sierra Leone—nearly twice as many cases and deaths as for all previous outbreaks that have occurred since the Ebola virus first appeared in 1976, and nearly ten times as many as there were for the biggest previous outbreak, in Uganda in 2000–01. The heaviest burden right now is in Liberia, where 14 of 15 counties are affected, with 1871 cases and 1089 deaths, mostly in the capital, Monrovia.

Delegates at the WHO consultation meeting about potential Ebola therapies and vaccines were concerned by these numbers. “The scale of this epidemic has been vastly underestimated”, says Michael Kurilla, Director of the Office of Biodefense Research Resources and Translational Research at the US National Institutes of Health. “Up to now Ebola epidemics have been mostly located in isolated rural settings and were responsive to infection control practices. But we just don't have the resources that we need to cope with such an unprecedentedly huge outbreak. The good news, though, is that over the past decade work has generated multiple promising candidate tools, including vaccines and therapeutics, to tackle the disease.”

Armand Sprecher, a Médecins Sans Frontières (MSF) doctor who specialises in haemorrhagic fevers, is living and working with the stark reality of this epidemic. He gave the meeting an insight into the obstacles he and his colleagues are struggling with in Monrovia. “This outbreak is getting well past our capacity to manage it”, he told The Lancet. “We have a 160-bed unit here that is full. We're admitting patients at the same rate as they are dying. If all goes well we'll scale up our capacity to 400 beds, and that will quickly be full. But where can the patients go. Right now, there are no hospitals providing inpatient care in Monrovia.”

Sprecher attributes the scale of this outbreak to at least two factors. One is the tendency of patients not to come for care. “It's understandable. They see our treatment centres as places you go into but never come out of.” The other factor, he says, is the extraordinary mobility of the affected populations, which, aided by extensive social networks, has fuelled the geographical spread of the outbreak. “And we're still on the upslope of the epidemic curve. Most of the cases are still ahead of us”, says Sprecher.

First-hand accounts and photos presented by delegates from affected west African countries shook many participants at the meeting. “It was a sombre, sobering moment. It brought home to everyone just how terrible the situation really is”, says Jeremy Farrar, Director of the Wellcome Trust in London, UK. “What worries me is not only the terrible suffering and deaths directly caused by Ebola but also the impact this epidemic is having and is going to have for a long time on the already fragile health infrastructure and social fabric of these affected countries. It is putting an impossible strain on health systems across a whole range of diseases, such as malaria, tuberculosis, HIV/AIDS, maternal and child health, diabetes, mental health, and so on.”

The vivid first-hand accounts of the Ebola situation on the ground injected urgency into the main business of the meeting: to find a way of countering the outbreak as rapidly as possible with whatever therapies and vaccines might be available and effective. The meeting gave immediate priority to blood therapies using whole blood plasma obtained from survivors of the infection and containing antibodies to Ebola virus. There was consensus at the meeting that use of whole blood therapies and convalescent blood serums is an option worth prioritising, especially as the scale of the present epidemic is producing large numbers of survivors, and such therapies, if proven safe, could be used in the near future. “The affected countries have started transfusions and we should know pretty soon if this procedure works safely and effectively”, says Kieny.

WHO's Marie-Paule Kieny addresses the media after the Ebola meeting, Sept 5, 2014 Copyright © 2014 Salvatore Di Nolfi/epa/Corbis

Researcher works with samples of Ebola virus Copyright © 2014 Philippe Plailly/Eurelios/Science Photo Library

As for drugs, none has been tested for safety and efficacy in human beings. Among the many products discussed at the meeting, two were chosen as being the most promising for rapid deployment. One, ZMapp, is based on a cocktail of three monoclonal antibodies that attach to the virus and block its infective potential, at least in monkeys. A few people have already received this drug, on a compassionate basis, with variable results. The manufacturer, Mapp Biopharmaceutical, has run out of supplies and hopes to scale up production by the end of December.

The second drug, TKM-Ebola, made by Tekmira Pharmaceuticals Corporation, uses an “interfering” RNA molecule to silence expression of two genes that the Ebola virus needs to replicate. In early studies, the drug prevented infection in all the laboratory animals given a lethal dose of Ebola virus. Early this year the firm began a phase 1 clinical trial to assess the drug's safety, tolerability, and pharmacokinetics. The US Food and Drug Administration had placed a hold on TKM-Ebola after concerns about signs of cytokine release in patients given high doses of the drug, but later modified the clinical hold to a partial hold allowing the experimental drug to be used in patients with Ebola disease. Results of the phase 1 trial should be forthcoming in a few weeks. The firm plans to produce 900 treatment courses by early 2015. Kurilla sounds a note of caution, however, about testing candidate drugs. “There are so many options to consider and so many criteria to take into consideration with such a gargantuan disease. For example, if you give a drug to people and it doesn't work, that doesn't really tell you that the drug doesn't work. It may mean you just used it too late. We need to know, among other things, what the best time is for an intervention.”

The meeting also picked two vaccine candidates that are relatively advanced in the development process. Both have protected against Ebola infection in animal studies. One vaccine, ChAd-EBO, is made by GlaxoSmithKline (GSK) and uses a chimpanzee adenovirus to deliver the Ebola gene that codes for an immunity-provoking antigen. All animals given the vaccine were protected after inoculation of a lethal dose of the Ebola virus. A phase 1 clinical trial of this vaccine has just begun in the USA and further trials will soon start in the UK and Africa. GSK is scaling up production of the vaccine and could have about 10 000 doses available by December. The second vaccine, VSV-EBO, originally developed in Canada and currently licensed to a US company, NewLink Genetics, uses a vesicular stomatitis virus to deliver Ebola antigens. Animals given the vaccine were all protected against the Ebola virus, whether they received the vaccine before or after inoculation of the virus. Clinical trials should begin this month in the USA, the European Union, and an African country. Canada has already donated 800 doses of the VSV-EBO vaccine to WHO and, depending on the results of the trials, distribution might start by the end of November.

The first recipients of the potential vaccines are likely to be health-care workers on the frontline of the battle against Ebola who are exposed to the risk of infection. “In Monrovia”, MSF's Sprecher says, “in mid-August, about half our patients were health-care workers. There was a lot of a health-care transmission going on”. Kurilla notes, “It's not just health-care workers who are at high risk of infection. There are laboratory technicians, janitors in health facilities, and health staff helping with burial procedures, who are all exposed to infection”.

Farrar, of the Wellcome Trust, urges that action is needed after the meeting. “We've all been too slow in responding to this epidemic. This meeting, with such a wide spectrum of participants, must not prove to be just another talking shop. We all have to make up for lost time. The meeting has reinforced our conviction that we need to change the way we've been working. We need to prove immediately that these drugs and vaccines are safe and then very quickly learn whether they can save lives and prevent infection and we can only do that during this epidemic. We have to make the right decisions and then back them up with action. This is a crisis not just for people in west Africa but for all of us. The world has finally woken us up.”

Article Info Publication History Identification DOI: https://doi.org/10.1016/S0140-6736(14)61411-2 Copyright © 2014 Elsevier Ltd. All rights reserved. ScienceDirect Access this article on ScienceDirect