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Skip to 0 minutes and 13 seconds PETER PIOT: My hope is that this will be the last outbreak where all we have is isolation, quarantine– after all, quite mediaeval ways of dealing with an epidemic– and nothing to offer, or not much, to people who are infected or those who are at risk. And that’s why it’s so important to engage in research, for better means to fight Ebola outbreaks in the future while we are trying to bring this epidemic under control. And that would be a new paradigm. But the only way to find out whether experimental therapies, whether experimental vaccines are effective, is to test them during an epidemic.

Skip to 0 minutes and 59 seconds And we also need to better understand the best way of communicating, of behaviour change, of controlling the epidemic in the community, from safe and dignified, burials to the best way to do contact tracing, and all that. So it’s not only biomedical research, but also social and behavioural research. Now, that’s easier said than done. Why? Because we need to work in an environment where everything possible has to be concentrated on stopping the epidemic, caring for people who otherwise would die. After all, we can give them supportive care, which also brings down mortality.

Skip to 1 minute and 45 seconds We have to operate, also, and do research in an environment where there is a climate of suspicion, of lack of trust, if not paranoia, with lots of rumours of why doctors come in to experiment on us Africans, et cetera, et cetera. And then there are major ethical issues. Can you conduct a placebo controlled trial for an experimental treatment for a disease which has a 70% case fatality rate? But the key is that we don’t waste this opportunity to advance research and new tools to treat people with Ebola and to prevent infection.

Skip to 2 minutes and 33 seconds DAVID HEYMANN: When an outbreak occurs is the only time that research can be done on the effectiveness of drugs or vaccines, because that’s the only time Ebola is circulating. So there is a priority area for research right now, and the first priority is the best possible means of hydrating patients, of maintaining their electrolyte balance, so that they can themselves survive long enough for their immune systems to take over. The next is to study convalescent plasma from survivors, looking to see whether the antibody in that plasma can neutralise virus in patients. The third and fourth priorities are antivirals and, finally, a vaccine.

Skip to 3 minutes and 14 seconds IAN ROBERTS: Early on in the Ebola crisis, people made a sort of knee-jerk reaction. Well, Ebola’s a virus. Therefore, we need treatments directed against the virus. Looking at case reports that are coming out from West Africa, it’s clear that some patients die from dehydration. So if you can’t drink enough to maintain your circulating volume, enough fluid in your body, your kidneys shut down. And that can quickly lead to death. Now, this is a very treatable thing. So dehydration shouldn’t lead to death. It’s very treatable. And it’s treatable by putting in– if people can’t drink enough, you put in some sort of intravenous line and you give them fluids.

Skip to 4 minutes and 5 seconds So fluids are a known effective treatment for dehydration that’s not responsive to drinking. But there are questions about it. So, for example, in patients with Ebola disease, how much fluid do we give? You know, we could say, should we give 4 litres or 6 litres of fluid per day? Should we supplement with potassium or not? Should we add– there are different kinds of intravenous fluids. Should be use normal saline, or should we use, say, Ringer’s lactate? And these are questions that can and should be evaluated in randomised controlled trials. After all, most viral infections, we get over on our own. Ebola’s not like most viral infections. It’s very severe.

Skip to 4 minutes and 53 seconds But if we can support the patient through, give them more time, you know, many patients recover on their own. So for example, if we’re not monitoring electrolytes, then what we’ve got to do is decide what’s the best basic recipe that we give to everybody. Now how do we know what the best basic recipe is? Well, I met a doctor coming back from Sierra Leone, recently. And we asked her, in Sierra Leone– she was writing fluid protocols for patients with Ebola. I said, how did you know what to write? And she said, well, I didn’t. A lot of it was guesswork. Well, what you do is you do two lots of guesswork. You have two protocols.

Skip to 5 minutes and 36 seconds You say, well, it could be this, or it could be this. And then you evaluate them against each other. Then you find out which one’s the best. And then you might say, but supposing we gave a little bit more? Well, you evaluate those two against each other. And iterative processes of pragmatic clinical trials improve the care of patients.

Research priorities

The only time that treatments and vaccines for Ebola can be tested in people is during an outbreak. The priority areas for this research are, in order of importance, establishing the best ways of providing hydration, assessing the use of convalescent plasma from survivors, finding effective anti-viral drugs, and vaccines.

In addition, research is needed on simpler, ideally point-of-care diagnostic tests, and social and behavioural research is needed around improving community trust.

Even without new drugs, it may be possible to reduce case fatality rates by improving supportive care. The need for this, and the practical obstacles, have been discussed in previous steps. Of the first 19 Ebola patients treated in Europe or the US, 4 died, giving a case fatality rate of 21%, much lower than the case fatality rates in West Africa. Many received experimental treatments, but they also received much more intensive and closely monitored rehydration therapy than has been possible in the Ebola Treatment Units. It is unclear how much the case fatality rate could be reduced by supportive treatment alone, but there have been repeated calls for research on this topic. In the video, Professor Ian Roberts argues for formal trials of different protocols of supportive treatments.

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Ebola in Context: Understanding Transmission, Response and Control

London School of Hygiene & Tropical Medicine