Ebola and "the perfect storm"

The new figures from the World Health Organization's (WHO) Ebola Response Team are sobering. If cases in the three worst affected countries continue to rise at the present rate, by the beginning of November more than 20,000 people in West Africa will have been infected. And despite earlier suggestions that this might be a less deadly strain of the Ebola virus, allowing half its victims to recover, the new figures show a much higher fatality rate, in the region of 70 percent.

The authors attribute this to better data, and the fact that this time they have only included cases they are absolutely sure of - cases they know had Ebola and where they are certain of the final outcome, whether the patient lived or whether they died. And unlike the previous estimates, these figures are consistent across all the three countries with major outbreaks - Guinea, Liberia and Sierra Leone. For patients who had been treated in hospital, the mortality rates were a little lower, ranging from 67 percent in Liberia down to just over 61 percent in Sierra Leone, so hospital treatment made some difference, but perhaps not as much as might have been hoped.

Where there was a marked difference between the three countries was in the rates of transmission. In the early days of the epidemic the disease was spreading fastest in Sierra Leone, with each case infecting 2.02 other people. This has now been reduced considerably, to 1.38. Liberia has managed to reduce its rate a little, while the rate of transmission in Guinea has actually increased. This means the numbers infected are doubling in Guinea every 16 days, compared with every 24 days in Liberia and every 30 days in Sierra Leone.

The two men who originally identified the Ebola virus, in 1976 in what is now DR Congo (DRC), Peter Piot and David Heymann, were among a group of experts who held a briefing on the current outbreak at the Wellcome Trust in London this week.

Piot, who is now director of the London School of Hygiene and Tropical Medicine, said this was on a totally different scale from previous outbreaks. "The reason for that," he said, "is what I call a perfect storm, of decades of civil war, corrupt dictatorship as a background, leading to a loss of trust in the authorities, dysfunctional health systems, strong traditional beliefs about disease causation, and also what I think frankly was the most important factor, that the response was so slow. It took three months between the first case and the cause being identified as Ebola. And it took another five months and 1,000 deaths before WHO declared this a public health emergency."

His colleague, David Heymann, now professor of infectious disease epidemiology at the London School, added that 25 previous outbreaks had been stopped while they were still in rural areas.

"There's a better organization in communities, there's a common language, there are village elders, village chiefs who help keep things in order, and it's much easier and more effective to stop an outbreak in rural areas. Kikwit, the major outbreak in DRC in 1995, was only five hours journey by road from the capital, yet by stopping the outbreak in a rural area it doesn't spread into the complex issues involved in the city, where there's a breakdown in traditional governance and where there are all kinds of challenges due to different languages and different cultures."

Speakers at the briefing all stressed the need for classic public health measures - contact tracing, isolation, health education - to check the spread. Heymann said it was up to African governments to find innovative ways to trace contacts. They were the ones who had to reach their own people in the way they knew best. Referring to the recent three-day lock-down in Sierra Leone, he told IRIN: "They were able to reach more than 70 percent of households with messages about how the community can protect itself. In addition, it seemed to pass without any violence. I think it went against much of the international advice that they were receiving but maybe in the end it was what the government felt it had to do, and maybe that's the innovation which will make a difference."

Chris Whitty, the chief medical adviser to the UK Department for International Development, said up till now contact tracing had relied on actively going out to look for cases. "What we need to do now is move over to some variant of passive case-finding where we incentivize people who have symptoms to come forward much earlier. But clearly to do that they are going to have to have a genuine possibility that they are going to be better treated than if they stayed at home. They've got to have other incentives too, but we have to take care not to over-incentivize it so we don't get a huge crowd at the centres which will actually increase transmission. You need to get everyone with symptoms to come forward, test them quickly and send home those who don't have Ebola. That sounds very easy, but getting the details right is very difficult."

Healthcare workers still getting infected

Then, of course, you have the challenge of treating them safely. Heathcare workers - even fully trained international staff in the best facilities - are still getting infected. Jeremy Farrar, director of the Wellcome Trust, said even the best systems weren't perfect. "It's bloody hot. It's very difficult to work in those things for hours. You're scared. You've probably got a family at home. You're as frightened as everybody else. It's just very difficult to keep [on top of] all of the things that you have to do. And what you see in the newspapers and the television, you have to remember that those are the more, as it were, `sanitized' clinics. Go into other rural clinics in West Africa, and there may not be PPE [personal protective equipment], there may not even be gloves for everybody."

"The critical period is when you take it off," added Piot, "with the sweat and so on. But most people have been infected outside these care facilities which are handling Ebola patients. Many have been infected while delivering a baby or what have you, and in the regular health services there are no gloves. And MSF rules are very draconian; you can only serve for 4-6 weeks, and at the slightest sign of distress or fatigue they send you back home because a micro-mistake can be fatal. But you can't apply that on the scale of a whole country."

A new vaccine “will not affect things in the next few months; let us be very clear about that. But if this epidemic continues into 2015, which it will, and there will be inevitable future epidemics because there is an animal reservoir, then this must be the last outbreak of Ebola where we do not have available vaccines and therapeutics to treat and prevent the infection.”

So the challenge is to make health care staff feel properly supported and get back those who have left their posts. The UK has asked for volunteers from its own health service to go to Sierra Leone. In its centre near Freetown, to be built by the British army and operated by Save the Children, 12 of the beds will be reserved for infected healthcare workers. Sally Davies, UK's chief medical officer, says: "While West Africa needs some experts, it probably doesn't need many more doctors and nurses. What it needs is to bring back into play their own health care workforce. once they see that they are safe and that they are going to be paid."

Ebola less infective than measles

With each patient infecting just one or two others, the good news is that Ebola is less infective than measles, for instance, and the WHO report makes the point that transmission only has to be a little more than halved to achieve control and eventually eliminate the virus from the human population. That is something which could be achieved by an immunization coverage of anything over 50 percent, if a vaccine were to become available.

Work is going on to develop a vaccine. There is a candidate vaccine, but small scale safety trials in humans only started in the past week in the US, and at Oxford University here in the UK. Even if it passes all trials and is fast-tracked into production this will take time. Farrar told the London briefing: "This will not affect things in the next few months; let us be very clear about that. But if this epidemic continues into 2015, which it will, and there will be inevitable future epidemics because there is an animal reservoir, then this must be the last outbreak of Ebola where we do not have available vaccines and therapeutics to treat and prevent the infection."

The current outbreak does at least provide a rare opportunity to try out possible new treatments, and work has started in West Africa to identify suitable sites for clinical trials and to collect the kind of basic data about the normal progression of the disease to make evaluation possible. Farrar says they also have to decide what they are going to test.

"As you can imagine, the WHO and all of us have been inundated with suggestions, from salt baths to chloroquine, and the usual suspects, steroids and statins, come up. And what is critical is some sort of sensible look at what is being put forward, so that the best interventions can be tried early, the ones that work can be upscaled as quickly as possible and - very, very, importantly - those that are demonstrated to not work, or are harmful, are stopped."

Plasma treatment

A WHO appointed committee is now working on this. One of the most promising lines of research may involve, not a drug as such, but blood from those who have recovered from Ebola and so should have developed antibodies to the virus. The British nurse who recovered after being flown back to London for treatment is one of those who has volunteered his blood to make plasma which might help others, and so something of a valuable commodity. Davies admitted: "We are all trying to capture a recovered patient to see if it works."

But Davies is a haematologist herself by training, and warns: "Doing Plasmapheresis [extracting blood plasma] on people is a complex operation. They have to be healthy, it involves quite a lot of kit, specialist nurses, aseptic technique, and to set it up in-country would be a major issue." Other participants warned that this kind of plasma treatment works for some diseases, but not others, and it sometimes makes things worse.

This brought a quick response from Heymann and Piot, who had used this very technique in Zaire in 1976. "Plasmapheresis is possible, in a rural setting," said Heymann. "I stayed on for two and a half months after the outbreak was over, collecting blood from 13 survivors on a weekly basis, taking the plasma from the patients and giving the red blood cells back... And that serum was used for the first time in the UK when one of the laboratory assistants working on Ebola got infected. In Kikwit [in southwestern DRC], for example, they used whole blood. This has been done ad hoc; they were not clinical trials. What it hasn't shown is that it is dangerous. Patients in Kikwit received whole blood from survivors. They didn't die, the laboratory technician didn't die. What's wrong is that the clinical trials haven't been done and they need to be done."

Virus could mutate

One final set of statistics from the new WHO report sheds light on another issue - the nature of this particular virus. In all respects - who it infects, the incubation times, the symptoms it produces, the mortality rate - the virus in this outbreak seems identical to previous "Zaire" strains of the disease.

Of course, mutation is still possible. Virologist Ben Neuman, from the University of Reading, says: "There are signs that the virus is adapting. Basically the longer it stays in humans the weirder it gets. There's no evidence, though, that this evolution is a malevolent force, that it's making the virus necessarily worse. What we've seen in past outbreaks, if we go back to something like the 2009 Swine Flu, is that the virus actually mellowed out with time as it adapted to living in people rather than its original host, and that may be what happens here."

What all the experts agreed on was that speculation about the virus changing its means of transmission and becoming airborne was irresponsible and wildly unlikely. Piot drew an analogy with HIV. "HIV in chimps is sexually transmitted. It's still not airborne, despite the fact that it's been passed though tens of millions of people. It would be such a jump of the architecture of the virus. The real question here for me is, will this virus become endemic or not? Meaning that it continues being transmitted at low levels, whereas in all previous outbreaks it just disappeared from its human host, retreated, as it were, back to its animal host. And that we just don't know."

eb/cb