The Ebola outbreak has loosened its grip on West Africa, as shown by Liberia being declared free of the disease a couple of days ago. This is cause for relief, but not complacency, explain Simon Lovell and David Robertson.
The 2014 outbreak of the Ebola virus arose from a single case in Guinea, probably transmitted to humans from a fruit bat. It went on to infect about 25,000 people, killing more than 10,000 to date. Previous outbreaks typically resulted in dozens to hundreds of infections, so the most recent outbreak is by far the largest recorded. It is also the first where modern molecular biology techniques allowed real time surveillance of the genetic changes occurring to the virus.
We analysed the viral sequence data published in Science magazine from samples collected in Kenema, Sierra Leone. There were substantial numbers of mutations within the sequences: this is not surprising. The mutation rate for viruses of this kind is typically very high. The key question was whether these mutations produced a deadlier virus and so were responsible for the unprecedented scale of the 2014 outbreak.
The biggest concern would be if the virus was better adapted to humans and became endemic in the human population. The longer the virus remains in the human population the more likely this is to occur. Either an increase or decrease in the fatality rate would be worrying. A decrease, counter-intuitively, would be expected to be associated with an increase in the rate of spread of the infection.
Usually a person infected with Ebola progresses to illness rapidly and is immobilised by their symptoms, which means they can be isolated and recent contacts traced. A change to milder symptoms associated with a less virulent virus could make the identification of infections much harder, resulting in more transmissions per infection. A milder virus, although less deadly on an individual basis, could spread more widely – resulting in many more deaths overall.
In terms of the evolution of the Ebola virus, the important factor is not the number of mutations, but instead the effect they have. The proteins that comprise the virus determine its capacity to cause disease. But mutations do not necessarily change any of the viral protein molecules. Of the 341 mutations specific to the 2014 outbreak, only 35 changed the viral proteins’ amino acid sequences.
When the data from previous outbreaks were examined, 177 mutations that potentially alter proteins could be identified. When we analysed these changes we found, surprisingly, that none appeared to make the virus either more or less fit. Of the large number of sites within the proteins that are important for infectivity or for entry into the host cell, none had changed.
These observations held for all sequences and for all outbreaks. There is therefore no evidence that the virus has become more or less fit over a period of nearly 40 years. Data published by the World Health Organisation also shows that neither the infection rate nor the fatality rate is different in the 2014 outbreak to previous ones.
We must look for different explanations for the large scale of the most recent outbreak. The most likely reasons are human-centred epidemiological differences. Some are specific to the current outbreak. The origin of the current epidemic in West, rather than Central, Africa led to a delay in initial identification. The early infections were not recognised as Ebola quickly enough and when they were identified the response was initially not sufficiently aggressive.
Controlling the spread of the disease was exacerbated by recent civil wars in Liberia and Sierra Leone, which detrimentally affected medical facilities. As a result, there was a lack of testing for the Ebola virus and a three month gap between the initial transmission and the start of effective containment.
With available molecular and epidemiological information we can now build up a prediction of what is likely to happen in the future. The periodic transmissions of the virus – presumably from bats to humans – will continue to occur and may become more frequent. The severity of the disease is likely to remain the same and, unless we can alter the patterns of transmission, future outbreaks could be equally severe.
The WHO has made a series of recommendations to reduce transmission. Involving local communities is important; where this has happened in Sierra Leone the epidemic has been controlled much more effectively than by NGOs acting alone. Treatment, usually in the form of hydration therapy and control of fever, reduces the fatality rate from 70% to 50%. Tracking infected patients and their contacts has controlled the spread of the disease.
Two traditions in Sierra Leone and Liberia contributed to the early spread of infection. One is the burial of individuals in their place of birth, which led to bodies being transported between towns. The second is the ceremonial washing of bodies, which brought mourners into close contact with the dead. Infection control is now central to the process of burying Ebola victims.
Despite the probability and potential severity of future outbreaks of Ebola, the good news is that we now know the measures required for future containment, they are not likely to change over time and they are inexpensive. Early identification of the virus is essential for effective containment, so monitoring for further outbreak is of prime importance.
Ongoing sequencing of the virus is also important and the authors of the first 2014 study are to be praised for immediately releasing their data to the wider scientific community. Our results suggest that should the vaccines currently under trial prove effective, they are likely to remain so over time. However, these evolutionary studies are inevitably retrospective, so we must be vigilant if we are to identify future Ebola virus evolution that has consequences for infection dynamics.