Four questions about the Ebola virus

In its 30 October issue, the journal Nature published a news feature about some of the scientific questions surrounding the Ebola virus and more generally the family of viruses it belongs to. If you are interested in knowing more about Ebola, I recommend reading the whole article (free access). Alternatively, here are the main points:

1. What is the Ebola virus?

The virus responsible for the current outbreak in West Africa is Zaire ebolavirus and is the one that is generally called “the Ebola virus”. It is one of five known species of ebolaviruses, which themselves belong to a family of viruses called filoviruses. This family also includes the Marburg virus, discovered in the 1960s, and the Lloviu virus, identified in 2011 in Spain.

Most known filoviruses cause a life-threatening hemorrhagic fever in humans, but not all of them. For example, one of the five known species of ebolavirus, Reston ebolavirus, seems to be relatively harmless to humans, as some people have been found harboring antibodies to the virus (which shows they had been infected) but had no record of becoming ill.

Researchers think it likely that more filoviruses are yet to be discovered, especially as humans spread more and more to previously unpopulated or low-populated areas and increasingly encroach on land occupied by other animals that are hosts to these viruses, thereby giving more opportunities to the viruses to jump from their natural reservoir into the human population.

2. What is the Ebola virus natural reservoir?

The fact that most filoviruses are highly lethal to humans and other apes indicates that primates are not a natural host for them. Indeed, a virus cannot reproduce on its own and needs to use the cellular machinery of the organism it infects to multiply and keep on propagating – and therefore to survive as a species. So, if a virus kills too many of the organisms it infects too quickly, it destroys its resource base in doing so and may therefore precipitate its own extinction.

Researchers have identified fruit bats as a natural host for the Marburg virus: although the bats harbored the virus, they did not show symptoms of disease. Scientists also suspect that bats are natural hosts for the ebolaviruses, but so far no ebolavirus has been isolated from a wild bat. Tracing the source of the virus is however extremely difficult, not only because of all the precautions that have to be taken in searching for a virus that’s so lethal to humans, but also because ebolavirus outbreaks are relatively rare and sporadic.

Filoviruses do not just infect bats and primates though. The Reston ebolavirus has been found in farm pigs in the Philippines in 2008 as well as in China in 2012.

3. Why is the current outbreak spreading so much?

So far, there is no data to suggest that the strain of Zaire ebolavirus causing the current outbreak is more transmissible than the strains that have caused previous outbreaks. Rather, scientists think that its wide spread is likely due to the fact that it emerged in a region of Africa that was unfamiliar with the virus and not prepared to respond to it quickly and adequately. Once the virus had reached urban areas, local healthcare infrastructures were soon overwhelmed and unable to contain the epidemic.

Although the NGO Médecins Sans Frontières called for international aid and intervention early in the epidemic, warning developed countries of what was to come if efforts were not made to contain the outbreak quickly, a response has been late to come (see some previous stories here and here). Even as efforts are being ramped up, experts worry that it may be not only too slow, but perhaps even too late: it might be that the outbreak has reached or will soon reach a stage where traditional public containment measures can no longer bring the epidemic under control. Some scientists suggest that the outbreak might reach its peak some time in 2015 and then begin to recede, as many people will either have died from the infection or survived to become immune to the virus, so that the reservoir in which the virus can keep on spreading diminishes. Others worry that the virus might become endemic in parts of Africa, going on infecting people for several more years.

4. Why is the Ebola virus so lethal?

The Zaire ebolavirus strain responsible for the current outbreak is one of the most lethal viruses known (rabies and smallpox are two other examples). So far, it is estimated that about 60-70% of people infected have died, and previous outbreaks have had mortality rates of up to 90%. However, the level of care available likely plays a role in the survival rates. Although patients treated in developed countries have been few, it seems that they are more likely to survive than people treated in Africa.

The Ebola virus infects innate immune cells that are normally the first line of defense against viruses. In doing so, the virus not only disables part of the immune response, but also triggers what is called a “cytokine storm”: a massive release of chemicals that are usually needed to mount an immune response but become destructive rather than beneficial when produced in huge and uncontrolled quantities. The virus also attacks other tissues besides the immune system, causing the liver, kidneys, lungs and other organs to fail and blood vessels to leak fluid into surrounding tissues.

The treatment currently available for patients infected with filoviruses is essentially focused on maintaining as much as possible a correct fluid and chemical balance in the body, hopefully preventing organs to shut down and giving the immune system time to fight off the infection. In African countries, this consists mostly in giving patients oral rehydration therapy. In developed countries where intravenous fluid replacement, close monitoring, and intensive care are available, the chance of surviving is better.

Therapies (such as ZMapp, a cocktail of antibodies initially produced in mice vaccinated with proteins from the Ebola virus) and vaccines (by pharmaceutical companies GSK and NewLink Genetics, see stories here and here) that specifically target the Ebola virus are being developed (and are now put on fast-track to be used in the current epidemic). However there is not enough data available yet to say anything on their safety and efficacy in humans. Phase II and phase III vaccine trials are set to start in affected African countries in December/January.

Useful links:
Center for Disease Control and Prevention
World Health Organization
Médecins Sans Frontières

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