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Symptomless Ebola – questions need to be answered before the next outbreak

Scientists know that Ebola can cause anything from severe hemorrhagic fever to no symptoms at all (asymptomatic infections). What wasn’t known, until now, is the number of people who experienced asymptomatic infections during the 2013-2016 outbreak of Ebola in West Africa.

This is not the first report of potential asymptomatic cases of Ebola. About one in five people who came into contact with individuals infected during the 1976 outbreak in Sudan had detectable antibodies against Ebola but had not been ill. A 2005-2008 survey of the public in Gabon, which had its first outbreak of Ebola in 1994, suggested 15% had been infected with Ebola but did not show symptoms. Interestingly, 7% of healthy Germans have antibodies against Ebola or closely related viruses.

Not uncommon

Ebola is not alone in this respect. There are several other viruses that cause severe disease but have also been suggested to cause asymptomatic infections in some people. Rabies virus kills well over 99% of infected people who have not previously received a rabies vaccine. However, antibodies to the virus have been detected in indigenous groups living in Amazonian villages who had not been vaccinated. It is also estimated that 88% of Crimean Congo hemorrhagic fever virus cases in Turkey are symptomless.

These studies have principally been based on detection of antibodies to these viruses. Antibodies are stimulated against the virus in the first few days following infection, but they can linger for months following clearance of the virus. Because of this, they can only really be used to document historical infections. So it’s not possible to say when these people were infected. Also, these studies rely on self-reporting of symptoms to determine severity of disease. Or, as in the asymptomatic cases, a lack of any. As a result, there is a significant risk of recall bias in these types of studies.

If the number of asymptomatic Ebola cases being reported are to be believed then this could have major consequences. Are these people infectious? Does the virus persist for weeks after clearance from the blood as has been reported for a fraction of symptomatic cases? If the answer to these questions is yes, then it should be taken into account when diagnosing and treating the disease.

Although these asymptomatic individuals are unlikely to be infectious – current dogma suggests that people are only infectious when symptomatic – it cannot be ruled out. Conversely, there are potential benefits. If large proportions of the population in an outbreak area are naturally generating an immune response against the virus without becoming ill, then this could limit the ability of the virus to spread in that population.

Elite controller

It also throws up questions about why there is such a wide spectrum of disease severity in people infected with the Ebola virus. Thanks to studies undertaken during the outbreak in West Africa, we are now aware of factors that can predispose someone to severe disease.

The virus has also been shown to have evolved during the outbreak, enabling it to more readily infect human cells. However, the existence of asymptomatic cases gives rise to the possibility that there may also be “elite controllers” – people who are able to naturally block infection by Ebola virus. This is something that has been seen with other viruses, including HIV.

Some of these elite controllers are thought to arise from a constant evolutionary battle between humans and pathogens, with each genetically adapting to get the upper hand – the so-called Red Queen hypothesis. But we don’t know if these people are genetically primed to have a much faster and more potent response to infection with Ebola. It is also possible that they were exposed to a smaller dose of the virus, not enough to cause infection but enough to stimulate an immune response.

The Red Queen has to keep running just to stay where she is. Wikimedia Commons

Given the vast amount of genetic information that was gathered during the West Africa outbreak, it would be of great interest to know what genetic version of the virus was circulating near the village at the time this study was conducted. Had the virus mutated to become weaker? There are reports that not all species of Ebola cause disease in humans.

So, while this new report of asymptomatic cases of Ebola virus infection is not unique, it does raise important questions that need to be answered. Over the last couple of years, governments and global public health agencies have increased resources to tackle these questions. Hopefully, we will be better equipped and prepared for the next outbreak.

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