A tarp at a U.S. treatment unit for Liberian healthcare workers infected with Ebola in Monrovia, Liberia, during the site's decommissioning on April 30, 2015. Image Credit: Zoom Dosso/AFP/Getty Images

The 2013–2016 West African Ebola outbreak claimed at least 11,325 lives and caused a recorded 28,652 infections before finally burning out.
 
What if we missed a quarter of those actually infected?

A new paper, published in the journal PLOS Neglected Tropical Diseases, lends further support to the idea that a significant number of individuals can become infected with Ebola but not show symptoms. The research team investigated Ebola virus survivors and their contacts, who often were quarantined together, between October 2015 and January 2016 in a village in Sierra Leone. Thirty-four cases of Ebola virus disease had been diagnosed before the research study began. Using antibody tests to identify potential infections lacking symptoms, an additional 14 potential infections were identified. Twelve of those—a full 25 percent of the 48 total infections—reported no symptoms at all. Two additional cases identified by antibody testing reported a fever but no other symptoms of disease.

We have recognized since 1989 that there is a species of Ebolavirus called Reston virus that can infect humans but appears to cause no symptoms. But even with the pathogenic species of Ebolavirus, it is becoming increasingly clear that the virus causes a spectrum of infections in humans, ranging from symptomless infections to death. This is not particularly surprising; though popular culture examples featuring Ebola–like pathogens, such as 12 Monkeys or Outbreak, suggest that almost 100 percent of those infected with their virus of choice will die, in reality, the severity of infection is a combination of many factors. If the host is generally healthy, usually they will be more likely to survive (though healthy hosts can, occasionally, make an infection more dangerous, as happened with the 1918 influenza pandemic). A host that has previously suffered a similar infection may have some immunity, and the disease will typically be less severe. Other chronic conditions, such as diabetes, may result in a more serious infection.

Prior work has come to similar conclusions with harmful species of Ebolavirus as well. Sixteen years ago, Ebola virus antibodies and low levels of viral RNA were detected in individuals exposed to body fluids from infected patients during outbreaks of the virus in Gabon. These individuals never themselves showed any symptoms of Ebola virus disease. During the first known Ebolavirus outbreak in 1976, reports suggested that 19 percent of the contacts of patients had also been infected, but with a very mild or asymptomatic infection.

However, studying Ebolavirus antibodies in the context of an epidemic is relatively easy—you have confirmed cases who have documented infections, so the timeline of exposure can be detailed even for those who were exposed and infected but did not develop symptoms. What has been more difficult to prove scientifically is that Ebolavirus antibodies in areas where there were not active outbreaks were a real phenomenon rather than a laboratory artifact.

A 1982 paper found evidence of Ebolavirus antibodies in Liberia—32 years before a full-blown outbreak surfaced there. A similar study of samples collected from 2006 to 2008 in Sierra Leone also suggested that 8.6 percent of those tested had antibodies to Ebolavirus. More than 5 percent of those tested in the Central African Republic, another country that has never seen an active Ebolavirus outbreak, also had antibodies. We can’t be sure these antibodies were due to asymptomatic cases—they may have been survivors of Ebolavirus infections that were misdiagnosed as Lassa fever, malaria, or other more common infectious diseases—but if this research had been accepted and circulated decades prior, perhaps additional surveillance could have identified the 2013–2016 outbreak earlier and responded appropriately before it spiraled out of control.

These studies suggest that the true burden of Ebolavirus infections is significantly underestimated. During an epidemic, many more people may be infected than is currently understood. An understanding of how commonly asymptomatic infections occur is critical, as an unrecognized population of immune individuals could alter the dynamics of the infection and modify mathematical models used to predict spread.

Indeed, when Reston virus was discovered, it was hoped that a virus that caused these asymptomatic infections could be used to create an effective and safe vaccine. That hasn’t worked in experimental work, but there is still hope that if we could understand why some individuals do not become ill from the pathogenic Ebola viruses, we could use that information to inform additional studies of vaccines or treatments.  

The recognition of asymptomatic infections also raises questions regarding long-term complications after Ebolavirus disease. Many survivors report chronic health problems years after the acute infection; could this happen in asymptomatic survivors too? We don’t know now because they’ve not been followed in these long-term studies.

Perhaps most importantly, can asymptomatic survivors transmit the virus to others? This seems unlikely given that when measured, the asymptomatic cases had much lower levels of virus than patients with symptoms. Furthermore, decades of epidemiological studies have repeatedly shown that the highest risk of acquiring Ebolavirus comes from contact with infected body fluids from a sick patient.

Finally, the increasing evidence for asymptomatic Ebolavirus infections suggests the need to test for the virus even in locations where no documented outbreaks have occurred. We were decades behind the ball looking for Ebolavirus in West Africa, and the result was the largest Ebolavirus outbreak on record by several orders of magnitude. Rather than playing catch-up, these findings should encourage us to get ahead of the curve and track more cases of Ebolavirus infection irrespective of symptom severity, before we end up with a repeat of the West African outbreak.