Some see a mild illness, or no obvious illness at all, after infection by Ebola virus as almost heretical. But new evidence adds to that which already exists – it really does happen.

Hints that Ebola virus cause mild or unnoticeable illness, or that it circulates unnoticed, are found in the scientific literature.[6,7,8]

What do we know about mild infection and Ebola virus?

A big new study has emerged, looking for asymptomatic or “paucisymptomatic” Ebola virus-infected people. To be clearer, the authors are talking those who may have been infected but showed no symptoms or just mild illness. They used the detection of antibodies specific to a Zaire ebolavirus as a marker that they had been infected.

Big new study

Scientists from France and Guinea enrolled people who had contact with a confirmed case of Ebola virus disease (EVD) in Guinea. None of 1,390 contacts followed, were vaccinated against EVD and none had officially developed EVD during the period between 12th May 2016 and 8th September 2017. Based on their recollection, none had developed symptoms that suggested to them that they had a viral haemorrhagic fever virus infection.

Antibodies in the contacts

The laboratory tests detected antibodies made against three different pieces (antigens) of the Zaire ebolavirus (glycoprotein or nucleoprotein or 40-kDa viral protein), in response to virus infection.[3] The tests were well evaluated beforehand so the results produced are reliable, an issue with earlier studies of this sort. The scientists considered samples that reacted with at least two of the three antigens as positive for past infection.

In a very handy approach, the scientists dried blood onto special filter paper. This avoided the need to send away whole blood which doesn’t store for long without separation and freezing. These dried blood spots (DBS) store well and can be shipped easily. Once reconstituted and heat-inactivated, DBS can be used to detect antibodies.[3]

More of those with some symptom(s) of illness (18 of 216 or 8%) developed antibodies to Ebola virus. Only 39 of 1,174 (3%) among those who reported no symptoms, developed antibodies.

There were signs of previous infection, but no severe disease

Most (1,174 or 84%) contacts did not report any symptoms of illness. About a sixth (216 or 16%) did notice a mild illness of some sort; most often a headache (81% of those with a symptom), fatigue (74%) and fever (73%).

30 of the 216 (14%) had a fever plus three other symptoms; enough for them to have been classified as suspected EVD cases according to the World Health Organization case definition. But it seems they were not classified as such so they weren’t tested at the time. Interestingly, this study already defines these people as contacts. A sudden fever should have resulted in most being reported to a surveillance team.

It mattered what sort of exposure people had

More of those with symptoms of illness had contact with a fatal EVD case (45 of 99 or 45%) than did those with no symptoms 67/280 or 24%). Those with contact with blood or vomit from a known EVD case, or who took part in a burial ritual were also more likely to have become symptomatic.

Among those who were asymptomatic but had been infected (antibody positive), there was a greater likelihood that they had taken part in a burial ritual or had contact with infectious fluids than had asymptomatic contacts without development of antibodies.

Why do some get exposed and feel nothing while others die from the experience?

Another interesting question to come out of this study is whether there is any illness-protective role for virus exposure outside of contact with a known case of EVD.

Did some number of these contacts already have antibodies to a Zaire ebolavirus strain? What about to another ebolavirus that we already know about, or to a strain or virus we’ve yet to find? Could those infections have provided some protection (cross-protection) against illness during this new Ebola virus contact? And if so, why didn’t they notice those infections at the time?

We do know that Zaire ebolavirus was in Guinea before the multi-country outbreak ravaged the region 2013-2016.[6] And there are new viruses being found all the time so this aspect of the story probably has a few more chapters.[9]

Where does that leave us?

We now know that contacts of an EVD case sometimes become infected even if they don’t notice anything, or only have a short illness.

Those in contact with infectious materials (fluids or a body) are more likely to have symptoms. Even in the absence of symptoms though, evidence that infection occurs is solid. This will surprise some. But not others.

We should keep this in mind when looking at previous studies that seek Ebola virus outside an outbreak or among those without severe illness. It may be that these latest findings mean earlier findings were correct all along.

The latest findings use an excellent and target-specific lab tool. They reinforce the need for better understanding of what is happening in less deadly Ebola virus infections. Some questions that need answering include:

• how often is mild illness occurring? This will impact on the fatality rate normally ascribed to Ebola virus.
• given these findings, how sure are we that Reston virus is as tame as we have labelled it to be? What if we simply haven’t experienced enough human outbreaks to see its dark side yet?
• can mildly ill, Ebola virus-infected people transmit and infect others? Some suspected cases were not flagged for testing.
• does a mild Ebola virus infection generate only low levels of virus. Presumably, it does. So does it still spread to and persist in tissues (reproductive tract, eye) as it does in more serious illnesses?

This study is a nice reminder that we need to keep our minds open to new and sometimes ‘out there’ concepts. We can talk about ideas on the edge of what existing data support as much as we like. These thoughts are resolved into hypotheses by data from science being funded and done. And that leads to new hypotheses and more data. And so on.

References.

1. Yes, there were signs that Ebola was in west Africa, perhaps as far back as 1973
   https://virologydownunder.com/yes-there-were-signs-that-ebola-was-in-west-africa-perhaps-as-far-back-as-1973/
2. Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study
   https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(18)30649-2/fulltext
3. Development of a Sensitive and Specific Serological Assay Based on Luminex Technology for Detection of Antibodies to Zaire Ebola Virus
   https://jcm.asm.org/content/55/1/165.long
4. The genesis of the Ebola virus outbreak in west Africa.
   https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30055-6/fulltext
5. Case definition recommendations for Ebola or Marburg Virus Diseases As of 09 August 2014 https://www.who.int/csr/resources/publications/ebola/ebola-case-definition-contact-en.pdf
6. Serological Evidence of Ebola Virus Infection in Rural Guinea before the 2014 West African Epidemic Outbreak
   https://www.ncbi.nlm.nih.gov/pubmed/29869602
7. Hemorrhagic fever virus infections in an isolated rainforest area of central Liberia. Limitations of the indirect immunofluorescence slide test for antibody screening in Africa.
   http://www.ncbi.nlm.nih.gov/pubmed/3092415
8. Serological Evidence of Ebola Virus Infection in Rural Guinea before the 2014 West African Epidemic Outbreak
   https://www.ncbi.nlm.nih.gov/pubmed/29869602
9. Scientists Discover New Ebolavirus in Bats in Sierra Leone
   https://www.mailman.columbia.edu/public-health-now/news/scientists-discover-new-ebolavirus-bats-sierra-leone