The Ebola virus can cause latent infections in survivors that can trigger new outbreaks.
National Institute of Allergy and Infectious Diseases / National Institutes of Health / Flickr (CC BY-NC 2.0)
By Kai Kupferschmidt
An Ebola outbreak in Guinea that has so far left at least 18 people sick and killed nine has brought back harsh memories of the devastating epidemic that hit the West African country between 2013 and 2016, along with neighboring Liberia and Sierra Leone, leaving more than 11,000 people dead.
But it may not be just the trauma that has persisted. The virus that caused the new outbreak differs little from the strain observed 5 to 6 years ago, showed genomic analyzes done by three independent research groups, suggesting that the virus was dormant in a survivor of the epidemic all this time. “This is very shocking,” says virologist Angela Rasmussen of Georgetown University. “Ebolaviruses are not herpesviruses” – which are known to cause long-term infections – “and generally RNA viruses don’t stop there without replicating themselves.”
Scientists knew that the Ebola virus can persist for a long time in the human body; a resurgence in Guinea in 2016 originated from a survivor who spread the virus in his semen more than 500 days after his infection and infected a partner through sexual intercourse. “But having a new outbreak of latent infection 5 years after the end of an epidemic is scary and new,” says Eric Delaporte, an infectious doctor at Montpellier University who has studied Ebola survivors and is a member of one of the three teams. Outbreaks triggered by Ebola survivors are still very rare, says Delaporte, but the discovery raises complicated questions about how to prevent them without further stigmatizing Ebola survivors.
The current outbreak in Guinea was detected after a 51-year-old nurse, originally diagnosed with typhoid and malaria, died in late January. Several people who attended the funeral fell ill, including members of her family and a traditional healer who treated her, and four of them died. The researchers suspected that Ebola may have caused all the deaths and, in early February, discovered the virus in the blood of the nurse’s husband. An Ebola outbreak was officially declared on February 13, with the nurse being the likely index case.
The Guinea Infectious Diseases Research and Training Center (CERFIG) and the country’s National Hemorrhagic Fever Laboratory have each read viral genomes of four patients; researchers at the Pasteur Institute in Dakar, Senegal, sequenced two genomes. In three posts today on virological.org, the groups agree that the outbreak was caused by the Makona strain of a species called Zaire Ebolavirus, as well as the past epidemic. A phylogenetic tree shows that the new virus falls among virus samples from the 2013–16 epidemic.
Until recently, scientists assumed that Ebola epidemics began when a virus leaps from a species of animal host to humans. Theoretically, this could have happened in Guinea, says virologist Stephan Günther, of the Bernhard Nocht Institute for Tropical Medicine, who worked with one of the three teams. But, given the similarity between the epidemic viruses and the new ones, “it must be incredibly unlikely”.
External scientists agree, but say that Ebola has not been proven to remain dormant in a person for 5 years. “From the tree, you would conclude that it is a virus that has persisted in some way in the area and, for sure, probably a survivor,” says Dan Bausch, a veteran of several Ebola outbreaks who leads the UK Department of Public Health for quick support. But scenarios such as a small, unrecognized chain of human-to-human transmission are difficult to rule out, Bausch adds: “For example, a 2014 survivor infects his wife a few years after recovery, which infects another man, who survives and carries the virus. for a few years, then infecting another woman, who is seen by a dying nurse ”- the index case in the new outbreak.
The nurse was not known to be a survivor, but she could have had contact with a survivor in particular or through her work, or she herself may have been infected years ago with few symptoms. “Finding out what exactly happened is one of the biggest questions right now,” says Bausch.
Another Ebola outbreak underway in North Kivu, in the Democratic Republic of Congo, was also started by the transmission of someone infected during a previous outbreak, notes Delaporte. (The survivor had tested negative for Ebola twice after his illness in 2020.) Taken together, this suggests that humans are now the source of a new Ebola outbreak as much as wildlife, he says. “This is clearly a new paradigm for how these outbreaks begin.” Outbreaks by survivors may become even more likely, now that increased mobility and other factors have made each Ebola outbreak bigger, resulting in more survivors, says Fabian Leendertz, a wildlife veterinarian who was involved in the sequencing .
This is clearly a new paradigm for how these outbreaks begin.
The cases raise important new research questions, says Bausch: “How do we need to change our response to escape the outbreak-response-reintroduction-outbreak cycle?” he asks. “Can we use new therapies to clear the virus from survivors?”
But the most immediate question is what these results mean for Ebola survivors, who already face many difficulties. Many have not only lost friends and family to the virus, but are also battling long-term side effects such as muscle pain and eye problems. In a study published in February, Delaporte found that about half of the more than 800 Ebola survivors in Guinea still reported symptoms 2 years after the disease and a quarter after 4 years.
In addition, survivors faced intense stigmatization. Many conspiracy theories emerged after the epidemic, including the claim that survivors sold family members to international organizations to save themselves, says Frederic Le Marcis, a social anthropologist at the École Normale Supérieure de Lyon and the French Institute for Research for Development , who is working in Guinea. One man, he says, was the only survivor of 11 family members, and when he returned, no one wanted to work with him. “He was seen as untrustworthy.” The news that a survivor has probably triggered the current outbreak may cause more problems for survivors, Le Marcis says: “Will they be highlighted as a source of danger? Will they be expelled from their own families and communities? “
Alpha Keita, a virologist who led the sequencing work at CERFIG, has been concerned with stigmatization and even violence against survivors since he obtained the surprising results a week ago. An important message to the public should be that some people infected with Ebola have few symptoms, which means that people can be survivors without knowing it. “So don’t stigmatize Ebola survivors – you don’t know that you’re not a survivor either,” says Keita.
Bausch calls for an educational campaign explaining that unprotected sex with an Ebola survivor can pose a risk, but casual contacts, such as shaking hands and working together, are not. And while some medical monitoring of survivors is needed, it’s not just about testing them for the Ebola virus, he says. “We need to recognize and help with all the other challenges, physical, mental and social, that survivors and their families face.” The key, says Bausch, is “not just treating survivors as a hot potato risk of starting another outbreak”. It also represents a challenge for the country’s health system if each patient with fever and diarrhea has to be considered a potential case of Ebola, says Le Marcis.
Fortunately, vaccines and treatments for Ebola have become available in recent years. Several thousand contacts from new Ebola patients, and contacts from those contacts, have already been vaccinated. Health workers are also being immunized. Vaccination of survivors may even help eliminate latent infections, says Rasmussen. And the fact that viral samples were sequenced in Guinea this time shows that the country’s scientific capabilities have improved, Delaporte says: “Seven years ago, when the epidemic started, there was no infrastructure in Guinea to do that.”