Virus World

A patient with the rare, but highly infectious Marburg virus disease has died in Guinea, according to a World Health Organization (WHO) statement on Monday. It's the first case of the Ebola-like virus in West Africa.  Samples of the virus, which causes hemorrhagic fever, were taken from the patient in Gueckedou. The statement added that the detection comes less than two months after Guinea declared an end to its most recent Ebola outbreak. "Gueckedou, where Marburg has been confirmed, is also the same region where cases of the 2021 Ebola outbreak in Guinea as well as the 2014--2016 West Africa outbreak were initially detected," according to the WHO statement. "Samples taken from a now-deceased patient and tested by a field laboratory in Gueckedou as well as Guinea's national haemorrhagic fever laboratory turned out positive for the Marburg virus. Further analysis by the Institut Pasteur in Senegal confirmed the result." Health authorities on Monday were attempting to find people who may have had contact with the patient as well as launching a public education campaign to help curb the spread of infection. An initial team of 10 WHO experts are on the ground to probe the case and support Guinea's emergency response. "We applaud the alertness and the quick investigative action by Guinea's health workers.

The potential for the Marburg virus to spread far and wide means we need to stop it in its tracks," Dr. Matshidiso Moeti, WHO regional director for Africa, said in the statement. According to WHO, the virus is transmitted to humans from fruit bats and can then be spread human-to-human through direct contact with the bodily fluids of infected people or surfaces and materials contaminated with these fluids. There are no vaccines or antiviral treatments to treat Marburg; however, there are treatments for specific symptoms that can improve patients' chances for survival. "Case fatality rates have varied from 24% to 88% in past outbreaks depending on virus strain and case management," the statement said. "In Africa, previous outbreaks and sporadic cases have been reported in Angola, the Democratic Republic of the Congo, Kenya, South Africa and Uganda." Marburg virus was first identified in 1967, when 31 people became sick in Germany and Yugoslavia in an outbreak that was eventually traced back to laboratory monkeys imported from Uganda. Since then the virus has appeared sporadically, with just a dozen outbreaks on record. Many of those involved only one diagnosed case. Marburg virus causes symptoms similar to Ebola, beginning with fever and weakness and often leading to internal or external bleeding, organ failure and death.

Guinea declared a new Ebola outbreak on Sunday when tests came back positive for the virus after three people died and four fell ill in the southeast - the first resurgence of the disease there since the world's worst outbreak in 2013-2016.  The patients fell ill with diarrhoea, vomiting and bleeding after attending a burial in Goueke sub-prefecture. Those still alive have been isolated in treatment centres, the health ministry said. “Faced with this situation and in accordance with international health regulations, the Guinean government declares an Ebola epidemic,” the ministry said in a statement. The person buried on Feb. 1 was a nurse at a local health centre and died after being transferred for treatment to Nzerekore, a city near the border with Liberia and Ivory Coast. The 2013-2016 outbreak of Ebola in West Africa started in Nzerekore, the proximity of which to busy borders hampered efforts to contain the virus. It went on to kill at least 11,300 people, with the vast majority of cases in Guinea, Liberia and Sierra Leone.

Fighting Ebola again will place additional strain on health services in Guinea as they also battle the COVID-19 pandemic. Guinea, a country of about 12 million people, has so far recorded 14,895 coronavirus infections and 84 deaths. The Ebola virus causes severe vomiting and diarrhoea and is spread through contact with body fluids. It has a much higher death rate than COVID-19, but unlike the coronavirus it is not transmitted by asymptomatic carriers. The ministry said health workers are trying to trace and isolate the contacts of the Ebola cases and will open a treatment centre in Goueke, which is less than an hour’s drive from Nzerekore. The authorities have also asked the World Health Organization (WHO) for Ebola vaccines, it said. The new vaccines have greatly improved survival rates in recent years.

“It’s a huge concern to see the resurgence of Ebola in Guinea, a country that has already suffered so much from the disease,” the WHO’s Regional Director for Africa, Matshidiso Moeti, was quoted as saying in a statement. Given how close the new outbreak is to the border, the WHO is working with health authorities in Liberia and Sierra Leone to beef up surveillance and testing capacities, the statement said. The vaccines and improved treatments helped efforts to end the second-largest Ebola outbreak on record, which was declared over in Democratic Republic of Congo last June after nearly two years and more than 2,200 deaths. But on Sunday, DRC reported a fourth new case of Ebola in North Kivu province, where a resurgence of the virus was announced on Feb. 7.

Genome analyses suggesting virus persistence raise worries about stigmatization of survivors. An Ebola outbreak in Guinea that has so far sickened at least 18 people and killed nine has stirred difficult memories of the devastating epidemic that struck 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 just be the trauma that has persisted. The virus causing the new outbreak barely differs from the strain seen 5 to 6 years ago, genomic analyses by three independent research groups have shown, suggesting the virus lay dormant in a survivor of the epidemic all that time. “This is pretty shocking,” says virologist Angela Rasmussen of Georgetown University. “Ebolaviruses aren’t herpesviruses”—which are known to cause long-lasting infections—“and generally RNA viruses don’t just hang around not replicating at all.” Scientists knew the Ebola virus can persist for a long time in the human body; a resurgence in Guinea in 2016 originated from a survivor who shed the virus in his semen more than 500 days after his infection and infected a partner through sexual intercourse. “But to have a new outbreak start from latent infection 5 years after the end of an epidemic is scary and new,” says Eric Delaporte, an infectious disease physician at the University of Montpellier who has studied Ebola survivors and is a member of one of the three teams. Outbreaks ignited by Ebola survivors are still very rare, Delaporte says, but the finding raises tricky questions about how to prevent them without further stigmatizing Ebola survivors. The current outbreak in Guinea was detected after a 51-year-old nurse who had originally been diagnosed with typhoid and malaria died in late January. Several people who attended her funeral fell ill, including members of her family and a traditional healer who had treated her, and four of them died. Researchers suspected Ebola might have caused all of the deaths, and in early February they discovered the virus in the blood of the nurse’s husband. An Ebola outbreak was officially declared on 13 February, with the nurse the likely index case. The Guinea Center for Research and Training in Infectious Diseases (CERFIG) and the country’s National Hemorrhagic Fever Laboratory have each read viral genomes from four patients; researchers at the Pasteur Institute in Dakar, Senegal, sequenced two genomes. In three postings today on the website virological.org, the groups agree the outbreak was caused by the Makona strain of a species called Zaire ebolavirus, just like the past epidemic. A phylogenetic tree shows the new virus falls between virus samples from the 2013–16 epidemic.

Until recently, scientists assumed Ebola epidemics start when a virus jumps species, from an animal host to humans. Theoretically, that 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 viruses from the epidemic and the new ones, “It must be incredibly unlikely.” Outside scientists agree but say it hasn’t been proved that Ebola lay dormant in one person for 5 years. “From the tree, you’d conclude that it is a virus that persisted in some way in the area, and sure, most likely in a survivor,” says Dan Bausch, a veteran of several Ebola outbreaks who leads the United Kingdom’s Public Health Rapid Support Team. But it is hard to rule out scenarios such as a small, unrecognized chain of human to human transmission, Bausch adds: “For example, a 2014 survivor infects his wife a few years after recovery, who infects another male, who survives and carries virus for a few years, then infecting another women, who is then seen by a nurse who dies”—the index case in the new outbreak. The nurse was not known to be a survivor herself, but she could have had contact with a survivor privately or through her job, or she might have been infected herself years ago with few symptoms. “Figuring out what exactly happened is one of the biggest questions now,” Bausch says. Another ongoing outbreak of Ebola in North Kivu, in the Democratic Republic of the Congo, was also started by transmission from someone infected during a previous outbreak, Delaporte notes. (The survivor had tested negative for Ebola twice after his illness in 2020.) Taken together, that suggests humans are now as likely to be the source of a new outbreak of Ebola as wildlife, he says. “This is clearly a new paradigm for how these outbreaks start.” Outbreaks sparked by survivors may even become more likely, now that increasing mobility and other factors have caused each eruption of Ebola to become bigger, resulting in more survivors, says Fabian Leendertz, a wildlife veterinarian who was involved in the sequencing. The cases raise important new research questions, Bausch says: “How do we need to change our response to escape from the cycle of outbreak-response-reintroduction-outbreak?” he asks. “Can we use new therapeutics to clear virus from survivors?” But the most immediate question is what these results mean for Ebola survivors, who face a lot of hardship already. Many have not only lost friends and family to the virus, but also struggle with long-term aftereffects, such as muscle pains and eye problems.

In a study published in February, Delaporte found that about half of more than 800 Ebola survivors in Guinea still reported symptoms 2 years after their illness, and one-quarter after 4 years. On top of this, survivors have faced intense stigmatization. Many conspiracy theories swirled in the aftermath of the epidemic, including the claim that survivors had sold family members to international organizations to save themselves, says Frederic Le Marcis, a social anthropologist at the École Normale Supérieure of Lyon and the French Research Institute for Development, who is working in Guinea. One man, he says, was the only one to survive out of 11 family members and when he came back, no one wanted to work with him. “He was seen as someone untrustworthy.” News that a survivor likely touched off the current outbreak could cause further problems for survivors, Le Marcis says: “Will they be highlighted as a source of danger? Will they be chased out of their own families and communities?” Alpha Keita, a virologist who led the sequencing work at CERFIG, worries about stigmatization and even violence against survivors have occupied him since he first got the surprising results a week ago. One important message to the public should be that some people infected with Ebola show few symptoms, meaning people may be survivors without knowing it. “So don’t stigmatize Ebola survivors—you don’t know that you are not a survivor yourself,” Keita says. Bausch calls for an educational campaign explaining that unprotected sex with an Ebola survivor may pose a risk, but casual contacts such as shaking hands and working together do not. And although there needs to be some medical monitoring of survivors, it cannot just be about testing them for Ebola virus, he says. “We need to recognize and assist with all the other challenges, physical, mental, and social, that survivors and their families face.” The key, Bausch says, is to “not just treat survivors as some hot potato risk of starting another outbreak.” It also presents a challenge to the country’s health care system if every patient with fever and diarrhea has to be a considered potential Ebola case, Le Marcis says. Fortunately, Ebola vaccines and treatments have become available in recent years. Already, several thousand contacts of the new Ebola patients, and contacts of these contacts, have been vaccinated. Health care workers are being immunized as well. Vaccinating survivors might even help clear latent infections, Rasmussen says. And the fact that viral samples were sequenced in Guinea this time around shows the country’s scientific capabilities have improved, Delaporte says: “Seven years ago, when the epidemic started, there was no infrastructure in Guinea to be able to do this.”

Sequences of the EBOV strain available  in Virological (March 12, 2021):

https://virological.org/t/guinea-2021-ebov-genomes/651 

Ebola survivors in Guinea face a more than five times greater risk for mortality after hospital discharge than the general population, according to findings from a retrospective cohort study published in The Lancet Infectious Diseases. Most deaths among survivors were tentatively attributed to renal failure, and the risk for death was higher in survivors who had longer stays inEbola treatment units, researchers reported.

“Ebola survivors are more vulnerable than previously thought, and therefore should be offered improved care, with a focus on available resources in the first few months and ideally up to a year after recovery,” WHO epidemiologist Lorenzo Subissi, PhD, told Infectious Disease News. The 2013-2016 West African Ebola epidemic resulted in 28,646 cases and 11,323 recorded deaths, giving West Africa the largest cohort of survivors of Ebola virus disease at more than 17,000 people, Subissi and colleagues noted. However, little information is currently available about deaths that have occurred in patients discharged from Ebola treatment units.

Subissi and colleagues sought to address this gap in mortality data by developing and implementing a community monitoring program called Surveillance Active en ceinture using WHO guidelines. They attempted to contact and follow up all Ebola survivors in Guinea who were discharged from Ebola treatment units from December 2015 through September 2016, recording deaths that had occurred up until the endpoint. They conducted verbal autopsies with the closest family members of the deceased and reviewed medical records shared by those family members.

A total of 1,270 survivors of Ebola virus disease were discharged from Ebola treatment units in Guinea. Of these, the researchers collected information for 1,130 (89%). They found that survivors of the disease had a more than five times increased risk of mortality up to Dec. 31, 2015 (age-standardized mortality ratio = 5.2; 95% CI, 4-6.8), a mean of 1 year of follow-up after discharge. From Jan. 1, 2016, to Sept. 30, 2016, mortality did not differ between survivors and the general population (age-standardized mortality ratio = 0.6; 95% CI, 0.2-1.4). A total of 59 deaths were reported — 37 attributed to renal failure, mostly based on reported anuria, according to the researchers. Stays in Ebola treatment units that were equal to or longer than the median stay were associated with an increased risk for late death compared with shorter stays (adjusted HR = 2.62; 95% CI, 1.43-4.79). 

Original findings published in September 4, 2019 in the Lancet Infectious Diseases:

https://doi.org/10.1016/S1473-3099(19)30313-5