Some doctors call it “walking Ebola” – symptoms of the rare Bundibugyo strain appear to worsen slowly, leaving patients sick enough to spread the virus but not so unwell to stop them moving through their communities.
The pattern emerging in the Democratic Republic of Congo resonated with virologist Corri Levine, who devoted her doctoral research to Bundibugyo years before it caused the fastest-growing Ebola outbreak on record.
Studying the virus in a biocontainment laboratory at the University of Texas Medical Branch, Levine found it replicated more slowly than the Zaire strain responsible for a devastating epidemic that swept West Africa a decade ago.
“‘Walking Ebola’ was “an ‘aha’ moment for me,” Levine said. “If it’s growing slower in the person, you might start having some symptoms, but not enough to make you feel so crummy that you can’t move. It’s this longer, prolonged disease course.”
That slower progression carries another risk. Patients with Ebola have consistently had the best chance of survival when treated early, before rising virus levels drive the disease towards septic shock and multi-organ failure.
If Bundibugyo gives doctors a longer opportunity to intervene before reaching that point, antiviral drugs may have a better chance of altering the course of the disease.
The possibility has renewed interest in antiviral drugs such as Gilead Sciences’ remdesivir, which Levine’s lab found was more active against Bundibugyo than Zaire Ebola in petri-dish experiments.
Researchers in July began testing remdesivir alongside Mapp Biopharmaceutical’s antibody therapy MBP134 in a World Health Organization-sponsored clinical trial in Congo, while a separate study is evaluating Gilead’s experimental oral antiviral obeldesivir in people recently exposed to the virus.
The need for new tools is becoming increasingly urgent.
Deaths have almost doubled in July, more than 90 per cent of confirmed fatalities are occurring before patients reach treatment centres, and four out of every five new infections are now arising outside known chains of transmission, according to the WHO.
Overcrowded Ebola units and delays in diagnosis are allowing infected people to remain in their communities longer, fuelling further spread.
Congo has reported 2,181 confirmed cases and 864 deaths, pushing the outbreak’s crude case-fatality ratio to 40 per cent, the National Institute of Public Health said on July 17.
Convincing people to seek care has always been one of the biggest challenges in Ebola outbreaks.
During the West African epidemic, many of the more than 28,000 it infected saw treatment centres as places to die rather than places to recover because there were no vaccines and no proven treatments to offer, said Joanne Liu, the former international president of Doctors Without Borders (MSF), who helped lead the response.
Early treatment can make a profound difference. Patients who reach care have “three to four times” better odds of survival than those who remain in the community, Chikwe Ihekweazu, executive director of the WHO’s health emergencies programme, told reporters on July 16.
Better care
The West African epidemic transformed Ebola treatment centres from places focused largely on isolation into facilities delivering aggressive supportive care alongside experimental medicines, said Daniel Chertow, a critical care physician at the US National Institutes of Health who helped care for Ebola patients while working with MSF in Liberia.
The lesson from West Africa was that treating Ebola means more than targeting the virus itself.
“It takes supporting the whole human,” Chertow said. Patients need aggressive fluids, treatment for shock, respiratory support and management of organ failure alongside antiviral drugs and antibodies.
The Bundibugyo outbreak could similarly improve understanding of when antivirals work best, how to tailor supportive care and whether slowing the virus early changes the course of disease.
If Levine’s hypothesis proves correct, the virus’ slower progression may give clinicians more time to deliver the intensive supportive care and antiviral medicines that have helped reduce Ebola mortality over the past decade.
The current outbreak has already generated more than 10 times as many confirmed cases as the two previous Bundibugyo outbreaks combined, giving scientists an unprecedented opportunity to study the virus – and increasing the opportunities for it to evolve, as the Zaire virus did during the outbreak in West Africa.
The more the Bundibugyo circulates, the more opportunity it has to undergo “genetic change that could cause untold devastation”, said Pardis Sabeti, a geneticist at the Broad Institute of MIT and Harvard whose Sentinel programme is supporting genomic sequencing in Congo.
“Any mutation can affect the biology,” she said.
When Levine began studying Bundibugyo Ebola for her PhD almost a decade ago, it had caused only two relatively small outbreaks and attracted a fraction of the scientific attention devoted to Ebola Zaire.
“Everybody’s like, ‘Oh, it’s just that little one,’” she recalled.
Today, the virus has caused the third-largest Ebola outbreak on record, turning years of obscure laboratory work into one of the most urgent scientific questions in global health.
“Anything can happen in this world,” Levine said. BLOOMBERG
