Confirmation on Friday that a rare Ebola virus was sickening people in the Democratic Republic of the Congo (DRC) shocked many scientists—mainly because of the outbreak’s sheer size: 246 suspected cases and 80 deaths at the time. It appeared to have been spreading undetected for many weeks, which would make it that much harder to control. Since then, researchers and public health experts have been sprinting to make up for lost time.
By Friday night, the World Health Organization (WHO) and Africa Centres for Disease Control and Prevention (Africa CDC) had convened a meeting and chosen the most promising candidate drugs to test in a clinical trial. The next morning, a trial protocol had been adapted to those drugs for submission to regulatory authorities in the DRC and Uganda. By this evening, two teams from Uganda and the DRC had published three genome sequences from the virus online, which should help scientists track how it is spreading. “Amazing work from those two teams—bloody fast turnaround!” says Kristian Andersen, an evolutionary biologist at Scripps Research.
But the outbreak has also grown in the meantime, to 395 suspected cases including 106 deaths. Ituri province in the northeast of the DRC is the outbreak’s center, but the 10 confirmed cases so far include one in Goma in the neighboring province of North Kivu and two in Kampala, the capital of neighboring Uganda. WHO declared the outbreak a public health emergency of international concern (PHEIC) on Sunday. And today, Africa CDC followed suit, declaring the outbreak a public health emergency of continental security. “I'm really worried this has spread so far, so quickly,” says Salim Abdool Karim, an epidemiologist who runs the Centre for the AIDS Programme of Research in South Africa and chairs the Africa CDC committee that recommended the emergency declaration. “It just crept up on us.”
One reason is the cause, a rare Ebola species named Bundibugyo after the region in Uganda where it first emerged in 2007. (A second Bundibugyo outbreak was recorded in 2012 in the DRC.) “We have no widely available diagnostic, no treatment, no vaccine” for the species, Karim says. “So we sort of have our hands tied behind our back here.”
In recent Ebola outbreaks health workers relied on a diagnostic tool called GeneXpert, a machine that automates polymerase chain reaction (PCR) technology. But the reagents needed to detect the viral DNA are available only for the Zaire species of Ebola virus that caused most past outbreaks. The lack of a handy test is one reason the new outbreak took longer to detect, and it will also make it harder to manage. Discussions are underway to have GeneXpert cartridges made for Bundibugyo, Karim says. For now, another kit called RadiOne is being used, says Placide Mbala, head of epidemiology and global health at the National Institute of Biomedical Research (INRB) in Kinshasa. “We are still waiting for more RadiOne reagents to deploy to all remote labs close to where suspected cases are being reported,” he says.
A lack of reagents for replicating Bundibugyo’s genome also hampered efforts to sequence the virus, Mbala says. Researchers have been using a workaround: a catch-all kit designed to amplify all kinds of different viral genetic material. “It works well but is much more expensive, takes longer, and is potentially less sensitive for very degraded samples,” says Andrew Rambaut, an evolutionary biologist at the University of Edinburgh.
Advertisement
Still, a full genome sequence was posted online on Sunday from a patient in Uganda, followed on Monday by two from the DRC. The virus appears to be about equally related to the culprits in the two previous outbreaks, Rambaut says. “It looks exactly what I would expect a new spillover from the reservoir in the area would look like.” More sequences could help pinpoint how long the virus has been spreading in humans, Andersen says. For now, the earliest known case is a nurse who fell ill on 24 April and died 3 days later in Bunia, the capital of Ituri province. But it’s highly likely she was infected by a patient, Karim says.
Efforts are underway to start clinical trials of promising candidate drugs and vaccines, says Vasee Moorthy from WHO’s Office of the Chief Scientist. At WHO’s Friday night meeting, a monoclonal antibody cocktail called MBP134 and the antiviral drug remdesivir were chosen as the best candidates for a clinical trial. A trial protocol called PARTNERS, developed at the University of Oxford for an emergency situation like the current outbreak, could be used to test both.
PARTNERS had begun to test remdesivir and a different antibody during a 2024 outbreak of Marburg disease in Rwanda, but paused the effort when the outbreak ended. “Effectively this protocol was sleeping and lying in wait,” says Amanda Rojek, a clinical scientist at Oxford. The researchers have updated it for the current outbreak and are now awaiting approval from ethics committees in the DRC and Uganda.
WHO has scheduled a meeting tomorrow to discuss tests of candidate vaccines. Thomas Geisbert, a virologist at the University of Texas Medical Branch who has conducted Ebola vaccine research in animal models since 2000, developed candidates by stitching the gene for the surface proteins of various Ebola strains into vesicular stomatitis virus (VSV), a harmless “vector” that copies itself after being injected into the animals. VSV carrying the gene for a Bundibugyo virus surface protein protected 100% of monkeys challenged with that strain, and 83% of monkeys who were injected shortly after a Bundibugyo infection. Because that candidate vaccine is not available right now, another strategy could be to combine two available vaccines against other Ebola species: Geisbert and colleagues achieved 100% protection against a Bundibugyo challenge in monkeys by giving a prime shot of VSV-Sudan followed by a boost 2 weeks later with VSV-Zaire.
Geisbert says pharmaceutical companies have long shied away from building on his monkey successes because they do not want to shoulder the high costs of producing “clinical grade” material for human studies and conducting the trials. He notes that a VSV-Zaire vaccine that worked in monkeys didn’t move forward in humans until the 2014 explosion of disease from Zaire virus in West Africa. “It’s the same story,” Geisbert says. “I have lived this for 26 freaking years.”
The DRC has stopped more than a dozen previous Ebola outbreaks despite a lack of drugs or vaccines simply by isolating patients and identifying and quarantining their contacts, Jason Kindrachuk, a virologist at the University of Manitoba, points out. Those low-tech measures, too, will need people and resources from partner organizations and the international community.
Karim says his team is feeling the absence of the United States Agency for International Development (USAID), which played a role in managing the mpox emergency in 2024 but was dismantled last year. “Basically, the U.S. has become unreliable as a partner, so we have to carry on.”
The U.S. Centers for Disease Control and Prevention has 25 staff stationed in the DRC and will send more technical experts to help. It also issued travel restrictions today that for the next 30 days bar non-U.S. passport holders who have been to the DRC, Uganda, or South Sudan in the past 3 weeks from entering the United States. A medical missionary from the United States who was working in the DRC and who tested positive for the virus on Sunday will be flown to Germany for treatment, where other “high-risk contacts” will also be monitored.
For now, it’s unclear just how big the outbreak really is, Kindrachuk says. “But I think we also have to appreciate that, with each hour, with each day, there's a potential that this will expand.”
Dr Margaret Connolly was one of six Irish citizens detained, flotilla organisers have said
