The Democratic Republic of the Congo has moved a step closer to using an unlicensed vaccine to battle an Ebola outbreak that began last month in a remote northeastern part of the country. Yesterday, the country's government submitted a formal vaccine trial protocol, developed with Epicentre, the Paris-based research arm of Doctors Without Borders (MSF), to an ethical review board.
If the plan gets the green light, the first doses of the vaccine could go into the arms of people at risk within 2 weeks, according to an official at the World Health Organization (WHO) in Geneva, Switzerland. WHO today issued a “donor alert,” urgently requesting a 6-month budget of $10.5 million to support the vaccine study (which may require 5000 doses), as well as surveillance, treatment, and conventional prevention and control efforts.
But whether the shots will actually be needed is unclear. So far, there have been only two confirmed Ebola cases and 41 suspected or probable cases. More than 350 contacts of cases were being monitored. But samples from several dozen suspected cases tested negative on Monday, raising the possibility that the outbreak may be quite small, and perhaps already nearing the end.
The outbreak is in the northeastern Bas-Uélé province, about 500 kilometers north of Kisangani, a city of 1.6 million people. The location slows spread but poses huge challenges. Poor and conflict-ridden, the area has few passable roads and bridges. Helicopters carry teams and equipment to the town of Likati, where motorbikes take over. Workers set up two mobile labs, but a generator failed in one and had to be replaced.
The vaccine, made by Merck and stored in the United States, was tested in 2015, during the massive outbreak in West Africa that left more than 11,000 dead. WHO and MSF set up a trial in Guinea with an unusual “ring vaccination” design that selectively gave shots to people most likely to have had contact with a known case. People in a control group, also potentially exposed, received shots 3 weeks later. The results showed 100% protection 10 days after immunization, but the unconventional approach led Merck to put off applying for regulatory approval so it could gather more safety and immune data from other studies. For the moment, the vaccine can only be used in experimental settings.
Epicentre and the DRC’s Ministry of Health (MoH) have written a protocol for a new ring vaccination study in the DRC. The trial would carefully evaluate safety, but this time there will be no control group because withholding the vaccine from some participants is no longer seen as ethical. As a result, the trial cannot evaluate the vaccine’s efficacy. “We’ll try to bring more data in to help with licensing, but we’re using the vaccine as a public health intervention,” says MSF’s Micaela Serafini in Geneva, Switzerland. If approved, the protocol could also be used in any future outbreaks.
We should really leave some of the decision-making to people on the ground.
The MoH did not respond to emailed questions about why it didn’t request the vaccine sooner. One reason, says Epicentre Director of Research Rebecca Grais, is that the outbreak’s extent remains so unclear. “It’s not like they were dragging their feet,” she says. DRC officials may also feel confident they can stop the outbreak without vaccines, as they have seven times in the past, says Peter Piot, who heads the London School of Hygiene & Tropical Medicine and was part of the team that responded to the first known Ebola outbreak, near Likati, in 1976. “We should really leave some of the decision-making to people on the ground,” Piot says.
But Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis, says authorities should have been prepared to deploy the vaccine more quickly. Every African country at risk of Ebola by now should have approved a study protocol, he says, and the DRC should keep the vaccine ready in a freezer in Kinshasa. Under a WHO emergency-use status, the vaccine could also have been deployed without trials, Osterholm notes. A Merck application for that status filed in December 2015 is in limbo; a WHO spokesperson says “there was not necessarily sufficient data to enable a full assessment.”
Even without the vaccine, Ebola experts don’t expect the outbreak to explode as it did in West Africa. “My gut feeling,” says Piot, “is this is going to be more like the outbreaks we had before in DRC,” the largest of which had 318 cases. “Proper isolation of patients and care plus contact tracing and quarantine should really bring this epidemic under control—except if someone gets to Kisangani or Kinshasa.”
There's another reason to be optimistic: The international response to the outbreak so far has been overwhelming. Acutely aware of its failings in Liberia, Guinea, and Sierra Leone in 2014 and 2015, the international community is determined to help end the outbreak as soon as possible.
Matshidiso Rebecca Moeti, WHO's regional director for Africa, immediately traveled to Kinshasa from her office in Brazzaville, in the neighboring Republic of the Congo, to help coordinate the battle. The United Nations dispatched cargo planes and helicopters, and DRC government officials began holding daily coordinating committee meetings attended by representatives from international aid, and development organizations, WHO, and the U.S. Centers for Disease Control and Prevention. “All those actors have strengthened their presence because of what happened in West Africa,” says epidemiologist Yap Boum, Epicentre’s Africa representative. “People are afraid.”