The Ebola response teams in the Democratic Republic of the Congo are having increasing trouble keeping track of where the virus is spreading, a problem that threatens containment efforts and undermines the effectiveness of the vaccination program there.

Public health officials had been hopeful that an experimental vaccine could help curb the spread of the outbreak. But, for that to happen, response teams must be able to identify people who have been in contact with Ebola patients. Persistent violence in the outbreak zone has made that hard to do.

More than half of the recently detected cases haven’t been on lists of contacts. And even retrospective detective work is failing to piece some of these people into the transmission chain, the World Health Organization acknowledged.

“We have a number of indicators right now showing that our ability to quickly detect cases and follow up on their contacts has been seriously challenged by the safety issues,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, who has been tracking the epidemic.

Vaccine, he said, “can’t be given to people you don’t know exist.”

The severe insecurity problems in North Kivu, the province in northeastern DRC where Ebola is spreading, are throwing up major challenges for the outbreak response. There have been repeated attacks by rebel forces on Beni, the current Ebola hot spot, stymying efforts to track Ebola patients and their contacts.

The further behind the virus that the response teams get, the more difficult it will be to use the still-unlicensed vaccine, made by Merck, to its maximum effect, experts acknowledged.

The response team in North Kivu has vaccinated a prodigious number of people — more than 20,000 so far in the province and in parts of neighboring Ituri province, where a few cases have occurred. That count rises by hundreds of people most days.

“It’s extremely impressive,” Anne Rimoin, an associate professor of infectious diseases epidemiology at UCLA’s Fielding School of Public Health, told STAT.

But vaccination efforts were not conducted Monday in Beni, after the weekend’s violence there.

So far there have been 238 confirmed and probable cases reported in this outbreak and 155 deaths.

As gaps grow in the response team’s understanding of where the virus is circulating and who has been exposed, the capacity of the vaccine to contain the outbreak diminishes. Osterholm explained the problem as if it were an equation.

Conventional Ebola control measures — isolating the sick, identifying and monitoring the health of contacts of cases, and isolating them if they become symptomatic — are variable A in the equation. On their own, these measures have contained decades of Ebola outbreaks in the past.

But then along came vaccine, variable B in the equation. The Merck vaccine was proved to work during the West African outbreak of 2014-2015 and was first used as a containment tool in an outbreak in western DRC this past spring. That outbreak was brought under control fairly rapidly.

A plus B should lead to containment of the outbreak, potentially faster than in outbreaks past. But if A falters, B — the vaccine — can’t do the job on its own, Osterholm said. “It only works when you get it to the people who need it,” he said.

That’s because of ring vaccination, the type of vaccination strategy being deployed in North Kivu. It was used in the successful smallpox eradication campaign of the 1960s and 1970s.

The idea behind the strategy seems simple: Rather than trying to vaccinate everyone in a place where Ebola is spreading, focus on the people who are at risk of actually contracting the disease. Beni is a city of more than 200,000 people, but only a tiny fraction of them would have been exposed to the virus up to this point.

The goal is to throw up a wall of immunity that Ebola cannot scale.

But effective contact tracing is required to draw up the list of people who should be offered vaccine. And increasingly, contact tracing isn’t identifying all of the at-risk people.

Since the beginning of October, a period during which cases have surged, a growing proportion of new cases in Beni have come from outside the contact lists and can’t be fitted into the chain of transmission, said Dr. Peter Salama, the WHO’s deputy director-general of emergency preparedness and response.

The contract tracing performance is measured in percentages — the proportion of known contacts that are followed up daily. Ideally that figure should be in the mid-to-high 90s. And it has generally been that high elsewhere in North Kivu, said Salama.

But in Beni, it has been highly variable, he said, adding that after episodes of violence, the contact tracing performance at Beni has dipped to 30 percent or 40 percent.

The longer contact tracing flags, the more likely it is that the percentage of people being missed grows in an invisible fashion.

Rimoin, who has a long-standing research project in DRC, knows the difficulties the responders face. “The area in which this outbreak has emerged is a very difficult and complex place to have to do this work — to do any work. But to have to combat Ebola in this area is mindbogglingly difficult,” she said.

Last week a panel of international experts who reviewed the outbreak and the response to date suggested that the WHO consider adapting the vaccination strategy, moving to a more geographic approach — vaccinating whole neighborhoods rather than just health care workers, contacts, and contacts of contacts.

Salama told STAT that approach comes with its own challenges. Merck has committed to maintaining a supply of 300,000 doses of the vaccine at all times and has been making additional vaccine as it ships doses to the DRC. So far in 2018, the company has shipped more than 32,000 doses of vaccine, said Pamela Eisele, a spokesperson for Merck.

While 300,000 doses seems like a substantial supply, Salama said he worried using the vaccine geographically could draw down the stockpile quickly. He noted the WHO has to also consider what might happen if this outbreak spreads into neighboring Uganda — which is expected to soon start vaccinating health care workers in locations where cross-border cases might turn up — or Rwanda or South Sudan.

Vaccinating all of Beni, for instance, would make a huge dent in the global stockpile, which would take time to replenished. “So obviously we have to just continue to ration it, according to the best evidence,” he said.

Salama also said he is concerned a geographic approach to vaccination might not solve the underlying problem — the fact that some people in the outbreak area continue to resist all of the control measures the responders use.

“If your high-risk contacts are actively avoiding follow-up or vaccination or care, they’re going to avoid vaccination or geographic targeting strategy presumably as well,” he said. “So you might end up thinking you’ve got great coverage geographically, but you’ve missed the same high-risk contacts that we’re unable to follow up on now. So it will have very limited impact in that sense.”