An Ebola outbreak that has killed more than 20 healthcare workers in the Democratic Republic of Congo (DRC) is proving a trial by fire for an experimental vaccine, but there are insufficient data to establish the efficacy of the immunization.

While thousands of healthcare workers have been immunized, it is not clear whether those who have contracted Ebola delivering care to patients had been vaccinated.

“A previous trial1 showed 100% [vaccine] effectiveness, which is possibly unrealistic,” says Jennifer B. Nuzzo, DrPH, SM, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore. “They are offering it to healthcare workers, and many healthcare workers have been vaccinated. But what we haven’t seen is a denominator to know what percentage of [infected] healthcare workers have been vaccinated.”

As of Feb. 17, 2019, the Ebola outbreak in the DRC region of North Kivu totaled 840 cases, including 775 confirmed and 65 probable. A total of 537 deaths were reported, for a case-fatality rate of 64%. Since the outbreak began in August 2018, 68 healthcare workers have been infected and 21 have died, the World Health Organization (WHO) reports.1

“In DRC, more than 66,000 people have been vaccinated — more than 21,000 of them are health and other frontline workers,” the WHO reports. “The yet-to-be-licensed rVSV-ZEBOV vaccine has been shown to be highly protective against the Zaire strain of the Ebola virus in a major trial.”2

A request to clarify the number of infected healthcare workers who were immunized had yielded no WHO response as this story was filed. In one of its outbreak reports, the WHO listed immunization of healthcare workers as one of the areas being strengthened to interrupt chains of transmission.3

The outbreak is complicated by armed conflict and civil disruption in the region, meaning the efficacy of the vaccine may have to be determined in the aftermath.

“That analytic component is needed,” Nuzzo says. “The unofficial impression from the folks on the ground there is that it has been effective, but I think there are some instances in which people have been vaccinated and haven’t been protected, which is pretty common with any vaccine.”

Healthcare workers receive the vaccine pre-emptively, and the strategy for the general population is ring vaccination. “When a case is identified, they try to find their contacts and offer them vaccine,” she adds.

“Healthcare workers are one of the few, if not the only, group that do not have to be tied to cases in order to get the vaccine,” she says. “Some people have called for an enlargement of pre-emptive vaccination that they are doing, some kind of geographic campaign to try to anticipate where future cases may be headed. So far, that hasn’t been done yet.”

U.S. Worker Discharged

A missionary from the U.S. exposed to the Ebola virus while caring for a patient in the DRC was given the vaccine within 24 hours and subsequently did not develop infection. After the exposure and vaccination, the caregiver was flown out of Africa and quarantined in a state-of-the-art facility for the requisite three-week incubation period at the Nebraska Medical Center in Omaha, says Ted Cieslak, MD, the infectious diseases specialist who oversaw the case.

As employee health professionals know, with cases of post-exposure prophylaxis it often cannot be determined whether the vaccine or treatment prevented infection or if the caregiver would have remained healthy regardless.

“We will never know whether that was the critical factor or whether he was just lucky and if his exposure was not intense enough [to seroconvert],” Cieslak says. “We think the Ebola vaccine is good for the first few days post-exposure.”

If he had developed Ebola, the plan was to transfer care to the nearby Nebraska Biocontainment Unit, where three infected healthcare workers were treated during the 2014-2016 outbreak in West Africa.

“He cared for a patient who ultimately proved to have Ebola,” he says. “They considered it a high-risk exposure.”

Congolese healthcare workers who cared for the same patient also were vaccinated post-exposure.

“There are these concerns about any perceptions that the American or Western providers may get [the vaccine] and it is not as available to the Congolese,” he says. “I think that has led to some [care units] not giving it until there is an exposure or there is high risk in their particular province.”

It is encouraging that the aforementioned Ebola vaccine trial was 100% efficacious, but further data are needed to really determine whether it will become a pre-emptive measure beyond outbreak settings, he notes.

“There has been some criticism of that trial — it wasn’t big enough, etc.,” Cieslak says. “I’m sure more studies need to be done before the U.S. Food and Drug Administration would be willing to license that vaccine. Certainly, the preliminary data look very promising.”

The U.S. caregiver entered voluntary quarantine in Nebraska and was routinely assessed for fever and other symptoms. He remained asymptomatic.

“Under the terms of [the quarantine] agreement, providers were supposed to remain three feet away from him unless they were wearing gloves and mask,” Cieslak says. “I would postulate that is an abundance of caution. It’s technically not necessary, since again he was incapable of transmitting [Ebola] since he was not symptomatic.”

This factor is worth underscoring, as some completely asymptomatic healthcare workers were quarantined upon return from the last Ebola outbreak — even though the public health consensus was they could have simply stayed home and reported any symptoms.

“It is the political impulse with every scary-sounding outbreak to try to keep it out of our country,” Nuzzo says. “That is something we have to anticipate and develop strategies to try and prevent.”

There are political implications to the DRC outbreak that are hampering control efforts, she adds. Last October, the WHO convened a committee to review the outbreak but declined to issue a Public Health Emergency of International Concern.

“The WHO has not elected to reconvene the committee since then, even though the outbreak has gotten much worse,” she says. “It’s very political. The fear is that countries would take non-evidence-based actions, like decide to make it harder to travel to and from the area.”

Call to Action

In a recent perspective piece, Nuzzo emphasized that the international response has been inadequate.

“Though the current outbreak doesn’t yet match the scale of the West Africa epidemic, its trajectory thus far and the underlying conditions in the DRC are cause for worry,” she wrote.4

“North Kivu is home to more than 6 million people. If the outbreak goes unchecked, it could … lead to travel, trade, economic, and security implications reaching far beyond the region.”

The response was dealt a serious blow when the U.S. government, citing security concerns, pulled the CDC workers from the DRC, Nuzzo says.

“They have unmatched knowledge,” she says. “The CDC has been responding to Ebola outbreaks for 40 years. There are over 500 WHO personnel there, and they have been able to operate with security personnel.”

According to the WHO, the last Ebola outbreak, which lasted from December 2013 to April 2016, led to 28,000 cases and 11,000 deaths.

WHO’s post-mortem report of that outbreak concluded that “the weight of evidence suggests that a rapid response to the discovery of new Ebola cases can stop transmission, preventing minor outbreaks from becoming major epidemics in large, mobile populations.”5

REFERENCES

  1. Henao-Restrepo AM, Longini IM, Egger M, et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Lancet 2015;386:857-866.
  2. WHO. Ebola virus disease, Democratic Republic of Congo. External Situation Report 29, Feb. 19, 2019. Available at: https://bit.ly/2ED5ZGA.
  3. WHO. South Sudan vaccinates health workers against Ebola. Jan. 28, 2019. Available at: https://bit.ly/2GssX4u.
  4. WHO. Ebola virus disease — Democratic Republic of the Congo. Update: Jan. 31, 2019. Available at: https://bit.ly/2SvYitE.
  5. Nuzzo JB, Inglesby TV. Perspective: Ramping Up the Response to Ebola. N Engl J Med 2018; 379:2490-2491.
  6. WHO Ebola Response Team. After Ebola in West Africa — Unpredictable Risks, Preventable Epidemics. N Engl J Med 2016;375:587-596.