More than 1 year into Ebola outbreak, DRC facing ‘a new normal’

The Democratic Republic of the Congo, or DRC, has experienced 10 outbreaks of Ebola since the virus was discovered there in 1976. None have challenged the country and the global health community like the latest outbreak, which was declared Aug. 1, 2018, in an area of insecurity in the country’s northeast.

Despite the availability of an effective and widely used vaccine, the outbreak has resulted in more than 3,000 infections and 2,000 deaths — more than the country’s nine previous outbreaks combined. It has grown to become the second-largest outbreak of Ebola in history after the West African epidemic, which included more than 28,000 cases and 11,000 deaths.

According to Pierre Rollin, MD, retired deputy chief of the CDC’s Viral Special Pathogens Branch and a prominent Ebola expert, the conditions are in place for Ebola to become endemic in northeast DRC — a catastrophic prospect for its inhabitants and the international community, he said.

“Some experts don’t want to say ‘endemic’ because it’s a dirty word that nobody wants to hear,” Rollin told Infectious Disease News. “But I’d like to see the data on the better response, better results and improvement that say otherwise.”

Source: Majid Sadigh, MD

Experts acknowledge that numerous circumstances have prevented the outbreak from reaching its end, including “local instability, violence and large nearby refugee populations,” said Ronald Klain, who coordinated the United States’ Ebola response during the West African epidemic. WHO declared the current outbreak a Public Health Emergency of International Concern (PHEIC) in July. The timeline for that decision, as well as the overall response from WHO and the international community, drew both praise and criticism from experts.

Infectious Disease News spoke with Klain, Rollin and other experts to gain a better understanding of how the outbreak has evolved and what needs to be done to bring about its end.

Distrust and security concerns

Containing the outbreak has been complicated by governmental and social dynamics, said Majid Sadigh, MD, director of global health for the Western Connecticut Health Network and University of Vermont Larner College of Medicine and the first chief medical officer for the second American-built Ebola treatment unit in Liberia during the West African epidemic.

“In the West African outbreak, there was strong governmental leadership,” Sadigh said in an interview. “Like the DRC, the people of West Africa did not trust the government, and there was a significant misunderstanding between the locals and the international response presence.”

However, according to Sadigh, certain governmental leaders in West Africa — particularly Ellen Johnson Sirleaf, then the president of Liberia — worked to gain the trust and support of affected populations, which made intervening during the outbreak more feasible.

Conversely, governmental mistrust has held much firmer in the DRC, and much of this stems from a “bloody history” that far surpasses that of most African countries, Sadigh said. He offered examples that ranged from King Leopold II of Belgium, whose rule over the Congo resulted in millions of deaths, to the more recent example of former DRC Prime Minister Patrice Lumumba, who was executed by state authorities, his body dissolved in acid and his bones ground and dispersed.

Further, because of the DRC’s abundance of gold, diamond and cobalt mines, some multinational agencies and governments continue to support various warring gangs and factions within the country to bolster their own respective interests, Sadigh said.

“This current outbreak has been particularly challenging to control, largely due to its location in a region that has been plagued by long-running conflict,” Anne W. Rimoin, PhD, MPH, professor of epidemiology at the University of California, Los Angeles Fielding School of Public Health and director of the UCLA-DRC Research Program in Kinshasa, told Infectious Disease News. “It is difficult to overstate the complexity of trying to contain an Ebola outbreak in a conflict zone, especially one with such a vast and mobile population.”

Last September, an attack in the city of Beni — the base for WHO’s response operation — resulted in at least 21 deaths, including 17 among civilians. It marked the first attack in which civilians were indiscriminately targeted instead of state forces or United Nations peacekeepers, and violence has continued to plague the outbreak.

In April, WHO Director-General Tedros Adhanom Ghebreyesus, PhD, MSc, warned that the violence being perpetrated by armed militia groups like Mai-Mai rebels and the Allied Democratic Forces threatened to reverse any gains made in the outbreak and declared that “security remains our No. 1 threat.”

“There remain issues of access to certain areas with insecurity,” Rimoin said. “There is restricted movement in many of the areas affected by Ebola because of security concerns, and this can inhibit a team from being able to go in and do contact tracing and provide vaccines. Interruptions of outbreak response activities due to violence targeting the response teams is a very big problem.”

Vaccine proves vital

Although insecurity remains a major hurdle to ending the outbreak, Merck’s experimental Ebola virus vaccine V920 has helped contain it. The vaccine has proved more than 97% effective, according to a preliminary estimate. Merck announced in September that the FDA accepted a biologics license application and granted priority review for the vaccine.

The vaccine, which was initially tested during the West African epidemic, was first used in the DRC in 2018 during an outbreak in Equateur Province in the northwest part of the country. As in that outbreak, the vaccine is currently being used in a ring vaccination trial, under which contacts of confirmed cases — and contacts of contacts — are immunized.

V920 has been used to immunize more than 225,000 people in the DRC, as well as thousands of health care and other front-line workers in bordering countries. But its distribution has not gone uncriticized. In September, Doctors Without Borders said WHO was “rationing” the vaccine and offering it based on “unclear” eligibility criteria. The aid organization said hundreds of thousands of people who should have already received the vaccine had not.

WHO spokesman Tarik Jašarević called the statement “an extrapolation that does not reflect the social nature of Ebola transmission.”

“While the first ring of contacts may be 150 to 200 [people], where a cluster of cases occurs — for example, in a family — the contacts may be the same people. In fact, the number of people vaccinated and defined rings has increased markedly,” he told Infectious Disease News.

According to WHO, Merck had provided 245,000 doses of V920 for the DRC and neighboring countries as of the end of September and was maintaining 190,000 more stockpiled doses. Overall, 390,000 doses were available and an additional 1.3 million will be available — an amount that meets guidelines from WHO’s Strategic Advisory Group of Experts (SAGE), WHO noted.

“We have not experienced any shortage of vaccine on the ground so far during this outbreak,” Jašarević said. He said WHO continues to collaborate with Merck to monitor supply and demand of the vaccine.

“Whether or not the available doses are sufficient to fulfill the demands depends on the evolution of the outbreak, the access to the communities and the successful expansion of the production of additional doses by Merck in early 2020,” he said.

According to Jašarević, a person at risk for Ebola who does not receive the vaccine is 70 times more likely to become infected, but those who are vaccinated have an almost zero chance of falling ill.

The average incubation time for Ebola is 10 days, Rollin noted, meaning those who come into contact with an infected individual have this much time to receive the vaccine for improved survival.

“Many who received the vaccine after this window developed the disease, but the disease is much milder, and they were more likely to survive the disease than if they were not vaccinated,” Rollin said.

There has been some disagreement over the benefits of introducing a second vaccine, made by Janssen, which was recommended by SAGE for use in people with a lower risk for infection in impacted areas. WHO confirmed in September that the vaccine would be introduced in the outbreak starting in mid-October in an effort to prevent further spread of the virus. The vaccine, given in two doses 56 days apart, will be provided to at-risk populations in areas without active Ebola transmission “as an additional tool to extend protection against the virus,” Mike Ryan, MD, MPH, who heads WHO’s health emergency program, told Infectious Disease News.

“The second vaccine requires two doses, and it does not provide immunity until several days after the patient receives the second dosage, which can be a month or more after receiving the first dose,” Rollin said. “In that case, it cannot really be used for post-exposure intervention because the patients will never be immune in time to be protected, but it can be used to do some preventive vaccination in areas close to the endemic area but where the virus is not yet present. It requires significant time to receive the two injections and to develop immunity.”

Although WHO is not directly involved in the Janssen vaccine trial in Uganda, it has collaborated with Johnson & Johnson, which owns Janssen, to plan for the evaluation of that vaccine, according to Jašarević.

“We support properly regulated, planned and nationally accepted research,” he said. “SAGE has repeatedly stated that it is important to advance the clinical evaluation of other vaccines against Ebola and to accrue additional information on their immunogenicity, safety and efficacy if possible.”

Emergency declaration

In October 2018, Tedros convened an emergency committee for the first time to discuss declaring the outbreak a PHEIC. On that occasion, and two others, the committee determined that the outbreak did not meet the criteria of a PHEIC. Committee chairman Robert Steffen, MD, offered the same explanation each time: The outbreak had not spread beyond the DRC.

In June, however, the first cross-border case was reported in a boy who crossed into Uganda from the DRC, and not long after, reports that a man with Ebola traveled to the large Congolese city of Goma and died prompted Tedros to convene the committee for a fourth time.

At its fourth meeting on July 17, the committee determined that the outbreak met the criteria to be declared a PHEIC.

According to Lawrence O. Gostin, JD, director of the O’Neill Institute for National and Global Health at Georgetown University and an author of the International Health Regulations (IHR) that helped define what a PHEIC is, the declaration should have come sooner.

“It is always difficult to predict the course of an epidemic, but by the time WHO declared a global health emergency, it was already spreading rapidly within the DRC and to Uganda,” Gostin told Infectious Disease News. “WHO waited many months before declaring a PHEIC, and by then it was much harder to bring the epidemic under control.”

Gostin noted that the resources available to WHO have been insufficient — Tedros has repeatedly asked partners for additional funds — and that the Trump administration had banned CDC personnel from going to the “hot zone,” further complicating response efforts.

“The failure to act quickly may have made it more difficult to marshal the resources and political will to act before the epidemic spread too widely,” he said.

Upon the declaration of a PHEIC, the IHR authorized Tedros to make formal recommendations for the affected country, surrounding countries and international response efforts to follow, Gostin said. Although a PHEIC does not unleash additional funding, WHO can use the emergency declaration “as a tool to ramp up political engagement and funding for the response, which is what happened in this instance, as well as prior PHEICs,” Gostin explained.

Source: CDC

“I don’t think that declaring the outbreak a PHEIC is a silver bullet,” Rimoin said. “Nothing is. The outbreak is complex, and so are the solutions to contain it.”

Rimoin noted that declaring a PHEIC also can create problems, such as travel and trade restrictions that can hamper the outbreak response.

A ‘new normal’?

In addition to the vaccine trial, the DRC outbreak also has been the site of a groundbreaking trial of several investigational Ebola treatments. Preliminary findings from the ongoing randomized PALM trial showed favorable results for two of the therapies, REGN-EB3 (Regeneron) and mAb114 (Ridgeback Biotherapeutics), officials announced in August.

According to National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, the overall mortality rate among patients receiving REGN-EB3 was 29%, and it was 34% for mAb114. The results were “even more impressive” in patients with low viral loads, Fauci added, with mortality rates of 6% for REGN-EB3 and 11% for mAb114. Two other therapies, ZMapp (Mapp Biopharmaceutical) and remdesivir (Gilead Sciences), were dropped from the trial.

Despite promising agents for prevention and treatment, experts fear a prolonged outbreak.

“If you look at the outbreak in West Africa, a year after it began, there was huge progress and the trend was really going down,” Rollin said. “We are now more than 1 year into the DRC outbreak, and we haven’t seen much progress. The same problems that we encountered last year are still present.”

Ebola remains a priority in the DRC, but it is not the only pathogen causing a health crisis.

“This year, more people have died from measles and malaria than Ebola in the DRC,” Rimoin said. “Ebola is scary, dangerous and acute, but there are many important ongoing issues in the DRC that were problems before the outbreak started and are worsening as the outbreak continues.”

According to Rimoin, rapid diagnostics are vital to ending the Ebola outbreak because they “shorten time between symptoms or onset of disease and diagnosis and enable teams to get in front of the outbreak instead of chasing far behind,” she said.

Rollin believes a coordinated response should be prioritized, which could include efforts such as a shared database of patient information between WHO, the DRC Ministry of Health and other groups overseeing the response.

Gostin said a major global mobilization is needed, including a “surge of funding, experienced staff like CDC officials and diplomacy to calm the violence and protect responders.” He noted the importance of community engagement to gain the trust of the population.

According to Sadigh, the safety of health care workers also should be prioritized, since they are the ones identifying patients. He said it is vital to develop culturally acceptable strategies to establish trust between them and locals.

“We must be able to respond rapidly and effectively, everywhere, and instead of shifting teams from one place to another, response teams should be left in place when case numbers drop so they continue to work to detect and prevent Ebola transmission,” Jašarević said.

He noted the importance of increased community engagement and education “so we can leave behind people able to provide effective surveillance, vaccination and health care in their own communities.”

According to Klain, the U.S. must do more.

“U.S. leadership has been lacking compared to prior outbreaks, and while WHO is doing a better job than in the past, our response system is still too reliant on courageous but underfunded [nongovernmental organizations] who have no security support,” he said. “We should not see the Congo situation as a ‘perfect storm’ of difficult conditions aligned to create a particularly vexing outbreak — rather we should see it as a ‘new normal’ scenario that we need to be better prepared to address.”

On Sept. 14, HHS Secretary Alex Azar II, CDC Director Robert R. Redfield, MD, and Fauci led a U.S. delegation to the DRC, Rwanda and Uganda.

“The U.S.A. is here for you not just for Ebola, but also health care after Ebola,” Azar said during a meeting with community leaders in Butembo, a city in North-Kivu province that has been hit hard by the outbreak. “The U.S. recognizes that health challenges in the DRC extend past Ebola and also supports efforts to fight measles, malaria, HIV, tuberculosis, cholera and other diseases.” – by Joe Gramigna

• References
• CDC. 2014-2016 Ebola outbreak in West Africa. https://www.cdc.gov/vhf/ebola/history/2014-2016-outbreak/index.html. Accessed September 16, 2019.
• Henao-Restrepo AM, et al. Lancet. 2016;doi:10.1016/S0140-6736(16)32621-6.
• HHS. Secretary Azar to lead U.S. delegation to Democratic Republic of the Congo, Rwanda and Uganda regarding Ebola outbreak. https://www.hhs.gov/about/news/2019/09/09/secretary-azar-to-lead-u-s-delegation-to-democratic-republic-of-the-congo-rwanda-and-uganda-regarding-ebola-outbreak.html. Accessed September 16, 2019.
• WHO. Ebola dashboard RDC. https://who.maps.arcgis.com/apps/opsdashboard/index.html#/e70c3804f6044652bc37cce7d8fcef6c. Accessed September 16, 2019.
• WHO. Ebola virus diseases. https://www.who.int/ebola/historical-outbreaks-drc/en/. Accessed September 16, 2019.
• WHO. Preliminary results on the efficacy of rVSV-ZEBOV-GP Ebola vaccine using the ring vaccination strategy in the control of an Ebola outbreak in the Democratic Republic of the Congo: an example of integration of research into epidemic response. https://www.who.int/csr/resources/publications/ebola/ebola-ring-vaccination-results-12-april-2019.pdf. Accessed September 16, 2019.
• WHO. WHO adapts Ebola vaccination strategy in the Democratic Republic of the Congo to account for insecurity and community feedback. https://www.who.int/news-room/detail/07-05-2019-who-adapts-ebola-vaccination-strategy-in-the-democratic-republic-of-the-congo-to-account-for-insecurity-and-community-feedback. Accessed September 16, 2019.

• For more information:
• Lawrence O. Gostin, JD, can be reached at gostin@georgetown.edu.
• Tarik Jašarević can be reached at jasarevict@who.int.
• Ronald Klain can be reached at ron.klain@revolution.com.
• Anne Rimoin, PhD, MPH, can be reached at arimoin@g.ucla.edu.
• Pierre Rollin, MD, can be reached at boisverdun23@gmail.com.
• Mike Ryan, MD, MPH, can be reached at mediainquiries@who.int.
• Majid Sadigh, MD, can be reached at majid.sadigh@wchn.org.

Disclosures: Azar, Fauci, Gostin, Jašarević, Klain, Rollin, Ryan, Sadigh, Steffen and Tedros report no relevant financial disclosures. Rimoin reports funding from the Bill and Melinda Gates Foundation for vaccine-related studies.