It hasn’t been the longest, nor has it been the deadliest. But the Ebola outbreak that has ravaged a corner of the Democratic Republic of the Congo for much of the past two years has been one of the most challenging on record. With some long overdue luck, the outbreak will be declared over later this week.

The North Kivu-Ituri epidemic, named after the two provinces in eastern DRC where it has raged, is the second longest and second deadliest in history. If, as fervently hoped, Congolese authorities announce that Ebola has been vanquished there on Wednesday or Thursday, the outbreak will have lasted nearly 23 months. At least 3,463 people have been infected, and 2,280 of them having died. Those numbers could still rise: 490 so-called suspect cases are still being investigated to see if they should be added to the tally, according to the Congolese health ministry.

“This outbreak has been one of the most complex, dangerous, and difficult challenges that WHO has ever had to face,” Tedros Adhanom Ghebreyesus, director-general of the World Health Organization, told STAT.

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“We’ve lost colleagues. Families in DRC have lost loved ones. … This outbreak has taken so much from so many.”

The deadliest Ebola outbreak occurred in West Africa, mainly Guinea, Sierra Leone, and Liberia. That outbreak, which ran from late March 2014 to June 2016, infected and killed multiple times more people than had been infected and killed by all previous Ebola outbreaks combined. More than 28,600 people contracted Ebola during the West African outbreak and more than 11,300 people died.

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Northeastern Congo has long been enmeshed in conflict; a United Nations peacekeeping force has been stationed there since 1999. In a region where rebel forces fight government troops and local militias — which are known as Mai Mais — fight any intruders, Ebola had free range to spread while health responders could not.

“This was one of the major constraints,” said Michel Yao, the WHO’s response incident manager from the outset of the outbreak until last December. “Because you cannot move everywhere and the rule of law was not [in force] across the different areas.”

Although the teams trying to fight the virus often found their movement limited, people living in the region are highly mobile. Yao said it was not uncommon to go looking for a contact of a new case only to discover that, in the course of a day, the person could be nearly 200 miles away.

Within a month of the Aug. 1, 2018, declaration that Ebola had been found to be circulating in North Kivu and Ituri, rebel forces attacked government troops near Beni, where the response was headquartered, prompting the United States to pull government employees from the outbreak zone.

A number of experts from the Centers for Disease Control and Prevention were already in country assessing the situation. The government deemed the risk too high for American personnel, forcing some of the world’s best Ebola responders to offer advice from a distance for the remainder of the outbreak.

 

The outbreak response was run by the Congolese government, with assistance from the WHO, other UN agencies, and a multitude of aid groups and emergency medical response organizations such as Doctors Without Borders and ALIMA.

Time and again, efforts to bring the outbreak under control were crippled when violence erupted in the region. The people of the region, fed up with the endless violence, would respond with protests known as “villes mortes,” or dead cities. All activity would be shut down, sometimes for days. While the Ebola responders waited for permission to resume their jobs, the virus spread.

In February 2019, when inroads appeared to be being made, the outbreak response faced a new and dangerous phase — angry locals began to attack Ebola treatment centers, burning a couple to the ground.

Two months later, an epidemiologist from Cameroon working for the WHO, Richard Valery Mouzoko Kiboung, was killed in an attack. Over the course of the outbreak, 11 people working for the response have been killed, and another 86 have been injured.

For Yao, who is WHO’s program manager for health emergencies in Africa, this was the most difficult part of a difficult job. “It was the first time in my operation that I had to bring back home dead colleagues. … It was very tough,” he said.

Tedros, who visited the outbreak zone 10 times, was there during three attacks. At one point, he refused to evacuate from a dangerous location unless the helicopter also ferried out a response worker who had been gravely injured.

In addition to the attacks, there was always the risk that the virus would jump the borders of DRC and ignite additional epidemics in neighboring countries. While a few infected people crossed into Uganda, and there were concerns there may have been unreported cases in Tanzania, Congo’s neighbors were largely spared.

The science of containing and treating Ebola made some significant advances during the North Kivu outbreak.

Alima rolled out an apparatus known as “the cube,” which allowed medical professionals to treat Ebola patients from the outside of a plastic enclosure, without requiring them to wear onerous layers of personal protective equipment.

This was the first Ebola outbreak in history in which vaccine was used from the very start to control it. More than 300,000 people were vaccinated with Merck’s Ervebo, which in late 2019 became the world’s first fully licensed Ebola vaccine.

Late in the outbreak, a second vaccine, made by Johnson & Johnson, was put into the field in a clinical trial. That vaccine has been recommended for licensure in Europe; the Food and Drug Administration may soon approve it as well.

A large clinical trial tested four experimental therapeutics. For the first time, two were found to improve survival: a cocktail of three monoclonal Ebola antibodies made by Regeneron Pharmaceuticals and mAb114, a single monoclonal antibody developed by the National Institute of Allergy and Infectious Diseases in conjunction with DRC’s National Institute of Biomedical Research.

Until a few years ago it was thought to be impossible to conduct clinical trials during an Ebola outbreak. Now researchers have seen it’s possible — and must seize opportunities to test vaccines or drugs when they present themselves, said Josie Golding, epidemics lead for the Wellcome Trust.

“Carrying out clinical research and trials to develop tools to treat or prevent such an epidemic disease has to be norm, otherwise we are left without any hope for our communities, and only with fear,” Golding said via email. “But we are all aware how challenging it is to do such research in outbreaks, and it is remarkable that it was carried out under such high-security settings.”

Golding said countries at risk of having Ebola outbreaks should proactively approve Ebola vaccines and have protocols in place for use of experimental therapeutics — neither the Regeneron monoclonal cocktail nor mAb114 has yet been licensed — so they can be quickly deployed if the need arises.

The North Kivu outbreak has “given the world valuable lessons, and valuable tools. A vaccine has been licensed, and effective treatments identified. When we get to zero, we will celebrate but we must collectively resist complacency,” said Tedros, noting that “viruses do not take breaks.”

DRC already has evidence of that: Across the country, on the western border, a new outbreak is already underway. To date 18 cases — 15 of them fatal — have been reported in Équateur province.

North Kivu was thought to be nearly over once before, in early April. But days before the announcement could be made, a new cluster of seven cases appeared in Beni. The last of those patients was released from hospital on May 14, starting the clock for the declaration that this long outbreak would be finally over. Forty-two days — two full incubation periods — must elapse before an outbreak can be deemed to be over.

Yao is watching the situation nervously. “Crossing fingers tightly,” he said.

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