BENI, Congo -- Rebels killed four Ebola response workers in an overnight ambush in eastern Congo, the World Health Organization said Thursday, warning that the attack will give the waning outbreak new momentum in what has been called a war zone.

“We are heartbroken that our worst fears have been realized,” WHO chief Tedros Adhanom Ghebreyesus said. It was by far the deadliest such attack in the second-worst Ebola outbreak in history, the United Nations health agency said.

The dead included a member of a vaccination team, two drivers and a police officer. Many of the six others wounded were with Congo’s health ministry.

Mai-Mai fighters attacked a camp housing scores of aid workers overnight in Biakato, local official Salambongo Selemani told The Associated Press. Warnings had been posted demanding that the health workers leave or face “the worst,” Selemani said.

The other attack targeted an Ebola response coordination office in Mangina, WHO said. Allied Democratic Forces rebels are to blame, Beni territory administrator Donat Kasereka Kibwana said.

WHO’s emergencies director Dr. Mike Ryan, however, said neither the attackers’ identities nor their motivation had been confirmed but it was “unmistakably a directed attack at the response.” More than 100 WHO staffers and other aid workers were evacuated.

This is not the first time that health workers trying to contain the outbreak have been targeted. Overall, health workers and infrastructure have been attacked 386 times with seven people killed and 77 wounded, Ryan said.

Some have called this outbreak more complicated than any other. Several rebel groups are active in the region, and local officials say some believe Ebola is nothing but a political ploy.

“Imagine, a doctor leaves home in the U.S. or elsewhere to come sleep in a tent to help save us from this scourge of Ebola and yet poorly educated young people want to attack him. ... It is very deplorable,” said Fiston Kamango, a youth leader in Biakato.

The latest attacks come after days of deadly unrest in the city of Beni, where residents outraged by repeated rebel attacks stormed the local U.N. peacekeeping base, demanding more protection. WHO evacuated 49 of its staffers there, leaving 71 in place.

The United States, Britain, Canada and Switzerland on Thursday issued a joint statement condemning the “senseless acts of violence” by armed groups and appealing for calm while saying they understood the local frustrations.

Ebola response work was put on lockdown in Beni, dismaying health experts who say every attack hurts crucial efforts to contain the deadly virus. Most of the recent new cases have been reported in the newly targeted communities of Biakato, Mangina and Beni.

“The last strongholds of the virus were in these areas,” WHO’s Ryan said. He called working conditions in the remote areas difficult at the best of times.

The number of cases had been dropping in the yearlong outbreak which has killed more than 2,100 people and was declared a rare global health emergency earlier this year. Several days this month, zero cases were reported. Just seven cases were reported in the past week, WHO said.

Cases have surged after previous attacks on health workers and facilities. “Ebola was retreating. These attacks will give it force again,” the WHO chief said.

In one example of how any pause can sharply affect Ebola containment efforts, WHO has said no one in Beni could be vaccinated against the virus on Monday. The health agency previously could trace more than 90% of contacts of infected people in the city but now that figure is just 17%, a U.N. spokesman said Tuesday.

Residents accuse Congolese and U.N. forces of not doing enough to protect civilians from the rebels who fight for control of the region’s vast mineral wealth. The ADF alone is blamed for the murders of more than 1,500 people in and around Beni in the past four years.

The latest rebel attack outside Beni killed 19 people, the U.N. said Wednesday.

After an emergency meeting Monday, President Felix Tshisekedi decided to allow joint operations between Congolese and U.N. forces in Beni following the protests that also burned the town hall.

Far from the capital, Kinshasa, some traumatized residents in the densely populated border region near Uganda and Rwanda are wary of outsiders, further complicating the Ebola containment work in a part of Congo that had never recorded the virus before.

Despite two promising new Ebola vaccines, health workers continue to battle misinformation and reluctance to seek treatment for the virus that is largely spread via close contact with the bodily fluids of infected people, including the dead.

In addition, many local health workers have been recruited by the “well-paying” Ebola response, leading to shortages of trained people to deal with other serious health issues such as an even deadlier measles outbreak and malaria, the medical charity Doctors Without Borders said in a statement.

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Anna reported from Johannesburg.

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