Ebola researchers fight to test drugs and vaccines in a war zone

This story was supported by the Pulitzer Center on Crisis Reporting.

Beni, Democratic Republic of the Congo

Heart and biochemical monitors flash next to a woman lying on a cot in an Ebola treatment center. His bed is enclosed in a clear plastic cube to contain the virus, and an experimental drug flows through his veins.

The race to develop treatments for the Ebola virus has accelerated since the largest epidemic of all time devastated in West Africa between 2014 and 2016. Scientists who responded to the outbreak in the Democratic Republic of Congo (DRC) enrolled more than 500 participants in an unprecedented study of experimental drugs that vaccinated nearly 170,000 people and sequenced the genomes of more than 270 Ebola samples taken from patients.

"This outbreak is clearly a milestone for rigorous and quality research," said David Heymann, epidemiologist at the London School of Hygiene and Tropical Medicine. "We will have definitive answers."

Progress is badly needed. The DRC epidemic, which lasted one year, is the second largest and the first to occur in a war zone. The violence has hindered efforts to contain the virus, prompting the World Health Organization (WHO) to declare July 17 "a public health emergency of international concern." According to the agency, nearly 2,600 people in the DRC have been infected with the Ebola virus and more than 1,700 have died.

Working in a conflict zone has forced researchers to adapt and persevere in an extraordinary way. They have learned to conduct rigorous studies in areas where murders, kidnappings and arson are commonplace and where people at the origin of the Ebola virus have been the subject of repeated attacks. . Although biomedical advances alone can not defeat Ebola, scientists studying this epidemic continue to believe that their growing knowledge will help end it – and limit future ones.

"It's not easy," says Jean Jacques Muyembe Tamfum, a microbiologist who has contributed to the discovery of the Ebola virus and now heads the National Institute of Biomedical Research (INRB) in Kinshasa. "You do that and people shoot."

In concert with other Congolese researchers, he is also working to ensure that any breakthrough benefits their home country, which has experienced more outbreaks of Ebola. "It's very important that the research be done here because ultimately, the Ebola virus is our problem," said Sabue Mulangu, an infectious disease researcher at INRB.

Desperate measures

Muyembe first encountered the Ebola virus in 1976 when he was investigating a series of deaths in Yambuku, a village in northern DRC. By collecting the blood of the sick, he noticed that their wounds did not coagulate. "My fingers were covered with blood," he says. The samples were sent to laboratories located in Antwerp (Belgium) and Atlanta (Georgia), where virologists isolated the Ebola virus and named it after the river that feeds Yambuku.

Scientists knew nothing about the virus until 1995, when an epidemic in Kikwit, DRC, killed 245 people in six months. Muyembe, Heymann and other researchers have documented how the virus causes internal bleeding to a person until the organ fails. Desperate for healing, Muyembe transfused the blood of people who had beaten the Ebola virus – which he suspected was rich in anti-virus antibodies – to eight people plagued by the disease. Seven survived.

Subsequent studies in monkeys at the US National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, did not reproduce the result, but Muyembe refused to "keep it up to date." to abandon. "In my mind, I said that there should be a truth here," he recalls in his office in Kinshasa. A poster depicting the portraits of four nuns who died in Kikwit hangs on the wall.

In 2006, Muyembe sent two Kikwit survivors to NIAID, where researchers – including Mulangu – isolated and studied volunteers' antibodies. One of the drugs tested during the last outbreak, mAb114, is based on the antibodies of these Kikwit survivors.

The drug was one of many drugs approved by the DRC government shortly before the outbreak was declared, in August 2018. Two other antibody treatments – ZMapp and REGN – EB3 – and one drug antiviral, remdesivir, were also included.

But the researchers pushed for a clinical trial to determine which therapy worked best. "It would be frustrating to use these interventions, but at the end of the epidemic, do not have more knowledge than when you started," says Anthony Fauci, director of NIAID.

With other scientists, he eventually developed a randomized clinical trial project comparing the four drugs, ensuring that each participant received one of the treatments. Their innovative design allows tests to stop and start as needed. This flexibility has proven crucial in the face of the ubiquitous violence in the Far North Region, where the Ebola virus is spreading.

"People want to kill me"

All aspects of the epidemic are affected by the long history of conflict and trauma in the region. Residents have endured more than two decades of terror from armed groups, as well as exploitation of resources, political instability and neglect from around the world. This has sparked mistrust of authorities – including foreign health workers – and conspiracy theories about the reasons for the Ebola outbreak. According to a popular rumor, people infected with the Ebola virus would inject lethal substances into people at treatment centers and vaccination sites.

According to WHO, these misconceptions have resulted in nearly 200 attacks against Ebola responders and treatment centers so far this year, according to WHO. Seven people were killed and 58 injured.

In order to adapt to the conflict, clinical researchers at an Ebola center in Beni operated by the French medical charity ALIMA give cell phones to patients leaving the clinic. This allows them to stay in touch with persistent symptoms, even if the violence prevents them from following the follow-up appointments. According to Émilie Gaudin, support officer at ALIMA, many people use this service as an emergency telephone support service. "Sometimes a patient calls us and says," People want to kill me "or" I want to kill myself. "

Despite this challenging environment, the trial of the drug is almost complete. The researchers are 14 people away from their goal of recruiting 545 participants, a threshold that should allow them to draw strong conclusions about the effectiveness of drugs. But there is already evidence that treatments work. The death rate in Ebola treatment centers, where all patients receive one of the experimental drugs, is between 35 and 40% – compared to 67% for the whole of this outbreak. This last figure reflects the large number of people who have died at home or in facilities that are not equipped to treat the Ebola virus.

Violence has also hindered immunization efforts. A few months ago, Diallo Abdourahamane, WHO coordinator for the Ebola vaccine, heard about a man from the city of Katwa that his team had immunized with an experimental vaccine against the Ebola virus manufactured by the pharmaceutical company Merck. The man had told skeptical witnesses that the vaccine would protect against the disease. "But after the departure of the team," said Abdourahamane, "the neighbors came and surrounded him at night, they said," You are the one helping to bring Ebola back to our area "and they killed him. "

This traumatic experience has prompted Abdourahamane and his colleagues to change the way they vaccinate people. Their initial strategy, used by Abdourahamane with the same vaccine in Guinea in 2016, was to install a vaccination site near the home of a patient's contacts and to offer him the injection. Now, they offer contacts the opportunity to be vaccinated in nearby cities, away from prying eyes. Borrowing a term from the short-term sales spaces known as ephemeral shops, they call this "ephemeral vaccination".

The team has also developed a strategy for vaccinating people when violence makes contact tracing too risky. This has evolved when the Ebola virus began to spread among the May-May, militias in eastern DRC. "If they accept vaccination, they usually do not want us to come with security," say soldiers and police, Abdourahamane said. "So we come without security, but we do not want to stay long."

But attacks on Ebola workers thwarted Ebola virus genome sequencing projects in Katwa. An Ebola treatment center was set on fire in February and a target shot in March. In April, a WHO epidemiologist was killed in the neighboring city of Butembo. For now, INRB researchers have decided to continue shipping to Kinshasa most of the blood samples of patients with Ebola virus disease across the country, for purposes of genomic badysis.

Build knowledge

Mosquitoes invade the INRB campus at dusk in mid-June and goats graze on the lawn. This is the first time of the day that microbiologist Steve Ahuka is taking a break. He and his colleagues have been inundated with work since the beginning of the epidemic and had to prioritize research that could have the greatest immediate impact.

Early genetic badyzes by scientists on Ebola virus samples confirmed that the Merck vaccine, rVSV-ZEBOV, would trigger an effective immune response. Now, they are hastily sequencing virus samples taken from areas affected by the Ebola virus, including Uganda, where three people were diagnosed in June. By comparing these data with the genetic makeup of Ebola samples taken elsewhere, they can determine where people have been infected. People who respond to the Ebola virus use this information to locate other people who may have been exposed to the virus.

When the outbreak is finally over, Ahuka said his colleagues would have time to publish their work and upload the genomic sequences. They also hope to explore issues they have not had time to address, such as whether certain Ebola mutations are badociated with a higher risk of death.

The INRB uses the Japanese government's money to create a biobank to store blood samples containing Ebola virus. Once completed, researchers outside the DRC may request to study the samples in Kinshasa – but the DRC government will not send specimens out of the country. "We would like to avoid what has happened in West Africa," said Ahuka, who was working in a molecular biology laboratory in Guinea during the 2014-2016 epidemic. "We handled a lot of samples and badumed they belonged to the country," he recalls. "But all the samples have been shipped."

In the end, many scientific articles and patents based on blood samples taken during hatching in West Africa were written by scientists from American and European institutions. This frustrated researchers in countries devastated by the virus, who hoped that studying certain aspects of the epidemic would enhance their ability to respond to future outbreaks of infectious diseases.

Heymann, who collaborated with Muyembe during the Kikwit epidemic 25 years ago, understands the position of Congolese researchers. "We should want them to have the ability to do it themselves," he says, "because they know their culture better."