Ebola virus disease in DR Congo.

As the outbreak of Ebola virus disease in the Democratic Republic of Congo is ending, there are important lessons to be learnt. Talha Burki reports.

As The Lancet Infectious Diseases went to press, the Democratic Republic of Congo (DRC) had not reported any new cases of Ebola virus disease since Feb 17, 2020. On March 3, the last patient with a confirmed diagnosis of the disease was discharged from an Ebola Treatment Centre in Beni, North Kivu, the former epicentre of the epidemic. Since the DRC Ministry of Health gave notice of the nation's tenth Ebola outbreak in August 2018, there have been 3444 cases and 2264 deaths. WHO has classified the situation as a Public Health Emergency of International Concern, a designation it reaffirmed earlier this year.

WHO cautioned that there remains a high risk of additional cases of Ebola emerging in DRC. “Outbreaks have historically always been a bit bumpy as you get to the tail-end”, agrees Charlie Weller, from the Wellcome Trust. In a statement to the media, Ibrahima Socé Fall, from WHO, pointed out that it was possible that transmission was occurring among groups who were not being monitored. “It is critical to maintain surveillance and rapid response capacities”, said Socé Fall. He added that there is an immediate funding shortfall of US $20 million. “If no new resources are received, we will run out of money before the end of the outbreak”, warned Socé Fall. “If we are forced to scale back operations because of a lack of funds, and then a new case emerges, we might not have the people and resources on the ground that we need to shut down transmission quickly.”

WHO will not declare an end to the Ebola epidemic until 42 days have passed without any confirmed or probable new cases; the countdown began when the Beni patient tested negative for Ebola virus disease for the second time. There is still the chance that a patient may relapse. When this occurred earlier in the outbreak, it took several months to put an end to the chain of transmission. The virus can linger for months or even years in a few bodily fluids. WHO advises continuing to test survivors’ semen samples until there are two consecutive negative results. It also recommends maintaining heightened vigilance for at least 6 months after the initial 42 day period without a new case, which implies active surveillance and post-mortem testing. Passive surveillance should continue indefinitely. After all, Ebola is endemic to the region.

Nonetheless, experts are cautiously optimistic. “Most of us think that the decrease in cases is real”, said Daniel Bausch (Director of the UK Public Health Rapid Support Team, led by Public Health England and the London School of Hygiene & Tropical Medicine). He believes that the epidemic could easily have run out of control. “In the worst-case scenario, we could have seen 30 000 plus cases and further destabilisation of an already-unstable area, with all the resultant political and economic consequences”, Bausch told The Lancet Infectious Diseases.

The neighbouring provinces of North Kivu and Ituri, where the outbreak has been concentrated, are among the most troubled areas in the world. Years of neglect and warfare have taken their toll. The region is home to dozens of militias. In June 2019, villages in Ituri came under attack. 117 people were murdered. Some were beheaded. 420 healthcare facilities have been attacked since the Ebola outbreak was first declared. Measles, malaria, and malnutrition have added to the chaos.

“We were coming into a situation where there had been two decades of violence, kids dying of all kinds of other diseases, and no-one was around to worry about it”, explains Bausch. “Then Ebola arrives, a disease that these people have never heard of or seen before, they are not even convinced it exists, and even if it does exist, they think maybe you are the one who brought it. Quite predictably and understandably, you are not going to get immediate community buy-in.” The highly mobile nature of the population further complicated control efforts.

“There has been a remarkable public health response”, said Weller. “Part of that is the vaccine but it is also to do with infection prevention and control and the efforts of frontline workers. There has been local ownership and a pattern of working pretty quickly.” Some 300 000 people have received Merck's rVSV-ZEBOV vaccine in a ring vaccination strategy. Preliminary results indicated an acceptance rate of 90·8% and efficacy of 97·5%. The vaccine has been rolled out on a compassionate use basis. Late last year, WHO prequalified the Merck vaccine. Four African nations, including DRC, subsequently licensed it, which will simplify its use in any future outbreaks. 11 laboratories testing around 3500 samples per week have been established in DRC, as well as 11 Ebola Treatment Centres. 250 000 contacts have been registered.

Researchers have also identified two promising therapeutics for Ebola, after early results from a randomised clinical trial run in DRC. A trial of Johnson & Johnson's Ad26.ZEBOV/MVA-BN vaccine started in November 2019. The vaccine is intended as a preventive measure, to be deployed in at-risk areas with no active transmission. It requires two doses, given 56 days apart. More than 20 000 people in Goma have received the first dose of the vaccine.

The trial is designed as an effectiveness study, but without any cases of the disease it will not be possible to accrue any data. Bausch is co-principal investigator. He points out that even if the trial fails to achieve its primary aim, there is still considerable utility in establishing the protocol and examining the feasibility of the two-dose schedule. After all, phase 3 clinical trials for Ebola therapeutics and vaccines are only possible during an outbreak. “You learn how to put things in place and it pushes you further ahead in terms of figuring out the cold chain, logistics, and supply”, said Bausch. “And in the event of a new outbreak, you are better prepared.” A decision is pending on whether to recast the trial to collect other data, such as immunogenicity.

WHO has set up multi-disciplinary survivor programmes for those who have recovered from Ebola, including specialised services such as ophthalmology and psychosocial counselling. The programmes will run for at least 18 months. Take-up is high. DRC's experience with Ebola could also stand them in good stead with another Public Health Emergency of International Concern. At a meeting of the African Union and the Africa Centres for Disease Control and Prevention in February 2020, WHO Director-General Tedros Adhanom Ghebreyesus noted that DRC was “leveraging the capacity they have built up to test for Ebola, to test for COVID-19”.

In the long-term, it will be vital to bolster the resilience of the healthcare system in DRC. “We definitely have to build capability and trust in the areas that are vulnerable to Ebola”, said Weller. As the epidemic took hold, policymakers were forced to divert resources that were needed elsewhere. “This is a major area that we desperately need to focus on”, said Bausch. “In some settings, the response to Ebola undermined the overall health system—we were commandeering services and personnel to fight a single disease. We need to figure out a way to strengthen systems so that they can deal with Ebola at the same time as everything else.”