The Ongoing Ebola Epidemic in the Democratic Republic of Congo, 2018–2019

Article initially published in The New England Journal of Medicine on July 25, 2019 and written by Oly Ilunga Kalenga, M.D., Ph.D., Matshidiso Moeti, M.D., Annie Sparrow, M.B., B.S., M.D., M.P.H., Vinh-Kim Nguyen, M.D., Ph.D., Daniel Lucey, M.D., M.P.H., and Tedros A. Ghebreyesus, Ph.D.

Abstract

The international response to the evolving Ebola epidemic in eastern Democratic Republic of Congo (DRC) has had interim successes while facing ongoing difficulties. The outbreak has occurred in an area of intractable conflict among multiple armed groups at a time of contentious national elections. Despite porous international borders and considerable population movement, however, transmission has been confined to North Kivu and Ituri provinces. Factors potentially contributing to this containment include conduct of about 55 million screenings, surveillance of contacts (12,591 under surveillance currently), testing of 280 samples per day, provision of safe and dignified burials for most deaths, vaccination of high-risk people (112,485 vaccinated as of May 7, 2019), and medical treatment including four investigational therapies. Major challenges remain. Since late February 2019, a sharp rise in cases and increased transmission have been observed. These coincide with organized attacks by armed groups targeting response teams, deteriorating security, and the population’s increasing distrust of the response effort. The risk of local and regional spread remains high given the high proportion of deaths occurring outside treatment facilities, relatively low proportions of new patients who were known contacts, ongoing nosocomial transmission, and persistent delays in detection and reporting. Stopping this epidemic will require the alignment of the principal political and armed groups in eastern DRC in support of the response.

The ongoing epidemic of Ebola virus disease (EVD) in the Democratic Republic of Congo (DRC) is the tenth and largest EVD outbreak in the DRC since Zaire ebolavirus was first discovered there in 1976.¹ Though the current epidemic involved 1600 patients as of May 7, 2019, with a case fatality rate of 67%,² it is still an order of magnitude smaller than the West African EVD epidemic of 2013–2016, which caused more than 28,000 cases.³ Each of the countries involved in that outbreak³ had more cases than the DRC does today (Sierra Leone, 14,124; Liberia, 10,678; and Guinea, 3814). This EVD outbreak is occurring in North Kivu and Ituri provinces of eastern DRC, a region characterized by intractable armed conflict, proliferating armed groups, and massive population movement across porous international borders with Uganda, Rwanda, and South Sudan. Numerous operational challenges posed by chronic insecurity are compounded by political tensions associated with contested national elections. Violence has increasingly been targeted at EVD response teams and facilities, exacerbating the spread of the virus. Despite the high risk of regional spread, however, no cases had been identified outside North Kivu and Ituri provinces of eastern DRC as of mid-May.

The DRC Ministry of Health (MOH), in accordance with the International Health Regulations,⁴ notified the World Health Organization (WHO) about the outbreak on August 1, 2018.⁵ The declaration came a week after the official end of the ninth outbreak in Equateur province in western DRC.⁶ Genetic sequencing identified a strain of Zaire ebolavirus unrelated to the one implicated in Equateur.⁷ Of DRC’s 10 outbreaks, this is the first in North Kivu and Ituri provinces and the first time two epidemiologically and genetically distinct outbreaks of EVD have emerged within weeks of each other.

Response efforts include real-time epidemiologic surveillance, with widely disseminated daily updates and weekly situation reports informing the response and strategic planning. Additional response efforts have included a rapid rollout of the rVSV-ZEBOV-GP vaccine, systematic screening of tens of millions of travelers at 80 points of entry, and investigational treatments made available at scale to all eligible persons with laboratory-confirmed EVD through either a compassionate-use protocol or a randomized, controlled trial. Here we examine key approaches and ongoing challenges for the operational response within this climate of insecurity, with reference to the epidemiologic trajectory and data gathered by MOH and WHO field teams.

Context

To set the stage: in the DRC, malaria is the leading cause of premature death, followed by neonatal disease, pneumonia, diarrheal disease, and tuberculosis.⁸ Ongoing outbreaks of measles and four distinct strains of circulating vaccine-derived poliovirus reflect critically low coverage of preventable childhood illnesses.⁹ Other outbreaks include cholera, yellow fever, and monkey pox. Considered the setting of the world’s longest humanitarian crisis, the DRC is economically and politically fragile. Life expectancy at birth is 60 years, and the infant mortality rate in 2017 was 70 deaths per 1000 live births.¹⁰ In comparison, in neighboring Rwanda, life expectancy is 67.5 years, and the infant mortality rate is 29 deaths per 1000 live births.¹⁰ The DRC’s Healthcare Access and Quality Index — a summary measure of 32 causes of death that are considered avoidable if high-quality health care is available (range, 0 to 100, with lower scores indicating poorer access to and quality of health services)¹¹ — is 29.6, with an average increase of 1.9% per year since 2000⁸ (Rwanda’s index of 36 has increased by an average of 4% per year over the same period¹²).

The Equateur outbreak, involving just 54 cases, underscores the magnitude of the challenges of the current outbreak. Eastern DRC is plagued by intractable armed conflict, which has necessitated the continued presence, since 1999, of the world’s largest United Nations (U.N.) peacekeeping force. Dozens of armed groups, the remnants of regional wars sparked by the Rwandan genocide, compete for control of illegal taxation, territory, and trade of resources including gold, timber, charcoal, fuel, and illegal drugs. Decades of insecurity have resulted in appalling poverty, widespread unemployment, fragile social structures, and entrenched distrust of both the state and outsiders.

The North Kivu population of 8.3 million includes 2.5 million displaced persons and refugees,¹³ and many essential health care services are lacking. Chronic insecurity compromises access by disease-control programs — few areas outside the provincial capital city of Goma, for example, have rapid diagnostic tests or insecticide-treated bed nets for malaria prevention.

Escalating political and military violence between armed groups and members of the Congolese security forces is especially evident in the city of Beni, where between April 2017 and April 2019, as many as 888 civilians were violently killed, 1156 were abducted (many as child soldiers), and 269 were kidnapped for ransom.^14,15 Sexual violence, looting, and destruction of property are commonplace.¹⁴ Daily traffic across international borders (Uganda shares an 872-km border with the DRC) for trade, education, and social and health reasons is compounded by the flight of Congolese refugees.

The Epidemic

After investigation of a cluster of cases of acute hemorrhagic fever in Mangina village in the Malabako rural health zone in North Kivu, the outbreak was reported by the North Kivu Provincial Health authority on July 28, 2018, and was confirmed as EVD by the Institut National de Recherche Biomédicale (INRB) in Kinshasa on August 1, 2018.⁵ Although it was officially reported in August 2018, probable cases date back to April 30, 2018 (Figure 1).¹⁶ In late July 2018, nosocomial transmission within health centers amplified the outbreak, prompting detection and spread of the outbreak northward to Ituri province. Transmission in Ituri was largely brought under control by late August 2018. Successive infected people traveling eastward brought the virus to Beni in early August and from Beni south to Butembo and Katwa in September; all these areas are important commercial hubs with close ties to Uganda.

Sustained transmission in Butembo and Katwa led to clusters in neighboring towns and introductions of the virus into distant villages (Figure 2). By early February 2019, endogenous transmission in Beni and Ituri province was largely under control, and declines in transmission were observed in Katwa and Butembo.

Since late February 2019, increasing trends in incident cases and high proportions of community deaths have been observed. These have coincided with large-scale organized attacks targeting the response, which have resulted in recurrent suspension of response activities and reduced effectiveness of interventions.

As of May 7, 2019, a total of 1600 cases (1534 confirmed and 66 probable) have been recorded, and 1069 people have died — a case fatality rate of 67%.² Of all the infected people whose age and sex were recorded, 57% (907) were female and 30% (475) were children under 18 years of age.² Six percent (97) of total cases occurred in health care workers.²

The Response

A coordinated, multistrategy response in North Kivu and Ituri provinces has been led by the DRC MOH, supported by the WHO and more than 50 national and international partners. Preparedness measures have been implemented in bordering provinces and neighboring countries that are at risk, with prioritization of Uganda, South Sudan, and Rwanda and in close coordination with their ministries of health.

The data presented below represent information available through May 7, 2019. Data are derived from DRC MOH¹⁷ and WHO reports available online^18,19 and are informed by analyses provided by the WHO.

SURVEILLANCE

Case detection and investigation activities have been gradually strengthened over time and with the evolution of the outbreak. Of more than 1000 alerts reported each day from outbreak-affected areas, 88 to 92% are investigated within the first 24 hours.²⁰ Combined with cases detected by other mechanisms, this results in a daily average of 280 suspected cases.

The timeliness of identification of suspected cases and alerting of health authorities continues to be suboptimal. The median time from an alert of onset of illness to official report as a confirmed case of EVD is 6.0 days (interquartile range, 3.0 to 9.0). It takes time to investigate alerts, refer patients to testing sites, process and transport specimens to laboratories, and return laboratory results.

CONTACT TRACING

Timely identification of EVD cases in contacts of patients with EVD remains challenging. Examination of 911 patients with confirmed cases reported between January 1 and May 7, 2019, revealed that only 398 (44%) were registered as contacts before the onset of illness. These low numbers reflect the multifaceted challenges that response teams face in trying to list and identify contacts of patients who present to one or more community clinics where record-keeping is poor and in working among families and communities that are reluctant to cooperate. The challenge of finding contacts and detecting early symptoms is all the more acute in the context of insecurity and a highly mobile population often fearful of the response effort, with individuals often hiding, refusing to subject themselves to follow-up examinations, or traveling to distant homes in heavily forested areas and other destinations. Moreover, the difficulty field teams have in matching individuals from extensive contact lists probably leads to an underestimation of the proportion of cases among registered contacts. Nonetheless, most of the people with EVD who were initially deemed “nonregistered” contacts were retrospectively linked to cases or likely sites of exposure through epidemiologic investigation. Future phylogenetic studies should illuminate the transmission dynamics.

Patients who escape detection and in whom EVD subsequently develops play an important role in sustaining transmission and mitigate the broader effect of vaccination on epidemic control. As of May 7, 2019, approximately 88,000 contacts had been registered, of whom 12,777 are currently under surveillance, with follow-up rates of 79 to 84%.²⁰

SCREENING

Extensive population mapping and identification of high-risk areas informed a coordinated effort to screen, on average, more than 200,000 people per day at 80 points of entry and control, including the borders with Uganda, Rwanda, and South Sudan. Of more than 55 million screenings conducted, 896 resulted in alerts. All alerts from outside the DRC have turned out to be negative to date. Of 354 people whose alerts were validated, 9 had laboratory-confirmed EVD.²⁰ Three of these 9 people were identified while they were traveling to Goma. Since the city is connected by air to Addis Ababa, Ethiopia, and Bujumbura, Burundi, and since tens of thousands of people cross the border between Goma and Rwanda each day, Goma is a high-risk point for regional spread.²¹ In addition to a multisectoral protocol for the activation and deactivation of entry and exit screening at the airport, training sessions and refreshers have been provided to local screeners, including training on the use of a thermal camera (which enables rapid screening of large groups of people) at Goma Airport and the Grande Barriere border crossing.

VACCINATION

Vaccination with rVSV-ZEBOV-GP began on August 8, 2018. Rapid rollout was possible because the necessary protocols, cold chain, and trained teams were available after the Equateur outbreak. The rVSV-ZEBOV-GP vaccine is designed to work in the postexposure setting. A ring strategy is used to identify contacts and contacts of contacts. In addition, high-risk groups such as health care workers are being vaccinated, and targeted geographic vaccination and pop-up vaccination are being undertaken in high-risk areas. Vaccine uptake among eligible participants is more than 90%, with 112,485 people vaccinated through May 7, 2019,¹⁷ including nearly 30,000 health care workers.^18,19 This includes 4915 health care workers in Uganda and 1471 in South Sudan. The WHO has reported preliminary results that indicate efficacy of 97.5% in analyses of EVD onset 10 days or more after vaccination and 88.1% in analyses of EVD onset regardless of timing.²²

As recommended by the Strategic Advisory Group of Experts (SAGE), vaccination eligibility was expanded in February to include pregnant women,²³ and in April to include children over 6 months of age and lactating women,²⁴ in light of the high attack and case fatality rates in these groups and accumulating data on safety and efficacy in other groups. Although a WHO-sponsored clinical trial conducted in Guinea in 2014–2015 provided evidence of efficacy of both the vaccine and the vaccination strategy, no data are available for these populations.²⁵ The vaccine strategy was recently revised to take into consideration rising incidence, insecurity, and concerns over vaccine shortages.²⁶

LABORATORY DIAGNOSIS

Laboratory capacity was established initially in the Beni, Mangina, and Butembo health zones and was subsequently expanded to include Komanda, Goma, Katwa, and Bunia. More than 37,000 samples have been tested, with about 280 samples tested per day in the 5 weeks leading up to May 7, 2019; all laboratories use GeneXpert (Cepheid) polymerase chain reaction as the diagnostic tool. Laboratory confirmation or exclusion is limited by distances between health facilities and laboratories and by institution of a curfew between 6 p.m. and 6 a.m. The INRB laboratory in Kinshasa provides whole-genome sequencing, and real-time sequencing capacity has now been established in Katwa. A total of 167 of 188 viral sequences have been reported.²⁷ Limited genetic variation among virus isolates obtained from patients at different times and geographic locations suggests that all cases are related.²⁷²⁸ Strengthening laboratory capacity will allow genomic sequencing to be leveraged to support epidemiologic investigation by linking cases for which epidemiologic information is limited to ongoing chains of transmission and by identifying new chains of transmission.

SAFE AND DIGNIFIED BURIALS

Between 28 and 43% of deaths each week occur outside Ebola treatment and transit centers, in private hospitals and clinics, in community health centers, or at home. These cases pose a major transmission risk. The majority of these patients receive safe and dignified burials, which are crucial in cutting further chains of transmission. Patients who die in the 24 to 36 hours before laboratory tests are available are also given safe and dignified burials. Of 5223 alerts for safe and dignified burials received as of May 6, 2019, a total of 4150 (79.5%) were successfully managed by Red Cross, Civil Protection, and community emergency harm-reduction burial teams.²⁰ Safe management in cases of suspected or proven EVD requires minimal handling of human remains, disinfection, and internment in a specified site, while maintaining respect for religious and cultural sensitivities.²⁹ Oral swabs are obtained for detection of EVD. Despite the high numbers of alerts, relatively few people whose deaths triggered safe and dignified burial alerts have been confirmed to have had EVD.

INFECTION PREVENTION AND CONTROL

Concerted attempts have been made to rapidly decontaminate facilities where cases have been identified and to ensure that health care facilities and key sites (schools, public offices, and transit points) are equipped with training, infection prevention and control equipment (including personal protective equipment), and essential consumables such as chlorine, soap, and water. However, continuing nosocomial transmission (in up to 25% of cases) underscores the difficulty of implementing effective infection prevention and control. Among patients with confirmed EVD between January 1 and May 7 with a recorded history of exposure, 16% (161 patients) had visited a health center 2 to 21 days before the onset of EVD symptoms; 4% (43 patients) were health care workers. Nosocomial transmission may be accounting for higher proportions of EVD cases among children and women — vulnerable groups who must present for child and maternal health care — than it did in previous outbreaks in the DRC.¹ Of 1183 confirmed or probable EVD cases through April 11, 2019, in which age and sex were recorded, 36% (426) were in women of child-bearing age (15 to 49 years) and 26% (305) were in children younger than 15 years, including 77 (7%) infants younger than 12 months.¹⁷ The high risk to health care workers is evident. The lack of systematic collection of data on pregnant women and breast-feeding mothers in addition to the lack of official statistics on total numbers of health care workers in North Kivu and Ituri provinces limits more nuanced analysis.

CASE MANAGEMENT

Ebola treatment centers provide aggressive rehydration, correction of electrolyte imbalances, and nutritional support. This supportive care is not only a prerequisite to the use of novel therapeutics, but is also lifesaving in itself — the patient’s immune system plays a key antiviral role, and each day the patient survives improves the chance of cure. A compassionate-use protocol (Monitored Emergency Use of Unregistered and Investigational Interventions, or MEURI) is offered to all patients with laboratory-confirmed EVD.³⁰ This protocol includes three antibody-based therapies (MAb114, ZMapp, and REGN-EB3) and one antiviral agent (Remdesivir). A randomized, controlled trial of these four investigational treatments began on November 24, 2018 (ClinicalTrials.gov number, NCT03719586. opens in new tab); the trial was interrupted because of attacks on Ebola treatment centers in Katwa and Butembo, but it has since resumed.

RISK COMMUNICATION, COMMUNITY ENGAGEMENT, AND SOCIAL MOBILIZATION

Distrust of government extended to the health care provided by state-sponsored facilities. This was considered to be inferior to costly private health care and traditional healers. The nonspecific clinical signs of EVD — vomiting, diarrhea, sweating, dehydration, and hypovolemic shock — together with undifferentiated symptoms of fever, headache, fatigue, and myalgia — complicate diagnosis in the context of a high burden of other febrile infectious diseases and in a population in which coexisting conditions are common. In October 2018, a concurrent wave of malaria cases in Beni increased the difficulty of diagnosis and also the number of people exposed to Ebola in overcrowded health care facilities with inadequate infection prevention and control measures. Mass distribution of malaria drugs and bed nets, organized by the WHO with the support of the Global Fund, cut malaria cases, reduced the likelihood of EVD transmission at health centers, and increased community engagement.

Efforts to encourage greater local participation in and ownership of the response are ongoing and have yielded some success in areas that were initially difficult to reach. Community dialogues involving more than 100 participants have been held in areas where tension was observed between community members and Ebola response teams. Community Ebola committees are being set up in these areas to lead Ebola surveillance and interventions such as safe and dignified burials.

Social and Political Violence

Communities had no direct experience with Ebola, since it was previously unreported in this part of the DRC. Community reluctance was initially interpreted as a misunderstanding of public health practices such as isolation and safe burials, rather than as rejection of responses that required total separation from loved ones, denial of human touch at the point of death, and substitution of safe burials for traditional funeral rites that are of central importance to cultural and social life.³¹

In the politically charged atmosphere of impending national elections, tensions, resistance, and even violent incidents rose. Escorts of armed police or U.N. forces for community-response teams in insecure areas — militarization of the response — exacerbated tensions and further distanced the community from the response effort. The suspension of Beni and Butembo from the presidential vote in December fueled rumors that the epidemic was a political ruse to disenfranchise voters.^31,32 Other community members perceived the Ebola response as a business benefiting the rich and powerful.

Major violent events, such as the massacre of civilians in Beni in September 2018, the violence accompanying elections in December, and lethal attacks on Ebola treatment centers since late February 2019, have been accompanied by an uptick in infections and deaths¹⁷ (Figure 3). Beginning in 2019, community resistance (spontaneous attacks targeting response teams or facilities, triggered by fear or emotion) has escalated dramatically, in parallel with an escalation in armed conflict activities (any activity by armed groups that affects response operations, including direct attacks on EVD facilities and health care workers, and military operations in response areas) (Table 1 and Figure 4). Lethal attacks on the Ebola treatment centers run by Médecins sans Frontières (MSF) in Katwa³³ and Butembo³⁴ in the last week of February forced MSF to evacuate both epicenters.³³ With support from the WHO, the MOH reopened the Butembo Ebola treatment center, but after another lethal attack on March 9, patients fled to inaccessible areas.³⁵ Three more attacks on Ebola treatment centers or associated health facilities had occurred by May 7, 2019. On April 19, a Cameroonian doctor with the WHO was deliberately killed at Butembo University hospital.³⁶ These attacks arouse concern that armed groups are exploiting the epidemic for broader military or political ambitions, and they have resulted in recurrent temporary suspension of response activities in affected areas.

Discussion

This outbreak’s trajectory underscores the imperative to understand the complex interplay of biologic and social factors against the backdrop of a longer ecologic and political history. Although other outbreaks have occurred in conflict zones,³⁷ the events in eastern DRC illustrate the difficulties that can be generated by national, regional, and local politics and various power-holding groups, as the MOH and WHO strive to control EVD amid layers of armed, political, and social violence.

Violence associated with community resistance, which may be defused by careful community engagement, must be distinguished from organized attacks on highly visible symbols of the response. Attacks by armed groups targeting health facilities and medical personnel in settings of armed conflicts are a clear violation of the protection of health care provided under international humanitarian law.³⁸ Humanitarian space, which is necessary to operate in war zones, is generated by international humanitarian law governing the conduct of warring parties, in combination with the humanitarian principles laid out by the International Federation of Red Cross and Red Crescent Societies.³⁹

Compounding community resistance, these attacks have had a catastrophic effect on transmission and control. Early treatment with isolation is the most effective way to stop transmission. Attacks targeting Ebola treatment centers result in contagious patients fleeing to areas inaccessible for follow-up and vaccination. Fear of further attacks reduces the likelihood of new patients presenting for health care. The loss of operational capacity is further compromised by threats and violence directed against human resources. The consequences of such attacks in the DRC were recognized by the U.N. Security Council in October 2018, in Resolution 2439.⁴⁰ This resolution reaffirmed UNSC 2286, which specifically condemned attacks on medical facilities and personnel in armed conflicts.⁴¹ Medical personnel already at risk for contracting EVD are now faced with the risk of direct violence. With a density of 0.05 doctors per 1000 population, the DRC cannot afford to lose any more medical personnel.⁴² Distrust and militarization of the response breed further violence, engendering a vicious cycle.³¹

Contextual factors, local and regional interests, and the variable degree of community distance all play a role in explaining both the successes of the internationally supported national response in containing the epidemic and the worrisome failure to curb transmission. Compliance with control measures premised on an understanding of basic biosafety and public health cannot be assumed. Investigational treatments and vaccination are no substitute for culturally appropriate, endogenous social responses that support early detection and treatment. Even the best biomedical advances require social traction to work.

The third strategic response plan for this outbreak, covering mid-February through July 2019, emphasizes that a successful response must be anchored in the community.⁴³ Although the immediate goal is to end this outbreak, it is unlikely to be the DRC’s last, and the plan provides pragmatic opportunities to address other global concerns such as malaria and antimicrobial resistance. Community-based surveillance of EVD could benefit from the training of community health workers in the diagnosis of malaria using rapid diagnostic tests and in compliance with correct antimalarial regimens to reduce deaths from malaria and the risk of antimicrobial resistance.⁴⁴ Such actions could also reduce the number of alerts for safe and dignified burials, decrease nosocomial spread, address popular concerns about meeting other health care needs, and build trust, engagement, and outbreak preparedness.

Conclusions

Global health and protection from global contagious threats rest on the public health capacity of each country. Even in the middle of intractable conflict, success in controlling Ebola must be achieved. We have the tools of global disease surveillance, rapid-response systems, and biomedical solutions — if there is the political will to protect health workers in conflict zones while gaining the confidence of communities as primary partners in fighting outbreaks such as Ebola. Vigorous governmental leadership of the response must be balanced with attention to community concerns. The alignment of key political and armed groups behind the response effort is essential to stop the violence against health care and rehabilitate the humanitarian space required for outbreak control.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on May 29, 2019, at NEJM.org.

We thank the hundreds of colleagues on the ground who were responsible for gathering and analyzing data and the medical personnel and community health workers who put their lives on the line each day to treat patients and protect the most vulnerable.

Author Affiliations

From the Ministry of Health, Democratic Republic of Congo (O.I.K.); the World Health Organization Regional Office for Africa, Djoue, Brazzaville, Republic of the Congo (M.M.); the Graduate Institute of International and Development Studies (V.-K.N.), and the Office of the Director-General, World Health Organization (T.A.G.) — both in Geneva; the Icahn School of Medicine at Mount Sinai, New York (A.S.); and Medstar Georgetown University Hospital, Washington, DC (D.L.).

Address reprint requests to Dr. Sparrow at the Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, Box 1077, 1 Gustave L. Levy Pl., New York, NY 10029, or at [email protected].

Read the full article on nejm.org