The DRC's Ebola Outbreak and the Limits of Preparedness

As the Bundibugyo Ebola outbreak spreads across the DRC, advances in vaccines and therapeutics are being outpaced by conflict, mistrust, and gaps in contact tracing

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The number of confirmed Ebola cases in the Democratic Republic of Congo (DRC) has surpassed 4,000, including 1,887 deaths. The epidemic has primarily affected Ituri and North Kivu provinces and is characterised by delayed detection, the absence of a specific vaccine or treatment, a fatality rate of 30–50 per cent, and an outbreak response hindered by prolonged conflict. This is the third known outbreak of Bundibugyo virus (BDBV), highlighting a gap in Ebola preparedness, even as significant progress has been made in developing medical countermeasures for Zaire Ebolavirus. The World Health Organization (WHO) declared the outbreak a public health emergency of international concern on 17 May, although it is likely to have started as early as mid-January this year. Presently, ongoing transmission is confined to the DRC, with Uganda having reported no new cases since 21 June. The speed at which transmission is occurring, coupled with difficulties in contact tracing and containment, highlights challenges to epidemic preparedness.

The WHO is exploring the possible effectiveness of MSD's (Merck) Ervebo vaccine — an Ebola vaccine used to prevent Zaire Ebolavirus — to address BDBV. Until last week, however, the organisation had advised against the use of Ervebo for the current outbreak, highlighting that studies had not indicated whether sufficient cross-protective immunity could be provided to offset a BDBV infection. Following pre-clinical trials on Ervebo and BDBV infection, a WHO Technical Advisory Group on candidate vaccine prioritisation recommended on 7 August that clinical trials commence as a priority. Gavi, the Vaccine Alliance, currently has stockpiles of 500,000 Ervebo doses that can be utilised in a Phase III clinical trial set to commence shortly.

Research and Development as an Outbreak Response

Nevertheless, preference still lies with developing a specific vaccine against BDBV. A vaccine candidate, ChAdOx1 BDBV, being developed by a team at the Oxford Vaccine Group (University of Oxford), has entered Phase I clinical trials. It uses the same platform as the Oxford-AstraZeneca Covid-19 vaccine. If clinical trials find the candidate to be both safe and efficacious, the global foundation Coalition for Epidemic Preparedness Innovations (CEPI) will work alongside the University of Oxford and the Serum Institute of India (SII) in conducting additional studies to support eventual licensure or emergency use authorisation. SII has provided 4,000 doses of this investigational vaccine for the ongoing studies and has stockpiled 620,000 doses for future ones. Under its current agreement with CEPI, SII will produce master seed stock and clinical-grade doses.

CEPI has also backed an mRNA vaccine candidate. Moderna began its first in-human testing of mRNA-1469, against BDBV, at three sites in Canada. In addition, CEPI is supporting two other vaccine developers — the International AIDS Vaccine Initiative (IAVI) and Public Health Vaccines. They are using a recombinant vesicular stomatitis virus (rVSV) engineered platform, similar to MSD's (Merck) Ervebo vaccine. Pre-clinical studies with a single rVSV dose have been observed to induce protective immunity, with plans underway to prepare pre-master virus seed stock ahead of future clinical trials. Gavi is prepared to supply doses with a fund of approximately US$40 million and is developing incentive structures for long-term investment in emergency outbreak responses.

As treatments are being developed, the DRC plans to use the antiviral remdesivir — which nearby Uganda claims to have used during its outbreak — to manage symptoms. The WHO has recommended its use on its own as well as in combination with monoclonal antibodies in a scientific trial. PARTNERS (Platform Adaptive Randomised Trial for New and Repurposed Filovirus TreatmentS), a WHO-sponsored clinical trial examining the combinatorial effect of remdesivir and the monoclonal antibody MBP134, is investigating its therapeutic effect on those diagnosed with BDBV. It is coordinated by the Institut National de Recherche Biomédicale in the DRC, the Institute of Tropical Medicine in Belgium, and the University of Oxford in the United Kingdom, and is currently recruiting patients in the DRC. MBP134 is used as a treatment for Sudan Ebolavirus in primate studies, while another monoclonal antibody, maftivimab, is used to treat Zaire Ebolavirus. The US Department of Health and Human Services has made MBP134 available for Americans with high-risk exposure to BDBV.

Reports indicate that more than 80 percent of cases are not on patients' contact lists, indicating that chains of transmission are being missed. The same applies to vaccine strategies for Ebola, which typically follow a ring vaccination strategy that relies on strong contact tracing. When contact tracing weakens, promising vaccines and therapeutics may not be effective.

Finally, the antiviral obeldesivir is also being prioritised for development as a post-exposure prophylaxis for high-risk (exposed) contacts, following encouraging pre-clinical studies. However, such interventions depend on identifying high-risk contacts early in the disease course, highlighting the importance of contact tracing. Reports indicate that more than 80 percent of cases are not on patients' contact lists, indicating that chains of transmission are being missed. The same applies to vaccine strategies for Ebola, which typically follow a ring vaccination strategy that relies on strong contact tracing. When contact tracing weakens, promising vaccines and therapeutics may not be effective.

Trust Alongside Innovation

The ongoing conflict in the DRC adds another layer of complexity to the epidemic. With a highly mobile population, contact tracing is difficult, creating a persistent strain on healthcare systems attempting to keep containment measures ahead of the pace of transmission. Further, healthcare workers, who face considerable risk, have gone on strike in many regions over pay issues, weakening response capacity.

Militarised responses during the 2018 Ebola outbreak, combined with colonial legacies surrounding biomedicine, have contributed to mistrust in global health response mechanisms. Continuous community engagement is essential to building trust alongside healthcare innovations.

A major factor contributing to the challenges in contact tracing stems from fear of the humanitarian response rather than the disease itself. Militarised responses during the 2018 Ebola outbreak, combined with colonial legacies surrounding biomedicine, have contributed to mistrust in global health response mechanisms. Continuous community engagement is essential to building trust alongside healthcare innovations.

Conclusion

The current Ebola outbreak highlights how far R&D on vaccines and therapeutics has progressed, while showing how much work remains. Vaccine platforms, monoclonal antibodies, and antivirals demonstrate significant progress since the 2014 outbreak. However, this BDBV outbreak shows the limitations of preparing for one kind of virus while others go unaccounted for. Epidemic preparedness involves not only developing a single vaccine, but planning for outbreaks of genetically similar viruses, multiple vaccine platforms, and financial mechanisms to support production. Technology, however, cannot substitute for strong surveillance and trust in healthcare systems. An enduring lesson from Ebola is that while science can provide the necessary tools to contain an outbreak, trust in it is essential to putting these tools to work.

Lakshmy Ramakrishnan is an Associate Fellow with the Centre for New Economic Diplomacy at the Observer Research Foundation.

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