Uncovering the Drivers of Ebola Virus Disease Resurgence in DRC: A Root Cause Analysis of the 16th Outbreak in Mwaka, Kasai Province (2025)

Background

Ebola Virus Disease (EVD) remains a significant threat to global public health. Although its outbreaks are mostly localized to Afri- ca, the 2014–2016 West African epidemic highlighted EVD’s po- tential to cause international crises. Its high mortality rate, risk of international spread, and requirement for high-level containment have made it a WHO priority disease for research and response [1]. In North America, significant investments have been made into EVD vaccine research and deployment, such as the devel- opment and use of the rVSV-ZEBOV vaccine. Agencies like the U.S. Centers for Disease Control and Prevention (CDC) and the Public Health Agency of Canada (PHAC) have also contributed expert teams and resources during major outbreaks in Africa [1]. Australia has played a role primarily through funding and interna- tional health deployments, supporting WHO emergency response missions and vaccine development [2]. In Asia, countries like Chi- na and India have extended logistical and technical support, and engaged in research collaboration and construction of healthcare infrastructure in EVD-affected regions [3].

Europe’s response includes field deployments by Médecins Sans Frontières (MSF), genomic surveillance by the European Centre for Disease Prevention and Control (ECDC), and major sequenc- ing and bioinformatics contributions from institutions such as the Institute of Tropical Medicine (ITM) in Antwerp. Africa remains the epicenter of EVD, with the Democratic Republic of the Congo (DRC) reporting 16 outbreaks since the virus was first discovered in 1976. Despite this history, the country continues to face chal- lenges in surveillance, diagnostics, and health system resilience. The 16th outbreak in Mwaka (2025) occurred in the context of simultaneous public health emergencies—namely, mpox, cholera, and malaria—highlighting gaps in multioutbreak management ca- pacity [4,5].

Aim

This Root Cause Analysis (RCA) aims to systematically identify and understand the upstream factors and operational failures that led to the resurgence of EVD in Mwaka, Kasai Province (2025). The findings are intended to inform sustainable health systems strengthening, outbreak preparedness, and response strategies in DRC and comparable settings.

Methods

Design and Framework

The RCA was conducted using the “5 Whys” method integrated with systems thinking to investigate upstream and system-level drivers of the outbreak. Data sources included Ministry of Health reports, laboratory data from the Institut National de Recherche Biomédicale (INRB), WHO bulletins, and peer-reviewed genomic and epidemiological publications [4,6,7].

Laboratory and Bioinformatics

Approaches Laboratory confirmation involved molecular diagnostics using GeneXpert, the BioFire Global Fever Panel, and the Altona Re- alStar Filovirus RT-PCR Kit [4]. Positive samples were sequenced on an Oxford Nanopore GridION system using R10.4.1 flow cells. The sequencing produced a 99.97% complete genome, with a 99.52% match to the 1976 Yambuku-Mayinga strain [4]. Bioin- formatics tools included iVar for consensus genome generation, MAFFT for multiple sequence alignment, and IQTREE for phylo- genetic inference [6,7].

Ethics Statement

This Root Cause Analysis was based on data collected through routine public health surveillance activities during an officially declared outbreak. All genomic sequencing and clinical data were anonymized in compliance with DRC national health policies and reviewed by the INRB and the Ministry of Public Health. The analysis was conducted under ethical guidelines provided by the DRC National Health Ethics Committee. No personally identi- fiable information was used, and genomic data are shared under pre-publication agreements [4].

Results

A detailed root cause analysis (see Table 1) identifies several crit- ical weaknesses that contributed to the 16th Ebola Virus Disease (EVD) outbreak in the Democratic Republic of Congo (DRC). The outbreak likely originated from a zoonotic spillover event, ev- idenced by a 99.52% genetic similarity to the 1976 Yambuku strain and no linkage to recent human cases, highlighting an unmanaged wildlife-human interface. Surveillance systems failed to detect the outbreak early, with cases only identified after deaths—including among healthcare workers reflecting a lack of community-based surveillance. Diagnostic confirmation was delayed due to reliance on centralized laboratories in Kinshasa and the absence of region- al lab capacity and cold chain logistics. Concurrent epidemics of mpox, cholera, and malaria further strained health system resourc- es and weakened infection prevention and control (IPC) practices. Structural gaps such as fragmented preparedness and poor multi- sectoral coordination perpetuate the vulnerability of affected zones to repeated outbreaks.

                                                                          Table 1: Root Cause Summary Table

The outbreak, officially declared on 4 September 2025, centred in Bulape Health Zone, Kasai Province, with a single suspected spillover case in the neighbouring Mweka Health Zone (see Ta- ble 2). The causative virus was confirmed as Zaire ebolavirus, genetically like the 1976 strain, supporting the zoonotic spillover hypothesis. A total of 28 suspected, probable, or confirmed cas- es were reported, with 15 deaths, resulting in a provincial case fatality rate of 53.6%. The index case, a 34-year-old pregnant woman presenting with haemorrhagic symptoms, died rapid- ly, triggering further transmission, including nosocomial infec- tions. Bulape experienced a high case fatality rate of 62%, while Mweka reported one fatal suspected case, raising concerns about surveillance and containment capabilities in this isolated zone.

                                                          Table 2: Summary of Mwaka (Kasai, 2025) Ebola Outbreak 

When compared to the much larger North Kivu outbreak of 2018–2020 (see Table 3), the Kasai outbreak was smaller in scale but similarly exposed underlying systemic weaknesses. North Kivu’s outbreak was exacerbated by armed conflict and commu- nity mistrust, while Kasai’s challenges were primarily geographic isolation, weak logistics, and ecological risk. Importantly, North Kivu benefited from decentralized laboratory networks and dig- ital surveillance tools, enabling faster diagnostics and contact tracing. In contrast, Kasai relied on centralized confirmation in Kinshasa and lacked rapid detection mechanisms. Both outbreaks highlight the urgent need to strengthen multi-sectoral prepared- ness, including local laboratory capacity, community-based sur- veillance, rapid response logistics, and effective cross-zone coor- dination to mitigate future Ebola emergence in known hotspots.

                                                   Table 3: Comparison: Mwaka vs. North Kivu EVD Outbreaks

Discussion

The 2025 outbreak was genetically distinct from recent trans- mission chains and was most closely related to the 1976 Yam- buku-Mayinga strain [4]. This finding supports the conclusion that the outbreak was due to a novel zoonotic spillover event. Defor- estation, bushmeat consumption, and increased climate-related displacement of reservoir species—particularly bats—have ele- vated the risk of such spillovers in forest-edge communities [10]. A One Health framework is essential to address these intersecting environmental and biological drivers. The outbreak in Mwaka was detected only after several fatalities had occurred, including among healthcare workers [4]. This indicates a critical breakdown in local surveillance systems, which failed to detect early warning signs. Traditional, topdown alert systems are not functional in remote zones like Bulape, where community mistrust and limited health education persist. Implementing trusted communication channels, mobile reporting tools, and trained community health workers can significantly improve early detection [11].

Although sequencing was rapidly completed once samples reached Kinshasa, the centralization of diagnostic infrastructure created substantial delays. Geographic remoteness, lack of regional PCR capacity, and weak cold chain logistics contributed to a delayed outbreak confirmation [4]. In contrast to North Kivu, where mobile labs were available, Bulape lacked such decentralization. Priori- tizing the deployment of GeneXpert systems and biosafety-level diagnostics in provincial hubs is essential to reduce confirmation timeframes [12]. The outbreak coincided with active epidemics of mpox, cholera, and malaria, all competing for the same personnel, laboratory time, and financial resources [1,8,9]. This multi-out- break burden overwhelmed the already fragile health system and diluted the response to the Ebola outbreak. Compounded by donor fatigue and fragmented funding, the situation underscores the im- portance of integrated emergency management systems and con- sistent funding strategies [13].

Persistent Structural Weaknesses

Despite multiple EVD outbreaks in the DRC over the past two decades, health system resilience remains weak. The recurrence of outbreaks in similar geographic zones demonstrates the absence of sustained investment in preparedness, poor intersectoral coordina- tion, and limited local ownership [14]. Emergency interventions alone are not sufficient. Long-term solutions require the institu-tionalization of public health training, the development of region- al genomic labs, and governance reform to support decentralized outbreak response.

Conclusion

The 2025 Mwaka outbreak of Ebola Virus Disease reveals that zoonotic spillovers remain a pressing threat, particularly in areas marked by ecological fragility and weak public health systems. Although DRC has made strides in genomic surveillance and rapid outbreak declaration, diagnostic centralization, poor surveillance, and inadequate system resilience continue to hinder response ef- forts. Effective future containment will require localized outbreak detection, decentralized diagnostic capacity, and a coordinated One Health strategy to manage ecological and structural risks sus- tainably.

Declaration

Ethics approval and consent to participate

This Root Cause Analysis was conducted based on data collect- ed through routine public health surveillance activities during an officially declared outbreak. All genomic sequencing and clinical data were anonymized and handled in accordance with the Demo- cratic Republic of Congo’s national health policies. The study was reviewed and approved by the DRC National Health Ethics Com- mittee. Individual informed consent was waived due to the use of de-identified secondary data collected for public health purposes.

Consent for publication

Not applicable. This manuscript does not contain any person’s data in any form.

Availability of data and materials

All data generated or analyzed during this study are included in this published article and its supplementary information files. Ge- nomic sequence data are available under pre-publication agree- ments and can be accessed upon reasonable request to the corre- sponding author.

Competing interests

The authors declare that they have no competing interests.

Funding

This study was supported by institutional funding from Walter Si- sulu University, University of South Africa, and the University of Mbuji-Mayi. No specific external funding was received for this research.

Authors’ contributions

MJP conceived the study, conducted the root cause analysis, and drafted the manuscript. MJP contributed to data collection and epidemiological analysis. INRB performed genomic sequencing and bioinformatics analysis. All authors critically reviewed and approved the final manuscript.

Acknowledgements

The authors acknowledge the Democratic Republic of Congo Min- istry of Public Health, the Institut National de Recherche Biomédi- cale (INRB), and all frontline healthcare workers involved in out- break surveillance and response. Special thanks to the WHO and CDC teams for technical support and data sharing.

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