Ebola disease caused by Zaire virus

Epidemiology

A severe viral haemorrhagic fever with a case fatality rate ranging from 25 to 90% (average case fatality rate of 50%) depending on the outbreak,¹˒² Ebola virus disease is caused by viruses of the genus Orthoebolavirus, of which only four (Bundibugyo, Sudan, Taï Forest and Zaire) have been associated with Ebola virus disease.³

Ebola first emerged in 1976 in outbreaks in South Sudan and the Democratic Republic of the Congo. Since then, 42 outbreaks have been reported in Africa, of which 31 were caused by Ebola virus (EBOV), also known as Ebola Zaire, resulting in 23,045 cases, including 14,885 deaths.⁴ The sporadic nature of outbreaks suggests a probable zoonotic origin, although human-to-human transmission is possible.⁴

Diagnosis and symptoms

The disease can be diagnosed using several methods: ELISA, antigen-capture detection, serum neutralisation, RT-PCR, electron microscopy and virus isolation in cell culture. These tests should be performed on blood samples, or oral fluid samples when blood collection is not possible.¹⁰

Several challenges affect diagnosis:

• Symptoms are non-specific in the early stages of the disease, and the stigma associated with infection may delay people seeking care and, consequently, diagnosis.
• Handling samples requires biosafety level 3 or 4 laboratories, which are scarce in Africa. Transporting samples is complex, requiring stringent packaging procedures for shipment to laboratories that are often far away.
• Laboratory capacity needs to be strengthened.
• Rapid diagnostic tests are needed, but they are expensive, and their specificity and sensitivity could be improved.

The incubation period ranges from 2 to 21 days, and the virus cannot be transmitted before symptoms appear. Symptoms develop suddenly in two phases: the dry phase and the wet phase. The dry phase includes symptoms such as fever, fatigue, muscle pain, headaches and a sore throat. The wet phase, which is the most contagious, is characterised by vomiting, diarrhoea, skin rashes, multiple organ failure, particularly kidney failure, and sometimes internal and external bleeding.⁵ Miscarriages may occur during pregnancy.⁸

Ebola survivors may experience persistent symptoms for two years or more, including vision problems, loss of appetite, weight gain, depression and anxiety, memory loss and fatigue.¹¹

Infected people cannot transmit the disease before developing symptoms, and they remain infectious for as long as their blood contains the virus.²

Research avenues

• Treatments

Extensive research into the genome and structure of EBOV has identified several proteins essential for viral replication that could be targeted for treatment development.

A preclinical study showed that MBP134AF, a cocktail of two broad-spectrum human monoclonal antibodies (ADI-15878 and ADI-23774) derived from an Ebola virus disease survivor, provided greater protective efficacy than the ADI-15878 antibody alone.²⁶ The broad-spectrum antiviral galidesivir demonstrated antiviral activity against EBOV in mice, and recent clinical trials have shown good tolerability in healthy adults. However, it has not yet been evaluated in infected individuals.²⁷˒²⁸

One of the therapeutic approaches prioritised by WHO was convalescent plasma. However, a non-randomised comparative study conducted in Guinea involving 99 patients with Ebola showed that this therapy did not significantly improve survival.²⁹

WHO is also organising the SOLIDARITY clinical trials, which aim to develop better vaccines and treatments against filoviruses, particularly the virus responsible for Ebola disease. Current priorities are remdesivir and low-dose corticosteroids in combination with monoclonal antibodies, with 28-day mortality selected as the primary endpoint.³⁰

• Vaccines

Adenoviral vector vaccine candidates ChAd3-EBOZ (chimpanzee vector, phase I/II)³¹˒³² and Ad5-EBOV (human vector, phase I/II)³³ have shown promising immunogenicity, sometimes in combination with Mvabea® (MVA-BN-Filo).

The bivalent ChAdOx1 biEBOV vaccine, based on a non-replicating adenoviral vector, demonstrated good tolerability and a strong immune response after a single dose, with 100% seropositivity against Ebola virus in a phase I clinical trial.³⁴

The Russian GamEvac-Combi vaccine, which combines VSV and Ad5 vectors, has also been evaluated in phase I/II trials, illustrating the potential of heterologous strategies to enhance the immune response.³⁵

Finally, several alternative approaches, including subunit, nanoparticle and virus-like particle vaccines, are being evaluated, mostly at the preclinical or phase I stage. Their potential advantages include improved tolerability and a strong humoral response.³⁶

Research activities of ANRS MIE on Ebola disease caused by Zaire virus and filoviruses

Leadership of the CORC on filoviruses

In early 2025, ANRS MIE was appointed to lead the Collaborative Open Research Consortium (CORC) on filoviruses and is set to become a WHO Collaborating Centre.

CORCs are international networks of research institutions whose mission is to strengthen global pandemic preparedness through collaborative research, knowledge sharing and the rapid development of countermeasures. An initial meeting, held on 13 February 2025, focused on therapeutic trials and priority research on medical countermeasures. Within the CORC, research priorities have been defined by ANRS MIE and WHO, and work is under way with all experts from the “CORC on filoviruses” to update the research priorities and gaps identified in the MARVAC consortium roadmap.

In response to the new outbreak of Ebola disease caused by Zaire virus in the Democratic Republic of the Congo, an initial international meeting was held on 5 September 2025. Three further research meetings are planned on diagnostics, treatments and vaccines, as well as a meeting to present their findings.

The ten research priorities for EBOV Zaire, established within the Filovirus CORC on 5 September 2025³⁷

1. Improve rapid diagnostic tests and laboratory capacity: Delays related to logistical constraints, accessibility and sample collection supplies hinder case confirmation. Priorities include validating rapid diagnostic tests and expanding metagenomic sequencing for suspected cases.
2. Advance therapeutic evaluations: Adaptive clinical trials must remain central to research during outbreaks. The Partners Trials framework, already activated during Marburg and Ebola outbreaks earlier in 2025, provides a platform for evaluating small-molecule antivirals, monoclonal antibodies and host-directed therapies. Current priorities include evaluating remdesivir and low-dose corticosteroids in combination with monoclonal antibodies, as well as investigating higher doses of monoclonal antibodies.
3. Accelerate clinical trial approvals and regulatory preparedness: Rapid trial activation requires streamlined regulatory processes. Early submission of protocols through AVAREF and national ethics committees is essential, despite logistical constraints during outbreaks. Collaborative frameworks such as the CORC on filoviruses, together with substudies on pathophysiology, diagnostics and the organisation of treatment centres, can strengthen regulatory preparedness for a rapid response.
4. Optimise clinical care and supportive therapies: Supportive care remains the cornerstone of Ebola treatment in low-resource settings, where advanced interventions are often not feasible. Research is needed to refine standard protocols for fluid and electrolyte management, transfusion thresholds, tranexamic acid use, antimicrobial treatment of co-infections and oxygen therapy, thereby reducing mortality.
5. Deepen understanding of pathophysiology and clinical complications: Major gaps remain in our understanding of Ebola-associated complications, such as acute kidney injury, coagulation disorders, neurological sequelae and bacterial or malaria co-infections, limiting treatment effectiveness. Specific populations, including pregnant women, children and survivors, require particular attention. Characterising these complications informs clinical guidelines and trial design, improving care for the most vulnerable.
6. Strengthen research on pre- and post-exposure prophylaxis: Recent evidence confirms low incidence among contacts and strong vaccine protection with Ervebo®. These findings raise questions about the statistical power and feasibility of post-exposure prophylaxis trials, which must incorporate this new evidence into their design.
7. Continue deploying licensed vaccines and develop the next generation: Ervebo® remains central to the ring vaccination strategy recommended by WHO. SAGE has confirmed the efficacy of a single dose of rVSV∆GZEBOV-GP from the tenth day after vaccination, including in children from birth and pregnant and breastfeeding women.
8. Expand research on treatment centre design and operational innovations: Models such as IDTM, HEF and CUBES must be evaluated for effectiveness, safety and community acceptability. Operational research on logistics and water and energy infrastructure is also a priority to improve patient care and protect healthcare workers.
9. Strengthen training, preparedness and data sharing: Building the clinical and research skills of African teams through programmes such as FiloTreat is essential. Harmonising clinical and research data is equally crucial. The CORC framework facilitates coordination among multiple stakeholders and transparent data sharing.
10. Support social science research and community engagement: Experience from 2018–2020, when more than 95% of contacts were identified and vaccinated, demonstrated the importance of trust and community involvement in clinical trial participation.

A multidisciplinary approach involving virology, epidemiology and the social sciences is essential to address gaps in Ebola research, particularly in identifying mechanisms of cross-species transmission and understanding viral persistence.

Activation of an Outbreak Response unit

In March 2025, the ANRS MIE “Epidemic Monitoring and Response” division activated a level 1 Outbreak Response unit on filoviruses. On 1 September 2025, the Democratic Republic of the Congo reported an outbreak of Ebola virus disease in Kasai Province, in the south-west of the country. As of 13 September 2025, 81 suspected cases, including 28 deaths, had been reported, with initial healthcare-associated transmission followed by community transmission.

Coordinated action on viral haemorrhagic fevers

In 2024, ANRS MIE established a coordinated action on viral haemorrhagic fevers chaired by Sylvain Baize, Marie Jaspard and Abdoulaye Touré. This group for discussion and strategic reflection focuses particularly on scientific research on filoviruses and aims, through its working groups (therapeutics, wildlife, vaccines), to generate research projects through international collaborations, primarily with our partners in Africa.