Ebola Virus Disease Explained: Complete Guide to Structure, Replication, Diagnosis & Prevention

Table of Contents

• Introduction to Ebola virus
• Structure and Genome of Ebola Virus
• Epidemiology of Ebola Virus
• Transmission of Ebola Virus
• Replication of Ebola Virus
• Pathogenesis of Ebola Virus
• Clinical manifestations of Ebola Virus
• Lab Diagnosis of Ebola Virus
• Treatment of Ebola Virus
• Prevention and control of Ebola Virus
• Conclusion
• References

Introduction to Ebola virus

• Ebola Virus Disease (EVD), formerly known as Ebola hemorrhagic fever, is a severe and often fatal viral infection caused by ebolaviruses belonging to the Filoviridae family. It is considered one of the most dangerous zoonotic diseases due to its high mortality rate and rapid progression in infected individuals.
• The disease was first identified in 1976 during simultaneous outbreaks in Sudan and near the Ebola River in the present-day Democratic Republic of the Congo, from which the virus derived its name.
• Several species of ebolaviruses can infect humans, including Zaire ebolavirus, Sudan ebolavirus, Bundibugyo ebolavirus, and Taï Forest ebolavirus, while Reston ebolavirus primarily affects animals and has not been associated with severe human illness.
• Ebola is a zoonotic disease, meaning it is transmitted from animals to humans. Fruit bats are considered the primary natural reservoir hosts, and initial human infections often result from direct contact with infected wildlife such as bats or non-human primates.
• Following the initial animal-to-human transmission, the virus spreads between humans through direct contact with infected blood, body fluids, or contaminated surfaces and objects. Unlike respiratory viruses, airborne transmission in humans has not been scientifically confirmed.
• The incubation period typically ranges from 2 to 21 days, after which infected individuals may develop symptoms such as fever, fatigue, headache, muscle pain, vomiting, and diarrhea. In severe cases, the disease can progress to internal bleeding, organ failure, and shock.
• Ebola virus disease has historically shown high case fatality rates, with mortality varying depending on the outbreak, virus species, and availability of supportive medical care.
• Diagnosis is primarily confirmed through laboratory testing, especially RT-PCR, while treatment mainly involves supportive care such as fluid replacement, electrolyte management, and monitoring of complications.
• In recent years, the development of effective vaccines and monoclonal antibody therapies has significantly improved prevention and management strategies, strengthening global efforts to control Ebola outbreaks.
• Due to its epidemic potential and severe health impact, Ebola virus disease remains a major concern in global public health and highlights the importance of surveillance, rapid response, and infection control measures.

Structure and Genome of Ebola Virus

• The Ebola Virus Disease virus is a filamentous, enveloped, negative-sense single-stranded RNA virus belonging to the Filoviridae family. It possesses a complex structural organization composed of multiple concentric layers that work together to ensure viral stability, replication, assembly, and infectivity.
• Structurally, the Ebola virion is composed of an inner nucleocapsid core, a surrounding matrix protein layer, and an outer host-derived lipid envelope studded with glycoprotein spikes. This organized arrangement enables efficient genome protection, host-cell attachment, membrane fusion, and viral budding.
• The viral genome consists of approximately 19 kilobases of non-segmented negative-sense RNA, encoding seven major structural and functional proteins, including:
• NP (Nucleoprotein) – binds and protects viral RNA
• VP35 – polymerase cofactor and immune antagonist
• VP40 – matrix protein involved in assembly and budding
• GP (Glycoprotein) – mediates host-cell attachment and entry
• VP30 – transcription activator
• VP24 – structural support and immune evasion
• L protein – RNA-dependent RNA polymerase responsible for genome replication and transcription
• The Ebola virion has a distinctive thread-like or filamentous morphology, often appearing as elongated curved structures resembling the shapes of “U”, “6”, or shepherd’s crook-like forms. Virion length can vary considerably, and some particles may contain multiple genome copies, resulting in polyploid structures.
• At the center of the virion lies the nucleocapsid, which consists of viral RNA tightly wrapped by nucleoprotein (NP) to form a helical ribonucleoprotein complex. This structure protects the genome from degradation and provides the template required for viral transcription and replication.
• The nucleocapsid forms a helical architecture with defined pitch and diameter, as demonstrated through cryo-electron microscopy studies. This highly ordered arrangement is essential for maintaining structural stability and ensuring efficient packaging of the viral genome.
• Several proteins are associated with the nucleocapsid:
• VP35 binds to NP and supports RNA synthesis
• VP24 stabilizes nucleocapsid assembly
• VP30 regulates transcription initiation
• L protein carries out RNA synthesis

• Together, these proteins form the ribonucleoprotein complex, which is central to viral replication.
• Surrounding the nucleocapsid is the matrix layer, primarily composed of the VP40 matrix protein. VP40 forms a lattice-like scaffold beneath the viral envelope and is essential for:
• maintaining virion shape
• organizing viral assembly
• facilitating budding from infected host cells
• regulating structural flexibility
• VP40 is structurally dynamic and can exist in dimeric, hexameric, and octameric forms, allowing it to perform both structural and regulatory roles during the viral life cycle.
• The outermost layer of the virion is the lipid envelope, which is derived from the host cell membrane during viral budding. This membrane surrounds the matrix layer and provides a protective outer covering for the virus.
• Embedded within the lipid envelope are trimeric glycoprotein (GP) spikes, which project outward from the viral surface. These glycoproteins are critical for:
• binding to host-cell receptors
• mediating membrane fusion
• enabling viral entry into host cells
• Ebola virus also produces a related secreted glycoprotein (sGP), which shares significant sequence similarity with GP but is soluble rather than membrane-bound. This protein is believed to contribute to immune modulation and pathogenesis.
• The coordinated arrangement of these structural components ensures that Ebola virus can effectively package its genome, attach to host cells, enter target cells, replicate efficiently, and generate new infectious particles.
• Advanced structural studies using cryo-electron microscopy and cryo-electron tomography have provided detailed insights into how the nucleocapsid, matrix proteins, and glycoprotein spikes interact, revealing the highly modular architecture responsible for Ebola virus infectivity and pathogenicity.

Epidemiology of Ebola Virus

• Ebola Virus Disease is a highly infectious zoonotic disease that has caused repeated outbreaks since its first identification in 1976. The disease has remained a major public health concern because of its high fatality rate, rapid transmission during outbreaks, and potential to spread across regions when surveillance and infection control measures are weak.
• Since its discovery, Ebola outbreaks have occurred mainly in Central and West Africa, with most cases reported in countries such as Democratic Republic of the Congo, Sudan, Uganda, Gabon, Guinea, Liberia, and Sierra Leone. These outbreaks were initially small and localized but have increased in scale and geographic reach over time.
• Between 1976 and 2019, approximately 34 to 38 Ebola outbreaks were reported across 10 to 11 African countries, resulting in more than 34,000 confirmed and suspected cases and approximately 15,000 deaths, highlighting the severe epidemiological burden of the disease.
• The case fatality rate (CFR) of Ebola virus disease is exceptionally high, generally ranging between 50% and 70%, although some outbreaks have reported mortality rates as high as 88% to 90%, particularly in regions with delayed diagnosis and limited healthcare resources.
• Epidemiological data suggest that the fatality rate has gradually declined over time, likely due to:
• improved outbreak surveillance
• earlier case detection
• better supportive clinical care
• strengthened public health response systems
• introduction of vaccines and monoclonal antibody therapies
• Historically, most Ebola outbreaks occurred in remote rural areas, particularly in forested regions where close contact with wildlife increased the risk of zoonotic transmission. However, more recent outbreaks have increasingly affected peri-urban and urban populations, increasing transmission potential.
• The 2013–2016 West African Ebola epidemic remains the largest Ebola outbreak ever recorded. It resulted in approximately 28,646 reported cases and 11,323 deaths, primarily affecting Guinea, Liberia, and Sierra Leone.
• This epidemic was epidemiologically significant because it demonstrated Ebola’s potential for international spread, with exported cases identified in:
• Europe
• the United States
• several neighboring African countries
• This event emphasized the importance of global surveillance and coordinated international outbreak response.
• The increasing geographic spread and population at risk indicate that Ebola outbreaks are becoming more complex due to factors such as:
• increased population mobility
• urbanization
• environmental changes
• deforestation
• weak healthcare infrastructure in endemic regions
• Ebola outbreaks usually begin with zoonotic spillover events, where the virus is transmitted from infected animals to humans. Fruit bats are considered the most likely natural reservoir hosts, while transmission may also occur through contact with infected forest animals such as non-human primates during hunting, handling, or consumption of bushmeat.
• Once introduced into human populations, transmission occurs through direct contact with infected blood, body fluids, or contaminated materials, including:
• medical equipment
• bedding
• clothing
• contaminated surfaces
• Healthcare-associated transmission has historically played a major role in amplifying outbreaks, particularly in settings where infection prevention and control practices are inadequate.
• Traditional funeral and burial practices involving direct contact with deceased individuals have also contributed significantly to Ebola transmission in affected communities.
• Molecular epidemiological studies have shown that Ebola outbreaks often consist of multiple transmission clusters, with spread influenced by:
• human mobility patterns
• population density
• regional connectivity
• social interactions
• Genomic evidence has demonstrated that viral spread often follows “gravity-like transmission patterns,” where infection spreads more readily between larger and geographically closer population centers.
• Over the years, significant improvements have been made in epidemiological surveillance and outbreak control, including:
• faster reporting to the World Health Organization
• improved case tracking
• stronger laboratory diagnostic capacity
• better contact tracing systems
• The use of genomic sequencing and molecular epidemiology has greatly enhanced outbreak investigation by allowing researchers to:
• identify spillover sources
• detect survivor-linked flare-ups
• trace transmission chains
• monitor viral evolution during outbreaks
• Epidemiological patterns also vary according to the Ebola virus species involved. For example, outbreaks caused by Zaire ebolavirus generally show higher mortality than those caused by Sudan ebolavirus, influencing outbreak severity and control strategies.
• Despite advances in surveillance and response, Ebola remains a persistent epidemiological threat because recurring outbreaks continue to emerge in vulnerable regions.
• Current epidemiological trends indicate that while fatality rates are gradually decreasing and detection is becoming faster, the disease continues to pose serious challenges due to expanding geographic spread, repeated spillover events, and health system limitations in affected regions.

Transmission of Ebola Virus

• Ebola Virus Disease is transmitted mainly through direct contact with infected animals or infected human body fluids, making close physical exposure the primary route of spread.
• The disease usually begins through zoonotic spillover, where humans become infected after contact with infected wild animals such as fruit bats, chimpanzees, gorillas, monkeys, and forest antelope. This commonly occurs during hunting, butchering, handling carcasses, or consuming undercooked bushmeat.
• After the initial spillover event, Ebola spreads from person to person through direct contact with blood or other body fluids, including saliva, vomit, urine, feces, sweat, breast milk, and semen of infected individuals.
• Infection can also occur through contact with contaminated objects and surfaces, such as needles, syringes, bedding, clothing, medical instruments, and other materials exposed to infected body fluids.
• Ebola transmission is especially high during the later stages of illness, when the viral load in body fluids becomes significantly elevated.
• The bodies of deceased Ebola patients remain highly infectious, and traditional funeral practices involving washing, touching, or kissing the body have played a major role in amplifying outbreaks.
• Household transmission is common among family members providing direct care to infected individuals, particularly without protective measures.
• Healthcare settings are major transmission hotspots when infection control practices are inadequate. Reuse of medical equipment, lack of personal protective equipment, delayed isolation, and poor sanitation can rapidly increase spread.
• The virus can survive for several days to weeks on contaminated surfaces or within body fluids, making environmental contamination an important source of indirect transmission if proper disinfection is not performed.
• Airborne transmission has not been confirmed in humans, and current evidence shows Ebola primarily spreads through direct physical contact rather than through the air.
• Casual contact such as talking, sitting near an infected person, or sharing the same room without direct exposure to body fluids is generally considered low risk.
• Effective prevention of Ebola transmission depends on avoiding contact with infected body fluids, using personal protective equipment, practicing safe burial procedures, isolating infected individuals, and maintaining strict infection control measures.

Replication of Ebola Virus

Ebola virus has a negative-sense RNA genome that relies on a small set of viral proteins plus many host factors to complete its life cycle inside cells.

1. Entry and Uncoating

Virus attaches and is taken up by macropinocytosis, then traffics through endosomes; in late endosomes/lysosomes, glycoprotein is processed and fusion releases the nucleocapsid into the cytoplasm.

2. Inclusion Bodies: Viral “Factories”

• After entry, viral proteins and RNA form membrane-less cytoplasmic inclusion bodies / viral factories, which are phase‑separated condensates.
• Nucleoprotein (NP), VP35, VP30, VP24, and VP40 concentrate in these inclusions; GP is made in the cytoplasm and goes to the plasma membrane separately.

• Viral RNA synthesis (both transcription and genome replication) occurs inside inclusion bodies.

3. Transcription and Genome Replication

• Minimal replication complex: NP + VP35 + L polymerase; transcription additionally needs VP30.
• L polymerase initiates de novo replication at the 3′ leader RNA, which adopts a bent conformation critical for elongation.

Host factors are crucial:

• CAD is recruited by NP into inclusion bodies to supply pyrimidines for RNA synthesis.
• Genome‑wide screens highlight de novo pyrimidine synthesis and many other host pathways as essential for replication/transcription.
• Several host RNA decay and decapping proteins (e.g., GSPT1, UPF1, EDC4, DCP2) are co‑opted to promote early viral RNA synthesis.
• Antiviral factors like RBM4 bind the 3′ leader and suppress viral mRNA production.

4. Assembly, Transport, and Budding

• Newly made genomes and structural proteins assemble into nucleocapsids within inclusions, which then move toward the plasma membrane.
• VP40, VP24, and GP at the membrane drive particle assembly and budding, releasing progeny virions.

Pathogenesis of Ebola Virus

Ebola pathogenesis involves early infection of immune cells, massive immune dysregulation, vascular damage, coagulopathy, and multi‑organ failure.

Early Infection and Viral Spread

• Initial targets: Monocytes/macrophages and dendritic cells are early and major replication sites; they then disseminate virus to lymph nodes and organs.
• Tropism: Productive infection in macrophages, DCs, fibroblasts, hepatocytes, adrenal, epithelial, and other cells leads to broad tissue damage.

Immune Evasion and Dysregulation

• Innate evasion: Viral proteins VP24 and VP35 block type I interferon production/signaling and dendritic‑cell maturation, crippling antiviral responses.
• Cytokine storm: Infected macrophages/monocytes release high levels of pro‑inflammatory cytokines and chemokines, driving fever, shock, vascular leak, and recruiting more target cells.
• Lymphocyte loss: Massive “bystander” apoptosis of T and NK cells causes lymphopenia without direct infection, via death‑receptor pathways and soluble mediators.

Major Pathogenic Mechanisms and Outcomes

Mechanism	Clinical Consequence	Citations
IFN suppression, dendritic cell dysfunction	Uncontrolled viremia and impaired adaptive immune response	(Ansari, 2014; Ficenec et al., 2025; Hoenen et al., 2006; Basler, 2017; Misasi & Sullivan, 2014; Rasmussen, 2017; Geisbert et al., 2003)
Cytokine storm and macrophage activation	Shock and sepsis-like systemic inflammatory response	(Falasca et al., 2015; Ficenec et al., 2025; Zampieri et al., 2007; Eisfeld et al., 2017; Hoenen et al., 2006; Basler, 2017; Vucetic et al., 2023; Liu et al., 2023)
Coagulation activation (tissue factor, DIC)	Hemorrhage and organ ischemia	(Falasca et al., 2015; Ficenec et al., 2025; Hoenen et al., 2006; Basler, 2017; Martines et al., 2015)
Endothelial activation and glycoprotein-mediated effects	Vascular leakage and hypotension	(Ficenec et al., 2025; Zampieri et al., 2007; Bray & Geisbert, 2005; Moni et al., 2022; Martines et al., 2015; Geisbert et al., 2003)
Direct organ infection (liver, adrenal glands, kidneys)	Liver failure, hypotension, renal injury, and multi-organ failure	(Falasca et al., 2015; Ansari, 2014; Ficenec et al., 2025; Zampieri et al., 2007; Eisfeld et al., 2017; Hoenen et al., 2006; Basler, 2017; Martines et al., 2015)

Vascular Injury, Coagulopathy, and Organ Failure

• Vascular damage arises mainly from inflammatory mediators and coagulopathy, with only limited direct endothelial cytolysis in vivo.
• Liver infection impairs synthesis of clotting factors; macrophage tissue factor and DIC cause bleeding and microthrombosis.
• Combined shock, capillary leak, and direct infection of liver, kidneys, adrenals, and GI tract lead to multiorgan dysfunction and death.

Clinical manifestations of Ebola Virus

• Incubation period ranges from 2–21 days, with an average of 8–12 days after exposure.
• The disease usually begins suddenly with fever, severe fatigue, weakness, headache, chills, muscle pain, and joint pain.
• Early symptoms are often non-specific and can resemble malaria, typhoid fever, or Lassa fever, making early diagnosis difficult.
• Co-infection with Plasmodium species is common and may worsen disease severity.
• The gastrointestinal phase usually develops 3–7 days after symptom onset.
• Patients often develop profuse watery diarrhea, repeated vomiting, abdominal pain, and loss of appetite.
• Severe fluid loss may result in dehydration, tachycardia, orthostatic dizziness, and hypotension.
• Laboratory findings commonly include elevated liver enzymes (AST greater than ALT), lymphopenia, thrombocytopenia, electrolyte imbalance, and progressive coagulopathy.
• In severe cases, Ebola progresses to multiple organ dysfunction syndrome (MODS).
• Critically ill patients may experience shock, acute kidney injury, respiratory failure, and metabolic acidosis.
• Some patients develop hemorrhagic manifestations such as mucosal bleeding, gastrointestinal bleeding, petechiae, ecchymosis, and bleeding from venipuncture sites.
• Clinical deterioration usually peaks around day 7–10 after symptom onset.
• High viral loads are strongly associated with poor prognosis and increased mortality.
• Survivors generally have lower peak viral loads and less severe organ dysfunction.
• Viral clearance from blood usually occurs within 2–3 weeks in recovering patients.
• Many survivors experience post-Ebola syndrome, including persistent fatigue, headache, joint pain, memory problems, anxiety, and depression.
• Long-term complications may include uveitis, meningoencephalitis, and other inflammatory disorders.
• Ebola virus may persist for months or years in semen, ocular fluid, and cerebrospinal fluid.
• Persistent viral reservoirs can lead to relapse, delayed complications, and sexual transmission after recovery.

Lab Diagnosis of Ebola Virus

Laboratory diagnosis is essential to confirm EVD, guide patient management, and control outbreaks. Testing must balance speed, accuracy, biosafety, and feasibility in low‑resource settings.

Main Laboratory Tests

Real-time RT‑PCR (reference standard)

• Detects viral RNA in blood within 3–10 days after symptom onset.
• Widely used commercial assays: RealStar Altona (L gene), Cepheid GeneXpert (GP & NP genes), Roche, Fast‑Track, Life Technologies kits. 
• GeneXpert and other commercial kits show high sensitivity and specificity, suitable for field use and viral load estimation.

Antigen detection / Rapid Diagnostic Tests (RDTs)

• Detect EBOV proteins (VP40, GP, NP or secreted GP) in blood or swabs.
• Pooled lateral‑flow RDT performance vs RT‑PCR: sensitivity ~86%, specificity ~95–97%.
• Individual kits: ReEBOV VP40 test and others often show high sensitivity in high‑viraemia cases but **do not reach the 99% sensitivity** WHO recommends; negatives must be confirmed by PCR.
• New sGP‑targeting and SERS‑based multiplex assays (Ebola/Lassa/malaria) can reach ~85–90% sensitivity and ≥97% specificity.

Specimen Choice and Biosafety

• Blood is most sensitive for live patients; oral swabs have little value in living patients but are highly sensitive post‑mortem.
• All body fluids from suspected/confirmed cases are highly infectious, so strict biosafety and specimen transport controls are required. 

Point‑of‑Care and Future Directions

• Isothermal assays (LAMP, RT‑RAA) and cartridge‑based PCR (GeneXpert) enable near‑patient testing with 2–40 min turnaround.
• Reviews emphasize microfluidics, nanotechnology, and connected PoC systems to deliver fast, affordable, decentralized EVD diagnostics in future outbreaks.

Treatment of Ebola Virus

• Management of EVD combines aggressive supportive care with specific anti‑Ebola therapies, mainly monoclonal antibodies. Survival has improved markedly where this combination is available.

Supportive and Critical Care

• Core measures: oral and IV rehydration, correction of electrolytes, monitoring of vital signs and volume status, pain control, treatment of coinfections, and adequate staffing.
• In severe disease: vasoactive drugs, oxygen, mechanical ventilation, and renal replacement therapy are often needed.
• High‑quality intensive care alone reduced mortality to ~18–20% in Europe/US cases, even when experimental antivirals were unproven.

Specific Anti‑Ebola Therapies

Monoclonal antibodies (current standard for Zaire ebolavirus)

• PALM randomized trial:  
• Mortality at 28 days: MAb114 (Ebanga) 35.1% vs ZMapp 49.7%, REGN‑EB3 (Inmazeb) 33.5% vs ZMapp 51.3%**; both clearly superior.
• Network meta‑analysis of RCTs:  
• REGN‑EB3 RR 0.40 and mAb114 RR 0.42 vs standard care (moderate‑certainty evidence).
• Both clearly better than ZMapp and remdesivir.
• FDA has approved Ebanga and Inmazeb; use is recommended as first‑line during outbreaks caused by Zaire ebolavirus.
• Benefit is greatest with early administration, before advanced organ damage.

Antivirals and other agents

• Remdesivir showed no clear mortality benefit vs ZMapp or standard care in human RCTs (very low‑certainty).
• Earlier agents (favipiravir, brincidofovir, TKM‑130803, interferon, convalescent plasma) have inconclusive or low‑quality evidence.
• Animal data suggest single agents may only partially rescue late‑stage infection, supporting future combination therapy approaches.

Prevention and control of Ebola Virus

Safe Burials and Avoiding Contact With Corpses

• Bodies of Ebola victims are highly infectious, and traditional washing/touching rituals caused many “superspreading” events.
• Unsafe burials generated on average 2.5–2.6 secondary cases per death in West Africa.
• “Safe and dignified burials” using trained teams, PPE, body bags, disinfection and deep graves significantly reduced transmission and were associated with up to 40% lower incidence when a high proportion were performed successfully.
• Surveys showed large behavior change: willingness to wait for burial teams and accept alternatives to traditional rituals rose sharply during the epidemic.

Avoiding Exposure to Bats, Primates, and Bushmeat

• Ebola is zoonotic; bats are assumed main reservoirs, and human outbreaks often follow contact with infected bats, chimpanzees, gorillas, or forest antelopes, including hunting, butchering, or eating bushmeat or raw/undercooked meat and blood.
• Reviews emphasize reducing bushmeat exposure and monitoring its trade as important primary prevention measures.

Healthcare Worker Protection and Infection Control

• Healthcare workers (HCWs) have much higher Ebola incidence than the general population; infections are linked to breaches in infection prevention and control (IPC) and lack of PPE.
• Effective measures include:
• Early triage, testing, and isolation of suspected cases.
• Full PPE and barrier nursing (gloves, impermeable gown, mask or respirator, eye protection; added shoe/leg covers when high fluid exposure) plus careful donning and doffing with trained observers.
• Strengthening IPC systems (hand hygiene, decontamination/sterilization, waste management, dedicated isolation areas) markedly improved facility scores in Uganda and DRC.

Conclusion

• Ebola virus disease is a severe zoonotic viral infection caused by members of the Filoviridae family, with high fatality rates and major public health significance.
• The disease primarily originates through animal-to-human transmission, especially from infected fruit bats and wild animals, followed by rapid human-to-human spread through infected body fluids.
• Ebola has a complex filamentous structure with a negative-sense single-stranded RNA genome that encodes proteins essential for viral replication, immune evasion, and pathogenicity.
• The virus replicates efficiently inside host cells by hijacking cellular machinery, leading to rapid viral multiplication and systemic dissemination.
• Ebola pathogenesis is characterized by immune suppression, cytokine storm, vascular injury, coagulation abnormalities, and multi-organ failure, which contribute to severe clinical outcomes.
• Clinical manifestations range from early flu-like symptoms to severe hemorrhage, shock, and organ dysfunction in advanced disease.
• Early laboratory diagnosis, particularly through RT-PCR and rapid molecular testing, is essential for prompt patient management and outbreak containment.
• Current treatment relies on supportive care combined with monoclonal antibody therapies, which have significantly improved survival rates when administered early.
• Effective prevention depends on strict infection control practices, safe burial procedures, surveillance, vaccination, contact tracing, and community awareness.
• Despite advances in diagnostics, treatment, and prevention, Ebola remains a persistent global health threat, emphasizing the continued need for preparedness, research, and rapid outbreak response systems.

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