Ebola Virus Disease (EVD)

Virology & Classification

Epidemiology & History

• First described in 1976 simultaneously in Sudan and Zaire (now DRC), near the Ebola River - hence the name.
• Natural reservoir: Fruit bats (Pteropodidae family) are strongly suspected; the virus has been detected in multiple bat species. The precise spillover mechanism to humans remains under study.
• Index cases in outbreaks are typically linked to handling of dead animals (bats, bushmeat) or exposure to infected body fluids.

Major Outbreaks

Transmission

• Direct contact with blood, secretions, organs, or other body fluids of infected humans or animals.
• Fomite transmission: contact with contaminated surfaces/objects.
• NOT airborne under natural conditions (no evidence of droplet or aerosol transmission in community settings).
• Semen: EBOV can persist in semen for months to over a year after recovery - sexual transmission has been documented.
• Burial practices: Unsafe handling of bodies of the deceased is a major transmission route, as viral loads remain high post-mortem.
• Individuals are NOT contagious during the incubation period - only once symptoms begin.

Pathogenesis

1. Entry: EBOV GP binds to multiple cell surface receptors (including Niemann-Pick C1/NPC1 within endosomes). Primary targets are monocytes, macrophages, and dendritic cells.
2. Immune evasion: VP35 and VP24 proteins inhibit interferon signaling, enabling the virus to replicate unchecked in early infection.
3. Cytokine storm: Infected macrophages release massive amounts of pro-inflammatory cytokines (TNF-α, IL-6, IL-8, IL-1β), triggering systemic inflammatory response.
4. Vascular damage: Infection of endothelial cells leads to increased permeability, leading to fluid extravasation and shock.
5. Coagulopathy: DIC develops due to endothelial injury, tissue factor expression, and hepatic dysfunction - driving the hemorrhagic manifestations.
6. Multi-organ failure: Progressive hepatic, renal, and adrenal necrosis culminates in fatal shock.

Clinical Features

Incubation Period

• 2-21 days (most commonly 5-7 days)

Phase 1 - Early/Prodromal (Days 1-5)

• High fever (often >38.5°C)
• Severe headache
• Myalgia and fatigue
• Sore throat
• Nausea, profuse vomiting and diarrhea
• Abdominal pain

Phase 2 - Late/Hemorrhagic (Days 5-10+)

• Hemorrhagic manifestations: petechiae, ecchymoses, mucosal bleeding (gums, nose), gastrointestinal bleeding, conjunctival injection
• Maculopapular rash: erythematous, non-pruritic, eventually desquamates
• Hypovolemia from massive GI fluid losses
• Jaundice (hepatic involvement)
• CNS involvement: confusion, seizures, coma
• Progressive shock and multi-organ failure in fatal cases

Note: Not all patients develop frank hemorrhage. The hallmark is actually the profound GI syndrome.

Laboratory Findings

Diagnosis

• RT-PCR (reverse transcriptase polymerase chain reaction) on plasma/blood is the gold-standard confirmatory test. Sensitivity is highest after symptom day 3.
• Rapid antigen point-of-care tests: 15-minute turnaround, good sensitivity/specificity vs. RT-PCR - useful in field settings.
• ELISA for IgM/IgG antibodies: useful for seroprevalence studies and retrospective diagnosis.
• Testing criteria: patient must have both epidemiological exposure history AND compatible symptoms before testing is indicated.

Differential Diagnosis

• Malaria (most important to exclude in endemic areas)
• Typhoid fever
• Meningococcemia
• Marburg virus disease
• Other viral hemorrhagic fevers (Lassa, Crimean-Congo, Rift Valley)
• Leptospirosis
• Septicemia from bacterial causes

Management

1. Infection Control (Paramount)

• Isolate immediately in a single-patient room with negative air pressure if available.
• Full PPE: surgical hood covering head and neck, full-face shield, N95 or PAPR respirator, fluid-resistant gown, double gloves, boot covers. No skin should be exposed.
• Rigorous donning and doffing protocols with trained monitor - the CDC mandates demonstrated competency.
• CDC tiered system: Frontline facilities → Ebola Assessment Hospitals → Ebola Treatment Centers.

2. Supportive Care (Cornerstone of Treatment)

• Aggressive IV fluid and electrolyte resuscitation - combats hypovolemia from GI losses.
• Empirical antimalarial treatment (malaria coinfection common).
• Broad-spectrum antibiotics for secondary bacterial infections.
• Antipyretics (acetaminophen preferred over NSAIDs due to platelet effects).
• Organ support: renal replacement therapy (RRT) for AKI, mechanical ventilation, vasopressors for shock, blood product transfusion (FFP, platelets, PRBCs for DIC/hemorrhage).

3. Specific Antiviral Therapies

Prognosis & Mortality

• CFR ranges 25-90% depending on the species, outbreak setting, and available care.
• Zaire EBOV historically: ~60-80% without care; ~37% with optimized supportive + specific therapy (PALM trial).
• Patients treated in high-resource settings (US, Europe) during 2014-2016: mortality ~18.5%, far lower than African outbreak rates.
• Predictors of poor prognosis include: high viral load at presentation, coma, severe hemorrhage, AKI, very young or very old age. (Per the 2026 meta-analysis [PMID: 42163115], high viral load and neurological involvement are the strongest mortality predictors.)

Post-Ebola Syndrome

• Uveitis and other ocular complications (EBOV can persist in the aqueous humor)
• Arthralgia and myalgia
• Fatigue, sleep disturbances
• Neuropsychiatric symptoms (PTSD, depression)
• Reproductive health: A 2025 meta-analysis ([PMID: 39689367]) documented significant impacts on female reproductive health including menstrual irregularities and adverse pregnancy outcomes post-EVD.
• Viral persistence in immune-privileged sites (eye, CNS, testes, placenta) for months to years.

Prevention & Vaccines

Ervebo (rVSV-ZEBOV)

• Live attenuated recombinant vaccine: vesicular stomatitis virus (VSV) vector expressing the Ebola Zaire glycoprotein.
• FDA approved in December 2019 - first approved Ebola vaccine.
• Single intramuscular dose.
• Indications: persons ≥18 years who are outbreak responders, staff at federally designated Ebola treatment centers, or biosafety level-4 facility workers.
• Adverse effects: injection site reactions, headache, fever, arthralgia/arthritis (more common in women and those with prior arthritis history).
• Post-vaccination precautions: avoid blood donation for 6 weeks; use barrier contraception for 2 months; avoid sharing utensils/razors for 2 weeks (live virus shedding possible).
• Deployed with ring vaccination strategy in the 2018-2020 DRC outbreak with considerable success.

Zabdeno + Mvabea (Two-dose regimen)

• Ad26.ZEBOV prime + MVA-BN-Filo boost (8 weeks apart).
• Approved in Europe; used in DRC and neighboring countries.

General Prevention

• Avoid contact with blood/body fluids of infected persons or animals.
• Safe burial practices with full PPE.
• Contact tracing and 21-day surveillance of exposed contacts.
• No travel to active outbreak areas without appropriate preparation.

Public Health Response Framework

1. Case surveillance and contact tracing (21-day monitoring period for contacts)
2. Laboratory diagnosis network
3. Dedicated Ebola Treatment Centers (ETCs)
4. Safe and dignified burials
5. Ring vaccination of contacts and contacts-of-contacts
6. Community engagement and risk communication
7. International coordination (WHO, MSF, CDC, etc.)

Key Numbers to Remember

Recent evidence note: A 2026 systematic review and meta-analysis ([PMID: 42163115], BMC Infectious Diseases) identified high viral load at presentation and neurological features as the strongest independent predictors of mortality in EVD - reinforcing the importance of early diagnosis and rapid initiation of monoclonal antibody therapy.