Ebola virus disease is a severe, often fatal illness caused by Ebola virus (family Filoviridae), with an average case fatality rate of ~50% (range 25–90% depending on species and outbreak context). [1-2] It is transmitted through direct contact with blood and bodily fluids of infected individuals or contaminated objects, with an incubation period of 2–21 days (typically 6–10 days). [3] Two FDA-approved monoclonal antibody therapies — Inmazeb (REGN-EB3) and Ebanga (ansuvimab/mAb114) — significantly reduce mortality and are strongly recommended by WHO. [4-5]
1. History
- Travel history is paramount: recent travel to or residence in sub-Saharan Africa (especially DRC, Guinea, Sierra Leone, Liberia, Uganda) [1][3]
- Exposure history: direct contact with a known EVD case, funeral attendance, healthcare facility consultation, or contact with bushmeat (fruit bats, non-human primates) [6-7]
- Timing of symptom onset: abrupt onset of fever, malaise, fatigue, myalgia, headache — initially indistinguishable from other febrile illnesses [2-3]
- Progression: after 3–5 days, gastrointestinal symptoms dominate — nausea, vomiting, profuse watery diarrhea (up to 5–10 L/day fluid loss) [2][5]
- Later symptoms: dysphagia, sore throat, chest/abdominal pain, hiccups, conjunctival injection, maculopapular rash [3]
- Hemorrhagic features: bleeding gums, petechiae, oozing from venipuncture sites, hematemesis, melena — occur in <50% of patients and are less common than previously believed [3][5]
- Key negatives to elicit: vaccination status (rVSV-ZEBOV), prior EVD infection, known contacts with confirmed cases
2. Alarm Features
- Hemorrhage from any site (injection site bleeding has the highest OR for confirmed EVD: 33.9) [6]
- Confusion, delirium, coma — neurological involvement correlates with mortality [5]
- Hypotension and tachycardia — hypovolemic shock from massive GI losses [5]
- Anuria — renal failure is strongly correlated with death [2][8]
- High viral load at presentation (Ct <22) — mortality reaches 67% even with best available therapy [5]
- Tachypnea, hypoxia (SpO₂ <92%) — pulmonary involvement develops in nearly half of patients during disease course [5]
- Each day of delay from symptom onset to treatment increases mortality by ~5–12% [5][9]
3. Medications
FDA-Approved Therapeutics (for Zaire ebolavirus only)
- Inmazeb (REGN-EB3): triple monoclonal antibody cocktail (atoltivimab + maftivimab + odesivimab) — single IV infusion; 28-day mortality 33.5% vs ~50% with control [4-5]
- Ebanga (ansuvimab/mAb114): single monoclonal antibody — single IV infusion; 28-day mortality 35.1% [4-5]
Other agents
- Remdesivir: inferior to mAb114 and REGN-EB3 in the PALM trial; WHO conditionally recommends against its use for EVD [10]
- Favipiravir: alternative if mAbs unavailable; limited clinical evidence [10-11]
- ZMapp: inferior to mAb114 and REGN-EB3; no longer first-line [12]
Contraindicated/Cautions
- Avoid NSAIDs (coagulopathy risk) and IM injections (bleeding risk)
- Empiric antibiotics may be considered for suspected bacterial co-infection [11]
- Antimalarials should be given empirically in endemic areas given high co-infection rates [13]
4. Diet
- Aggressive oral rehydration with ORS when tolerated; IV fluids when not
- Electrolyte-rich fluids to replace massive GI losses (potassium, sodium, calcium) [2][5]
- Small, frequent, calorie-dense meals during recovery
- Nutritional support is a core component of Ebola treatment center care [14]
5. Review of Systems
- Constitutional: fever, fatigue, malaise, myalgia, arthralgia
- GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, dysphagia
- Hemorrhagic: bleeding gums, epistaxis, hematemesis, melena, petechiae, oozing from IV sites
- Neurologic: headache, confusion, agitation, seizures
- Ocular: conjunctival injection, visual changes (uveitis in survivors)
- Respiratory: cough, dyspnea, tachypnea
- Dermatologic: maculopapular rash (may be subtle on dark skin) [2-3]
- Musculoskeletal: severe myalgia, arthralgia
- Other: hiccups (associated with poor prognosis), sore throat, oral ulcers [2]
6. Collateral History and Family History
- Household contacts: identify all individuals with direct contact with the patient's bodily fluids
- Funeral attendance: traditional burial practices involving washing of the body are a major transmission route [6]
- Healthcare worker status: occupational exposure is a significant risk factor [15]
- Vaccination status of patient and contacts (rVSV-ZEBOV) [16]
- Community outbreak context: active outbreak in the region?
- No hereditary predisposition, though HLA-B27 may be associated with post-EVD uveitis [5]
7. Risk Factors
- Direct contact with blood/bodily fluids of an infected person (OR 11.9 for EVD positivity) [6]
- Healthcare workers — disproportionately affected in every outbreak [15]
- Funeral attendance in endemic areas (OR 2.1) [6]
- Extremes of age — children <5 and elderly have higher mortality [5][8]
- Pregnancy — high mortality, high risk of miscarriage and stillbirth [2]
- Unvaccinated status — vaccinated patients have 1.7× lower mortality [9]
- Delayed presentation to treatment centers [5][9]
8. Differential Diagnosis
- Malaria — most common differential in endemic settings; co-infection is frequent; rapid diagnostic test essential [8][13]
- Typhoid fever — overlapping febrile GI presentation [7]
- Marburg virus disease — clinically indistinguishable; requires PCR differentiation [8]
- Lassa fever — similar VHF presentation in West Africa [8]
- Dengue fever — fever with hemorrhagic features [8]
- Shigellosis — bloody diarrhea mimic [7]
- Meningococcal septicemia — fulminant sepsis with petechiae [7]
- Fulminant viral hepatitis — transaminitis and coagulopathy [7]
- Yellow fever, Chikungunya — in appropriate geographic context [7]
- Distinguishing feature: exposure history is the strongest early predictor, not clinical symptoms [6]
9. Past Medical History
- Prior EVD infection (confers some immunity but viral persistence/relapse possible) [2]
- Immunocompromised states (HIV, malnutrition)
- Chronic liver or renal disease (worsens prognosis)
- Pregnancy status (critical for management and prognosis) [2]
- Vaccination history (rVSV-ZEBOV alters clinical presentation and reduces severity) [5][16]
10. Physical Exam
Vital Signs
- Fever (may be absent in ~10% of cases) [2]
- Tachycardia, hypotension (hypovolemic shock)
- Tachypnea, hypoxia (late finding)
Focused Exam
- Eyes: conjunctival injection, subconjunctival hemorrhage
- Oropharynx: oral ulcers, pharyngeal erythema, bleeding gums
- Skin: maculopapular rash (often subtle), petechiae, ecchymoses, oozing from venipuncture sites
- Abdomen: diffuse tenderness, hepatomegaly
- Neurologic: altered mental status, confusion, delirium (late and ominous)
- Volume status: signs of severe dehydration — sunken eyes, poor skin turgor, dry mucous membranes [2-3]
11. Lab Studies
- RT-PCR (gold standard for diagnosis) — detectable from day 3 after symptom onset; may be negative in first 72 hours [7-8]
- CBC: variable anemia, thrombocytopenia (though severe thrombocytopenia is generally absent), leukocyte changes variable [2][5]
- CMP: hypokalemia, hyponatremia, hypocalcemia; elevated BUN/creatinine (renal dysfunction in up to 50%) [2]
- LFTs: markedly elevated AST (often >ALT due to myositis component); elevated bilirubin [2-3]
- Coagulation: prolonged PT/INR, elevated D-dimer, DIC pattern [1][8]
- CK and amylase: elevated (myositis, pancreatitis) [2]
- ABG/VBG: metabolic acidosis, lactic acidosis [5]
- Malaria RDT: essential to rule out co-infection in endemic areas [13]
- Blood cultures: to evaluate for bacterial co-infection [11]
12. Imaging
- Imaging is generally not a priority in acute EVD management and poses infection control challenges
- CXR if respiratory symptoms develop — may show pulmonary edema [8]
- Point-of-care ultrasound (POCUS): useful for volume assessment, pleural/pericardial effusions without transporting the patient
- Dedicated imaging equipment should be used; decontamination protocols are critical [17]
13. Special Tests
- RT-PCR for Ebola virus RNA — primary diagnostic test; Ct value correlates inversely with viral load and prognosis [5][8]
- Antigen detection ELISA — alternative rapid diagnostic [7]
- IgM/IgG ELISA — useful for retrospective diagnosis and serosurveys; IgM appears as early as day 2, IgG by day 6–18 [7]
- Viral culture — reference lab only; BSL-4 required [8]
- Point-of-care rapid diagnostic tests — available for field use in outbreak settings
- Semen testing (RT-PCR) in male survivors — viral persistence documented up to 16+ months [2]
14. ECG
- ECG indicated if hemodynamic instability, electrolyte derangements, or suspected myocarditis
- Myocarditis has been reported as a complication [8]
- Monitor for arrhythmias — sudden death in recovering patients has been reported, possibly cardiac in origin [2]
- Hypokalemia-related changes: U waves, prolonged QT, ST depression
- Hypocalcemia: prolonged QTc
15. Assessment
EVD is a biphasic illness: an initial non-specific febrile prodrome (days 1–3) followed by a severe gastrointestinal phase with risk of multiorgan dysfunction. [2-3] The clinical course averages 8–10 days. [1] Key prognostic factors include:
- High viral load (Ct <22) — strongest predictor of death [5]
- Renal and hepatic dysfunction — strongly correlated with mortality [2][5]
- Hemorrhage and confusion — associated with fatal outcomes [5]
- Delay to treatment — each day increases mortality by 5–12% [5][9]
- Mortality in well-resourced settings with aggressive supportive care: ~18.5% vs 40–70% in resource-limited settings [11]
The following figure from the PALM trial demonstrates the survival benefit of mAb114 and REGN-EB3 over ZMapp and remdesivir, stratified by viral load:
16. Treatment Plan
Immediate Stabilization
- Strict isolation with appropriate PPE (see below) before any clinical intervention [19]
- Aggressive IV fluid resuscitation — Ringer's lactate or normal saline; replace ongoing GI losses volume-for-volume [5][14]
- Electrolyte correction — potassium, sodium, calcium, magnesium monitoring and replacement [2]
Specific Therapy
- Inmazeb (REGN-EB3) or Ebanga (mAb114) — administer as soon as PCR-confirmed Zaire ebolavirus infection; single IV infusion [5][11]
- WHO strongly recommends these agents for all confirmed cases including neonates born to PCR-positive mothers [10-11]
Supportive Care
- Antipyretics/analgesics (acetaminophen preferred; avoid NSAIDs)
- Antiemetics (ondansetron)
- Empiric antimalarials in endemic settings [13]
- Empiric antibiotics if bacterial co-infection suspected [11]
- Blood products for significant hemorrhage; correct coagulopathy
- Renal replacement therapy if available and indicated [11]
- Nutritional support [14]
Infection Control/PPE
- Clinically stable patients without bleeding/vomiting/diarrhea: fluid-resistant gown, full face shield, facemask, double gloves with extended cuffs [19]
- Confirmed cases or unstable patients with bleeding/vomiting/diarrhea: impermeable gown or coverall, PAPR or N95 respirator, double gloves, boot covers, apron [19]
- Trained observer must supervise donning and doffing [15][17]
- Minimize personnel entering the room; maintain a log of all entries [19]
17. Disposition
- All confirmed or suspected EVD cases require admission to an isolation facility or designated Ebola treatment center [14][19]
- In the U.S., transfer to a regional Ebola treatment center (tiered hospital preparedness system) is recommended [15]
- ICU-level care for patients with shock, renal failure, hemorrhage, or altered mental status [11]
- Immediate notification of hospital infection control, local/state health department, and CDC Emergency Operations Center (770-488-7100) [19]
- Contact tracing must be initiated for all identified contacts [14]
Discharge criteria
- Clinical improvement with resolution of symptoms
- Negative RT-PCR on blood (ideally two consecutive negatives)
- Ability to maintain oral hydration
- Coordinated with public health authorities
18. Follow Up / Return Precautions
Post-Discharge Survivor Care
- Post-Ebola syndrome affects the majority of survivors: 75% report at least one symptom at ~1 year, declining to ~52% at 5 years [5][21]
- Common sequelae: joint pain, headache, fatigue, memory loss, muscle pain, hearing loss, visual changes [21-22]
- Uveitis is a significant complication — ophthalmologic follow-up is essential; may be associated with viral persistence in aqueous humor [2][5]
- Neuropsychiatric: depression, anxiety, cognitive impairment — may persist for decades [5]
- Musculoskeletal: arthralgia and immobility are leading causes of disability [5]
Viral Persistence and Transmission Risk
- Ebola virus can persist in semen for ≥16 months after recovery; sexual transmission has been documented [2]
- Male survivors require semen RT-PCR testing and counseling on safer sex practices until viral clearance confirmed [2]
- CNS may serve as a viral reservoir — meningoencephalitis relapse reported 9 months post-recovery [2]
Return Precautions
- Return immediately for recurrence of fever, bleeding, severe diarrhea/vomiting, confusion, visual changes
- Regular follow-up with rheumatology, ophthalmology, audiology, and mental health services [2]
- Long-term follow-up recommended for at least 12–48 months post-discharge [23]
Vaccination (Prevention)
- rVSV-ZEBOV-GP (Ervebo): single-dose live vaccine; 97.5% efficacy when given ≥10 days before exposure; used in ring vaccination strategy [14][24]
- Post-exposure prophylaxis: mAb114 or REGN-EB3 preferred over vaccine alone for high-risk exposures due to immediate activity; rVSV-ZEBOV has been used as PEP within 48 hours of exposure [10][25]
References
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16. Case Fatality Risk Among Individuals Vaccinated With rVSVΔG-ZEBOV-GP: A Retrospective Cohort Analysis of Patients With Confirmed Ebola Virus Disease in the Democratic Republic of the Congo. — Coulborn RM, Bastard M, Peyraud N, et al. The Lancet. Infectious Diseases. 2024.
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19. Post-Travel Evaluation to Rule Out Viral Special Pathogen Infection. — Catherine Brown, Mary J. Choi, Susan McLellan, and Trevor Shoemaker CDC Yellow Book. 2025.
20. Putting On and Removing Personal Protective Equipment. — Ortega R, Bhadelia N, Obanor O, et al. The New England Journal of Medicine. 2015.
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