01Approach to the Critical Patient/attcp55

Immediate isolation and PPE

›Isolation priority

›Immediate placement in negative-pressure private room before any assessment

›Door closed at all times

›Anteroom for donning and doffing if available

›Notify infection control, hospital epidemiology, and public health immediately

›Local and state health department

›CDC Emergency Operations Center: 770-488-7100

›PPE for suspected or confirmed EVD with bleeding, vomiting, or diarrhea

›Impermeable gown or coverall

›PAPR or N95 respirator with face shield

›Double gloves with extended cuffs

›Boot covers and impermeable apron

›PPE for stable patients without hemorrhage or profuse body fluids

›Fluid-resistant gown

›Full face shield and facemask

›Double gloves with extended cuffs

›Trained observer required for all donning and doffing

›Log all personnel entering the room

›Minimize number of personnel in isolation

Airway and breathing

›Airway threats

›Depressed mental status with inability to protect airway

›Altered mentation correlates with mortality

›GCS trend over hours

›Hypoxemia developing in up to 50% during disease course

›SpO2 target >= 94%

›HFNC preferred over NIV given secretion risk

02History/hx66

Exposure and travel history

›Geographic exposure

›Recent travel to or residence in sub-Saharan Africa

›Democratic Republic of Congo

›Guinea, Sierra Leone, Liberia

›Uganda and other Central/East African outbreak zones

›Active outbreak awareness in region

›Consultation with public health authorities on current outbreak status

›Specific exposure risk

›Direct contact with blood or bodily fluids of infected person

›OR 11.9 for EVD positivity in cohort studies

›Healthcare facility consultation in endemic area

›Healthcare workers disproportionately affected in every outbreak

›Funeral attendance with traditional burial practices

›Body washing practices are major transmission route

›OR 2.1 for EVD positivity

›Contact with bushmeat

›Fruit bats as likely reservoir host

›Non-human primates as amplifying hosts

Symptom timeline

›Early phase (days 1-5)

›Abrupt onset fever

›May be absent in up to 10% of cases

›Fatigue, malaise, myalgia, arthralgia

›Clinically indistinguishable from malaria and other febrile illness

›Headache

›Severe and persistent

›Sore throat, dysphagia

03Physical Exam/exam55

Vital signs

›Hemodynamic status

›Fever

›Present in majority but absent in up to 10%

›Absence does not exclude EVD

›Tachycardia

›Hypovolemic from massive GI losses

›Sepsis physiology

›Blood pressure

›SBP < 90 mmHg as shock threshold

›MAP < 65 mmHg as vasopressor trigger

›Respiratory rate

›Tachypnea developing in up to 50% during disease course

›Hypoxia SpO2 < 92% as escalation trigger

›Temperature trend

›High fever supporting active viremic phase

Fluid and volume status

›Dehydration assessment

›Sunken eyes and poor skin turgor

›Dry mucous membranes

›Capillary refill prolonged

›Urine output assessment

›Anuria as critical finding correlating with death

›Oliguria as early renal involvement marker

Focused organ systems

›Ocular exam

›Conjunctival injection

›Subconjunctival hemorrhage in late disease

04Differential Diagnosis/ddx54

Viral hemorrhagic fevers

›Filovirus mimics

›Marburg virus disease

›ICD-10 A98.3

›Clinically indistinguishable from EVD

›Requires PCR differentiation

›Lassa fever

›ICD-10 A96.2

›Similar VHF presentation in West Africa

›Arenavirus family

›Crimean-Congo hemorrhagic fever

›ICD-10 A98.0

›Tick exposure history

›Other VHFs

›Yellow fever

›ICD-10 A95

›Vaccination history relevant

›Dengue hemorrhagic fever

›ICD-10 A91

›Thrombocytopenia and leukopenia

›Southeast Asia and Americas geographic context

Common febrile illness mimics

›Most common differential in endemic settings

›Malaria

›ICD-10 B50-B54 depending on species

›Most frequent differential in sub-Saharan Africa

›Co-infection is frequent; RDT essential

›Cannot be excluded clinically without testing

05Laboratory Tests/lt57

Diagnostic confirmation

›RT-PCR (gold standard)

›Blood sample preferred

›Detectable from day 3 after symptom onset

›May be negative in first 72 hours

›Repeat if initial negative with strong clinical suspicion

›Viral load prognostication

›Ct value < 22 (high viral load) associated with 67% mortality

›Even with best available therapy

›Specimen handling

›Triple packaging with appropriate biosafety level

›Coordinate with public health laboratory

›Antigen detection RDT

›Point-of-care rapid antigen tests available in field settings

›Lower sensitivity than RT-PCR

›Useful when PCR not immediately available

Hematology and coagulation

›Complete blood count

›Thrombocytopenia

›Usually moderate; severe thrombocytopenia less common than historically believed

›Leukocyte pattern variable

›Early leukopenia then leukocytosis as disease progresses

›Anemia from hemorrhage and bone marrow suppression

›Coagulation panel

›PT and INR prolonged

›DIC pattern in severe disease

›D-dimer elevated

›Fibrinogen depleted in DIC

06Diagnostic Tests/dt54

Scoring Systems

›EVD risk stratification tools

›Malaria-sensitive triage score (Hartley et al.)

›Developed for high-burden settings to differentiate EVD from malaria

›Variables include fever, vomiting, diarrhea, unexplained bleeding

›Malaria RDT result integrated into score

›Sensitivity 88%, specificity 85% for EVD identification

›Viral load prognostic stratification

›RT-PCR Ct value < 22 indicates high viral load

›Mortality 67% with high viral load even with mAb therapy

›Ct > 24 lower mortality with specific therapy

›WHO clinical severity classification

›Mild: fever and systemic symptoms only

›Moderate: GI involvement with dehydration

›Severe: hemorrhage, neurological involvement, shock, organ failure

MRI

›MRI role in EVD

›Extremely limited acute utility

›Infection control risks of transporting EVD patient to MRI suite

›Decontamination of MRI environment extremely challenging

›CNS relapse evaluation in survivors

›Meningoencephalitis diagnosis

›Brain MRI for confirmed neurological relapse cases

›Performed in specialized biocontainment facilities only

›Contraindications in acute EVD

›Patient instability

›Inability to maintain adequate PPE in scanner environment

07Disposition/dispo41

Mandatory isolation admission

›All EVD cases require isolation facility admission

›Confirmed EVD

›Designated Ebola treatment unit or regional Ebola treatment center

›Biocontainment unit at specialized center preferred

›Suspected EVD pending PCR

›Maintain isolation until two negative PCR results

›Do not discharge or transfer without public health coordination

›Transfer to regional Ebola treatment center

›Tiered U.S. hospital preparedness system

›Coordinate with state health department and CDC

›Transfer by specialized transport team with appropriate PPE

Level of care

›ICU-level care indications

›Hemodynamic instability

›Persistent hypotension after fluid resuscitation

›Vasopressor requirement

›Respiratory failure

›SpO2 < 92% despite supplemental oxygen

›HFNC or mechanical ventilation requirement

›Renal failure

›Anuria or oliguria with rising creatinine

›Renal replacement therapy consideration

›Hemorrhagic complications

›Significant active bleeding

›Blood product requirement

›Neurological involvement

›Altered mental status

08Treatment/t93

Specific antiviral therapy

›First-line FDA-approved monoclonal antibodies (Zaire ebolavirus only)

›Inmazeb (REGN-EB3, atoltivimab + maftivimab + odesivimab)

›Triple monoclonal antibody cocktail

›Single IV infusion

›28-day mortality 33.5% vs approximately 50% with control

›PALM trial 2019 (NEJM) demonstrated superiority over ZMapp and remdesivir

›WHO strongly recommends for all confirmed cases including neonates born to PCR-positive mothers

›Ebanga (ansuvimab, mAb114)

›Single monoclonal antibody

›Single IV infusion

›28-day mortality 35.1%

›Non-inferior to Inmazeb; either agent acceptable

›Non-preferred alternatives when mAbs unavailable

›Favipiravir

›Limited clinical evidence

›Oral formulation option in resource-limited settings

›Not first line

›Remdesivir

›Inferior to mAb114 and REGN-EB3 in PALM trial

›WHO conditionally recommends against for EVD

›ZMapp

›No longer first line after PALM trial results

›Inferior to current FDA-approved agents

Fluid resuscitation and electrolyte management

›IV fluid resuscitation

›Ringer's lactate first choice

›Normal saline as alternative

›Replace ongoing GI losses volume for volume

›Monitor hourly urine output target > 0.5 mL/kg/hour

›Reassess volume status every 2-4 hours in severe disease

›Electrolyte correction

›Potassium

›IV replacement for hypokalemia

›Monitor cardiac rhythm during correction

›Calcium

›Calcium gluconate 1-2 g IV for symptomatic hypocalcemia

›Sodium

›Careful correction of hyponatremia

›Avoid rapid correction to prevent central pontine myelinolysis

›Magnesium

›Replace hypomagnesemia

›Magnesium sulfate 1-2 g IV infusion

Symptomatic and supportive care

›Antipyretics and analgesia

›Acetaminophen preferred

›500-1000 mg orally or IV every 6 hours

›Avoid NSAIDs

›Coagulopathy risk

›Platelet dysfunction risk

›Antiemetics

›Ondansetron

›4-8 mg IV every 8 hours

›Reduces vomiting and improves fluid tolerance

›Metoclopramide as alternative

›10 mg IV every 8 hours

›Antidiarrheal therapy

›Loperamide for profuse diarrhea

›Reduces volume of GI losses

›Use cautiously; avoid if bloody diarrhea severe

›Oxygen therapy

›Nasal cannula for mild hypoxemia

›Target SpO2 >= 94%

›HFNC for moderate hypoxemia

›Preferred over NIV given secretion risk

›Mechanical ventilation with full aerosol precautions if required

Empiric co-infection treatment

›Antimalarials

›Empiric therapy in endemic settings before PCR result

›Artemether-lumefantrine first line

›Artesunate IV for severe malaria

›Malaria RDT result guides continuation

›Antibiotics for bacterial co-infection

›Empiric coverage if secondary bacterial sepsis suspected

›Ceftriaxone 1-2 g IV daily as initial coverage

›Broaden based on clinical trajectory and cultures

›Avoid IM injections

›Bleeding risk from coagulopathy

›Anticoagulation and blood products

›Avoid routine anticoagulation given hemorrhagic risk

›Packed red blood cells for significant anemia with hemodynamic compromise

›Fresh frozen plasma for active hemorrhage with coagulopathy

›Cryoprecipitate for fibrinogen depletion

Infection control measures

›PPE compliance

›Impermeable gown or coverall plus PAPR or N95 for confirmed cases

›Plus double gloves, boot covers, impermeable apron

›Fluid-resistant gown plus full face shield for stable suspected cases

›Plus facemask and double gloves

›Trained observer mandatory for all donning and doffing

›Observer must verify each step

›Environmental decontamination

›Sodium hypochlorite 0.5% for all surfaces

›Single-use equipment where possible

›Waste managed as category A infectious substance

›Avoid procedures generating aerosols unless airway protection mandates

›Limit nebulizer use; MDI with spacer preferred

›Full airborne PPE if aerosol-generating procedures unavoidable

09Special Populations/sp64

Pregnancy

›Maternal and fetal risk

›High maternal mortality in EVD

›CFR among pregnant women historically among highest in outbreaks

›High fetal and neonatal loss

›Miscarriage and stillbirth common

›Neonates born to PCR-positive mothers at extreme risk

›Placenta as viral reservoir

›Vertical transmission documented

›Management modifications

›Inmazeb and Ebanga recommended for pregnant women

›WHO strongly recommends specific therapy regardless of trimester

›Neonates born to PCR-positive mothers should receive mAb therapy

›Obstetric care in biocontainment setting

›Specialized multidisciplinary team required

›Extreme PPE for obstetric procedures

›Fluid resuscitation targets

›Aggressive replacement for GI losses

›Fetal monitoring when viable gestation and resources permit

›Breastfeeding

›EVD RNA detected in breast milk

›Breastfeeding contraindicated in confirmed EVD

Geriatric

›Age-related risk

›Higher mortality in elderly patients

›Age as independent risk factor in outbreak analyses

›Reduced physiologic reserve

›Dehydration tolerated less well

10Background/b82

Epidemiology

›Outbreak history and distribution

›First identified 1976 simultaneously in DRC and Sudan

›Named after Ebola River in DRC

›Major outbreaks

›2014-2016 West Africa: largest in history, over 28,000 cases and 11,000 deaths

›2018-2020 DRC North Kivu: approximately 3,470 cases, 2,287 deaths

›Ongoing sporadic outbreaks in DRC, Uganda, Guinea

›Case fatality rate approximately 50% average

›Range 25-90% depending on species and outbreak context

›Species: Zaire (highest CFR), Sudan, Bundibugyo, Tai Forest, Reston

›Better outcomes in high-resource settings

›18.5% mortality with aggressive supportive care and mAb therapy

›40-70% mortality in resource-limited settings

›Transmission and incubation

›Incubation period 2-21 days

›Typical onset 6-10 days after exposure

›Transmission through direct contact with blood and body fluids

›Not airborne in natural conditions

›Healthcare worker disproportionate impact in every outbreak

›Fruit bats likely natural reservoir host

Pathophysiology

›Viral biology

›Family Filoviridae, genus Ebolavirus

›Negative-sense single-stranded RNA virus

›Five pathogenic species in humans: Zaire, Sudan, Bundibugyo, Tai Forest, Reston

›Cell tropism

›Primarily macrophages, monocytes, dendritic cells initially

›Spreads to hepatocytes, adrenal cortex cells, endothelial cells

›Widespread dissemination via lymphatics and blood

›Immune evasion

›Viral proteins VP35 and VP24 suppress interferon response

›Allows unchecked viral replication in early phase

›Dendritic cell dysfunction impairs adaptive immune response

›T cell activation delayed and impaired

›NK cell exhaustion with high viral load

›Pathological cascade

›Cytokine storm

›Massive pro-inflammatory cytokine release

›TNF-alpha, IL-6, IL-1 beta as key mediators

›Vascular endothelial injury

›Increased vascular permeability

›Fluid shift and distributive component

›Liver injury

›Hepatocyte necrosis and inflammation

›Coagulation factor production impaired

›Adrenal insufficiency

›Adrenocortical cell destruction

›Contributes to refractory hypotension

›DIC development

›Tissue factor expression by infected monocytes

›Microthrombi and consumption coagulopathy

›Hemorrhagic manifestations in minority of patients

Therapeutic Considerations

›Specific therapy evidence base

›PALM randomized trial 2019 (NEJM)

›mAb114 and REGN-EB3 superior to ZMapp and remdesivir

›Low viral load survival rate 89-94% with mAb therapy

›Trial stopped early due to clear benefit

›WHO strongly recommends Inmazeb and Ebanga for all confirmed Zaire ebolavirus

›Both agents have equivalent efficacy

›Choice may depend on availability

›Timing of therapy critical

›Earlier initiation associated with better outcomes

›Viral load at presentation strongest predictor of response

›Supportive care principles

›Aggressive electrolyte and fluid management backbone of care

›ORS when tolerated; IV fluids when not

›Nutritional support as core component

›Empiric antimalarials reduce mortality through co-infection treatment

›Avoid nephrotoxic drugs and NSAIDs

›Vaccination strategy

›rVSV-ZEBOV-GP (Ervebo)

›Single-dose live vaccine

›97.5% efficacy when given 10 or more days before exposure

›Used in ring vaccination strategy in outbreak response

›Vaccinated patients have 1.7x lower mortality if infected

›Post-exposure prophylaxis

›mAb114 or REGN-EB3 preferred for high-risk exposures

›Immediate activity without 10-day gap of vaccine

›rVSV-ZEBOV used as PEP within 48 hours in some settings

›Infection control as therapeutic strategy

›Early isolation reduces transmission and allows aggressive care

›PPE compliance protects healthcare workforce

›Contact tracing breaks transmission chain

11Patient Discharge Instructions/pdi39

copy discharge instructions

›Post-Ebola recovery instructions

›Complete all prescribed medications exactly as directed

›Maintain adequate oral fluid intake

›At least 2-3 litres of fluid daily

›Electrolyte-containing drinks (sports drinks or ORS)

›Rest and gradual return to activity

›Fatigue may persist for months after discharge

›Post-Ebola syndrome awareness

›Most survivors experience at least one long-term symptom

›Joint and muscle pain very common

›Headache and fatigue may persist

›Memory and concentration difficulties

›Hearing loss possible

›Eye and vision problems: uveitis can cause vision loss

›Neuropsychiatric symptoms common

›Depression and anxiety: seek mental health support

›Cognitive changes may require evaluation

›Important precautions

›Male survivors: Ebola virus can persist in semen for 16 months or longer

›Use condoms consistently until viral clearance confirmed by testing

›Semen testing required before unprotected sex

›Breast milk may contain Ebola virus

›Avoid breastfeeding until cleared by medical team

›Follow-up appointments required

›Ophthalmology appointment for eye examination

›Uveitis can develop and cause vision loss if untreated

›Primary care physician within 1 week of discharge

12References/r37

Guidelines and key sources

›Primary clinical references

›Chavez S, Koyfman A, Gottlieb M et al. Ebola Virus Disease: A Review for the Emergency Medicine Clinician. American Journal of Emergency Medicine. 2023

›Comprehensive emergency medicine review

›Symptom epidemiology and diagnostic approach

›Malvy D, McElroy AK, de Clerck H et al. Ebola Virus Disease. Lancet. 2019

›Comprehensive clinical review

›Pathophysiology and clinical management

›Feldmann H, Sprecher A, Geisbert TW. Ebola. New England Journal of Medicine. 2020

›Virology and epidemiology review

›Rojek A, Fieggen J, Apiyo P et al. Ebola Disease: Bridging Scientific Discoveries and Clinical Application. Lancet Infectious Diseases. 2025

›Most recent comprehensive clinical review

›Landmark therapeutic trials

›Mulangu S, Dodd LE, Davey RT et al. PALM Trial. New England Journal of Medicine. 2019

›Randomized controlled trial establishing mAb114 and REGN-EB3 superiority

›Pivotal evidence base for current WHO recommendations

›Gao Y, Zhao Y, Guyatt G et al. Network Meta-Analysis of EVD Therapies. Lancet Microbe. 2022

›Systematic review confirming mAb superiority

›Vaccine and prevention references

›Kuehn R, Ryan H, Okwaraeke KC et al. Vaccines for Preventing Ebola Virus Disease. Cochrane Database of Systematic Reviews. 2024

›rVSV-ZEBOV-GP efficacy data

›Muyembe JJ, Pan H, Peto R et al. rVSV-ZEBOV-GP Ring Vaccination. New England Journal of Medicine. 2024

›Ring vaccination strategy in DRC outbreak

›Coulborn RM et al. Case Fatality Risk Among Vaccinated Individuals. Lancet Infectious Diseases. 2024

›1.7x lower mortality in vaccinated patients

›Long-term outcomes

›Wohl DA, Fischer WA et al. Post-Ebola Symptoms 7 Years After Infection. Clinical Infectious Diseases. 2023

›75% of survivors with symptoms at 1 year declining to 52% at 5 years

Evidence & Review