emDOCs Podcast – Episode 121: Ebola Virus Disease

Authors: Jessica Pelletier, DO, MHPE (EM Physician/APD, University of Missouri-Columbia); Steve Liang (EM Physician, Washington University in St. Louis); Gaston Omba (EM Resident Physician, Makerere University, Kampala, Uganda); Brit Long, MD (@long_brit)

Background:

• Ebola virus disease (EVD) is a viral hemorrhagic fever first identified in the Democratic Republic of the Congo in 1976.
• Natural reservoir of the disease is not entirely clear but is thought to be fruit bats; humans serve as accidental hosts.
• Six known species in the Ebolavirus genus:
  • Bombali ebolavirus – type virus Bombali virus (BOMV)
  • Bundibugyo ebolavirus – type virus Bundibugyo virus (BDBV)
  • Reston ebolavirus – type virus Reston virus (RESTV)
  • Sudan ebolavirus – type virus Sudan virus (SUDV)
  • Tai Forest ebolavirus – type virus Taï Forest virus (TAFV)
  • Zaire ebolavirus – type virus Ebola virus (EBOV)
• EBOV most virulent species; responsible for most EVD outbreaks

Epidemiology:

• All outbreaks to date have occurred in sub-Saharan Africa.
• EBOV has 90% mortality rate without appropriate medical care, compared with 50% mortality for SUDV and 30% for BDBV.
• Other species of Ebolavirus are less common and have not been responsible for large outbreaks.

Figure 1. EVD outbreaks in sub-Saharan Africa since 1976. Source: https://www.cdc.gov/ebola/outbreaks/index.html

Pathophysiology:

• Negative sense, single-stranded RNA.
• Transmission occurs via direct contact with infected body fluids or broken skin of an infected person.
  • Sexual transmission, handling infected corpses, or eating bushmeat of infected animals can also lead to viral spread.
• Human-to-human transmission occurs in the majority of cases.
• Virus replicates in antigen-presenting cells (dendritic cells and macrophages) but then spread.
• Virus able to evade the immune system by impairing the function of natural killer cells and dendritic cells, disrupting regulation of the cytokine network, and inhibiting type I interferon activity.
• Later stages of the disease marked by cytokine storm with multiorgan failure.

Presentation:

• Incubation period for Ebolaviruses lasts from 2-21 days. This is followed by three phases:
  • Flu-like illness (dry phase) – fevers, chills, myalgias
  • Gastrointestinal symptoms (wet phase), including nausea, vomiting, profuse diarrhea (up to several liters daily, similar to cholera), abdominal cramping.
  • Hemorrhage may also occur in this phase, but < 50% with EVD develop hemorrhagic symptoms. May range from petechiae, bruising, bleeding from gums, subconjunctival hemorrhage, and oozing from IV sites up to GI bleed and fulminant hemorrhage.
  • Multiorgan failure, shock, and death – which usually manifest within 16 days of the flu-like illness.
• If patients recover, it typically occurs around day 7.

Figure 2. Common manifestations of EVD. Source: By Mikael Häggström – Own work. Source information: Ebola Hemorrhagic Fever from Centers for Disease Control and Prevention.P age last updated: January 28, 2014., CC0, https://commons.wikimedia.org/w/index.php?curid=34449291

Figure 3. EVD timeline. Adapted from: Chavez S, Koyfman A, Gottlieb M, et al. Ebola virus disease: A review for the emergency medicine clinician. The American Journal of Emergency Medicine. 2023;70:30-40. doi:10.1016/j.ajem.2023.04.037

Diagnosis:

• Key is obtaining a good travel history.
• Major risk factor for acquiring EVD is travel to/living in an outbreak area in sub-Saharan Africa with known exposure to someone infected.
• If have any suspicion that a patient may have been exposed to an Ebolavirus, wear appropriate PPE.
• EVD usually diagnosed via serum RT-PCR looking for the presence of viral RNA.
  • RT-PCR requires expensive equipment and trained staff.
• Rapid diagnostic tests (RDTs) do exist, but are unlikely to be available in settings like the US where EVD does not have a high incidence; these are more likely to be used in outbreak areas.
  • RDTs do not perform as well as RT-PCR.
• Obtain CBC, type and screen versus cross, coagulation tests, renal and liver function, electrolytes.
  • CBC: leukopenia/lymphocytopenia, neutrophilia, and thrombocytopenia common
  • Renal and liver injury
  • Electrolyte derangements
  • D-dimer usually elevated.
  • Urinalysis may reveal proteinuria.
• Imaging based on signs/symptoms.
  • Head CT for seizures/altered mental status.
  • If pregnant, obtain transabdominal/transvaginal US due to risk of miscarriage with EVD.
• If respiratory symptoms present, consider for alternate causes (pneumonia, PE, CHF).

Other conditions to consider:

• Flu like mimics: pneumonia, endocarditis, myocarditis, spinal epidural abscess, toxic shock syndrome, acute retroviral syndrome, CO toxicity, meningitis, malaria.
  • Severe malaria: presents with altered mental status, hemodynamic instability, headache, fevers, rash, myalgias, nausea/vomiting. Similar lab abnormalities compared to EVD. Obtain blood smear or rapid diagnostic test for malaria antigen (where available).
  • Meningitis: altered mental status, meningismus, nausea/vomiting, headache, fever, rash. Sub-Saharan Africa is known as the “meningitis belt” due to high incidence. Obtain LP and administer antibiotics.

Management:

• Supportive care: blood products for hemorrhage, IV fluids for hypovolemia due to vomiting and diarrhea. Oral rehydration for those who are PO tolerant.
  • Treat symptoms (nausea/vomiting).
• Consider and treat other conditions.
• Monoclonal antibodies: mAb114 and REGN-EB3.
  • FDA approved; may decrease mortality compared to supportive treatment alone.
  • WHO provides a strong recommendation for mAb114 or REGN-EB3 for patients with EVD infection confirmed via PCR AND for neonates born to mothers with confirmed EVD who are ≤ 7 days old (whether or not the neonate has confirmed EVD infection). There are conditional recommendations against the use of remdesivir or ZMapp for patients with EVD.
  • mAb114 is also known as ansuvimab (Ebanga™).
  • REGN-EB3 is a combination of atoltivimab, maftivimab, and odesivimab (Inmazeb™).

Prevention:

• There is an EVD vaccine against the Zaire strain (Ervebo).
• The Advisory Committee on Immunization Practices (ACIP) recommends that US adults at high risk for occupational exposure receive the Ervebo vaccine:
  • Are responding to an EVD outbreak.
  • Are health care personnel at federally-designated EVD treatment centers in the US.
  • Work in biosafety level 4 facilities that handle Ebolaviruses.
• Isolate suspected EVD patients immediately.
• Appropriate PPE:
  • Cover all body surfaces when working with EVD patients: gowns, boot covers, double gloves, eye protection, and ideally N95 masks or PAPRs.
  • If using an N95, wear a full face shield and surgical hood to cover the rest of the head and neck.
• Airborne precautions should be used for aerosol-generating procedures.

Disposition:

• Admit persons under investigation (PUI) for EVD to avoid contaminating others in the community.
• A negative RT-PCR test 72 hours after symptom onset is adequate to exclude EVD.
• If treating a PUI for EVD in the US, contact health department (https://www.cste.org/page/EpiOnCall) to determine whether they recommend transfer to a designated Ebola treatment center within the multitiered National Special Pathogens System (NSPS) (https://netec.org/nsps/).
• The Centers for Disease Control (CDC) also has a Viral Special Pathogens Branch (VSPB); call 770-488-7100 and ask for the VSPB epidemiologist.

Summary:

• EVD is a viral hemorrhagic fever with high morbidity and mortality.
• Outbreaks typically occur in sub-Saharan Africa, and Ebolaviruses are spread by direct contact.
• Three phases of disease – dry, wet, and recovery or multiorgan failure/death
• Diagnosis involves RT-PCR or RDT, where available
• Treatment is mainly supportive; monoclonal antibodies are now available.
• Prevention involves vaccination for those at high risk of acquiring the disease, appropriate isolation of PUI, and ensuring excellent PPE compliance.

References:

1. Centers for Disease Control and Prevention (CDC). Ebola Outbreak Caused by Sudan virus in Uganda. Accessed April 6, 2025. https://www.cdc.gov/han/2025/han00521.html#:~:text=On%20January%2029%2C%202025%2C%20the,outbreak%20in%20Uganda%20since%202000
2. Centers for Disease Control and Prevention (CDC). Clinical Guidance for Ebola Disease.; 2025. Accessed April 7, 2025. https://www.cdc.gov/ebola/hcp/clinical-guidance/index.html
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