Definition: Ebola virus disease (EVD), also known as Ebola hemorrhagic fever, is due to a virulent pathogen spread by human-human transmission. The disease has the potential of causing multi-organ failure with high mortality rates in the absence of a standard treatment or vaccination.

Epidemiology:

  • Endemic to parts of Western Africa
  • Current outbreak (December 2013 to present): 26,933 total cases and 11,120 deaths (Ebola 2015)
    • Predominant transmission occurring in West Africa (Sierra Leone, Guinea, Liberia)
  • Incubation period: 3-21 days

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Pathophysiology:

  • Current strain 97% homology with Zaire ebolavirus, which is the most virulent strain with prior fatality rates as high as 90% (Tattevin 2014)
  • Ebola virus causes a systemic inflammatory response that impairs the vascular, coagulation, and immune systems (Feldman 2011)
  • Transmission requires direct contact through broken skin or mucous membranes with body fluids of symptomatic infected or convalescent patients
    • Symptoms (incubation period) occur within 21 days of direct contact
    • Mean incubation time from prior outbreaks ranged from 3-13 days (Tattevin 2014)
    • If a patient presents with symptoms greater than 21 days post-contact, can likely be ruled out.
  • Fatalities due to combination of hypovolemic (vomiting/diarrhea) and septic shock, massive bleeding (typically GI), and end-organ failure

Symptoms:

  • Fever
  • Nausea/vomiting/diarrhea
  • Flu-like symptoms (i.e. headache, myalgias/arthalgias)
  • Anorexia

 Physical Exam Findings: poly-organ involvement and life-threatening signs manifests later as disease progresses

  • HEENT: conjunctival injection, oropharyngeal erythema
  • CV: hypotension
  • Resp: tachypnea, rales (pulmonary edema late finding)
  • Abdomen: hyperactive bowel sounds
  • GU: anuria/oliguria
  • Skin: diffuse non-pruritic maculopapular rash, desquamation, petechiae/ecchymosis, mucosal membrane hemorrhage
  • Neuro: altered mental status, lethargy

ED Management/Treatment:

  • Identification/Isolation
    • Who to Isolate: patients with concerning symptoms + fever AND who have traveled to/reside in high-risk countries OR have had direct contact with an Ebola positive or suspected patient.
    • Immediate identification precludes all management given the high susceptibility of transmission to other patients and health care providers.
    • Patients should remain in isolation until alternative diagnosis can be proven.
    • Medical staff should be trained in donning/doffing personal protective equipment, and receive frequent recertification to practice of applying PPE.
  • Supportive Care
    • Supportive care central as there is no specific treatment for Ebola
    • Fluid substitution and electrolyte repletion will likely be the most immediate problem to be addressed.

Diagnostic Testing:

  • Physical Exam Diagnosis
    • Given the delay in serologic testing and potential of false negative results (depending on time course of illness), diagnosis should be based on clinical assessment.
    • Differential diagnosis should also include malaria, typhoid fever, Chikugunya, yellow fever, fulminant viral hepatitis, influenza and sepsis.
  • Serologic Diagnosis
    • Definitive diagnosis of EVD based upon detection of viral antigen via ELISA or viral RNA by RT-PCR.
    • Viral antigen and nucleic acid can be detected as early as day 3 of symptoms, but can take up to 10 days (Meyers 2015).
    • Antibody testing can also be tested using ELISA, but is less frequently used.
    • Specimens should be collected and sent to international/national reference centers.
    • Other common laboratory findings may include: leukopenia, thrombocytopenia, elevated BUN/Cr, elevated AST/ALT, prolonged PT/PTT

Convalescent Period

  • In Ebola positive patients, virus will clear from blood and urine first, however viral antigens may still be present in semen as long as 3 months into convalescent period.
  • Newly reported in NEJM May 2015, found a recovering Ebola patient who developed ocular symptoms (blurring of vision, foreign body sensation, and photophobia) 10 weeks after clearance of viremia in blood (Varkey 2015)
    • +EVD within aqueous humor, but negative in tears/conjunctiva
    • Sight threatening panuveitis improved with prednisolone, atropine and timolol drops, in addition to oral prednisone.
  • Limited data of other convalescent symptoms.

Take Home Points:

  1. Identify and isolate patients with concerning symptoms who have either traveled to or reside in high-risk/endemic areas (Guinea/Sierra Leone/Liberia) AND/OR have had direct contact with persons with known or suspected Ebola within a three-week timeframe.
  2. Diagnosis based on clinical assessment as serologic testing may provide a false negative result or a delay in diagnosis.
  3. No standard of treatment, however important to provide supportive care (airway management, fluid/electrolyte resuscitation) with appropriate personal protective equipment.

References:

Ebola Situation Report — 20 May 2015. Geneva: World Health Organization, 2015. (http://apps.who.int/ebola/en/current-situation/ebola-situation-report-20-may-2015)

Feldman H, Geisbert TW. Ebola haemorrhagic fever, Lancet 2011;377:849-62. PMID: 21084112

Meyers L, Frawley T, Goss S, Kang C. Ebola virus outbreak 2014: Clinical review for emergency physicians. Ann Emerg Med 2015;65:101-8. PMID: 25455908

Tattevin P, Durante-Magoni E, Massaquoi M. Does this patient have Ebola virus disease? Intensive Care Med 2014;40:1738-41. PMID: 25183574

Varkey JB, Shantha JG, Crozier I, Yeh S. Persistence of Ebola virus in ocular fluid during convalescence. NEJM 2015. PMID: 25950269