Ebola differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; Guillermo Rodriguez Nava, M.D. [3]

Overview

Ebola must be differentiated from other diseases that cause hemorrhage and/or high fever as part of their presentation such as Marburg virus, Lassa fever, Typhoid fever and Malaria. The clinician must first rule out other more common causes of the fever before considering a viral hemorrhagic fever (VHF) such as Ebola, and the consideration of a VHF should be based upon epidemiology and demographics as well as sign and symptoms. A VHF such as Ebola, should be suspected in febrile persons who, within 3 weeks before onset of fever, have either: 1) traveled in the specific local area of a country where VHF has recently occurred; 2) had direct unprotected contact with blood, other body fluids, secretions, or excretions of a person or animal with VHF; 3) if the patient had any contact with someone who was ill with fever and bleeding or who died from an unexplained illness with fever and bleeding; 4) had a possible exposure when working in a laboratory that handles hemorrhagic fever viruses; 5) If a fever continues after 3 days of empiric treatment, and if the patient has signs such as bleeding or shock, the clinician must consider a VHF; 6) if no other cause is found for the patient’s signs and symptoms, the clinician must suspect a VHF.

Differentiating Ebola from other Diseases

The table below summarizes the findings that differentiate Ebola from other conditions that cause fever and hemorrhage:

Disease	Findings
Shigellosis & other bacterial enteric infections	Presents with diarrhea, possibly bloody, accompanied by fever, nausea, and sometimes toxemia, vomiting, cramps, and tenesmus. Stools contain blood and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and blood smears, should be made. Presence of leucocytosis distinguishes bacterial infections from viral infections.
Typhoid fever	Presents with fever, headache, rash, gastrointestinal symptoms, with lymphadenopathy, relative bradycardia, cough and leucopenia and sometimes sore throat. Blood and stool culture can confirm the presence of the causative bacteria.
Malaria	Presents with acute fever, headache and sometimes diarrhea (children). A blood smears must be examined for malaria parasites. The presence of parasites does not exclude a concurrent viral infection. An antimalarial should be prescribed as an empiric therapy. Although both Malaria and Ebola virus may present with constitutional symptoms and similar lab abnormalities, Malaria is more likely to involve paroxysms of fever, hypoglycemia, acute respiratory distress syndrome (ARDS), whereas Ebola virus is more likely to involve hemorrhagic sequelae.
Lassa fever	Disease onset is usually gradual, with fever, sore throat, cough, pharyngitis, and facial edema in the later stages. Inflammation and exudation of the pharynx and conjunctiva are common.
Yellow fever and other Flaviviridae	Present with hemorrhagic complications. Epidemiological investigation may reveal a pattern of disease transmission by an insect vector. Virus isolation and serological investigation serves to distinguish these viruses. Confirmed history of previous yellow fever vaccination will rule out yellow fever.
Others	Viral hepatitis, leptospirosis, dengue fever, rheumatic fever, typhus, acute leukemia, systemic lupus erythematosus, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and mononucleosis
Table adapted from WHO Guidelines For Epidemic Preparedness And Response: Ebola Haemorrhagic Fever

Differentiating Ebola from Influenza

Ebola virus should be differentiated from influenza virus since both occur in outbreaks and may present with similar signs and symptoms. The following table provided by the Centers for Disease Control and Prevention (CDC) demonstrates the key differences in transmission, risk factors, and clinical features between Ebola and influenza virus.

	Influenza (Flu)	Ebola
Cause	The flu is a common, contagious mild/severe respiratory illness caused by infection with influenza virus.	Ebola is a rare and deadly disease caused by infection with Ebola virus
Transmission	Transmission of influenza virus is mainly by droplets during cough, sneeze, or talk. Less commonly, the influenza virus can also spread on surfaces.	Transmission of Ebola is mainly by direct contact with blood or body fluids from: A person who is sick or who has died of Ebola Objects like needles that have been in contact with the blood or body fluids of a person sick with Ebola Ebola cannot spread in the air or by water or food.
Susceptible patients	Anyone can be infected by influenza virus. Patients at higher risk include young children, elderly, and individuals with co-morbidities	At-risk individuals include healthcare providers taking care of Ebola patients and friends/family who have had unprotected direct contact with blood or body fluids of a person sick with Ebola
Signs and Symptoms	Signs and symptoms usually develop within 2 days following exposure. Symptoms often develop rapidly and simultaneously. Fever Headache Myalgia Fatigue Cough Sore throat Runny nose	Signs and symptoms of Ebola can appear 2 to 21 days following exposure, with an average time of 8-10 days. Symptoms of Ebola often develop over several days and progressively worsen. Early symptoms include: Fever Headache Myalgia Fatigue Vomiting Diarrhea Abdominal pain Unexplained bleeding or bruising Late signs and symptoms include: Visceral and mucosal hemorrhage Neurological impairment Convulsions Stupor and coma

^{Table adapted from the Centers for Disease Control and Prevention (CDC) - Is it Flu or Ebola?}