Marburg hemorrhagic fever differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief:

Differentiating Marburg Hemorrhagic Fever from other Diseases

Marburg hemorrhagic fever must be differentiated from other diseases that may cause fever, abdominal pain, diarrhea, vomiting and bleeding such as:

• Ebola hemorrhagic fever
• Lassa hemorrhagic fever
• Crimean-Congo hemorrhagic fever

• Malaria
• Typhoid fever
• Shigellosis
• Cholera
• Leptospirosis
• Plague,
• Rickettsiosis
• Relapsing fever
• Meningitis
• Hepatitis
• Other viral hemorrhagic fevers

		Incubation Period	Symptoms						Laboratory findings
			Prodromal phase					Illness phase
			Fever	Headache	Myalgia	Abdominal pain	Hemorrhage
Filoviruses	Marburg Hemorrhagic Fever	5-10	+	+	+	+	+	Clinically indistinguishable Maculopapular rash on the trunk (chest, back, stomach) Multiorgan failure
	Ebola	2-21	+	+	+	+	+
Bunyaviruses	Crimean-Congo hemorrhagic fever (CCHF)	13	+	+	+	+	+	Red eyes, a flushed face, a red throat, and petechiae (red spots) on the palate changes in mood and sensory perception.
	Hantavirus Infection	9 -33	+	+	+	-	+	Flushing of the face Injection of the conjunctiva Prostration
	Rift Valley fever	2-6	+	-	+	-	-	Most commonly mild disease with recovery in 2 weeks Encephalitis, or inflammation of the brain Hemorrhagic fever, which occurs in less than 1% of overall RVF
Arenaviruses	Lassa fever	7-21	+	+	+	-	-	Deafness Respiratory distress Repeated vomiting Facial swelling Pain in the chest, back, and abdomen, and shock.encephalitis Hemorrhage only 20% have severe disease
	Lujo hemorrhagic fever	7-13						Morbilliform rash of the face and trunk Face and neck swelling Pharyngitis Diarrhea
	Lymphocytic choriomeningitis (LCM)	8-13	+	+	+	-	-	Meningitis, encephalitis, meningoencephalitis Acute hydrocephalus Myocarditis
Flaviviruses	Alkhurma hemorrhagic fever (AFD)	2-4	+	-	+	-	-	Neurologic symptoms Hemorrhagic symptoms only in severe form. Multi-organ failure	Thrombocytopenia, Leukopenia Elevated liver enzymes
	Kyasanur Forest Disease (KFD)	3-8	+	+	+	+	+	Biphasic Complete recovery by 2 week Wave of symptoms in 3 rd week with tremors, and vision deficits.	Pancytopenia
	Omsk hemorrhagic fever	3-8	+	+	+	+	+	Biphasic Complete recovery by 2 week Wave of symptoms in 3 rd week with encephalitis	Pancytopenia

Treatment should be based on the most likely etiology of fever according to local epidemiology. If the fever continues after 3 days of recommended treatment, and if the patient has signs such as bleeding or shock, a viral hemorrhagic fever should be considered. It is important to review the patient’s history for any contact with someone who was ill with fever and bleeding or who died from an unexplained illness with fever and bleeding.

Shown below is a table summarizing the typical findings of the differential diagnoses of MHF.

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.
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 demonstrate causative bacteria.
Malaria	Presents with acute fever, headache and sometime diarrhea (children). Blood smears must be examined for malaria parasites. Presence of parasites does not exclude concurrent viral infection. Antimalarial must be prescribed in an attempt at therapy.
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 virus. Confirmed history of previous yellow fever vaccination will rule out yellow fever.
Others	Viral hepatitis, leptospirosis, rheumatic fever, typhus, and mononucleosis produce signs and symptoms that may be confused with Ebola in the early stages of infection.
Table adapted from WHO Guidelines For Epidemic Preparedness And Response: Ebola Haemorrhagic Fever