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:

Overview

Marburg hemorrhagic fever must be differentiated from other viral hemorrhagic fevers that may cause fever, abdominal pain,and bleeding such as Ebola, Crimean-Congo hemorrhagic fever (CCHF), Hantavirus Infection, Rift Valley fever, Lujo hemorrhagic fever and Lassa fever. Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases such as malaria or typhoid fever, leptospirosis, Marburg hemorrhagic fever must also be differentiated from those infections.

Differentiating Marburg Hemorrhagic Fever from other Diseases

Marburg hemorrhagic fever must be differentiated from other viral hemorrhagic fevers that may cause fever, abdominal pain,and bleeding such as Ebola, Crimean-Congo hemorrhagic fever (CCHF), Hantavirus Infection, Rift Valley fever, Lujo hemorrhagic fever and Lassa fever. Because many of the signs and symptoms of Marburg hemorrhagic fever are similar to those of other infectious diseases such as malaria or typhoid fever, leptospirosis, Marburg hemorrhagic fever must also be differentiated from those infections.

Virus	Disease	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

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

Disease	Incubation period	Symptoms							Physical signs		Lab findings		Other findings
		Fever	Cough	Rash	Joint pain	Myalgia	Diarrhea	Common hemorrhagic symptoms	Characterestic physical finding	Icterus	Plasma Creatine kinase	Confirmatory test
Leptospirosis	2 to 30 days	Fever last for 4-7 days, remission for 1-2 days and then relapse	+	Present over legs hemorrhagic rash	+	+ (Severe myalgia is characteristic of leptospirosis typically localized to the calf and lumbar areas)	+	Conjunctival hemorrhage, Hemoptysis	Conjunctival suffusion	+	Elevated	Microscopic agglutination test of urine	History of exposure to soil or watercontaminated by infected rodents Recent history travel to tropical, sub tropical areas, or humid areas
Dengue	4 to 10 days	Fever last for 1-2 days, remission for 1-2 days, and then relapse for 1-2 days (Biphasic fever pattern)	-	Pruritic rash over legs and trunk (may be hemorrhagic)	+	+	-	Upper gastrointestinal bleeding	Painful lymphadenopathy	-	Normal	Serology showing positive IgM or IgG	Recent travel to South America, Africa, or Southeast Asia
Malaria	Plasmodium falciparum: 9-14 days Plasmodium vivax: 12-18 days Plasmodium ovale: 18-40 days	Fever present daily or on alternate day or every 3 days depending on Plasmodium sps.	-	No rash	-	+	-	Bloody urine	Hepatosplenomegaly	+	Normal	Giemsa stained thick and thin blood smears	Recent travel to South America, Africa, or Southeast Asia
Ebola	2 to 21 days.	+	+	Maculopapular non-pruritic rash with erythema Centripetal distribution	+	+	+ May be bloody in the early phase	Epistaxis Mucosal bleeding	Sudden onset of high fever with conjunctival injection and early gastrointestinal symptoms	-	Normal	RT-PCR	Recent visit to endemic area especially African countries
Influenza	1-4 days	+	+	+/-	+	+	+	-	Fever and upper respiratory symptoms	-	Normal	Viral culture or PCR	Health care workers Patients with co-morbid conditions
Yellow fever	3 to 6 days	+	+	-	-	+	-	Conjunctival hemorrhage, Hemoptysis	Relative bradycardia (Faget's sign)	+	Normal	RT-PCR, Nucleic acid amplification test, Immuno-histochemical staining	Recent travel to  Africa, South and Central America, and the Caribbean Tropical rain forests of south America
Typhoid fever	6 to 30 days	+	-	Blanching erythematous maculopapularlesions on the lower chest and abdomen	+	+	+	Intestinal bleeding	Rose spots	-	Normal	Blood or stool culture showing salmonella typhi sps.	Residence in endemic area Recent travel to endemic area