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

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:

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 + + + - +
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 [1]

Disease Incubation period Vector Symptoms Physical signs Lab findings Other findings Treatment
Fever Cough Rash Joint pain Myalgia Diarrhea Common hemorrhagic symptoms Characterestic physical finding Icterus Plasma Creatine kinase Confirmatory test
Leptospirosis 2 to 30 days Rodents

Domestic animals

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 water

contaminated by infected rodents

Recent history travel to tropical, sub tropical areas or humid areas

NSAIDs
Dengue 4 to 10 days Aedes mosquito Fever last for 1-2 days,

remission for 1-2 days and then relapse for 1-2 days (Biphasic fever pattern)

- Over legs and trunk

pruritic rash May be hemorrhagic

+ + - Upper gastrointestinal bleeding Painful lymphadenopathy - Normal Serology showing positive IgM or IgG Recent travel to South America, Africa, Southeast Asia Supportive care

Avoid aspirin and other NSAIDs

Malaria Female Anopheles 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, Southeast Asia Anti malarial regimen
Ebola 2 to 21 days. No vector

Human to human transmission

Air born disease

+ + 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 Isolation of the patient,

supportive therapy

Influenza 1-4 days No vector

Air born disease

+ + +/- + + + - Fever and upper respiratory symptoms - Normal Viral culture or PCR Health care workers

Patients with co-morbid conditions

Symptomatic treatment

Oseltamivir or zanamivir

Yellow fever 3 to 6 days Aedes or Haemagogus species mosquitoes + + - - + - 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

Symptomatic treatment,

Anti-inflammatory drugs

Typhoid fever 6 to 30 days No vector

Air born disease

+ - 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

Fluoroquinolones,

Third generation cephalosporins,

Azithromycin

References

  1. "WHO Guidelines For Epidemic Preparedness And Response: Ebola Haemorrhagic Fever".