II. Epidemiology

  1. Marburg Virus
    1. Outbreaks in Europe 1967, Congo 2000, Angola 2005
  2. Ebola Virus
    1. Five species with varying regions affected and mortality rates
    2. Outbreaks in Zaire 1976, Sudan 1970, Philipines 1989, Zaire 1995, Uganda 2000, Sudan 2004, Uganda 2007
    3. Ebola epidemic in West Africa (2014) in Sierra Leone, Guinea and Liberia
      1. By far, the largest Ebola or Marburg outbreak
      2. As of November 2014, West Africa: 13000 cases (nearly 8000 lab confirmed) and 4800 deaths
      3. A few cases have presented in Mali, Senegal, Nigeria, Spain and the U.S.

III. Pathophysiology

  1. Ebola Virus (Filovirus family)
    1. Nonsegmented, negative-sense, single-stranded RNA Virus
    2. Structurally similar to Rhabdovirus (Rabies) and Paramyxovirus (Measles)
  2. Hemorrhagic Fever viruses (associated coagulation deficits, DIC)
    1. Other hemorrhagic fever viruses include Lassa Fever, Yellow Fever, Dengue Fever
  3. Host organism
    1. Small animal primary reservoir is suspected (e.g. fruit bats)
    2. Primates appear to be as susceptible as humans to high mortality rates
      1. Exposure to infected primates has been responsible for many of the initial source cases in epidemics
  4. Spread by close contact to infected bats, primates or other humans
    1. Infected blood
    2. Body fluid
      1. Especially blood, stool and vomit
      2. Semen transmission from previously infected source has been reported
    3. Body tissue
    4. Air borne transmission is unlikely (unless aerosolized, typically during medical procedures)

IV. Precautions

  1. Ebola and Marburg Viruses are among the most virulent infections in humans with mortality up to 70-90%
  2. Initial presentation may be non-specific and mild
  3. Maintain vigilance and ask a careful travel history in febrile patients (e.g. endemic region, known exposures)
    1. Fever, severe Headache, myalgias, Vomiting, Diarrhea, Abdominal Pain, unexplained bleeding
  4. Immediately and completely isolate patients suspected of Viral Hemorrhagic Fever (see prevention below)

V. Course

  1. Incubation Period: 8-12 days (ranges from 2 to 21 days)
  2. Mortality is highest days 6 to 16
  3. Surviving patients start to improve by the second week of illness
  4. Virus may persist in semen and Breast Milk for a prolonged period beyond recovery
  5. Prolonged recovery characterized by weakness, Fatigue and persistent weight loss

VI. Symptoms: Common

  1. Fever (87%)
  2. Fatigue (76%)
  3. Vomiting (68%)
  4. Diarrhea (66%)
  5. Anorexia (65%)

VII. Findings: Manifestations

  1. Influenza-Like Illness
    1. Abrupt onset fever, chills and malaise
    2. Weakness and Anorexia
    3. Severe Headache
    4. Trunk and back pain (myalgias)
    5. Nonproductive cough and Sore Throat
    6. May rapidly progress to Septic Shock and multi-organ failure
  2. Dermatitis
    1. Variably present by day 5-7 of illness
    2. Non-pruritic diffuse erythematous rash that may spare the legs (with or without Desquamation)
  3. Gastrointestinal symptoms
    1. Onset within a few days of initial symptoms
    2. Diarrhea, Vomiting and severe Abdominal Pain
    3. Bloody stools may occur (6% of cases)
  4. Bleeding
    1. Variably present in 20% of cases and a late manifestation
    2. Signs include Petechiae or Ecchymosis, mucosal bleeding or gastrointestinal Hemorrhage
  5. Neurologic
    1. Seizures, confusion and cerebral edema may occur
  6. Cardiopulonary
    1. Chest Pain, Shortness of Breath, Hiccups may occur
  7. Other findings
    1. Dark-red palatal discoloration
    2. Conjunctival injection

VIII. Labs

  1. Precautions
    1. CDC recommends that labs be performed on dedicated machine (e.g. iStat) not used for other patient's blood
    2. Logistically, labs are typically being deferred to tertiary center or department of health testing in high suspicion cases
  2. Complete Blood Count (CBC) with differential and Platelet Count
    1. Leukopenia
    2. Thrombocytopenia
  3. Coagulation tests
    1. Findings consistent with Disseminated Intravascular Coagulation (DIC)
    2. Prothrombin (PT/INR) prolonged
    3. Partial Thromboplastin Time (PTT) prolonged
  4. Liver Function Tests
    1. Serum Aspartate Aminotransferase (AST) increased (more than ALT)
    2. Alanine Aminotransferase (ALT) increased
  5. Ebola specific testing (coordinated with local health department and CDC)
    1. Ebola PCR
    2. Ebola ELISA
    3. Ebola Serology (IgM, IgG)
    4. Ebola Virus isolation

IX. Management

  1. Supportive care in isolation suite by medical team using Full Personal Protective Equipment (see below)
    1. IV Fluid and Electrolyte replacement
    2. Supplemental Oxygen
    3. Vasopressors
    4. Mechanical Ventilation
  2. Monoclonal Antibody options
    1. Atoltivimab/Maftivimab/Odesivimab (Inmazeb)
    2. Ansuvimab (Ebanga)
  3. Ribavirin (Virazole)
    1. See Viral Hemorrhagic Fever for protocol

X. Prognosis

  1. Mortality rates range from 50-90%
  2. West African Ebola epidemic in 2014 mortality: 70%
  3. Findings suggestive or worse prognosis
    1. Tachypnea
    2. Anuria
    3. Delirium to coma
    4. Refractory shock
    5. Persistently high or increasing Ebola Virus RNA titers

XI. Prevention

  1. Complete patient isolation
    1. Isolated room with designated bathroom or commode
    2. Designated care team in full PPE minimize broader exposures
  2. Full Personal Protective Equipment (PPE) for healthcare workers (donning and doffing)
    1. http://www.cdc.gov/HAI/pdfs/ppe/ppeposter148.pdf
  3. Vacinnation
    1. Ebola Zaire Vaccine (age over 18 years)
      1. Single dose 1 ml IM for preexposure, or immediate postexposure

XIII. References

  1. Black, Martin, DeVos (2018) Crit Dec Emerg Med 32(8): 3-12
  2. Bray in Hirsch (2014) Ebola and Marburg Virus Disease, UpToDate, accessed online 11/5/2014
  3. Nordurft-Froman and DeVos (2022) Crit Dec Emerg Med 36(4): 4-15
  4. (1995) MMWR Morb Mortal Wkly Rep 44:381-2 [PubMed]

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Related Studies

Ontology: Marburg Virus Disease (C0024788)

Definition (MSHFRE) Infection virale des singes Rhésus, des singes Vervet et du singe écureuil, transmissible à l'homme et due à un virus à ARN de la famille des Filoviridae.
Definition (NCI) A viral infectious disorder caused by Marburg virus. Signs and symptoms include fever, headache, myalgias, chest and abdominal pain, jaundice, liver failure, massive hemorrhaging, and multiple organ failure.
Definition (MSH) An RNA virus infection of rhesus, vervet, and squirrel monkeys transmissible to man.
Concepts Disease or Syndrome (T047)
MSH D008379
ICD10 A98.3
SnomedCT 123322008, 77503002
English Marburg disease, MARBURG VIRUS DIS, Marburg virus disease (diagnosis), Marburg Virus Disease, Marburg viral haemorrhagic fever, Marburg viral hemorrhagic fever, Marburg virus infection, Fever, Marburg Hemorrhagic, Marburg Disease, Hemorrhagic Fever, Marburg, Disease, Marburg, Marburg Hemorrhagic Fever, Marburg Virus Disease [Disease/Finding], marburg disease, green monkey disease, marburg virus disease, Marburg virus disease, Vervet monkey disease, Green monkey disease, Marburg virus disease (disorder), Marburg virus disease -RETIRED-, Marburg haemorrhagic fever, Marburg hemorrhagic fever
Italian Malattia di Marburg, Febbre emorragica virale di Marburg, Infezione da virus di Marburg, Malattia da virus Marburg
Dutch Marburg-virus hemorragische koorts, Marburg-virusinfectie, ziekte van Marburg, Marburg-virusziekte, Virusziekte, Marburg-, Ziekte, Marburg-virus-
French Infection par le virus Marburg, Infection par le virus Marburg avec fièvre hémorragique, Fièvre hémorragique de Marbourg, Maladie de Marbourg, Fièvre hémorragique à virus Marburg, Maladie de Marburg, Maladie à virus de Marburg
German Marburgvirus-Infektion, vom Marburg-Virus verursachtes haemorrhagisches Fieber, Marburg-Viruskrankheit, Marburg-Virus-Krankheit
Portuguese Infecção por vírus de Marburg, Febre hemorrágica por vírus de Marburg, Doença de Marburg, Doença do Vírus de Marburg
Spanish Infección por virus de Marburg, Fiebre hemorrágica vírica de Marburg, enfermedad por el virus de Marburg - RETIRADO - (concepto no activo), enfermedad por el virus de Marburg - RETIRADO -, enfermedad de los monos de Sudáfrica, enfermedad por virus de Marburg (trastorno), enfermedad por virus de Marburg, Enfermedad de Marburg, Enfermedad del Virus de Marburg
Japanese マールブルグウイルス出血熱, マールブルグウイルス感染, マールブルグビョウ, マールブルグウイルスシュッケツネツ, マールブルグウイルスカンセン, マールブルグ・ウイルス病, Marburgウイルス病, マールブルグ病, マールブルグウイルス病
Swedish Marburgsjuka
Czech marburgská virová nemoc, Marburgská nemoc, Infekce virem Marburg, Marburgská virová hemoragická horečka, marburská horečka
Finnish Marburgin tauti
Russian MARBURG-VIRUSNAIA BOLEZN', GEMORRAGICHESKAIA LIKHORADKA TSERKOPITEKOVAIA, ГЕМОРРАГИЧЕСКАЯ ЛИХОРАДКА ЦЕРКОПИТЕКОВАЯ, МАРБУРГ-ВИРУСНАЯ БОЛЕЗНЬ
Korean 마르부르그 바이러스병
Polish Choroba marburska
Hungarian Marburg betegség, Marburg vírus fertőzés, Marburg vírus vérzéses láz, Marburg vírus haemorrhagiás láz
Norwegian Marburg-virussykdom, Marburgfeber

Ontology: Hemorrhagic Fever, Ebola (C0282687)

Definition (MSH) A highly fatal, acute hemorrhagic fever, clinically very similar to MARBURG VIRUS DISEASE, caused by EBOLAVIRUS, first occurring in the Sudan and adjacent northwestern (what was then) Zaire.
Concepts Disease or Syndrome (T047)
MSH D019142
ICD10 A98.4
SnomedCT 123323003, 186746000, 37109004
LNC LA10453-1
English Ebola Hemorrhagic Fever, Ebola Virus Disease, Hemorrhagic Fever, Ebola, EBOLA VIRUS DIS, Ebola virus hemorrhagic fever, Ebola virus hemorrhagic fever (diagnosis), Ebola disease, Ebola virus infection, Hemorrhagic Fever, Ebola [Disease/Finding], disease ebola, ebola fever hemorrhagic, ebola hemorrhagic fever, ebola virus disease, ebola haemorrhagic fever, ebola virus infection, Ebola virus disease, Ebola haemorrhagic fever, Ebola hemorrhagic fever, Ebola virus disease (disorder), Ebola virus disease -RETIRED-
Dutch Ebola hemorragische koorts, Ebola-virusinfectie, Ebola-ziekte, Ebola-koorts, hemorragische, Ebola-virusziekte, Hemorragische Ebola-koorts, Koorts, hemorragische Ebola--
French Fièvre hémorragique à Ebola, Infection au virus Ebola, Fièvre d'Ebola, Fièvre hémorragique d'Ebola, Fièvre hémorragique à virus Ebola, Maladie à virus Ebola
German haemorrhagisches Ebola-Fieber, Ebola-Virusinfektion, Ebola-Viruskrankheit, Ebolaviruskrankheit, Ebola-hämorrhagisches Fieber, Hämorrhagisches Fieber, Ebola-
Italian Febbre emorragica da virus Ebola, Infezione da virus Ebola, Malattia da virus Ebola, Febbre emorragica di Ebola
Portuguese Febre hemorrágica de Ebola, Infecção por vírus de Ebola, Doença de Ebola, Doença pelo Vírus Ebola, Febre Hemorrágica do Ebola
Spanish Fiebre hemorrágica por virus Ébola, Infección por virus Ébola, Fiebre hemorrágica de Ebola, fiebre hemorrágica por virus Ébola, enfermedad por virus Ebola, fiebre hemorrágica de Ebola, fiebre hemorrágica virósica, enfermedad por virus Ébola, enfermedad por virus Ebola (trastorno), fiebre hemorrágica por virus Ebola, enfermedad por virus Ébola (trastorno), enfermedad por el virus Ebola - RETIRADO -, enfermedad por el virus Ebola - RETIRADO - (concepto no activo), Enfermedad de Ébola, Enfermedad del Virus Ebola, Fiebre Ebola Hemorrágica, Fiebre Hemorrágica Ebola
Japanese エボラウイルス感染, エボラウイルスカンセン, エボラシュッケツネツ, エボラウイルス病, 出血熱-エボラ, エボラ出血熱
Swedish Hemorragisk feber, Ebola
Czech hemoragická horečka Ebola, Hemoragická horečka Ebola, Infekce virem Ebola, Horečka Ebola, horečka Ebola
Finnish Ebola-tauti
Russian GEMORRAGICHESKAIA LIKHORADKA EBOLA, EBOLA GEMORRAGICHESKAIA LIKHORADKA, EBOLA VIRUSNAIA BOLEZN', ГЕМОРРАГИЧЕСКАЯ ЛИХОРАДКА ЭБОЛА, ЭБОЛА ВИРУСНАЯ БОЛЕЗНЬ, ЭБОЛА ГЕМОРРАГИЧЕСКАЯ ЛИХОРАДКА
Korean 에볼라 바이러스병
Polish Choroba wirusowa Ebola, Gorączka krwotoczna Ebola
Hungarian Ebola vírus fertőzés, Ebola haemorrhagiás láz, Ebola vérzéses láz, ebola betegség
Norwegian Ebola-virussykdom

Ontology: Filoviral hemorrhagic fever (C0343634)

Concepts Disease or Syndrome (T047)
SnomedCT 240525000
English Filoviral haemorrhagic fever, Filoviral hemorrhagic fever, Filoviral hemorrhagic fever (disorder)
Spanish fiebre hemorrágica filoviral (trastorno), fiebre hemorrágica filoviral

Ontology: Ebolavirus (C0949892)

Definition (NCI_CDISC) Any viral organism that can be assigned to the genus Ebola virus.
Definition (NCI) A genus of filamentous, enveloped viruses with glycoprotein surface spikes, in the family Filoviridae. The genome is composed of a linear single-strand of negative sense RNA. The primary product of gene transcription of the fourth gene is a small glycoprotein (sGP), while RNA editing allows expression of full length glycoprotein. The Ebolavirus natural reservoir is considered to be fruit bats of the Pteropodidae family and cause severe hemorrhagic fevers in humans.
Definition (MSH) A genus in the family FILOVIRIDAE consisting of several distinct species of Ebolavirus, each containing separate strains. These viruses cause outbreaks of a contagious, hemorrhagic disease (HEMORRHAGIC FEVER, EBOLA) in humans, usually with high mortality.
Concepts Virus (T005)
MSH D029043
SnomedCT 424206003, 407342005
English Ebola Virus, Ebola Viruses, Virus, Ebola, Viruses, Ebola, Ebola-like Viruses, Ebolaviruses, Ebola-like viruses, Genus Ebolavirus (organism), Genus Ebolavirus, Ebola virus, Ebolavirus, Ebola like Viruses, Ebola-like Virus, Genus Ebola-like viruses (organism), Genus Ebola-like viruses, Ebola-like virus, EBOV, EBOLA VIRUS
Portuguese Ebolavirus, Vírus Ebola-Like, Vírus Similares ao Ebola, Vírus Semelhantes ao Vírus Ebola, Vírus Similares ao Vírus Ebola
Russian ЭБОЛАВИРУС, ЭБОЛА-ПОДОБНЫЕ ВИРУСЫ, EBOLA VIRUS, SUDAN, EBOLA VIRUS, ZAIR, EBOLA VIRUS, EBOLA-PODOBNYE VIRUSY, KOT-D'IVUAR EBOLA VIRUS, EBOLA VIRUS, KOT-D'IVUAR, EBOLAVIRUS, КОТ-Д'ИВУАР ЭБОЛА ВИРУС, ЭБОЛА ВИРУС, ЭБОЛА ВИРУС, ЗАИР, ЭБОЛА ВИРУС, КОТ-Д'ИВУАР, ЭБОЛА ВИРУС, СУДАН
Italian Virus Ebola, Ebolavirus, Virus tipo Ebola
French Ebolavirus, Ebola virus, Virus Ebola, Virus de type Ebola
Swedish Ebolavirus
Spanish género Ebolavirus, género Ebolavirus (organismo), Ebolavirus, virus Ébola, género de virus tipo Ébola (organismo), género de virus tipo Ébola
Finnish Ebola-virus
Czech Ebolavirus, viry podobné viru Ebola
Japanese エボラウイルス-ザイール, レストンエボラウイルス, エボタウイルス-コートジボアール, エボラウイルス-レストン, コートジボアールウイルス, コートジボアール-エボラウイルス, スーダンエボラウイルス, 象牙海岸ウイルス, レストンウイルス, ザイールウイルス, ザイールエボラウイルス, スーダンウイルス, エボラウイルス-スーダン, エボラウイルス, エボラ様ウイルス
Polish Wirus Ebola, Wirusy grupy Ebola, Wirusy Ebola-podobne
German Ebola-artige Viren