Ebolavirus/Marburgvirus

Ebolavirus and Marburgvirus are members of the Filoviridae family. They are single-stranded, negative-sense RNA viruses with a characteristic filamentous, pleomorphic morphology. Transmission mainly occurs through contact with secretions from an infected individual. These viruses cause similar diseases, with flu-like symptoms, diarrhea, hemorrhage, multiorgan dysfunction, and shock. The diagnosis can be made using PCR, antigen detection, and serology. Management is mainly supportive, although monoclonal antibody therapy has been promising for treating Ebola virus disease.

 

Last update:

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Classification

RNA Viruses Flowchart Classification

RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA or RNA. RNA genome viruses can be further characterized by either a single- or double-stranded RNA. “Enveloped” viruses are covered by a thin coat of cell membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly used as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses use RNA-dependent RNA polymerase, a viral enzyme, to transcribe their genome into messenger RNA.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Taxonomy

  • Family: Filoviridae
  • Genus Ebolavirus:
    • Zaire ebolavirus
    • Tai Forest ebolavirus
    • Sudan ebolavirus
    • Bundibugyo ebolavirus
    • Bombali ebolavirus
    • Reston ebolavirus (does not cause disease in humans)
  • Genus Marburgvirus: Marburg marburgvirus

Basic features of Ebola and Marburg viruses

  • RNA virus:
    • Nonsegmented
    • Negative sense
    • Single stranded
  • Structure and morphology:
    • Helical nucleocapsid
    • Lipid membrane
    • Filamentous
    • Pleomorphic shape:
      • “6” shaped
      • “U” shaped
      • Circular

Associated disease

  • 5 species of Ebolavirus cause Ebola virus disease (EVD).
  • The Marburg virus causes Marburg virus disease (MVD), previously known as Marburg hemorrhagic fever.

Epidemiology

Ebola virus disease

  • Most outbreaks originate in sub-Saharan Africa.
  • Any age group can be infected.
  • No racial or sexual predilection
  • Case fatality rate (varies between outbreaks): approximately 40%‒90%

Marburg virus disease

  • Rare
  • Outbreaks and sporadic cases have been reported in: 
    • Angola
    • Uganda 
    • Democratic Republic of the Congo
    • Kenya
    • South Africa
  • Case fatality rate (varies between outbreaks): approximately 23%‒90%

Pathogenesis

Reservoir

  • Not completely known
  • Possibly fruit bats

Hosts

  • Primates
  • Humans

Transmission

  • Human to human: 
    • Direct contact with infected body fluids
    • Fomites
    • Sexual contact
  • Primate to human via infected body fluids
  • Possibly fruit bat to human

Host risk factors

  • At-risk occupations include:
    • Healthcare workers
    • Veterinarians 
    • Laboratory workers
    • Miners or spelunkers who enter fruit bat caves.
  • Sexual partner of an EBD or MVD survivor (viral shedding can persist in the semen for weeks to months after infection) 

Pathophysiology

  • The specific mechanisms underlying the pathogenicity of Ebola and Marburg viruses have not been fully delineated.
  • Both viruses enter through mucous membranes → 1st targets macrophages and dendritic cells
  • Replication → death of infected cells → release of new virions
  • Spread to regional lymph nodes → replication → dissemination through the bloodstream
  • Again, virions target dendritic cells and macrophages (and other cell types, including endothelial cells) in lymphoid tissues → tissue necrosis:
    • Liver
    • Spleen
    • Thymus
  • Virus causes:
    • Impaired adaptive immunity:
      • Infection of dendritic cells → unable to present antigens
      • Loss of lymphocytes (“bystander apoptosis”)
    • Release of inflammatory cytokines from macrophages → systemic inflammatory response → may be tied to:
      • GI symptoms
      • ↑ Vascular permeability → diffuse vascular leak
      • Multiorgan failure
      • Coagulation defects

Clinical Presentation

Ebola virus disease and MVD have very similar presentations and can be difficult to distinguish.

  • Incubation period: 
    • EVD: 2‒21 days
    • MVD: 5‒10 days
  • Initial signs and symptoms:
    • High fever
    • Chills
    • Headache
    • Arthralgia and myalgia
    • Fatigue
    • Pharyngitis
    • Abdominal pain
    • Watery diarrhea
    • Nausea and vomiting
    • Conjunctivitis
    • Maculopapular skin rash (may desquamate):
      • Face
      • Trunk
      • Arms
  • Later, more severe manifestations:
    • Dehydration → hypotension 
    • Bleeding:
      • Mucosal bleeding
      • Ecchymoses
      • Oozing from venipuncture sites
      • GI bleed
    • Neurologic:
      • Altered mental status
      • Hyperreflexia
      • Neck stiffness
      • Gait instability
      • Seizures
      • Coma
    • Bradycardia
    • Respiratory:
      • Dyspnea
      • Hypoxia
      • Respiratory failure
    • Hepatitis
    • Renal failure
    • Shock
  • After recovery from EVD, patients may experience:
    • Vision problems (e.g., cataracts, uveitis)
    • Hearing loss
    • Changes in cognition
    • Joint pain
    • Relapse (due to persistence of the virus in the body)
Signs and Symptoms of Ebola

Signs and symptoms of Ebola virus disease

Image: “Symptoms of ebola” by Mikael Häggström. License: CC0 1.0

Diagnosis and Management

Diagnosis

Diagnosing EVD and MVD early in the course can be difficult (early symptoms mimic other more common diseases). A high degree of suspicion is required.

  • PCR: 
    • Most commonly used to make a definitive diagnosis
    • Detects viral RNA
  • Antigen detection ELISA: 
    • Detects viral antigens
    • Results must be confirmed with PCR.
  • Serology:
    • ELISA
    • Indirect fluorescence antibody

Management

  • No specific treatment exists for these viral infections.
  • Management is generally supportive:
    • IV hydration
    • Electrolyte replacement
    • Mechanical ventilation for respiratory failure
    • Antipyretics (e.g., acetaminophen)
    • Pain control
    • Antidiarrheal medications (e.g., loperamide)
    • Blood products
  • Therapies used for EVD management:
    • Monoclonal antibodies
    • Convalescent plasma (unclear benefit)

Comparison of Viral Hemorrhagic Fevers

The following table compares and contrasts several viral causes of hemorrhagic fever:

Table: Comparison of viral hemorrhagic fevers
OrganismEbola virusYellow fever virusHantavirusLassa virus
FamilyFiloviridaeFlaviviridaeBunyaviridaeArenaviridae
Characteristics
  • RNA virus:
    • Single stranded
    • Linear
    • Nonsegmented
    • Negative sense
  • Filamentous, pleomorphic shape
  • Enveloped
  • RNA virus:
    • Single stranded
    • Linear
    • Nonsegmented
    • Positive sense
  • Spherical
  • Enveloped
  • RNA virus:
    • Single stranded
    • Linear
    • Segmented
    • Negative sense
  • Spherical
  • Enveloped
  • RNA virus:
    • Single stranded
    • Linear
    • Segmented
    • Negative sense
  • Spherical
  • Enveloped
Transmission
  • Direct contact with infected secretions
  • Fomites
  • Contact with infected primates or bats
Vector: mosquito
  • Aerosols
  • Contact with rodent excrement, urine, or saliva
  • Aerosols
  • Direct contact
  • Ingestion
  • Exposure to blood, secretions, tissues of infected individuals
Clinical presentation
  • Flu-like symptoms
  • Rash
  • Hemorrhagic manifestations
  • Neurologic manifestations
  • Flu-like symptoms
  • Hemorrhagic manifestations
  • Hepatic dysfunction (jaundice)
  • Fever
  • Hemorrhagic manifestations
  • AKI
  • Majority of patients are asymptomatic or with mild symptoms.
  • Hemorrhagic manifestations
  • Deafness is common.
Diagnosis
  • PCR
  • Viral antigen detection
  • Serology
  • Serology
  • PCR
  • Viral culture
  • Serology
  • PCR
  • Serology
  • PCR
Management
  • Supportive
  • Monoclonal antibody therapy
SupportiveSupportive
  • Supportive
  • Ribavirin

Differential Diagnosis

  • Malaria: a mosquito-borne infectious disease caused by Plasmodium species. Malaria often presents with fever, rigors, diaphoresis, jaundice, abdominal pain, hemolytic anemia, hepatosplenomegaly, and renal impairment. A blood smear in malaria shows a single pleomorphic ring. Rapid testing for Plasmodium antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs.
  • Typhoid fever: a systemic disease caused by the gram-negative bacteria, Salmonella enterica serotype typhi. Symptoms include high fever, abdominal pain, a rose-colored rash, and diarrhea. Gastrointestinal bleeding is a complication of an untreated infection. The diagnosis is confirmed by culture. Treatment includes fluoroquinolones or azithromycin.
  • Influenza: a common, self-limiting viral infection that typically presents with fever, myalgias, headache, and upper respiratory symptoms. Abdominal pain, vomiting, and diarrhea may also occur more commonly in children. Hemorrhagic manifestations are not seen. Diagnosis is confirmed using PCR or ELISA. Management is generally supportive, although neuraminidase inhibitors may be initiated within the 1st 48 hours of the disease.
  • Travelers’ diarrhea: a type of gastroenteritis usually caused by bacteria or viruses, such as enterotoxigenic Escherichia coli (ETEC) or norovirus, in the local water. Symptoms occur after consumption of contaminated water or food, and include watery diarrhea, malaise, and abdominal cramping. Unlike those in EVD and MVD, symptoms are usually confined to the GI tract. The diagnosis is clinical and the illness is self-limiting.
  • Bacterial meningitis: an acute infection of the meninges. Patients present with headaches, fever, nuchal rigidity, and rapid clinical deterioration. A lumbar puncture is performed to make the diagnosis. Cerebrospinal fluid analysis will show turbid fluid, low glucose, and high WBC count with neutrophil predominance. Gram staining and culture are used to determine the causative bacteria. Treatment includes antibiotics and corticosteroids.

References

  1. Emanuel, J., Marzi, A., Feldmann, H. (2018). Filoviruses: Ecology, Molecular Biology, and Evolution. Adv Virus Res. 100, 189–221. https://pubmed.ncbi.nlm.nih.gov/29551136/
  2. Negredo, A., et al. (2011). Discovery of an ebolavirus-like filovirus in Europe. PLoS Pathog. 7(10), e1002304. https://pubmed.ncbi.nlm.nih.gov/22039362/
  3. Dixon, M.G., Schafer, I.J. (2014). Ebola viral disease outbreak–West Africa, 2014. MMWR Morb Mortal Wkly Rep. 63(25), 548–551. https://pubmed.ncbi.nlm.nih.gov/24964881/
  4. Zawilińska, B., Kosz-Vnenchak, M. (2014). General introduction into the Ebola virus biology and disease. Folia Med Cracov. 54(3), 57–65. https://pubmed.ncbi.nlm.nih.gov/25694096/
  5. Maxmen, A. (2019). Ebola outbreak declared an international public health emergency. Nature. https://pubmed.ncbi.nlm.nih.gov/32669721/
  6. Nkoghe, D., et al. (2005). Multiple Ebola virus haemorrhagic fever outbreaks in Gabon, from October 2001 to April 2002. Bull Soc Pathol Exot. 98(3), 224–229. https://pubmed.ncbi.nlm.nih.gov/16267965/
  7. Jacob, S.T., et al. (2020). Ebola virus disease. Nat Rev Dis Primers. 6(1), 13. https://pubmed.ncbi.nlm.nih.gov/32080199/
  8. Baseler, L., et al. (2017). The pathogenesis of Ebola virus disease. Annu Rev Pathol. 12, 387–418. https://pubmed.ncbi.nlm.nih.gov/27959626/
  9. Sanchez, A., Geisbert, T., Feldmann, H. (2007). Filoviridae – Marburg and ebola viruses. In Knipe, D. (Ed.) Fields Virology. Lippincott Williams and Wilkins; PA, USA. pp. 1410–1448.
  10. Martini, G.A. (1971). Marburg virus disease. Clinical syndrome. In Martini, G.A., Siegert, R., (Eds.). Marburg Virus Disease. Springer–Verlag; NY, USA. pp. 1–9.
  11. Henderson, B.E., et al. (1971). Epidemiological studies in Uganda relating to the ‘Marburg’ agent. In Martini, G.A., Siegert, R., (Eds.). Marburg Virus Disease. Springer–Verlag; NY, USA. pp. 166–176.
  12. Martini, G.A., et al. (1968). On the hitherto unknown, in monkeys originating infectious disease: Marburg virus disease. Dtsch Med Wochenschr. 93(12), 559–571. https://pubmed.ncbi.nlm.nih.gov/4966280/
  13. Conrad, J.L., et al. (1978). Epidemiologic investigation of Marburg virus disease, Southern Africa, 1975. Am J Trop Med Hyg. 27(6), 1210–1215. https://pubmed.ncbi.nlm.nih.gov/569445/
  14. Peterson, A.T., et al. (2006). Geographic potential for outbreaks of Marburg hemorrhagic fever. Am J Trop Med Hyg. 75(1), 9–15. https://pubmed.ncbi.nlm.nih.gov/16837700/
  15. Bausch, D.G., et al. (2006). Marburg hemorrhagic fever associated with multiple genetic lineages of virus. N Engl J Med 355(9), 909–919. https://pubmed.ncbi.nlm.nih.gov/16943403/
  16. Kuhn, J.H., et al. (2010). Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations. Arch Virol. 155(12), 2083–2103. https://pubmed.ncbi.nlm.nih.gov/21046175/
  17. Spickler, A. (2014). Ebolavirus and Marburgvirus Infections. Retrieved June 17, 2021, from https://www.cfsph.iastate.edu/Factsheets/pdfs/viral_hemorrhagic_fever_filovirus.pdf
  18. WHO. (2018). Marburg virus disease-Fact sheet. Retrieved June 17, 2021, from http://www.who.int/mediacentre/factsheets/fs_marburg/en/
  19. Bharat, T.A.M., et al. (2011). Cryo-electron tomography of Marburg virus particles and their morphogenesis within infected cells. PLoS Biol. 9(11), e1001196. https://pubmed.ncbi.nlm.nih.gov/22110401/
  20. Bray, M., Chertow, D.S. (2021). Epidemiology and pathogenesis of Ebola virus disease. In Mitty, J. (Ed.), UpToDate. Retrieved June 17, 2021, from https://www.uptodate.com/contents/epidemiology-and-pathogenesis-of-ebola-virus-disease
  21. Chertow, D.S., Bray, M., and Palmore, T.N. (2021). Clinical manifestations and diagnosis of Ebola virus disease. In Mitty, J. (Ed.), UpToDate. Retrieved June 17, 2021, from https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ebola-virus-disease
  22. Chertow, D.S., Bray, M., and Palmore, T.N. (2021). Treatment and prevention of Ebola virus disease. In Mitty, J. (Ed.), UpToDate. Retrieved June 17, 2021, from https://www.uptodate.com/contents/treatment-and-prevention-of-ebola-virus-disease
  23. Bray, M., Chertwo, D.S. (2021). Marburg virus. In Mitty, J. (Ed.), UpToDate. Retrieved June 17, 2021, from https://www.uptodate.com/contents/marburg-virus
  24. Yuill, T.M. (2020). Marburg and Ebola virus infections. MSD Manual Professional Version. Retrieved June 17, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/arboviruses-arenaviridae-and-filoviridae/marburg-and-ebola-virus-infections
  25. Centers for Disease Control and Prevention. (2021). Ebola (Ebola virus disease). Retrieved June 17, 2021, from https://www.cdc.gov/vhf/ebola/index.html
  26. Centers for Disease Control and Prevention. (2014). Marburg hemorrhagic fever (Marburg HF). Retrieved June 17, 2021, from https://www.cdc.gov/vhf/marburg/index.html

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details