- 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:
- Negative sense
- Single stranded
- Structure and morphology:
- Helical nucleocapsid
- Lipid membrane
- Pleomorphic shape:
- “6” shaped
- “U” shaped
- 5 species of Ebolavirus cause Ebola virus disease (EVD).
- The Marburg virus causes Marburg virus disease (MVD), previously known as Marburg hemorrhagic fever.
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
- Outbreaks and sporadic cases have been reported in:
- Democratic Republic of the Congo
- South Africa
- Case fatality rate (varies between outbreaks): approximately 23%‒90%
- Not completely known
- Possibly fruit bats
- Human to human:
- Direct contact with infected body fluids
- Sexual contact
- Primate to human via infected body fluids
- Possibly fruit bat to human
Host risk factors
- At-risk occupations include:
- Healthcare workers
- 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)
- 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:
- 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
- Impaired adaptive immunity:
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
- Arthralgia and myalgia
- Abdominal pain
- Watery diarrhea
- Nausea and vomiting
- Maculopapular skin rash (may desquamate):
- Later, more severe manifestations:
- Dehydration → hypotension
- Mucosal bleeding
- Oozing from venipuncture sites
- GI bleed
- Altered mental status
- Neck stiffness
- Gait instability
- Respiratory failure
- Renal failure
- 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)
Diagnosis and Management
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.
- Most commonly used to make a definitive diagnosis
- Detects viral RNA
- Antigen detection ELISA:
- Detects viral antigens
- Results must be confirmed with PCR.
- Indirect fluorescence antibody
- 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:
|Organism||Ebola virus||Yellow fever virus||Hantavirus||Lassa virus|
- 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.
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