Viral hemorragic fevers

Ebola and Marburg viruses

Prof. Jeremiah Seni (MD, M.Med, Ph.D)

Department of Microbiology and Immunology
02nd March 2021
 Outline
• Overview
• Characteristics
• Pathogenesis
• Laboratory diagnosis
• Management, control and prevention
 Viral Hemorrhagic Fevers Overview
• A group of illnesses caused by several families of viruses
characterized by fever, vascular system damaged, and multi-organ-
system involvement

• The first Filovirus (Marburgvirus) was recognized in 1967 in

Germany and Yugoslavia, and Ebolavirus in 1976 in DRC (formerly
Zaire)

• Classified by CDC as Category A bioweapon agents and requires

Biosafety Level-4 (BSL-4) containment level
 Potential to cause widespread illness / death
 Ease of dissemination or person-to-person transmission
 Major public health impact requiring special responsive action
Note that Marburgvirus and Ebolavirus were recently detected in fruit bats in Africa
Family Filoviridae
• 3 genera: Cuevavirus, Marburgvirus and
Ebolavirus…..antigenically unrelated !

• 6 species of Ebolavirus (Zaire ebolavirus,

Sudan ebolavirus, Taï Forest ebolavirus,
formerly Côte d’Ivoire ebolavirus, Bundibugyo
ebolavirus, Reston ebolavirus, and Bombali
ebolavirus.

• The viral particle is enveloped (lipid/fatty),

has a negative-sense ssRNA of approx 19kB
and is pleomorphic: filamentous – long/short
80 x 800-14,000nm or “U” or “6” shaped
 Family Filoviridae

• New viral particles are created by budding from the

surface of their hosts’ cells.

• These viruses appear to be among the least successful of

negative strand RNA viruses in that they have a
restricted host range and limited distribution

• They are among the most feared because of their

spectacular symptomatology and often fatal outcome of
infection.
Overview of EBOV gene products and their interactions with the host cell.There are seven genes in the
Ebola virus: the NP, the viral proteins VP24-VP30-VP35-
VP40, L (polymerase) and the membrane protein GP.

In: Fields Virology, 3rd ed. Fields BN et al [editors]. Lippincott-Raven, 1996

Falasca et al., 2015. Cell Death and Differentiation (2015) 22, 1250–1259
 Pathogenesis

Incubation period for Marburg: 3–9 days, for Ebola: 2–21 days
Tropism for cells of the macrophage system, dendritic cells, interstitial fibroblasts, and
endothelial cells
Jacob et al., Nat Rev Dis Primers. 2020 Feb 20;6(1):13. doi: 10.1038/s41572-020-0147-3
Jacob et al., Nat Rev Dis Primers. 2020 Feb 20;6(1):13. doi: 10.1038/s41572-020-0147-3
Falasca et al., 2015. Cell Death and Differentiation (2015) 22, 1250–1259
Falasca et al., 2015. Cell Death and Differentiation (2015) 22, 1250–1259
 Pathogenesis
• Extensive liver involvement, renal damage, changes in vascular
permeability, and activation of the clotting cascade.
• Visceral organ necrosis is the consequence of virus replication in
parenchymal cells.
• The severe shock syndrome mediated by virus-induced release of
inflammatory cytokines
• Filovirus glycoproteins carry an immunosuppressive domain, and
immunosuppression
Acute phase characterized by fever, headache, sore throat,
and muscle pain (just like any other febrile illness)
Followed by abdominal pain, vomiting, diarrhea, and rash
(petechiae), with both internal and external bleeding
These, most often lead to shock, multi-organ failure and
death (CFR: 25–90%)……CFR varies with species !
 Diagnosis
• WHO Standard case definition:
Suspected Ebola or Marburg cases for routine
surveillance:
Illness with onset of fever and no response to treatment for usual causes of
fever in the area, and at least one of the following signs: bloody diarrhoea,
bleeding from gums, bleeding into skin (purpura), bleeding into eyes and urine.
Sensitivity: 81·5%(95% CI74·1–87·2); Specificity: 35·7% (28·5–43·6) !

Confirmed Ebola or Marburg cases for routine

surveillance:
A suspected case with laboratory confirmation (positive IgM antibody, positive
PCR or viral isolation)

http://www.afro.who.int/en/clusters-a-programmes/dpc/integrated-disease-surveillance/features/2775-technical-guidelines-
for-integrated-disease-surveillance-and-response-in-the-african-region.html
Caleo G, et al. Lancet Infect Dis 2020; published online June 25. https://doi.org/10.1016/S1473-3099(20)30193-6.
 Diagnosis
• Samples ? Collection ? Transportation ? Storage ?
• Electron microscopy can identify virus particles in tissues
• Virus isolation in many cell lines, including Vero cells.
• Detecting viral RNA with RT-PCR…..a gold standard
• The Xpert® Ebola Assay.
• Histopathology: necrosis & apoptosis of lymphocytes, Councilman-
like bodies in liver
 Diagnosis cont…
• Detecting antigens with an antigen-capture ELISA or immunostaining

• Rapid Ebola tests (e.g. OraQuick® Ebola Rapid Antigen Test Kit -
VP40, SD Q Line Ebola Zaire Ag - VP40, Dual Path Platform (DPP)
Ebola antigen system (Chembio) - GP1,2, NP & VP40 etc....)

• Serologic tests include IFA and ELISAs may be used in research or

for sero-surveillance (detection of specific- IgG versus IgM)

Jacob et al., Nat Rev Dis Primers. 2020 Feb 20;6(1):13. doi: 10.1038/s41572-020-0147-3
Outbreak response, treatment, prevention
and control measures

• Largely supportive in the highly containment ICU/HIDTU

(blood, convalescent serum, fluid, electrolyte
replacement, nutrition etc)

• Experimental antivirals e.g. ribavirin and remdesivir were

tried but results were unappealing

• On-going trials for vaccines on their effectiveness in

humans
Outbreak response, prevention and control
measures
• Intensified quarantine of all cases and contact tracing, prompt notification
of relevant authorities and coordinated responsive measures.

• Full PPE for prevention of viral hemorrhagic fevers; and decontamination

procedures need to be carefully done by trained people

• Avoid contact with bush meat esp from sick non-human primates and
bats in endemic regions
Role-play for donning and doffing