Viral Hemorrhagic Fevers (Bunyaviruses, Arenaviruses, Filoviruses) – Dra. Ma.

Ellery Mendez
Goku Notes

Usually, these viruses come from rodents. BUNYA VIRUS

Classification of Prominent Hemorrhagic Fevers Morphology

Arenaviridae Bunyaviridae Filoviridae Flaviviridae Spherical

Lunin Crimean- Ebola Kyasanur
Triple segmented
Congo Forrest
Hemorrhagic Disease Ambisense, single stranded RNA
Fever Enveloped
Machupo Hantavirus Marburg Omsik Replicate in the cytoplasm
Hemorrhagic Assemble and bud into Golgi apparatus
Fever
Sabia Rift Valley Yellow fever
fever
Guanarito Dengue Family Bunyaviridae
Lassa
5 genera
Classification of Viral Hemorrhagic Fever According 250 species
to Modes of Transmission
Genus Human Disease
Modes of Diseases Etiological Bunyavirus La Crosse encephalitis,
Transmission Virus others
Mosquito borne Yellow fever Yellow fever Phlebovirus Rift Valley fever, sandfly
Dengue fever Dengue types fever
1-4 Nairovirus Crimean-Congo
Chikungunya Chikungunya hemorrhagic fever
hemorrhagic rift valley fever Tospovirus Plant virus, no known
fever human disease
Tick borne Crimean Congo-Crimean Hantavirus Hemorrhagic fever with
hemorrhagic hemorrhagic renal syndrome
fever fever Hantavirus pulmonary
Kyasanur forest Kyasanur forest syndrome
disease disease
Omsik Omsik Bunya Virus (Hanta Virus)
hemorrhagic hemorrhagic
disease fever First isolated in 1976 in Korea from a rodent
Zoonotic Argentine Junin known as Apodemus Agrarius.
hemorrhagic
fever
Bolivian Machupo Cause of 2 Hemorrhagic Fatal Diseases
hemorrhagic
fever Hemorrhagic fever with Renal Syndrome
Lassa fever Lassa Hanta virus Pulmonary Syndrome
Unknown Korean Hanta an
hemorrhagic
fever Several distinct hantavirus with specific rodent host
Marburg virus Marburg Transmit to humans by inhaling aerosols of rodent
disease excreta (urine, saliva, feces)
Ebola virus Ebola
disease

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 Viral Hemorrhagic Fevers (Bunyaviruses, Arenaviruses, Filoviruses) – Dra. Ma. Ellery Mendez
Goku Notes

No guarantee that
Hemorrhagic Fever Hantavirus Pulmonary patient will live
with Renal Syndrome Syndrome (HPS) Prevention:
(HFRS)
Rodent control
Causes nterstitial 1993 – severe Avoid contact or
nephritis respiratory illness that exposure to rat
Later on results to respiratory droppings
developsrenal failure
failure Starts with flu like ARENA VIRUS
Later on develops illness and
hemorrhage and complicates into
shock serious respiratory “Arena” – sand like (ribosomal particles taken
illness from the host cells and contributes to granular
Novel Hantavirus (also appearance of arenavirus)
known as Sin Nombre
Spherical
which means no name)
Double segmented
Supportive Deer and mouse as
treatment reservoirs Ambisense, single stranded RNA
No guarantee that Ambisense means that this is a genome which
patient will live encodes for proteins and these proteins avoid
Prevented by rodent Signs and Symptoms: creating the double stranded RNA and this
control stops the transcription
Fever Enveloped
Headache
Large club shaped peplomers
Myalgia
Pulmonary edema Replicate in the cytoplasm
No hemorrhage Incorporate into ribosome and bud from the
plasma membrane
Pathogenesis:

Functional impairment
of vascular
endothelium
Virus causes
capillaries to leak
Results to progressive
fibrosis, pulmonary
edema and death
Laboratory:
RT PCR – detect the
viral nucleic acid
Immunohistochemistry
ELISA
Viral isolation is
difficult
Requires containment
facilities
Treatment:
Multiple Arenavirus cause human disease
Lassa
Junin
Machupo
Guanarito
Sabia
Whitewater-Arroyo
Lymphocytic Choriomeningitis
Humans infected when in contact with rodent
excreta
Infectious aerosols – high level containment
Natural host – rodents
Arthropods not involved

Supportive – Lassa Fever

oxygenation,
hemodynamic 1969 – first discovered and named after Nigerian
Ribavirin – some
village
benefit
Highly virulent
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 Viral Hemorrhagic Fevers (Bunyaviruses, Arenaviruses, Filoviruses) – Dra. Ma. Ellery Mendez
Goku Notes

Lassa virus Vertical transmission can cause serious defects

Transmitted through person to person contact and death to the baby.
Reservoir is the house rat
Very high fever
Laboratory
Mouth ulcers
Severe myalgia
ELISA – detect IgG, IgM antibodies
Skin rash with hemorrhages
Immunohistochemical staining for tissue –
Pneumonia
viral antigens
Kidney damage
RT-PCR
Deafness
Vero cell culture
High maternal-fetal mortality
Treatment is Ribavirin which is effective if given
early FILO VIRUS
Prevented through meticulous barrier, nursing and
standard precautions. “Fila” means thread like
Longest virus
Laboratory Non-segmented
Negative sense
ELISA – Ig detection Single stranded RNA
Immunohistochemistry Enveloped
RT-PCR Replicate in cytoplasm
Bud from plasma membrane
Glycoprotein surface spikes in the form of
South American Hemorrhagic Fevers trimers

Arenavirus which are members of Tacribe complex Pleomorphic, filamentous threads

Most have a rodent reservoir Highly virulent (Biosafety level 4)
Infections usually end in death
Junin hemorrhagic fever – Argentina
Machupo hemorrhagic fever – Bolivia Filovirus infectivity is destroyed by:
Guanarito - Venezuela
Sabia - Brazil Heating for 30 minutes at 60ºC
Ultraviolet and gamma radiation
Lipid solvents
Bleeding more common in Junin and other
Bleach
South American hemorrhagic fevers than in lassa
Phenolic disinfectants
fever

Lymphocytic Choriomeningitis Natural hosts and vectors: bats and possibly

rodents
LCM virus discovered in 1933 – widespread in
Europe and in the Americas African Hemorrhagic Fevers
Natural vector: wild house mouse
Transmit to humans by mouse droppings Marburg
No person to person spread but from mouse to Ebola virus
person
Acute disease manifested by aseptic meningitis,
CNS manifestations or flu-like illness
Serious in those with impaired immune system
In 2005, 3 of 4 organ transplant patients died

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 Viral Hemorrhagic Fevers (Bunyaviruses, Arenaviruses, Filoviruses) – Dra. Ma. Ellery Mendez
Goku Notes

Pathogenesis Rash with internal and external bleeding often

leading to shock and death
Africa, Philippines
Tropism for Cells in the:
Cause hemorrhagic fevers with high fatality
rates (up to 90%) Macrophage system
Infection appears to be by close contact with Dendritic cells
infected person Interstitial fibroblast
Highly contagious Endothelial cells

First outbreak – 1967 (Marburg, Germany; Very high titer of virus present in many tissues
Yugoslavia) like:

Liver
Vaccine company was processing primary kidney Spleen
cells from African green monkeys (Cercopithecus Lungs
aethiops). Kidneys
Several works developed a hemorrhagic fever.
Several dozen infected by person to person
transmission FILOVIRUS – Highest mortality of all viral
Fewer than half died hemorrhagic fevers

Filo virus Tropism Marburg Disease

Filovirus Species Infection confirmed or 1967 – Discovered among lab workers exposed to
suspected African green monkey imported into Germany and
Lake Victoria Marburg Human, monkey, fruit bat Yugoslavia
virus (1980) Transmission from patients to medical personnel
Lake Victoria Marburg with high mortality
Virus (2005)
Cause disease in monkeys and humans, outbreaks
Zaire ebolavirus (1976) Human, monkey (fruit
Zaire ebolavirus (1995) bat, duiker, dog)
Ebola Virus
Cote d’lvoire ebolavirus Human, monkey
(1994)
Bundibugyo ebolavirus human Discovered 1976: severe epidemics of Ebola
(2008) Hemorrhagic Fever
Sudan ebolavirus (1979) human Hospital staff became infected through close and
Sudan ebolavirus (1976) prolonged contact with patients their bodies or
Reston ebolavirus (1989) Monkey, pig (human, excreta
Reston ebolavirus (1992) fruit bat) Person to person transmission
Highly virulent strains: Zaire and Sudan (Zaire is
Manifestations for Marburg and Ebola the most deadly)
Mean time to death from symptom onset: 7-8
Fever days
Headache The 2003 outbreak first recognized in dead
Sore throat gorillas and chimpanzees
Muscle pain followed by abdominal pain In 1989 – Reston strain detected in Macaque
Vomiting monkeys from the Philippines, has low
Diarrhea pathogenicity (infect humans without causing
disease)

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 Viral Hemorrhagic Fevers (Bunyaviruses, Arenaviruses, Filoviruses) – Dra. Ma. Ellery Mendez
Goku Notes

Reston also causes mortality in pigs.

Filovirus infections appear to be immunosuppressive
(impaired humoral immune system)
Marburg and Ebola virus reservoir host: bat or
rodent
Transmitted to humans accidentally (direct contact
with blood or body fluids)
Monkeys die too soon to be considered reservoir
hosts

Laboratory

High containment needed

Bio hazard
Highly communicable
ELISA – rapid screening test of human
samples and detect viral antigens in tissues
RT PCR – culture in Vero and monkey cell lines
for fresh virus isolates

Supportive treatment
No specific antiviral drug
50-90% mortality

Prevention

Strict barrier nursing

Extreme caution in handling blood, secretions,
tissues, wastes in transport and care of non-
human primates

END

Recording and powerpoint pictures by JCC

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