4.2 WHITT Hemorrhagic Fever Viruses Flashcards

1
Q

Key Take-Home Points

A

-Viral hemorrhagic fevers (VHFs) are caused by RNA viruses from several viral families

–Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae

  • Infections can be aquired directly (exposure to infected blood or body secretions), through transmission via insect bites or via rodent vectors
  • VHF disease is characterized by fever, malaise, vomiting, mucosal and GI bleeding, edema and hypotension
  • For suspected cases in US, obtaining recent travel history is critical for diagnosis
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2
Q

Flaviviridae (Dengue & YFV)

A
  • Small, enveloped (+) strand RNA viruses
  • Transmitted by mosquitos
  • Yellow fever virus: first human illness shown to be caused by “filterable” agent
  • Pestiviruses: Animal Pathogens

Hepaciviruses: hep C virus

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3
Q

Flavivirus Replication, Transmission and Distribution

A
  • Enveloped virions bind to receptor and enter by receptor-mediated endocytosis
  • (+) strand RNA genome is translated into polyprotein and cleaved into viral polymerase and structural proteins
  • Transmitted by insect vectors and are found world-wide
  • Ones that cause disease in US: Dengue virus, Yellow fever and encephalitis viruses (West Nile)
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4
Q

Dengue Fever Virus (Flaviviridae)

A
  • Mosquito-borne viral disease of human
  • most important mesquite borne virus
  • Four serotypes, infecetion by one does not give immunity to other 3, can get secondary infection with a diff seriotype (bad)
  • Classic Dengue Fever: self-lim infection begins 2-7 day incubation, high fever, bonebreak fever

–Treatment: supportive (fluids and acetaminophen), avoid aspirin and NSAIDS

Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS): after initial fever subsides, diffuse capillary leakage of plasma and hemorrhagic diathesis (severe thrombocytopenia)

–Increased vas perm lead to hemoconcentration, reduced blood volume, tissue hypoxia, lactic acidosis and shock

–Greatest risk factor for severe dengue infection is secondary infection with a dengue serotype different from the intial dengue infection (mediated by cytokines)

-Diagnosis: lab confirmation of dengue infection

Treatment: platelet transfusion and aggressive fluid management

-vaccine is being developed, not yet approved

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5
Q

Yellow Fever (Flaviviridae)

A
  • Symptoms: flu-like malaise that progresses to a severe hemorrhagic fever
  • Black vomit=GI diathesis
  • There is a vaccine
  • Transmission cycle: jungle, urban and savannah (intermediate)

Disease Course: most mild illness, ppl who develop symptoms incubation is 3-6 days

  • fevers, chills, severe headache, back pain, general bodya aches, nausea and vomiting
  • Brief remission, 15% of cases progress to a more severe form of disease characterized by high fever and jaundice, bleeding and eventually shock and mult organ failure
  • Treatment: supportive care is critical:
  • vaccination: safe and effective
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6
Q

Bunyavirus

A
  • Enveloped, segmented, single stranded (-) sense RNA virus
  • Replication cycle:
    (1) virus binds and is endocytosed
    (2) Low pH in endosome triggers membrane fusion resulting in uncoating
    (3) Viral polymerase transcribed (+) sense mRNAs
    (4) Host ribosomes translate viral proteins
    (5) Viral RNA-dependent RNA polymerase (RdRP) replicates viral genome via (+) sense cRNA intermediate
    (6) (-) sense genomes are assembled and virus particles are released by budding (7)
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7
Q

Rift Valley Fever Virus (Bunyaviruses)

A
  • Mostly seen in live stock
  • Potential bioterroism agent (category A select agent)
  • Majority human infections resulted from direct or indirect contact with the blood or organs of infected animals
  • Transmission primarily via mosquitos
  • Immunation of livestock is the most effective control, humans are not usually immunized b/c of side effects
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8
Q

RVFV in Humans

A
  • Acute, self-lim febrile illness-flu like symptoms
  • 2% progress to severe form of disease -culminates hemorrhagic hepatitis, often confused for meningitis

Symptoms often include: fever, encephalitis, retinal vasculitis

-no established treatment

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9
Q

Crimean-Congo Hemorrhagic Fever (Bunyaviruses)

A
  • Transmitted by ticks
  • Middle east, africa and europe
  • Rare but severe
  • Targes liver and vascular endothelium

Symptoms: headache, pain in limbs, often bleeding from many orifices

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10
Q

Hantavirus (Bunyaviruses)

A
  • Hemorrhagic fever w/ renal syndrome
  • humans, exposure to aerosolized urine, droppings or saliva of infected rodents or after exposure to dust from thier nestings
  • Liver and vascular endothelium are targeted

Symptoms: fever, hemorrhage, acute renal failure

-Over 15% mortality

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11
Q

Arenaviruses

A

-Virions contain two RNA segments

–often contain cell ribosomes: Arena = sandy

–enter by endocytosis

  • Replication occurs by a noncoventional “ambisense strategy”
  • Release by budding from the cell surface
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12
Q

Arenaviruses: Transmission, Illness and Treatment

A
  • Inhalation of aerosolized rodent excreta and saliva
  • Most infections are mild or subclinical
  • Severe multisystem disease occur in ~5-10% of total infections
  • Lymphopenia, thrombocytopenia and defects of qualitative platelet func are found during this stage
  • No Vaccines are avaliable
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13
Q

Filoviridae

A

“Hot ZONE”

  • Enveloped, nonsegmented (-) strand RNA viruses, pleomorphic rod-shaped virions
  • Two members: marburg virus and ebola virus
  • Highly transmissible viruses that causes devastating hemorrhagic shock syndrome
  • Disease of both human and non-human primates
  • have highest case of fatality of all hemorrhagic fever viruses
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14
Q

Filovirus Replication Scheme

A
  • Endocytosed
  • Preteolytic processing activates membrane fusion resulting in uncoating
  • Viral polymerase transcirbes (+) sense mRNAs
  • Viral structure proteins cause switched from transcription to replication
  • (-) sense genomes are encapsidated and are released from the cell surface by budding
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15
Q

Filovirus: Transmission and Pathogenesis

A
  • Dircet contact with blood/body fluid, some evidence of aerosol transmission
  • Path: linked to disruption of the innate immune response (cytokine storm)
  • Gross path: bleeding from every orfice
  • Death from mult organ failure and shock
  • Treatment: NONE
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