4.2 WHITT Hemorrhagic Fever Viruses Flashcards Preview

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Flashcards in 4.2 WHITT Hemorrhagic Fever Viruses Deck (15):
1

Key Take-Home Points

-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

2

Flaviviridae (Dengue & YFV)

-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

3

Flavivirus Replication, Transmission and Distribution

-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)

4

Dengue Fever Virus (Flaviviridae)

-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

5

Yellow Fever (Flaviviridae)

-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

6

Bunyavirus

-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)

 

7

Rift Valley Fever Virus (Bunyaviruses)

-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

8

RVFV in Humans

-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

9

Crimean-Congo Hemorrhagic Fever (Bunyaviruses)

-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

10

Hantavirus (Bunyaviruses)

-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 

11

Arenaviruses

-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

12

Arenaviruses: Transmission, Illness and Treatment

-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

13

Filoviridae

"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 

14

Filovirus Replication Scheme

-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

15

Filovirus: Transmission and Pathogenesis

-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