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what are hte 4 familty of virus of the hemorrhagic fevers. what fever is in each family

1. Flavivirus: dengue, yellow fever
2. Bunyavirdase: rifft valley, hantaan, CCHF
3. Areavirus: lassa fever
4. filocirdea: ebola, marburg

**dieases range from mild to death
what fever is assoicated with the following groups

1. flavi
2. bunya
3. arena
4. filo
1. flavi: denguae, yellow fever
2. bunya: RVF, hantaan, CCHF
3. LAssa
4. filo: ebola, marburg
as a group what can you tell me about viral hemorrhagic fever

envelope
reservoir
distribution
transmission
control
1. enveloped RNA
2. most have animal or mosquito vector, humans are incidnetal hosts
3. disease only where animal reservoir is
4. contact with vector (mosquito ir rident) person to oerson
cases are SPORADIC
5. no real cures/drugs. better to controlthe vector population
general sx of hemorrhagic fever
1. fever! fatigue, dizzy, mm ache,
2. hemorrhagic manifestations- thrombocytopenia, shock, (bleed under skin, internal organ bleed, bleed from skin orrifice)
3. neurological disturbance
what types of sx will kill the pt w/hemorrhagic fever
shock
renal failure
nervous syst malfunction
coma
delirium
seizure

**goes from pretty non specific to things like this :/
whats the general pathogenesis of VHF (viral hemorrhagic fever)
1. infection as incidental host after exposure to vector

2. virus infects macro, dendrites adn cause cytokine release

3. cytokines stim inflammation and CLOTTING pahtway (often see a rash)

4. infected dendritic cells decrease expression of co stim molecules --> decreased immune system (decrease B7 co stim on APC)
the rash associated with VHF is associated with what

1. decreased perm of GI
2. lysis of macro
3. damage to endo
4. swelling of LN
5. type IV HS reaction
damage to endo!!

**hemorrhagic complications are multifactorial! hepatic damage/consumptive coagulopathy, thrombocytopenia. can be multi organ failure. VARIES among the specific fever
ok so the viral hemorrhagic fevers are the flavi, bunya, arena, and filvo virsuses. the are all RNA. what is the only + sense
flavi
what are hte specific micro thigns of flavi virus
denge, yellow fever (west nile, st lous encephalitis, hep C)
all were RNA, this isthe only + sence
envelope (ALL VHF have envelope)

AB facillitate viral uptake

cytoplasmic recation
where is dengue fever
flavivirus, not in us

more in mexico, africa,and S america adn india

**Aedes aegypti is the vector
aedes agypti
dengue fever

**there are 4 serotypes of dengue and NONE offer cross immunity (AB help viral uptake)

infects kids more than adults
are kids or adults more infected with dnege fever
kids, they have less immune response

**NO cross immunity btwn the 4 serotypes
denge hemorrhagic fever mortalitiy
3% die treated
50% die if untreated

**virtually NO deaths for just denge fever, w/no hemorrhage
what is the urban host, jungle host and vector for dengue fever
Urban: human
Jungle: primates (monkey)

Vector: aedes aegypti mosquito
whats a unique sx of denge fever
its the normal fever, HA, maliase, fatigue

but there is a rash that fades then you get another secondary rash that is maculopapular on the limbs and face that desqumates*** resolves in 2 weeks
how does denge fever resolve
immune clearance

**recall there are 4 types that offer NO immunity

**recall in DHF non neutralizing AB promote viral uptake into macro.
what causes the initial rash adn then the secondary maculopapular rash in DHF

1. anaphylaxis
2. AB mediated
3. AB:AG mediated
4. memory
AB:AG mediated
pathogensis of denge
virus taken up by macro, and endothelial cells. virus replicates and starts off the inflammatory process

secondary viremia spreads virus throughout the body
whats the deal with IgM AB in denge
IgM detected in like a week and IgG later. these help prevent spread of virus (secondary viremia) BUT can make AB:AG HS III reactions

**NO cross immunity among 4 denge strains
what are the strains of yellow fever and how is it transmitted
dakar and 17D (D is in the vaccien)

**vector is mosquito

*flavi virus
who gets yellow fever
all ages-kids have mild infection (recall denge was Kids>adult)

M>F

common in s america and central aftica
yellow fever

jungle host (sylvatic)
Urban host

Vector
Jungle: monkey
UrbanL human

transmission: aedes, haemagogus


**teh same as Denge except yellows transmission vectors are the aedes and haemagogous
what is the clinical of yellow fever
BIPHASIC

acute: fever, HA, mm pain, back ache, LOA, red tongue, flushed, red eyes. sx go away!

TOXIC Phase: 15% of pts progress to this. fever returns pt gets jaundice and has a GI hemorrhage (BLACK VOMIT) can then disseminate to kidney, heart, vasculature, widespread hemorrhage
what is the VHF that is biphasic and in the toxic phase has BLACK vomit
yellow fever

**its acute phase is pretty general (HA, fever, backache, then you get red tongue, red eyes)

in 15% of pts it then progresses to TOXIC adn they get jaundice, fever, and GI hemorrhage

disseminates to kideny, heart/vasculature, and causes widespread hemorrhage.

50% mortality- die from lactic acidosis and hyperkalemia
whats the pathogenesis of yellow fever
simliar to denge fever BUT it attacks kupffer cells adn hepatocytes more

COUNCILMAN BODIES**
T or F

a pathologist ID councilman bodies in the liver and notes extensive damage to hepatocytes and kupfur cells. is this dx of yellow fever
nope, its def seen in YF but also in others

**YF is like denge but there is more damage to kupfer and hepatocytes
we know with YF you can get GI hemorrhage and then widespread hemorrhage. but what is the mech of death (50% mortality)
lactic acidosis
hyperkalemia
tell me about the immunity and prevention of yellow fever
AB are specific to YF (simliar to denge)

LIVE ATTENUATED VACCINE!!!! good for 10 years :)
tell me the micro of bunya virus
RVF, Hantaan, CCHF

Envelope (-) sense

has G1, G2 glycoprotein in envelope

**like denge, replicate in cytoplasm and then bud off
tell me about rift valey fever virus
its in the phlebovirus group of bunya virus

passes to humans by several kinds of mosquito

E and S africa, resevoire is livestock
what HFV is in a livestock resevoir and transmitted to humans by several mostuito species. its common in E nad S africa
Rift valley fever
whats the mortality rate of RVF (rift valleyfever)
1% but 10% if you get the hemorrhagic part

if infected livestock are preggo they will abort
is RVF transmitted exclusively by the mosquitoes: Aedes, Cluex, adn Erethmapodites
nope, also through contact with secretions of infected livestock
whats the clinical for RVF
often asx (1% mortality, 10% if hemorrhagic)

mild: fever, liver problems, flu like sx. can then progress to the hemorrhagic fever and progress to shock, ocular disease and hepatic necrosis

in livestock its a MAJOR problem
tell me about the 1 and 2 viremia associated with RVF
1: flu like sx, replication in reticuloendothelial system

2. virus infects SPECIFIC things like the CNS, endothelium and other viscera

BLINDNES
what is the unique sx reported in some pts w/rift valley HEMORRHAGIC fever
blindness
what is the immunity/protection for rift valley fever
if you have it and recover you have LASTING IMMUNITY

**there is a vaccine for livestock bc its such a problem

*human vaccine not yet approved
what is the ROBO virus
hantaan virus,

it means rodent born (in the buyna virus family) infected when you contact infected secretions or tissue inthe striped field mouse
where is hantaan varus common
what is the transmiaation
asia, europe

resevoir is rodent- striped field mouse. human are infected when contact w/infected tissue or secreation
which virus causes a hemorrhagic fever with renal syndrome
hantaan (the one passes throgh the striped field mouse)

**clinical: fever, HA, comit, petechial hemorrhage, shoch. RENAL failure, thrombocytopenia
which compliment protein is key for regulating leukocyte recruitment
c5a

*potent chemoattractant, mast cell degranulation
ok so RVF can cause blinness in some pts, what virus is associated with retinal damage
hantaan virus is retinal. can lead to vision loss

*retinal inflammation is hantan
tell me about the pathogenesis of Hantaan virus
like RFV

Hantaan- transmission through rodent excrement (RFV is tick-hyalomma marginatum tik)

primary viremia- infecting cells,
Secondary viremia- HF sx (renal syndrome also)
tell me about CCHF (crimean congo hemorrhagic fever)
part of the nairovirus in the bunya family

*passed through mosquito

*occurs in SE europe, asia, africa

M>F

bioterrorism threat
waht is the virus that is passed by mosquitoes infected M>F nad is seen in SE europe, asia and africa. it is a bioterrorism threat
CCHF
what does the hyalomma marginatum tick spread
CCHF

**humans infected through tick bite or associated with infected animals
what are the clinical features of CCHF
ABRUPT onset of fever, HA, back/abd pain

bleed --> pulm edema, shock

*hrmorrhagic state: nose bleed, pee bleed, and melena

**often see hepatitis sx, liver/kidney failure
what is the pathogenesis of CCHF
simliar to denge

((replication at the tick bite site, later viremia spreads to distant organs
tell me about the micro of arena virus
envelope, - sense

segmented genoma

has G1/G2 envelope protein (like bunyavirus)

replicate in cyto and then bud from PM
what virus is in the arena virus family
LCMV-
LASSA multimammate rat

**both are rodent born
where is lassa virus seen
W africa


from the multimammate rat
how is lassa transmitted
multimammate rat, ingested food/water contamated with animal urine or direct contact w/the rat or PERSON TO PERSON
what can be transmitted person to person
lassa

also the multimammate rat urine/contact
what is teh hemorrhagic fever that has an insidious onset? whats hte clinical
lassa- get a fever, HA, FRY COUGH, pharyngitis, dirrhea

**sometimes facial edema and a maculopapular rash

*photophobia, deafness, necrosis
photophobia, facial edema, maculopapular rash and insidous onset describes what fever
lassa

also deafness
what are some of the end stage sx of lassa virus
its initially an insidious onset (fever, HA, dry cough, facial edema, rash, photophobia)

progress to multiorgan necrosis, GI hemorrhage, vascular collapse, shock hypotension etc

**some get deafness
how is the lassa virus acquired
inoculation, inhalation, ingestion (from the multimammate rat)

**virus infects macro and release inflammatory mediaors --> cell/vascular damage, also a T cell response
what cells are infected when you inhale multimammate rat poo
macrophages --> inflamm release

T cell damage (vascular damage)
tell me about the micro of arena virus
envelope, - sense

segmented genoma

has G1/G2 envelope protein (like bunyavirus)

replicate in cyto and then bud from PM
what virus is in the arena virus family
LCMV-
LASSA multimammate rat

**both are rodent born
where is lassa virus seen
W africa


from the multimammate rat
how is lassa transmitted
multimammate rat, ingested food/water contamated with animal urine or direct contact w/the rat or PERSON TO PERSON
what can be transmitted person to person
lassa

also the multimammate rat urine/contact
what is teh hemorrhagic fever that has an insidious onset? whats hte clinical
lassa- get a fever, HA, FRY COUGH, pharyngitis, dirrhea

**sometimes facial edema and a maculopapular rash

*photophobia, deafness, necrosis
photophobia, facial edema, maculopapular rash and insidous onset describes what fever
lassa

also deafness
what are some of the end stage sx of lassa virus
its initially an insidious onset (fever, HA, dry cough, facial edema, rash, photophobia)

progress to multiorgan necrosis, GI hemorrhage, vascular collapse, shock hypotension etc

**some get deafness
how is the lassa virus acquired
inoculation, inhalation, ingestion (from the multimammate rat)

**virus infects macro and release inflammatory mediaors --> cell/vascular damage, also a T cell response
what cells are infected when you inhale multimammate rat poo
macrophages --> inflamm release

T cell damage (vascular damage)
what virus are in the filoviridae family
ebola
maarburg

SEVERE fatal, esp ebola

sx are similar to both
whats the mortality of the filoviridae
BAD!!! its ebola (super deadly) and manburg
whats the micro of the flivo virus (ebola and manburg)
filamentous, pleomorphic, gram - ssRNA

enveloped, glycoprotein for attachment,

internalized from endocytosis. replication in the cytoplasm and virions bud from PM
where is manburg virus common
africa NO cases in US

**passed by fruit bats
what is associated with fruit bats
manburg virus- deadly
where is ebola virus common
africa

5 subtypes, also passes by fruit bats like manburg
ok so the sx of ebola nad manburg are the same, what are they
severe to fatal hemorrhagic fever

**initial- fever, HA, mylagia, sore throat, diarrhea

Then you get rash, lymphadenopathy and photophobia
the hemorrhage associated with ebola and manburg are associated with what
SEVERE thrombocytopenia

**these ones are severe/fatal hemorrhages

((shock, dic,

**in these viruses there is rapid replication and extensive tissue necrosis, VIREMIA persists
what is the pathogensis of ebola and manburg
virus enters blood and replcates FAST causes extensive tissue necrosis

viremia persistis

**macros release mediators that mimic septic shock, causes widespread hemorrhage and DIC

DEATH IS FAST!!
how is the dx of VHF made
epidemiology
vector
serology
PCR/Viral isolation

leukopenia, thrombocytopenia, increased HCT
increased liver enzymes, hypoalbuminemia, proteinuria, elevated BUN, elestrolyte imbalance
whats the tx of VHF
supportive
ribavirin- decrease mortality for lassa, lantaan, and RVF

Prevention: control the vector, isolate infected,

Vaccine: only for yellow,
denge- development
RVF- animals only
what VHF have vaccines available
1. yellow
2. denge- being developed
3. RVF- only for animals (livestock)
whats ribavirin used for
decrease morbidity associated with
lassa
hantaan
RVF
what 2 virus are in primates (monkey) and passed to us by mosquitoes, how can they be told apart
denge- seen world wide get hemorrhagic if infected with 2nd strain,

yellow- seen in africa, central/south america. see jaundice, black vomit, councilman bodies. HIGH mortality
what virus causes blindness has low mortalite and is associated with livestock
RVF- E/S africa

mosquitoes are vector
what virus causes inflammatino of the retina and is passed to us by the striped field mice
hantaan

seen in asia and europe
what virus is passed through ticks and can be a bioterrorism threat
CCHF

passed through tick and also contact with animals/inhalation of animal poo
what virus is passed through rodent urine nad causes hearing loss in some
lassa

multimmate rat transmission
multimammate rat


striped field mouse
lassa

hantaan
what is associated with fruit bats and extensive tissue necrosis
marburg