Lec 38 Vector-borne and zoonotic viral disease Flashcards
What are viral properties of arboviruses of alphaviruses? examples?
single strand pos sense RNA
examples: EEE, WEE, VEE
What are viral properties of flaviviruses? examples?
single strand pos sense RNA
examples: DENV, WNV, YF, SLE
What are viral propertiers of bunyaviruses? examples?
single strand neg sense RNA
examples: La Crosse, Hantaviruses
What is pathogenesis of alpha and flaviviruses?
- 2-3 days : mild or asymptomatic
- 3-7 days: prodrome viremia: mild systemic disease, fever, aches, chills, may infect macrophages, liver, spleen, lymph nodes
- after that: viremia: sever or life threatening – encephalitis, yellow fever, hepatitis, hemorrhagic fever –> DHF/DSS [dengue]
Where is dengue virus [DV] normally found?
mainly in tropical and subtropical
What is the main vector of dengue?
aedes aegypti mosquito
What is the aedes aegypti mosquito? what does it look like? importance?
- most common epidemic vector of dengue and yellow fever
- has white bands or scale patterns on legs and thorax
What is the importance of culex sp mosquito?
associated with transmission of WNV [west nile], SLE [st louis encephalisit], EEE [eastern equine], WEE [western equine], VEE [venezuelen equine]
How is dengue virus transmitted?
- aedes aegypti mosquito [major vector]
- aedes albopictus mosquito
- no human to human transmission
How do the 4 serotypes of denV differ? is there cross immunity?
- each serotype gives specific lifetime immunity and short-term cross immunity
- all lead to severe and fatal disease
- all types genetically distinct
What are markers present in serum with dengue infection?
- see high levels of NS1 antigen during dengue infection
- first antibody produced is IgM
- if you get secondary infection of same virus type will get IgG
How do you detect dengue?
- detect anti-DENV IgM in serum
- PCR to detect DenV genome in serum/mosquitoes/tissue
- detect NS1 with elisa
What are signs of dengue fever?
- fever, muscle pain, rash, hepatitis, cytopenias
- biphasic course
what are signs of DHF [dengue hemorrhagic fever] and dengue shock syndrome [DSS]?
- increased vascular permeability and plasma leakage, bleeding diathesis [from eyes, ears, etc]
- develops during 2nd phase of illness
- associated with 2ndary infection w/ different serotype
Who primarily gets DHF/DSS?
children, normally develops during second phase of biphasic DF and happens in secondary infection
What is antibody mediated immune enhancement [ADE]?
- cross-reactive antibodies allow uptake of virus by macrophages/monocytes that have Fc receptor –> virus infects these cells and replicates = massive superinfection with increased viral load
- get lots of cytokine release –> DHf/DSS
big problem = disease is caused by our own immune system
How do you prevent DENV?
- minimize reduction of human-vector contact
- 3 vaccine trials ongoing
How do you control dengue vector?
- eliminate egg-laying habitat [water/waste store/remove]
- insecticides/barriers
- sterilize male mosquitos [population control]
- intriduce wolbachia pipientis into A aeypti = bacteria that blocks denv transmission
What are the concerns about DENV vaccines?
- need to give protection against all 4 serotypes
- need to be safe in already dengue immune pop
- need protective antibody response and T cell immunity
- need to be accessible and affordable
What happens with CYD vaccine?
- only 30% efficacy, didn’t work against DENV-2
- need to go back to drawing board
Where is yellow fever endemic?
parts of south america and subsaharan africa
What is natural reservoir for yellow fever?
monkeys [humans can also act as source of infection]
What is vector for yellow fever to humans?
aedes aegypti
What are symptoms of yellow fever?
stage 1: fever, headache, leukopenia, can be asymptomatic
some people progress to stage 2: hepatitis, hemorrhagic diasthesis, multiorgan failure, mortality 50%
What is vaccine for YF? side effect? who gets it?
- live virus vaccine [17D]
- side effect: rare YF-like illness
- mandatory in some YF affected countries
- one of most efficient vaccines available
What are the viral agents of enceophalitis?
HEMP AIR
H = herpes virus [HSV-1] E = equine encephalitis [eastern + western + venezuelen + other arboviruses -- west nnile, st lous, la crosse] M = measles/mumps P = polio and other enteroviruses
A = Adenovirus I = Influenza R = rabies
What is port of entry for measle/mumps/varicella zoster viruses causing encephalitis?
respiratory tract
What is port of entry for polio + other enteroviruses causing encephalitis?
GI tract
What is port of entry for HSV causing encephalitis?
genital tract and oral mucosa
What is port of entry for arboviruses causing encephalitis?
subcutaneous tissue
When does encephalitis primarily occur and by what viruses?
primarily ocurs in summer [may-oct/nov] due to mostly enteroviruses and some tick/mosquito borne arboviruses
What is genus of west nile virus?
flavivirus
What are properites of west nile? host? vector?
host: mammals and bird
vector: mosquitors
properties: single strand RNA
What are signs of west nile infection?
~60-80% are asymptomatic or subclinical
- of the symptomatic:
- – west nile fever
- – neuroinvasive disease [meningitis, encephalitis]
What are risk factors for human WNV disease?
- increased age
- immunosuppression
- CCR5 deletion is risk factor for WNV
How is west nile virus transmitted?
- via mosquito
- also alternatively can get human –> human by: transfusion, transplantation, transplacental, breast milk
What is the primary pathologic feature of WNV in CNS?
multifocal encephalitis
How are hantaviruses transmitted?
by inhalation of virus-contaminated aerosols of rodent excretions
What is sin nombre virus [SN]? vector? disease? where?
- type of hantavirus
- causes HPS [hantavirus pulm syndrome]
- in US/Canada
- vector = deer mouse
What is New York virus [NY]? vector? disease? where?
- type of hantavirus
- causes HPS [hantavirus pulm syndrome]
- in US
- vector = white footed mouse
What is hantaan virus [HTN]? vector? disease? where?
- type of hantavirus
- causes HFRS [hemorrhagic fever with renal syndrome]
- in Russia/China/Korea
- vector = striped field mouse
What is structure of rhabdovirus?
- single stranded
- neg sense
- RNA
- has envelope
- covered by trimers of glycoproteins
- core has N, NS, and L proteins
What is post exposure prophylaxis for rabes?
- one dose of human rabies Ig pHRIG] and five doses of rabies vaccine given in month
What is function of rhabdovirus G protein?
- facilitates attachment, assembly, budding
- elicits neutralizing antibodies –> used in PEP
What is the function of the rhabdovirus M matrix protein?
facilitates assembly and budding
What is life cycle of rabies infection?
- cells most infected are neurons [with ganglioside and CD56 receptors] and muscles [with nicotinic receptor]
- attaches cell, fuses
- replicates in cytoplasm –> vRNA is template for mRNA and cRNA
- assembles/buds at cell surface
What are the receptors that rabies binds to? on which cells?
gangliosides and CD56 on neurons
nicotinic receptors on muscle
Where in cell does rhabdovirus replicate?
in cytoplasm
what is the pathogenesis of rhabdovirus infection?
- animal bites you
- virus enters through break in skin, mucosal surface or respiratory tract
- infects and replicates in muscle cells
- infects and replicates in nerve that innervates muscle spindle
- travels through axons and spreads to CNS
- travels to multiple organs through peripheral nerves
- becomes highly concentrated in saliva
- antibody response develops late
What are negri bodies?
- viral neucleocapsids
- eosinophilic pockets of rabies virus
- contained in cytoplasm of hyppocampal pyramidal cells, purkinje cells, cortical neurons
- pathologic sign of rabies infection
What is mech of injury of rhabdorvirus?
- minimal/no neuronal necrosis
- may interfere with neurotransmission
- induces apoptosis of T lymphocytes
What are clinical features of rabies?
- incubation period usually < 90 days but may be years
- have few days of viral prodrome
- symptomatic: personality change, parasehtesis, pain at site of exposure, other neuro symptoms
- comma in 2-4 days
- death in 18 days
How do you diagnose rabies?
- biopsy DFA of nape of neck
- PCR CSF/saliva/tissue
How do you prevent rabies?
- immunize animals
- targeted pre-exposure vaccination
- wound care, vaccination and rabies Ig after exposure
