Term
name of professor who runs virology blog |
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Definition
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Definition
organic nanoparticles
lean, mean machines
genetic info w/ a couple proteins in order to func
hijack the host cell machinery
virus mimicry uses combos of genetic engineering and chem modification |
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Definition
around 100 namometers
like holding an orange in a circus tent (mammalian cell) |
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Term
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Definition
host cell: animal, plant, fungal, bacteriophage
Shape of capsid: helix or icosahedron
virus struc: prescence or absence or envelope (phospholipid bilayer of host cell)
type of nucleic acid: DNA viruses (double stranded and less common than single)
RNA viruses (pos sense single stranded reverse transcribing DNA and less common double stranded)
reverse transcribing (double stranded reverse transcribing DNA, and single stranded reverse transcribing RNA) |
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Term
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Definition
codes the many different ways virus can get from genome to protein |
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Term
virus structure simplified |
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Definition
viral nucleic acid (all viruses have this)-single stranded, double stranded DNA or RNA, linear or circular
protein coat (all viruses have this)
envelope-not all viruses have this protective phospholipid bilayer |
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Term
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Definition
main func to protect nucleic acid from the enviro (1 or more repeating units, virus can't carry a lot of info), capsid is made up of repeating units which are proteins synthesized by the viral nucleic acids |
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Term
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Definition
nucleic acid-RNA or DNA, single or double strands, circ or linera
protein coat (capsid)-helical or iscosahedral, subunit construction
envelope-present or not |
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Definition
can be very diverse in structure shape and size |
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Term
three advantages of virion structures |
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Definition
1. protenction-protect the fragile nucleic acid genome from physical, chem, or enzymatic damage
2. specificity-recog and first interac w/ host cell
3. delivery of genome into the cell |
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Term
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Definition
protein subunit construc based upon hydrophobic and electrostatic interactions
make up the two basic struc or iscoasahedral (hexagon like shape) or helical |
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Definition
1. virus partical attracted to host cell, specific or general
2. delivery of genome
3.takes over machinery of host cell
4. more particles form and virus can go infect others |
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Term
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Definition
have endemics and outbreaks
worldwide problems
can get better with vaccines |
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Term
what is an antibody (and the 2 we need to know) |
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Definition
large protein produced by immune system to identify and neutralize foreign objects
IgG-majority of antibody response, monomer
IgM-early stages of antibody response, pentamer |
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Term
general sx of any hep infection |
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Definition
yellow tint to eyes and skin, inflammed stomach, espophogas liver stomach spleen pancrease, edema in legs, numbness, tingling |
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Term
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Definition
wide spread subclinical infections
enteral-fecal/oral route enteral
acute only-no carrier or chronic condtion
prejaundice phase lasts weeks to months, abrupt onset of fever, nauseas, vomiting, anoerxia
jaundice phase-lasts 1-2 weeks, dark urine (melanine) and or jaundice (yellow skin due to bile in skin)
immune respone w/ IgM detected first, and IgG detected for life
dx is raised Igm and igg anti HAV antibodies (6 weeks to several months)
elevated liver enzymes (especially ALT-alanine transaminase enzyme) |
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Term
clinical picture HAV infection |
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Definition
can be excreted in feces before even clinical illness develops
IgM detected first
IgG for life
ALT levels elevated |
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Term
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Definition
treatment-non speicifc tx, rest and avoid alcohol and toxic substance, most people recover w/in 3 months, nearly all px recover w/in 6 months
prevention-passive immunization w/ human gabba globuin or active immunization w/ inactivated hep A vaccine |
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Term
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Definition
major cause of chornic hep, cirrhoissi and primary hepatocellular carcinoma
transmission by bloodborne, infectious blood or body fluids (semen, vaginal fluids) also perinatal infection, cannot be spread by kissing, hugging, or breastfeeding
clinical sx-loss of appetite, fatigue, fever (low grade), muscle and joint aches, nausea and vomiting, yellow skin an dark urine due to jaundice
immune response-IgG antibodies for life
dx-liver func tests: ALT enzyme levels in blood |
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Term
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Definition
about a third of world's pop has been infected w/ HBV at some time in their lives
replicate through an RNA intermediate by activity of reverse transcriptase which relates them to retroviruses like HIV
HBV genome is a partially dsDNA molecule and has a viron assoc DNA polymerase
350 mill chronic carriers |
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Term
clincial pic HBV (3 types infection) |
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Definition
acute, asymptomatic, chronic |
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Term
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Definition
majority of infections are asymp, HBsAg in serum for short time (1-2 months)
antibodies against HBsAg persist for life providing lifelong immunity |
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Term
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Definition
long incubation period
sx as in acute hep a
hbsag in serum for less than 6 months (transient)
majority of px recover
antibodies against hbsag persist for lifelong immunity
hbv+ hdv=fulminant hep |
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Term
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Definition
one of the common long term results of acute hep b is calles persistant viral hep
hbsag in serum persists for greater than 6 months, probably life |
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Term
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Definition
interferon alpha-decreases the stability of the viral genetic material, casues side effects including fever, fatigue, muscle aches, depression
nucleoside/nucleotide analongs inhibit reverse transcriptase have been developed (originally for HIV tx)
still work to do to determine optimal tx's |
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Term
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Definition
passive immunity-hep b immune globulin, standarf immune serum globulin
active immunity-immunizations |
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Term
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Definition
transmitted Iv drug use, post transfusion, tattoos, manicure equip
clinical sx-abdominal pain (right upper abdomen), abdominal swelling (ascities), clay colored or pale stools, dark urine, fatigue, fever, itching, jaunice, loss of appetite, nausea, vomitting
immune response-igg antibodies for life
dx-blood tests (EIA enzyme), liver func test, genetic testing (six genotypes exit and have to test-most americans have type 1), liver biopsy can determine exent of damage |
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Term
clincial picture of Hep c |
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Definition
most infections are insidious (slow)
time to clinical hep greater than 10 years
time to cirrohis and cancer a couple decades
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Term
hcv treatment and prevention |
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Definition
combo of antiviral ribavirin for 24-48 weeks depending on HCV genotype, most effective 1st 6 months after infection as opposed to chronicity |
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Term
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Definition
transmission by bloodborne, sexual, needle sharing, infected blood products
clinc sx-more severe than others-abdonimal pain and swelling, loss of appetite, sore throat, joint and muscle pain, clay colored and pale stools, dark urine, fatigue, faver, itching, jaundice, loss of appetite, nausea, vomiting,
immune response-anti HD antiboidies do not always persist after acutre infection is cleared
dx-blood tests (anti delta antibodies, serum HDV RNA) |
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Term
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Definition
no effective antiviral tx
hyperimmune d globulin avail for pre or post exposure prophylaxis
progression to cirrohis usually takes 5 to 10 years but can appear after 2
high proportion of px get cirrohis and die of hepatic failure
liver transplants may be considered
mortality is 10x higher than hbv |
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Term
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Definition
key is that it is a sattelite virus and requires hbv infection first
defective RNA virus on its own
uses the hbsag antigen as its own viron coat
hbv vacc prevents against hdv based on this principle |
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Term
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Definition
transmission-fecal/oral, enteral, principally due to contaminated water
clinc sx-jaunice, anoerxia, hepatomegaly, abdominal pain and tenderness, nausea and vomitting, fever
immune response-noncytopathic (doesn't kill cells) but suspected to cause immune mediated liver damage through cytotoxic t cells
dx-speficic antibodies in blood, often epidemic outbreaks occur |
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Term
HEV prevention and treatment |
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Definition
treatment-none avail usually self limiting, hospitilzation required for px w/ fulminant dx
prevention-maintain safe public water sanitation, proper disposal of waste |
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Term
central dogma molecular biology |
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Definition
DNa is the start (orginal design of a machine from a factory)
made into RNA (blueprints of the machine) made into proteins (machines of a cell)
DNA can be made into DNA (DNA polymerase)
RNA can be made into RNA (RNA polymerase)
RNA can be made back into DNA by reverse trascripterase |
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Term
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Definition
virus that undergoes reverse transcription of RNA into DNA during the viral lifecycle (HIV) |
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Term
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Definition
HIV retrovirus integrates into the host cell genome
ancient retroviruses inserted bits of DNA into the primate genome millions of years ago
8 percent human genetic code consists of ERV's
researchers propose that insertion of DNA by ancient retroviruses helped genes like p53 become master gene regulators that can switch on and off many genes |
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Term
this week in virology article |
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Definition
protein called syncytin, a membrane fusion protein, is essential in formation of the placenta and the gene is from an ERV
ERV are necessary for the way humans are today |
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Term
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Definition
HIV is an RNA virus w/ 2 identical strands (but not double stranded) of RNA as the genome
HIV replicates in cells of the human immune system
HIV has been assoc w/ syndrome called AIDS
AIDS px develop anti HIV antibodies (key to testing for HIV infection |
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Term
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Definition
HIV1-high virulence, global prevalence, from common chimpanzee
HIV2-lower virulence, low infectivity, prevalence in west africa, origin from sooty mangabey
HIV 2 more closely related to SIV than it is to HIV 1 |
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Term
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Definition
can be from an ELISA (enzyme linked immosorbent assay, uses antibodies to change color)
western blot-anitbodies bind to proteins and change band color, like a pregnancy test, need 5 to show up for pos
oraquick-now in home, not as accurate, about 20 min
uni gold recombigen-plasma, serum, whole blood, must be performed by med professional, all rapid tests need western blot follow up |
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Term
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Definition
acute or primary HIV dx stage
acute retroviral syndrome
develops 2-8 weeks after exposure and lasts 2-4 weeks
charac by mono like illness with fever, sweat, lethargy, headache, diareha,
high levels of virus are produced and spread throughout body
no notable immune repsonse detectable
period is called window of infectivity before seroconversion
**transmission can occur |
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Term
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Definition
asymptomatic HIV disease stagelasts for 6 months to 10+ years
HIV in blood drops to a low level and antibiodoies against HIV produced
indiv appear healthy
dsDNA migrates to nuclease and integrates w/in the host chormosome exisitng as proviral DNA (latent state) for the rest of a person's life
transmission can occur |
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Term
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Definition
chronic stymptiomatic HIV dx stage
virus replications destroy CD4 t cellss and their numbers decline and viremia increases
results in an immune repsonse w/ the onset of opprotunisitc infections and cancer
cd4 t cell counts frop below 200 per microliter of blood
cd4 and t cell count very important makrer of dx progression
transmission can occur |
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Term
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Definition
crisis hiv dieases stage (aids)
virus replication contunues
marked destrucktion in cells of immune system
leads to marked immunodeficiency
px aquieies opprotunisitic infections and malignancies (cancer)
transmssion can occur |
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Term
HIV host cell tropism (preferential cell targets)
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Definition
CD4+ T cells infectes, macrophages infected
two receptors required for viral entry: CD4 receptor or chemokine coreceptor-CCR5 in initial infections or CXCr4 |
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Term
aquisistion and transmission HIV |
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Definition
sexual transmission
parenteral transmission
perinatal trasmission
transmitted during all 4 stages of disease
greatest risk stages 1 and 3
about 35% risk that HIV infected mothers will pass HIV to their babies
risk is reduced to 6% if tx is started before birth and 18% if started by 3 days |
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Term
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Definition
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Term
genome organization of HIV |
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Definition
gag, pal, and env are all in virus itself
all important drug targets
gag-makes capsid struc
pal-what codes for important enzymes **best for drug targets
env-2 proteins on surface |
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Term
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Definition
period from the first attachement of the virus to a cell through to the final maturation step after new virus buds off the cell |
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Term
Steps in HIV replication cycle (steps 1-5 of 11) |
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Definition
1.HIV viral attachment-envelope protein complex attaches to cd4 and the coreceptor (ccr5 or cxcr4)
2.virus endocytosed (uptake) into the cell
3. envelope complex promotes membrane fusion (late stage of entry) b/w the viral membrane and the cellular membrane
4. viral core is relaesed into the cytoplasm
5.virion assoc reverse transcriptase synth a double stranded DNA (cDNA) from the RNA genome |
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Term
steps in HIV replication cycle (6-11 of 11)
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Definition
6. cDNA (complementary DNA) migrates to the nucleus
7.enzyme integrase integrates it into the host cell genome (the inserted cDNA is called the provirus)
8.provirus transcribed to produce-genomic RNA; messenger RNA involved in production of virus specific proteins
9.assembly takles place in the cytoplasm
10. virions are release from cells by a process called budding
10. capsid struc changes create a mature virion (maturation) |
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Term
6 targets for drug tx HIV |
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Definition
1. receptor inhibitiors
2. fusion inhibitors
3. reverse transcriptase inhibitors
4. integrase inhibitors
5.protease inhibitors
6.maturation inhibitors (not approved clin use yet) |
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Term
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Definition
reverse transcripase is error prone
HIV replication is rapid
therefore the mutation rate is very high |
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Term
HIV latency and reservoirs |
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Definition
HIV can hide in reservoirs and if retroviral therapy is stopped then the virus can remerge
HIV latency is a very important area of research including: 1.optimizing low level detection
2.identifying all latent reservoirs
3. reactivating from latency in order to identify and kill latently affected cells |
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Term
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Definition
CCR5 deletion mutation found in patient that gave blood transfusion to px w/ HIV and leukemia and the levels of their virus dropped
promising concept but difficult to admin |
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Term
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Definition
non segmented genome
same H and N surface proteins
examples are parainfluenza, mumps, measles |
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Term
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Definition
segmented genome-allows reassortment
different H and N proteins
influenza |
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Term
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Definition
has lipid bilayer which means it can be destroyed by soap
have mRNA polymerase on capsule which helps it reproduce on outside |
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Term
human parainfluenza virus |
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Definition
has 4 serotypes (1,2,3,4) transmission through respiratory
replcation in respiratory tract
has no viremia and stays localized
clinical sx are croup-6mos to yrs, rhinorea
reinfections-common (transient immunity) no long term immunological immunity
lab dx is to detec t viral antigen in cells from nasal secretions
tx-no vaccine or anitviral drugs |
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Term
respiratory synctial virus (RSV) |
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Definition
important pathogen children and infants-most children get this by 2
transmission in respiratory tract
replicates in respiratory tract-no viremia
clinical sx-infacts (less than 6 months), bronchiolotis and pneumonitis
reinfections common
lab dx; detect viral antigen in cells of nasal secretion |
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Term
treatment and passive immunization for rsv |
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Definition
vaccine-non avail
antiviral drug-ribavin (fda approved aerosol)
passive immunization (doesn't induce immunity)-form of tx for an active infection
palivizumab-vaccine for high risk groups (expensive), preemie babies, babies w/ pulmonary probs |
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Term
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Definition
paramyoxvirdae
childhood dx w/ one serotype
high rate subclincial infections
transmission-respiratory route, incubation period 12-20 days
replication: respiratory tract and lymph nodes (indicative of viremia)
clinical sx are fever, headache, pain, and swelling of one or both parotid glands |
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Term
complications, immune response, and dx of mumps |
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Definition
complication: orchitis-rare in childhood (20-30% of adults), blood in semen, or sterility in adults, meningitis, CNS involvement
immune response: lifelong immunity
dx-based on clinical sx
lab dx can be made: serodx igM antibodies (indicative of recent infection), IgG (acute v convalesncent stage) |
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Term
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Definition
live, attenuated vaccine
MMR
recomendation: first dose at 12-15 months of age and second around 4-6 years or 11-12 years of age |
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Term
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Definition
paramyxovirdae
aka morbilivirus, rubeola
acute febrile exanthematous dx
one of the most infectious diseases
only one serotype
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Term
2 imporant facts about mumps |
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Definition
1. humans are the only natural host
2. no carrier state, therefore measeles could be eliminated as a human disease
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Term
mumps transmission and clincial sx
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Definition
transmission: respiratory route
incubation period: 10-14 days, infectious prior to sx
sx are the 3 C's; cough, coryza (inflammation of mucous membranes around nose), and conjunctivitis
koplik sports-roof of mouth to start, begin around day 3 before other sx, ulcerated membranes
warthin finkeldley synctial cells in cells of nasal secretions-packed full of viral particles
followed by viremia and maculopapular rash |
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Term
measles immunity, prevention, dx |
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Definition
immune response: lifelong immunity
lab dx; serodiagnosis HA test
prevention: live attenuated vaccine (MMR), 2 doses 1 at 12-15 months and the other at 4-6 years or 11-12 years old |
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Term
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Definition
orthomyxoviridae
1.respiratory infection accompanied w/ sig fever for 3-4 days, headaches, and myalgia, usually in winter, cases generally peak in february
2.contagious for about 1 day prior to sx appearing
3. 50,000 to 500,000 cases per year-highest infection rates in children
4.currently 4000 to 50000 deaths per year in the US (flu and assoc causes)-primarily in elderly, young children, px w/ med conditions
-h1n1 is an anamoly |
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Term
influenza a virion proteins |
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Definition
hemagglutinin (HA)-where most people develop immunity to this virus
RNA w/ 8 diff segments each with its own protein |
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Term
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Definition
believed to be related to lower levels of immunity
dryer times lead to the spike in yearly transmission |
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Term
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Definition
A, B, and C
serotypes a and b cause diease in humans |
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Term
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Definition
birds
water fowl believed to be asymptomatic reservoir (has it but doesn't cause disease)
land birds, pigs carriers as well
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Term
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Definition
antigentic type
host of origin
geographical origin
strain number
year of isolation
for influenza a, the hemagluttinin and neuraminidase antigen description in parantheses
ex; A/duck/Alberta/35/76 (H1N1) |
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Term
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Definition
oldest known is russian (asiatic) flu in 1889
1918 worst (spanish flu) killing 20-100 million (h1n1)
first vaccine attentated pandemic was hong kong fly in 1968
2009 swine flu was most recent w/ 18,000 deaths |
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Term
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Definition
relatively error prone RNA polymerases create 1 error/10,000 bases (1/viral genome)
with every viriron particle having a mutation, this created plenty of doffer for evolution of influenza but with slow chance, vaccines and natural immunity show cross protection |
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Term
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Definition
when there is a coinfetion of mult influenza types (usually in fowl, rarely in pigs)
diff combos rna genome segment (8) can result in REASSORTMENT
new subtypes resulting are charac by their major antigenic determinants (hemaglutinin (H) and neuraminidase (N) types) often little or no cross protection-epidemics |
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Term
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Definition
first detected in april 2009 near pig farm in mexico
declared pandemic in june (first in 40 years)
predominant circulating strain in 2009-10 flu season
peaked # of cases in october (seasonal flu jan-march)
WHO declared pandemic over by august 10th 2010 |
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Term
swine flu as a novel virus |
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Definition
quadrupple reassortment occured in pigs and contains segments from
1.north american swine flu (H)
2. North american avian flu (1)
3. human flu (N)
4. asian and euro swine flu (1)
transmission and clincal sx same as seasonal flu
virus has not mutated substantially and subsequent vaccines contain H1N1 |
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Term
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Definition
amantadine and rimatadine inhibit viral uncoating (viral M2 protein)-these inhibit only influenza A strains, not B strains
neuramindiase inhibitors: prevent release of virions from infected cells-zanamivir-nasal inhalant, oseltamivir (tamiflu)-tablet-inihibit a and b |
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Term
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Definition
all influenza vaccines contain
2 subtypes of a and 1 subtype of b
2 fda approved vaccines
1.innactivated vaccine for high risk group
2. live atteunated intranasal vaccine (viruses in LAIV are temperature sensitive mutants)
LAIV is only for healthy persons ages 2-49 years
not recommended for people w/ immune dysfunc, people with asthma, people on asprin therapy and pregnant women |
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Term
truth about antivaccine slides |
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Definition
not all vaccines produce immunity-some vaccines only 70% effective however recipients get disease a lot less severe
we were able to erradicate smallpox from the face of the earth with the use of vaccines
there is clear evidence for herd immunity substantially dec infection rates in uninfected populations
herd immunity plays a vital role in preventing dx in populations that can't receive vaccines
the toxins in vaccines are at marginal doses so they shouldn't concern recipients |
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Term
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Definition
iscosahedral non env capsids with 12 protein fibers with knobs involved in attachment to target cells
57 serotypes currently known
causes flu like, cold like sx, croup, bronchitis and sometimes GI distress, conjunctivitis, cystisis, and less commonly neurological dx
has 30-35 linear dsDNA genomes and encodes 22-40 proteins/ORFs
has resistance to drying (non env) and stable in pH/chem agents/physical agents making it able to have prolonged survival outside host
spread respiratory droplets, fecal routes |
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Term
adenoviruses genome depiction |
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Definition
has 3' to 5' genome dsDNA
has a TBP (terminal binding protein) at the 5' end
this is a mechanism which makes a copy of the oppostite strand
adenovirus also has early and later genes which can be transcribed and turned on later |
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Term
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Definition
antigen detection, PCR, virus isolation and serology
adenovirys typing is done using inhibition of hemagluttinin assay, or using type specific antisera, antibodies, or other molecular methods
possible causes of severe pneumonia cases or pneumonia outbreaks of unknown etiology |
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Term
treatment/prevention of adenoviruses |
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Definition
no vaaccine generally avail, types 4 and 7 vaccine was used before but were discontinued, oral vaccine for military use
use of infection control practices for general contact/droplet infections
sx generally mild, treated like other cold/flu infections
immunocompromised px can be treated with cidofovir |
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Term
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Definition
used for treatment of adenoviruses
looks like nucleotide to viral DNA polymerase and virus tries to use this
most reasonable efficacy over other analogs
some toxicity in higher levels because host cells try to use this too
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Term
mechanism to many of the nucleoside analogs |
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Definition
attaches to 3' hydroxyl group and many don't have this so it terminates the rest of the cahin
antivirals work bc they target the viral replication enzyme virus itself encodes |
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Term
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Definition
PV infects mammals, birds, and possibly reptiles
isolated from filtrate of wart tissue
infection of primarily epithelial, but sometimes fibroblast cells
currently over 150 isotypes, 50-60 sexually transmitted, about 1/3 to 1/2 of those fall into high risk category
most common STI of viral origin, comparable to most common bacterial STIs, at any time, 20m americans in US have infection, 5.5M every year |
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Term
cervical cancer and papilloma virus |
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Definition
responsible for about 99% of cervical cancer, most penile and angogential cancers, and about 60% of oropharyngeal cancers
worldwide, half mill new cases cervical cancer/year, quarter mill deaths, in US 14,000 new cases, 5000 deaths (due to vaccine use, this number dropping) |
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Term
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Definition
non env-like adeno, this is also resistant to drying etc
iscosahedral capsid
no viral proteins encapsulated-made of 2
55nm diameter-in theory probably could pass through latex
each capsomere is made up of 5 copies of viral protein L1-entergenically favorable |
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Term
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Definition
8kb dsDNA GENOME
8 open reading frames
L1 and L2 are structural capsid proteins
E1 and E2 involved in HPV replication and transcriptional regulation
E6 and E7 are involved in immortilzation and escape from cell apoptosis
produced once they go into the cell
LCR (rgulatory region) contains viral origin of DNA replication
LCR contrains viral promoters for mRNA synth |
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Term
schematic of epidedermis and pappilomavirus |
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Definition
has to infect basal cells
the cells about the basal have no cell cycle
only cells active in epidermis are basal and these just get displaced to upper layers |
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Term
papillomavirus life cycle |
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Definition
release of mature virion
virion assembly
vegetative viral DNA replication
expression of late viral capsid proteins L1 and L2
expression of later viral proteins E4 and E5
establisment phase-est of primary infection
expression of intermediate early proteins E1, E2, E6, and E7
steady state viral DNA replication-50 to 100 episomal copies of genome |
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Term
immortalization and papiloma virus |
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Definition
causes by E7, causes targets degradation of cellular pRB (tumor supressing protein)
results in more cells producing virus
shut down cells=shut down virus so virus stops this process |
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Term
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Definition
normally cells produce E2F which is a transcription factor which allows cells to grow
this factor will pause at phase G1 so cells don't grow uncontrollably (like outer epidermis)
pRM (tumor suppressor) is what pauses cells at G1
E7 takes away pRB so cells can continue to duplicate and bipass phase G1 |
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Term
lack of cell cycle blok and apoptosis (programmed cell death)
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Definition
caused by E6
targets degradation of p53 (tumor suppressor protein)
results in more cells producing virus |
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Term
p53 hijacking process and papilomavirus |
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Definition
in normal cells p53 produced at normal levels
viral infection, DNA damage or cell stress all cause levels of p53 to increase
this would then inc levels of BAX and cause Apoptosis
like using emergency brake on car-damages car but saves your life
E6 binds to p53 so the "emergency brake" never works and cell death does not occur |
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Term
end result of E6 and E7 protein process in papilomaviruses |
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Definition
hyperproliferation of epidermal cells resulting in hyperkeratosis characteristic of warts |
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Term
papillomavirus does not lyse cells but rather...
hijacks process of losing skin cells |
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Definition
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Term
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Definition
probably has diff mech than passing through basal cells w/ mild abrasion
less layers to go through on yo dick |
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Term
how does HPV drive cells to be cancerous |
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Definition
cells must be driven to proliferate (uncontrolled manner) and must not respond to DNA damage to stop cell cycle and or commit cellular suicide (prevent apoptosis)
e7 and e6 are the most critical oncogenes for HPV to cause cancer |
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Term
high expression e6 and e7 lead to |
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Definition
constantly proliferating cells (loss of pRB func)
lack of cell cycle control/DNA damage checkpoints (loss of p53 tumor suppressor)
lack of apoptosis which would kill damaged oncogenic cells (loss of p53)
resulting in cells primed for genomic/genetic instability |
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Term
prevention/treatment HPV infections |
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Definition
HPV vaccine-guardasil
HPV 6, 11, 16, 18 (all but 11 here are high risk), L1 proteins-"ghost" viral particles
cervarix (16 & 18)
current txs-removal-surgical, freezing, chemical etc trying to eliminate basal cells
imiquimod-immune stimulator, doesn't always work but shorten time for clearing |
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Term
types of antiviral agents |
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Definition
nucleotide analogs
inhibitors of proteases
inhibitors of retrovirus intregration
but none of these can work for HPV |
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Term
cancer treatments and HPV |
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Definition
prevention w/ the 2 HPV vaccines
PAP smears
surgical removal of lesions at early stages
radiations, various chemo agents
outlook still poor for those dx at later stage (about 50%) |
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Term
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Definition
not part of normal HPV life
infrequent molecular accident but w/ virus being so commone, it nonetheless has become a frequent cancer |
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Term
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Definition
look like papilomarviruses
not epidermal viruses-their life cycle not linked to differentiation, they usually have a normal 3-5 day lytic cycle
cell trophisms vary
45 nm non env iscoahedral capsids-72 capsomeres
circular dsDNA
encode 5 or 6 proteins (2 or 3 structural, and 2 or 3 non struc)
2 welll known are JC and BK viruses
both are very common (80%-get them as kids)-cause disease in immunocompromised |
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Term
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Definition
TCR is non coding region
large t antigen is functional protein (on same half as small t antigen)
other side encodes for various other proteins |
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Term
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Definition
neurologicl
progressive multifocal leukoencephalopahty in immunocompromised (white matter swelling-causes MS like sx)
happens in late stage aids
early normal infection probably like a tonsilitis |
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Term
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Definition
to kidneys, nephritis and neuropathy in kidney transplant px
most people get this while young but some people could still be excreting the active virus |
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Term
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Definition
simian virus 40
effective at causing cancer in monkeys cells
became a model for many other cellular functions |
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Term
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Definition
80% merkel cell carcinoma involved w/ this
found in immunocompromised/old people
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Term
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Definition
8 types that infect humans
HSV1, HSV2, and varicella/zoster (VSV) are neurotrophic and infect from skin cells and go to nerve cells
epstein barr, cytomegalovirus, and herpes 6-8 infect lymph and immune system |
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Term
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Definition
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Term
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Definition
major feature of pathogenesis is that these viruses est latent infections
following an intial infection (primary), the virus establishes itself in a non infectious form in neural or lymphoid tissues and can reactivate to give a secondary (recurrent) infection which is often the major cause of disease
ubiquitous infections-most indiv are infected w/ 5 of the 8 human herpesviruses |
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Term
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Definition
enveloped-can be disrupted by soap
not as resistant to drying
enveloped (lipid) covered w/ protein spikes-viral protein involved w/ attachement and structure
has inner tegument-has no real structure but has many important viral proteins carried to next host |
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Term
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Definition
encode about 7-200 proteins alone ( larger than other viruses)
vary in sizes
does ciruclate in cell
many proteins and functions than other DNA viruses |
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Term
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Definition
has lytic cycle where it injects DNA into cell and replicates and releases mature virion
tegument proteins remain assoc until fuse w/ cell
early proteins-DNA replication
late-structural func
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Term
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Definition
localized 1st infection very minor
travels along neuronal path and latent w very few viral proteins
generally occur when people are stressed (ex fighting a fever)
specific mech is still unknown
blisters tend to stay localized to the site of infection |
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Term
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Definition
HSV 1 can get transmitted to eye and cause induced keratitis
opaqueness can happen to cornea
second only to to trauma as cause of corneal blindness in US
kids can chew on fingers and transfer blisters to fingers, toes, etc ( why dental hygenists use gloves)
slight abrasion and herpres breaks out on wrestlers-herpes gladirorum-this can get transfered to face |
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Term
herpes and brain infections |
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Definition
usually doesnt cross BBB and occasionally does
HSV1 can cross trigeminal and cause herpes encephalitis
HSV2 can cross and cause meningitis |
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Term
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Definition
contracted during passage through genital canal
contracted postnatally from indiv shedding virus
disseminated HSV infection to major organs and CNS
progression of infection to CNS results in death, MR, or neurologic disability even w/ tx-80% mortality in absence of antiviral therapy
tx w/ prophylaxis or ceasarian |
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Term
acyclovir and valacycolvir |
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Definition
acyclovir one of the best antivirals out there
valacyclovir has greater bioavail and used in prevention congential transmission |
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Term
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Definition
infection conjunctivits and or mucosa URT
viral replication in regional lymp nodes
primary viremia
viral replication in spleen, liver and other organs
secondary viremia
infection of skin and appearance of vesticular rash |
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Term
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Definition
has marks that are full or virion
can get from touching one of these or from inhaling virus |
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Term
VZV latency and reactivation |
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Definition
zoster/shingles
reactivated from central nerves to skins and more toxic to neurological system than primary infection
can get pain from nerve damage ranging from years to lifetime
can also cause blindness if appears on face near eye
can cross placental barrier and cause limb atrophy in uterpo |
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Term
VZV intervention strategies
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Definition
acylovir and valacyclovir
effective vaccines against varicella and zoster are avail and in use-vaccine against zoster about 50% effective
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Term
lymphotrophic herpesviruses |
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Definition
viruses which infect cells of lympho-reticular system- T cells, B cells, monocyte/macrophages, dendritic cells
EBV, CMV, HHV6-8 |
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Term
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Definition
aka mono
invaces at cells and causes acute pharyngitis and has latent phase
goes into memory cells and can get reactivated by antigens |
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Term
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Definition
burkitts lymphoma-found in areas where malaria infectious-possibly aggravates latent EBV
nasopharyngeal carcinoma-diets high in salt and fish in asia
could get reactivated w/ persistant infection of immunocomprosmised |
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Term
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Definition
post transplant lymphoproliferative dx
bone marrow and solid organ transfers
EBV transfered in graft
EBV infects recipient B cells
recipient EBV seroneg and under high levels of immunosupresion
transplant recipients and donors need to be EBV neg |
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Term
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Definition
assoc w/ monocytes, polymorphonuclear lymphocytes and macrophages
primarily perinatal, and vereneal transmission
most infections in the normal host are asymptomatic or mild
spread by close contact, present in all body fluids
pop a risk; babies, embryos, immunocompromised, transplant recipients
major cause hearing loss and deafness in children
can cause worse dx in immunocompromised
**gancyclovir drug of choice
combo vaccine under development |
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Term
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Definition
transmission via fecal/oral route
polio virus and coxsackie (A and B) viruses
one of the largest families of small ssTNA pos sense viruses
human pathogens include the following
enteroviruses-polio, coxsackie
rhinoviruses-common cold (more than 100 types)
herpnavirus: hep A
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Term
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Definition
transmission via bite of rabid animal (zoonotic) rabies virus |
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Term
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Definition
transmission via fecal/oral route
rota virus |
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Term
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Definition
|
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Term
picronavirus pathogenesis |
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Definition
group of viruses causes effects after infecting gut
grow near oral part and seep into blood (primary viremia)
injest them
only infectious form humans therefore get from human feces (ex swimming pools)
can affect muscles, skin, brain meninges and liver
muscles can be problematic if heart muscle affected or breathing muscles affected
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Term
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Definition
transmitted fecal oral route (poor hygeine)
four outcomes: asymptomatic infections (90%), abortive polio, non paralytic polio, paralytic poliomyelitis |
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Term
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Definition
minor illness
5% infections
3-4 days after, HV, fever, malaise, sore throat,
self limiting
recovery in days |
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Term
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Definition
1-2% infections
virus infects CNS and meninges causing back pain, muscle spasms and minor illness sx |
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Term
paralytic poliomyeltities |
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Definition
.1%-2% infections
after the minor illness, a viremia occurs and virus infects spinal cord (anterior horn cells), motor cortex of brain
paralysis is based on extent of neural infection
one or all the 4 extremities infected
paralysis may result in complete recovery, residual paralysis or death |
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Term
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Definition
severist form of paralytic poliomyelitis
involves muscles of pharynx, vocal cords, respiration, mortality 75%
iron lung chambers in the 1950s
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Term
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Definition
may occur later life (30-40 years later)
20-80% of original victims
deteroriation in neurons-original affected muscles
no poliovirus is detected in these indiv |
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Term
|
Definition
uses trivalent vaccine
includes serotypes: 1,2,3
killed-Salk inactivated vaccine (IPV)
Live-SAbine, live attenuated oral vacine (OPV)
in usa: only IPV is recommended
recommended at 4 doses at ages 2, 4, 6-18 months and at 4-6 years |
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Term
|
Definition
the WHO currently pursuing a global eradication strategy for poliomyelitis
in 2010, there were 1300 cases worldwide
in 2011, 650, and in 2014, 358
endemic countries include pakistan, afghanistan, and nigeria
most of the world is now free of polio
traveller's vaccine? |
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Term
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Definition
incluces coxsackie A and coxsackie b |
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Term
|
Definition
self limiting, no specific treatment
includes herpangina and hand foot and mouth disease |
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Term
|
Definition
vesicular lesions in throat region, fever, sore throat |
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Term
hand-foot-and-mouth disease |
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Definition
vesicular lesions on hands, feet, mouth, and tongue |
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Term
|
Definition
pleurodynia (Bohnholms disease)
myocardial and pericardial infections |
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Term
pleurodynia (bohnholms disease)
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|
Definition
severe pleurtic chest pain (4 days)
fever
vomiting |
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Term
myocardial and pericardial infections |
|
Definition
cardiomegaly
hepatomegaly
tachycardia
fever
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Term
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Definition
|
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Term
|
Definition
ssRNA negative sense, bullet shaped and is the most important human pathogen in the gamily
zoonotic infection-no spread human to human
reservoir=wild animals, unvaccinated dogs/cats
major source is saliva in bite/lick of rabid animal (ex dog bites and teeth put saliva in bone)
minor source is aerosols in bat (rabid) caves |
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Term
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Definition
raccoon bats skunks
dog cat cattle |
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Term
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Definition
virus inoculated
viral replication in muscle
virion enters peripheral nervous system
replication in dorsal ganglia
rapid ascent in spinal cord
infec of spinal cord, brain stem, cerebellum, and other brain struc
can take a year to set in
while asymptomatic can be vaccinated to offset
doesn't like to grow anywhere but nerves
can do swallow test to see if in brain and if those nerves infected |
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Term
|
Definition
long incubation period: weeks, months, during which virus replicates
prodrome stage (2-10 days): virus infects peripheral nerves and travels via spinal cord to brain
neurologic stage: 2-10 days virus spreads to eyes (cornea), salivary glands, skin, and other organs, hydrophobia, seizures, disorientation, hallucination
comatose stage and death: the neurologic stage almost always leads to death due to neurologic and respiratory failure
once sx appear-universally fatal |
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Term
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Definition
once the neuro sx begin, death inevitable and intervention no longer useful
lab tests to confirm clinc dx in px or if animal was rabid (post mortem)
viral antigen detection by immunoflourensce in brain or skin biopsy materail is widely used in animals
ELISA assays are also used for ex to check the vaccination status of an indiv
rabies case was found in toronto from domicican in 2012 |
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Term
post exposure rabies treatment and prophylaxis |
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Definition
1.wash wound immed w/ soap and water
2.immunize w/ vaccine (one arm) in combo w/ admin of one dose of human rabies immunoglobulin (HRIG) in other arm
passive immunization (HRIG) provides antibodies until px produces antibodies in response to vaccination
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Term
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Definition
vaccine made in human diploid cells (HDCV) and virus is chem inactivated (also can be made in chick cells) (PCECV)
current vaccine is safe and effective
post exposure vaccine
HDCV is admin IM on day of exposure, and then on days 3, 7, 14, (+RIG, dO)
pre exposure vaccine: days 0, 7, 21/28 (no RIG) |
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Term
prevention of human rabies |
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Definition
1.key to prevention in humans is effective control of rabies in domestic (all cats and dogs must be vaccinated) and wild animals
2. a live recombinant vaccina virus vaccine expressing rabies virus G protein (envelope spike) is approved for use w/ wild animals
vaccine is injected in a bait and parachuted into forest, successfully immunized raccoons, foxes and other wild animals |
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Term
|
Definition
rotavirus
many viruses cause diareha
rota viruses are the major cause of infantile diareha worldwide
noroviruses (calcivirus) are major prob for older children and adults (cruise ships)
rotaviruses have an 11 segment dsRNA genome are relativeley stable at room temp and a wide range of pH in GI tract |
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Term
|
Definition
human disease is causes by group A and occasionally by group B and C rotaviruses
wheel shaped disease
transmission fecal-oral route
replication in epithelial cells of small intestine preventing the absorption of water and thus causing watery diareha
in undernourshed children-risk of dehydration and death (developing countries)
about 3m cases in the us prevaccine |
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Term
clincial syndrome rotaviruses |
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Definition
incubation period- 24-48 hours
major clincial sx are fever, vomiting, diarrhea and dehydration
large amounts of viruse released in stool
about 5 mill deaths worldwide (dehydration)
US: 2.7 mill cases about 50 deaths before vaccine
dx: commonly used techniques:
1. detect viral antigen in patients stool sample by enzyme immunoassay (ELISA)
2. PCR on stool sample |
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Term
rotavirus treatments and vaccines |
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Definition
general tx: supportive therapy, rehydration kits to replace fluid/salts
vaccines: recommended (US); WHO now recommends worldwide:
1.rotarix-human live monovalent (2,4 mo) 2. rotateq-bovine live pentavalent (2,4,6 mo)
control:wash hands and isolate known cases |
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Term
Emerging and reemerging viral dx |
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Definition
defined as infections that have newly appeared (ex HIV) in a pop or have existed but are rapidly inc in incidence or geographic range (ex denge)
global resurange in zooinotic viral diseases (transmitted by animals to humans). about 75% of emergin agents are zooinotic |
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Term
specific factors contributing to emerging an remerging dx |
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Definition
speicifc factors precipitating disease emergence can be identified in virtually all cases such as
ecological/enviro: interaction b/w organisms and their natural environment ex: farm animals and swine flu
demographic: populations that may be at increased risk of contact with previously unfamiliar agent or its natural host to promote dissemination ex-air travel now common but wasnt in past |
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Term
factors contributing to dengue virus, west nile, SARS |
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Definition
transportation/travel, urbanization, migration |
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Term
factors contributing to malburg virus |
|
Definition
importation of monkeys to malburg germany from jungle
no cases in USA as of yet |
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Term
Hantavirus contributing factors |
|
Definition
enviro changes in USA
in S korea, inc contact w/ rodent hosts (expansion or rice fields-rodent area) |
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Term
factors contributing to HIV/AIDS |
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Definition
travel, sexual transmission, IV drug use, congential
horizontal and vertical factors |
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Term
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Definition
many of these viruses are dangerous and need containment
BSL4 highest level
BSL3 bad but not as dangerous
need hazmat suits |
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Term
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Definition
memeber of paramyxovirdidae (neg sense RNA (compliment to mRNA) genome) (like measles virus)
first reported in malaysia in 1999
outbreak of fatal febrile encephalitis and respiratory illness in older men
remerged in bangladesh in 2001 w/ high mortality rate
reservoir-fruit bat
transmission is humans via intermediate host, pig or pig products
human to human |
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Term
clincial symptoms of nipah virus infection
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|
Definition
incubation period of 3-14 days
followed by drowsiness and disorientation and mental confusion
some paitients may experience respiratory illness during this stage (can get into lungs)
encephalitis can progress to coma and death w/in 1-2 days
also causes serious disease in pigs
no vaccine and ribavin generic antiviral can decrease mortality a little bit |
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Term
dengue and west nile viruses |
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Definition
both belong to family flavivirdae (most of which are arboviruses (arbo=insect, transmitted by insects)
ssRNA (Pos sense) viruses, replication sim to poliovirus
transmission via various birds and animals (reservoirs) w/ mosquito vectors
no vaccine
no antiviral agents
look like small non descript round |
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Term
Transmission of flaviviruses |
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Definition
st louis-west nile
transmits bidirectional culex mosquito and only to humans (we don't make enough virus to get back to the mosquito)
dengue (yellow fever) goes primate to mosquito and Aedes mosquito and back (jungle cycle); also goes aedes mosquito to human and back (urban cycle) |
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Term
|
Definition
first observed in 1780 asia, africa, and north america (southern US)
a very commone dx worldwide that is remerging as mosquitos (vector) spread (300 mill people every-pop of entire US)
reservoirs of dengue virus are humans and primates
clin sx are dengue fever (febrile rash) and dengue Hemorhaggic fever (DHF) or shock syndrome DSS
first mosquito/strain gets you the rash and a second strain/mosquito gets you the second (DSS or DHF)
DHF and DSS are serious illness that occur when ppl get infected serially w/ 2 diff strains (high mortality)
prevention: avoid mosquitos |
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Term
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Definition
in the 1930s, dengue was pretty widespread in south american and southern US
disappeared in 70s because of DVT but was taken off market because of enviro problems
now widespread again because we never found a replacement for DVT and also people cutting down the rainforest are moving into to mosquito areas |
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Term
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Definition
1999 birds were falling out of the air dead and disease spread rapidly in a month |
|
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Term
|
Definition
first case in 1937 in west nile district of uganda
since spread worldwide-africa, europe, middle east, and nyc in 1999
believed infected birds were smuggled in from middle east
spread to all lower 48 states in US as well as canada and mexico in several years since
clincial sx are encephalitis (fatal in elderly), no human to human since level virus low
no vaccine low
most infections asymtomatic |
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Term
|
Definition
family: bunyavirdae
virus: ssRNA (- sense) 3 segments
first isolated from field mouse in koreas hantaan river
causing hemorrhagic fever w/ renal syndrome (HFRS) w/ up to 10% case/fatality; virus spread directly from small animals through inhalation of dried fecal material and urine
since that time, the virus has causes HFRS in ASia and europe
four corners dx was this in the US in 1993 |
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Term
id of mystery illness of 1993 |
|
Definition
new strain of hantavirus-sin nombre virus and the dx is called hantavirus pulmonary syndrome (HPS)
reservoir: small mammals (mice and rats)
transmission: respiratory route by inhalation of virus present in the excreta (feces, urine, respiratory secretions from infected animals)
human to human transmission not documented in USA |
|
|
Term
clinical sx of hantavirus pulmonary syndrome |
|
Definition
incubation period is 1-5 weeks
early sx-fatigue, fever, muscle aches, headache and vomiting
late sx-4-10 days later-coughing, shortness of breath and severe respiratory depression that kills w/in hours
high rate of mortality (15-50%), depending on the virus strain
antiviral agent-none
vaccine-hantavax developed in USA but not approved by FDA |
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Term
|
Definition
snow in sierras led to increase in the deer mouse population |
|
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Term
|
Definition
there are major annual outbreaks in china of hemorrhagic fever w/ renal syndrome caused by hantaviruses
major virus is hantaan virus |
|
|
Term
ebola and marburg viruses |
|
Definition
family: filoviridae (long thread like particles)
ebola first emerged in the 70s near ebola river in Zaire
marburg virus appeared in marburg, germany in 1967-monkeys from uganda
outbreaks in africa on a regular basis-killing several 100 people both cause hemorrahagic fever in africa, both viewed as excellent bioweapon agents
reservoir: fruit bat
transmission repiratory or fecal oral, human to human efficient
clin sx: early flu illness, later hemorrhagic lesions on various organs w/ extensive internal bleeding mortaltity rate very high
no vaccine or antiviral |
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|
Term
ebola and marburg outbreaks |
|
Definition
there viruses have been recogonized for about 40 years but are liklely to be more ancient
on a regular basis outbreaks of both viral dx have occured in central africa
ebola>marburg
both cause highly fatal hemorrhagic fever
in 2014 a major outbreak of ebola spread to several countries in west africa
march 2015: liberia now ebola free but sierra leone and guinea still problematic
about 14k cases total and 10k deaths |
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|
Term
summary ebola and marburg viruses |
|
Definition
reservoir fruit bat; person to person
3 day to 3 week incubation period
fever, severe headache, muscle pain, diarehha, vomitting, hemorrhagin
case/fatality rate is 60-80%
if you recover, you are protected |
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Term
|
Definition
an alphavirus
causes fever, joint and muscle pain, rash
rarely fatal but often chronic
major indian outbreak
2500 cases in USA in 2014
25000 cases in the caribbean in 2014
mosquito borne |
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