Term
Into which family and genus does the measles virus fall into? |
|
Definition
Considered a "new" virus of human, it falls in the morbillivirus genus of Paramyxoviridae family. |
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Term
How is measles differentiated from other paramyxoviruses? (others we've studied= RSV, hPIV, Metapneumo) |
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Definition
lacks neuraminidase activity (has H protein rather than HN) and forms intracellular inclusion bodies |
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Term
Is measles + or - strand? |
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Definition
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Term
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Definition
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Term
Is rubella + or - strand? |
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Definition
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Term
How is measles the same as other paramyxoviruses? |
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Definition
same replication strategy and similar to all non-segmented, negative strand RNA viruses |
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Term
How is measles different from other paramyxoviridae? |
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Definition
Receptor usage: primary MV receptors are CD46 and SLAM; measles has H protein; forms intracellular inclusion bodies (dstinctive feature of cytopathology) |
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Term
What is the required population size of measles? |
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Definition
> 100,000; reservoir of susceptible individuals |
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Term
What was the avenue of transmission (historically) for measles? |
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Definition
trade between China, Europe, India, Middle East (massive epidemics in 2nd, 3rd, 4th centuries) |
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Term
What are the 3 steps of entry and replication of measles virus? |
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Definition
MV binds to receptor (CD46; SLAM/CDw150); binding activates F protein which causes membrane fusion (virus entry); replication and virus assembly is simlar to that of other negative strand RNA viruses |
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Term
What receptor does the vaccine strain of Measles virus use? |
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Definition
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Term
What does SLAM stand for (measles virus receptor)? |
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Definition
WT MV= SLAM= signaling lympohcyte activation molecule |
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Term
What is the pathogenesis of measles? |
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Definition
highly contagious; typically a childhood infection; spread via respiratory route; has a latent period and a prodrome that is followed by the characteristic maculopapular rash |
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Term
How long is the latent period in measles? |
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Definition
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Term
How long is the prodrome period of measles and what occurs during that period? |
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Definition
2-3 days of fever, cough, conjunctivities (followed by rash) |
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Term
What is the characteristic feature of measles? |
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Definition
appearance of maculopapular rash after prodrome symptoms |
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Term
What is mortality mainly due to in measles? |
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Definition
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Term
What does the measles rash coincide with (immunologically)? |
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Definition
T cell response and virus clearance (CD4 response peaks around 12 days, CD8 response around 15 days, IgM around 16 days; IgG climbs starting around 19 days)- see chart in prestudy notes |
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Term
What is the clinical case definition of measles? |
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Definition
Generalized rash lasting > 3 days; temperature >38.3°C (101°F); cough and/or rhinorrhea and/or conjunctivitis |
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Term
Should you report measles-like symptoms to MMWR/state health dept? |
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Definition
If patient with symptoms is epidemiologically linked ot another confirmed/probably case of measles, then YES |
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Term
What occurs during the early stage of measles infection? |
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Definition
Initially: virus replication restricted to tracheal and bronchial epithelium/ After 2-4 days: infection spreads to lymph nodes |
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Term
What does measles replication in lymphoid tissue result in? |
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Definition
appearance of lymphoid or reticuloendothelial giant cells--> AKA Warthin-Finkeldey cells |
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Term
What are Warthin-Finkeldey cells? |
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Definition
lymphoid/reticuloendothelial giant cells found in early stages of measles |
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Term
What does amplification in lymph nodes in measles lead to? |
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Definition
Viremia and infection of other tissues and organs |
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Term
When do symptoms of measles occur? |
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Definition
soon after onset of viremia |
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Term
When is patient infectious in measles? |
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Definition
1-2 days before symptoms occur (10-20 days following exposure) |
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Term
What are the symptoms of measles? |
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Definition
maculopapular (or morbilliform) rash and Koplik spots |
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Term
What is the measles rash a result of? |
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Definition
infection of dermal endothelial cells followed by spread to overlying epidermis |
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Term
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Definition
small red spots (typical to Measles) with blue-white centers on inside of upper lip and cheek; often seen BEFORE the rash |
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Term
What are some measles virus complications? |
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Definition
immune suppression during measles virus infection; postinfectious encephalomyelitis (PIE); measles inclusion body encephalitis (MIBE); and subacute sclerosing panencephalitis (SSPE) |
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Term
What happens during immune suppression in measles virus infx? |
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Definition
suppression of delayed type hypersensitivity skin test responses; antibody and cellular immune responses to new antigens are also impaired (see graphs in p2 of notes- it looks like reactions return as symptoms subside) |
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Term
How long does immune suppression last in measles? |
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Definition
DTH is suppressed from before onset of rash and continues for approx 1 month; Ab and cellular immune response to new Ag also impaired |
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Term
Why is there an impairment of Ab production and cellular immune response in measles? |
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Definition
infection of monocytes and other immune effector cells (probably) are the primary cause of measles virus-induced immune suppression |
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Term
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Definition
aka autoimmune demyelinating disease; associated with an immune response to myelin basic protein; mechanism for induction is not known |
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Term
What occurs with MIBE and SSPE? |
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Definition
result from establishment of persistent infections in the brain; mechanism of entry to CNS is not understood |
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Term
What is the timeline for the measles virus complications? |
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Definition
PIE may overlap somewhat with the rash, peaks at 21 days, and subsides after a month; MIBE begins around 1 month, peaks around 4-5 months, and subsides by 9 months; SSPE begins around 3 years and subsides around 12 years |
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Term
Inclusion body encephalitis: host? Typical age? MV in brain? Incidence? Pathology? Time course? |
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Definition
Immunosuppressed host, any age, MV in brain, incidence unknown, inclusion bodies, progressive over months |
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Term
Postinfectious ecephalomyelitis: host? Typical age? MV in brain? Incidence? Pathology? Time course? |
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Definition
normal host, >2 years, no MV in brain, 1:1000 cases, inflammation and demyelination, monophasic over weeks |
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Term
Subacute sclerosing panencephalitis: host? Typical age? MV in brain? Incidence? Pathlogy? Time course? |
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Definition
normal host, < 2 years, MV in brain, 1:106 cases, inclusion bodies and inflammation, progressive over years |
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Term
How do we prevent measles? |
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Definition
currently use a live-attenuated measles virus vaccine; provides "life-long" protection |
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Term
When are children vaccinated against measles? |
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Definition
use trivalent MMR at 12-15 months (can be earlier but not before 6 months); 2nd dose at 4-6 years; given SubQ |
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Term
What is an important characteristic of measles and mumps viruses (in terms of immunity)? |
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Definition
antigenically stable monotypic viruses; immune for life once recovered from measles (immune against all strains b/c neutralizing antibody to one strain will protect an individual against all currently circulating strains) |
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Term
Why a recent resurgence in measles virus? |
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Definition
dramatic increase from 1989-1991 and additonally in 2001, 2008, and 2011; 2001 and 2008 resurgence due to low vaccine coverage (parents refusing to vaccinate…he does not give explanations for resurgences in other years) |
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Term
MMR vaccine and autism???? |
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Definition
no scientific evidence of MMR vaccine causing vaccine!!! |
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Term
How are different measles strains defined? |
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Definition
amino acid differences in H or HN proteins |
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Term
Why are measles an ideal candidate for eradication through immunization (like mumps)? |
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Definition
only one serotype; most cases are clinically identifable; no animal reservoir; "herd immunity" is required (eradication=at least 98% of population is immune) |
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Term
What have been the resutls of the international vacciation campaign? |
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Definition
initiated in 2001 and seen global deaths from measles drop 50% |
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Term
Why should people who were vaccinated against MMR in 1963 and 1967 get revaccinated? |
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Definition
their inactivated vaccine was not effective; they should be revaccinated with live, attenuated dose |
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Term
What are factors limiting vaccination for measles? Aka what are the contraindications for vaccination? |
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Definition
anyone who has had a life-threatening allergic rxn to gelatin or neomycin; those who are moderately or severely ill at time of vaccination (wait until recovered); pregnant women (do not get pregnant until at least 4 weeks after vaccination); anyone on immunosuppressive drugs or immunocompromised for other reasons |
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Term
What family/genus is mumps a member of? |
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Definition
rubulavirus genus of Paramyxoviridae family |
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Term
Is mumps as infectious as measles? |
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Definition
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Term
What is the pathogenesis of mumps? |
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Definition
initially affects nasal mucosa and upper respiratory tract epithelium, incubates approx 18 days, spreads to draining lymph nodes, virus sheds in saliva for approx 6 days before onset of clinical disease |
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Term
What are the first clinical signs of mumps? |
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Definition
infection of parotid gland- 95% of all symptomatic cases |
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Term
What do mumps complications include? |
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Definition
CNS involvement: aseptic meningitis , deafness- approx 1/2 of mumps infections result in some virus replication in CNS |
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Term
How long does it take for aseptic meningitis caused by mumps to resolve? |
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Definition
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|
Term
How is deafness caused by mumps? |
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Definition
infection of cochlea (1/20,000) |
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Term
What are some other mumps complications? |
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Definition
symptomatic gonadal involvement ("orchitis") in post-pubertal men; correlation of mumps and type I insulin-dependent diabetes; myocardial invasion; high incidence of featal wastage leading to spontaneous abortion if contracted during 1st trimester of pregnancy |
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Term
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Definition
live-attenuated vaccine: safe, effective, few adverse effects |
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Term
What type of virus is Rubella? (genus, family, RNA or DNA, +/- strand, small or big, enveloped or not, segmented or not) |
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Definition
Togaviridae; genus Rubivirus; RNA, + strand, small, enveloped, nonsegmented |
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|
Term
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Definition
A genus of Togaviridae; Western equite encephalitis, EEE, VEE viruses; all are arthropod-borned viruses |
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|
Term
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Definition
Rubella is the only member of this genus that is part of Togaviridae; distiguished from alphaviruses by its limited host range (humans) |
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Term
In the rubella replication cycle, how does the virus enter the host? |
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Definition
enters by receptor-mediated endocytosis and viral envelope fuses with endosomal membrane in a pH-dependent manner |
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Term
In the rubella replication cycle , how is the viral polymerase translated? |
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Definition
genome serves as mRNA for translation of viral polymerase; polymerase synthesizes a negative strand antigenome (replicative intermediate) |
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Term
What is the negative sense antigenome use for (in rubella virus)? |
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Definition
used as a template to synthesize subgenomic mRNA encoding viral capsid and envelope proteins (as polyprotein) AND more full-length, positive strand genomic RNA (progeny) |
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Term
How is rubella transmitted? |
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Definition
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Term
Where does rubella virus replicate? |
|
Definition
initially in mucosa of upper respiratory tract and nasopharyngeal lymph nodes |
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Term
What are the 4 things to know about rubella virus replication? (from picture in slideset) |
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Definition
enters cell by receptor-mediated endocytosis; genome serves as mRNA; polymerase made first; negative strand antigenome is used as template for both progeny genomes and subgenomic mRNA, which encodes the viral capsid and envelope proteins |
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|
Term
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Definition
mild disease- low grade fever, occasional conjunctivitis, sore throad, lymphadenopathy, morbilliform rash (starts on face and spreads to rest of body) |
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Term
After exposure to rubella, what is the incubation period like, and when does virus shedding begin to occur? |
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Definition
7-9 days before virus appears in serium at which point shedding occurs and can be isolated from nasopharynx and stool |
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Term
When does rubella rash begin? |
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Definition
16-21 days after initial exposure |
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Term
Does rubella virus shed after rash disappears or does it stop? |
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Definition
IMPORTANT: virus continues to shed after rash disappears and can be shed for up to a month after initial exposure (go look at chart) |
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Term
Where are rubella's most devastating effects seen and what are highest risks? |
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Definition
fetuses (congenital birth defects aka congenital rubella syndrome): highest risk during 1st and 2nd trimester- usually after 2nd trimester, no CRS (though it has been reported); often spontaneous abortion if infx during 1st month |
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Term
What are the most common clinical manifestations of maternal fetal infx with rubella if fetus is carried to term? |
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Definition
mental retardation, motor disabilities, hearing loss, congenital heart disease, cataracts |
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Term
Are there antiviral treatments for rubella? |
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Definition
no- not necessary b/c disease is mild |
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Term
When was rubella vaccine introduced? |
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Definition
first licensed in 1969 with relatively low incidence in the US since then; epidemics used to occur every 3-9 years |
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|
Term
What is rubella vaccine directed towards (in terms of protective purposes)? |
|
Definition
protecting fetus from infx and NOT b/c of disease caused in children or adults (mild disease) |
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|
Term
Why is the MMR vaccine such a success? |
|
Definition
all 4 viruses are monotypic (one serotype) and humans are only known reservoir |
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Term
Which genuses (geni??) are included in Family Parvoviridae? |
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Definition
Genus parvovirus (ex: Parvovirus B19) and genus dependovirus (ex: adeno-associated virus) |
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Term
What is the structure of parvoviridae? |
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Definition
linear, single-stranded DNA (5.6 kilobases); icosahedral capsid; no envelope |
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Term
Are parvoviridae +/- stranded? |
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Definition
Equal number of progeny contain either positive or negative strand |
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Term
Where does replication and assembly occur in parvoviridae? |
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Definition
nucleius or rapidly dividing cells (provide replication function); note that Parvovirus have autonomous replication while dependovirus require a helper virus |
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Term
What does Parvo B19 cause? |
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Definition
erythema infectiosum (mild, common childhood rash) |
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Term
How much of the adult population is seropositive for ParvoB19? |
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Definition
50% seropositive; conversion usually after school age; antibodies offer protective immunity |
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|
Term
|
Definition
via direct contact with respiratory secretions, occurs prior to rash |
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Term
Describe the pathogenesis of Parvo B19. |
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Definition
Biphasic: 4 out of 5 will show symptoms; initial viremia may be associated with flu-like symptoms; 2nd phase= rash; symptoms are immune-mediated |
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Term
What are the 2 phases in the pathogenesis of B19? |
|
Definition
lytic, infection phase AND noninfectious, immunologic phase |
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Term
What happens during the lytic/infection phase of B19? |
|
Definition
post incubation; decreased reticulocyte and hemoglobin levels; viremia; virus in throat; virus-specific IgG antibody present (starting around day 12) non-specific flu-like symptoms (fever, headache, chills, myalgia); virus is hard to isolate from any site after this time |
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Term
What happens in noninfectious, immunologic phase of B19? |
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Definition
decreased reticulocyte and hemoglobin levels; virus-specific IgG antibody present; rash/arthralgia (erythemia infectiosum |
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Term
What is the "fifth disease?" |
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Definition
erythema infectiosum: characteristic "slapped cheek" rash; lacy red rash on trunks and limbs (called the 5th disease b/c there are at least 4 other childhood rashes caused by viruses) |
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Term
What are characteristics of erythema infectiosum? |
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Definition
"slapped cheeck" rash; lacy red rash on trunks and limbs; resolves in 7-10 days; joint pain or swelling (polyarthritis), flu-like symptoms, less rash in adults |
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Term
What does Parvo B19 cause in sickle cell patients and how? |
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Definition
transient aplastic crisis: B19 infects and lyses erythroid precursor cells; results in loss of RC production during infx (7-10 days); shortened life span of RBC in sickle cell patients cannot tolerate absence of precursor pool, results in severe anemia |
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|
Term
What happens to immunocompromised patients in B19? |
|
Definition
may develop chronic anemia |
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Term
Can B19 be transmitted to fetus during pregnancy? |
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Definition
yes, transplacentally, but most infx are not a concern;5% can result in severe fetal anemia, hydrops fetalis, or miscarriage (most common during 1st half of pregnancy) |
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Term
How do you diagnose Parvo B19? |
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Definition
apperance of rash (can be confused with rubella); serological and viral DNA testing of blood |
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|
Term
How do you treat Parvo B19? |
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Definition
treat flu-like symptoms and itchy rash; blood transfusion for anemic patients |
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Term
How do you prevent Parvo B19? |
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Definition
difficult to do so b/c infectious period begins before rash; no vaccine; general hygient practices |
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Term
What viruses are included under family Poxviridae? |
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Definition
Genus orthopox (Variola virus=smallpox, vaccinia virus-smallpox vaccine); Genus parapox; unclassified agent of molluscum contagiosum |
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Term
What is the structure of the Poxviridae family? |
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Definition
non-icosahedral, complex (brick-shaped) structure; can actually be seen under light microscope |
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Term
Is the Poxiviridae enveloped? |
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Definition
intracellular has core and lateral bodies surrounded by envelope; extracellular virus has additional envelope |
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Term
What type of genome does Poxviridae have? |
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Definition
large, double-strand linear DNA genomes that are complexed with proteins |
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Term
Where does replication of Poxviridae occur? |
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Definition
cytoplasmic replication (transcription, dNA synthesis, assembly) |
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Term
How does Poxviridae replicate in cell? |
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Definition
virus enters cell, releasing core particle into cytoplasm (uncoating I); core particle contains virus encoded DNA-dependent RNA polymerase, capping and methylating enzymes, and polyA polymerase; early proteins lead to copmlete uncoating (uncoating II); late transcripts and protein (structural proteins and virion enzymes) are produced in cytoplasm leading to virus assmebly in cytoplasm- virus factories; most virions remain intracellular with membrane derived de novo; "crescents" with no detectable contacts with existing membranes begin to envelope core structures; about 1% derive a 2nd envelope from Golgi membrane and are released from cell (extracellular enveloped virus= EEV) |
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Term
Where does mRNA synthesis occur in Poxviridae? |
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Definition
a round of early mRNA synthesis proceeds in the core; mRNAs travel to cytoplasm and are translated |
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Term
What do early proteins in Poxviridae replication do? |
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Definition
lead to complete uncoating: release DNA into cytoplasm; DNA replication begins in cytoplasm |
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Term
What are the pertinent infectious agents of Poxviridae in the real world? |
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Definition
extracellular enveloped viruses (EEVs) |
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Term
Which 2 Pox viruses specifically cause human disease? |
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Definition
only 2: variola (smallpox, eradicated in 1977) and agent of molluscum contagiosum (nodular skin lesions) |
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Term
What Pox viruses CAN cause human disease? |
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Definition
cowpox lesions on milker's fingers, for example |
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Term
What is the modern day Pox prototype and what is it used for? |
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Definition
vaccinia- a lab strain with no known natural reservoir and used for smallpox vaccination |
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Term
What are the 2 basic forms of smallpox and what is the fatality rate? |
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Definition
variola major (25% fatality) and variola minor (1% fatality) |
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Term
Is smallpox systemic or localized? |
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Definition
systemic with generalized rash |
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Term
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Definition
inhalation (release from ruptured mouth lesions) |
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Term
What occurs in the prodrome for smallpox? What follows? |
|
Definition
high fever, malaise, body aches, viremia; followed by small red spots in mouth and on tongue |
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Term
When is patient most contagious in smallpox? |
|
Definition
when small red spots on mouth and tongue rupture |
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Term
What happens after 2nd viremia in smallpox (aka toxemic phase)? |
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Definition
infected macrophages migrated to epidermis, causing lesions (toxemic phase)- initial skin lesion is a raised bump that has a depression in middle; bumps become pustules that feel as if a BB pellet is inside; pustules will scab over, leading to pitted scars; patients is contagious until last scab falls off |
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Term
How does smallpox conclude? |
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Definition
death or recovery (accompanied by complete clearance of virus) |
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Term
How do you distinguish smallpox from chickenpox at initial appearance? |
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Definition
febrile prodrome (chickenpox does not); firm, well-defined lesions, may develop a pit aka "umbilicated" (chicken pox lesions are superficial); lesions on a given body part will be in the same stage (chickenpox lesions at different stages) |
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Term
What forms are there of molluscum contagiosum? |
|
Definition
2 forms- childhood and young adulthood form |
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Term
Describe the chilhood form of molluscum. |
|
Definition
lesions on face, trunk, limbs; spreads by direct skin-to-skin contact; mostly tropical |
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|
Term
Describe the adulthood form of molluscum. |
|
Definition
mostly lower abdomen lesions; sexually transmitted |
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|
Term
How long does it take for molluscum lesions to disappear? |
|
Definition
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|
Term
How is molluscum diagnosed? |
|
Definition
apperance of lesions and confirmed by large cytoplasmic inclusions in eosinophils of affected area |
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|
Term
What is the history of smallpox vaccine? |
|
Definition
Jenner's cowpox starting in 1798; by 1950s, vaccinia had replaced cowpox |
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|
Term
What is the vaccine for smallpox like? |
|
Definition
live vaccine; can protect up to 3 days postexposure and up to 7 days can lessen severity; effectiveness wanes after 3 years and completely gone by 20 years |
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|
Term
How do you inoculate for smallpox? What happens? |
|
Definition
inoculate in epidermis, produces a localized lesion that heals within 2 weeks |
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|
Term
What 4 key features allowed eradication of smallpox by 1977? |
|
Definition
humans were only reservoir; no healthy carriers (virus was eliminated upon recovery); no sub-clinical infections, so cases were readily identified; effective vaccine available |
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|
Term
Are there adverse reactions to smallpox vaccine? |
|
Definition
vaccinia is our least safe vaccine:you must screen high-risk people but non-life threatening and life-threatning complications may occur |
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|
Term
Who should not receive the smallpox vaccine? |
|
Definition
pregnant/breast-feeding women; immunocompromised people (whether due to heredity, cancer tx, organ transplant, AIDS); those with eczema, atopic dermatitis, severe acne; non-emergent situations for those under 18 years, heart disease patients |
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|
Term
What are some non-life threatening complications of smallpox vaccine? |
|
Definition
generalized vaccinia, inadvertent inoculation, erythema multiforme (allergic skin rash) |
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|
Term
What are life-threatening complications of smallpox vaccine? (increasing order of frequency) |
|
Definition
progressive vaccinia (associated with CMI defects); postvaccinal encephalitis (autoimmune response?? 30% death rate); eczema vaccinatum (can lead to shock, death); myopericarditis or heart attack |
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|
Term
What can you use to treat smallpox vaccine complications? |
|
Definition
vaccinia immune globulin (VIG) or Cidofovir |
|
|
Term
Even with screening, for every 1 million vaccinees: |
|
Definition
50-1000 will suffer severe adverse reactions; 15 will suffer life-threatening complications; 1-3 will die |
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|
Term
What happens when sores in mouth break down during smallpox? |
|
Definition
rash appears on skin (face to extremities)- all parts of body within 24 hours; fever usually falls as rash appears (person feels better) |
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|
Term
By 3rd day of rash in smallpox? |
|
Definition
rash becomes raised bumps |
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|
Term
By 4th day of rash in smallpox? |
|
Definition
bumps fill with thick, opaque fluid, often with a depression at center- a MAJOR DISTINGUISHING CHARACTERISTIC OF SMALLPOX; fever often rises again at his time |
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|
Term
What is the pustular rash in smallpox? |
|
Definition
raised bumps following rash become pustules (sharple raise, round and firm); lasts about 5 days; CONTAGIOUS |
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|
Term
What happens after the pustules in smallpox? |
|
Definition
form a crust and then scab; by end of 2nd week after rash starts sores have scabbed over; this stage lasts about 5 days; CONTAGIOUS |
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|
Term
Discuss the "resolving scabs" in smallpox? |
|
Definition
This phase lasts about 6 days; scabs fall off, leaving marks on skin that become pitted scars; most scabs will have fallen off 3 weeks after rash appears; CONTAGIOUS UNTIL ALL SCABS HAVE FALLEN OFF |
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|
Term
When is person NOT contagious in smallpox? |
|
Definition
when scabs have completely resolved (all have fall off!!) |
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|
Term
When is person most contagious in smallpox? |
|
Definition
the early rash (about 4 days); hwen rash first emerges as small red spots on tongue and in mouth (spots develop into sores that break open and spread large amounts of virus into mouth and throat) |
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|
Term
What is structure of Family Papvaviridae (sub-families Papiloma, Polyoma, vacuolating virus SV40- monkey)? |
|
Definition
circular double-strand DNA genome (5-8 kilobase pairs) packcaged around a histone; non-enveloped icosahedral cells |
|
|
Term
What occurs during Papovaviridae replication in permissive cells? |
|
Definition
replication and assembly of progeny occurs in nucleus; virions are released by cell lysis |
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|
Term
What occurs during Papovaviridae replication in non-permissive cells? |
|
Definition
infection leads to transformation of cells; polyoma virus genome integrates into host chromosome (can lead to tumor formation) |
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|
Term
Polyoma viruses were the first viruses shown capable of transforming cultured cells in vitro. What are 2 transcriptional classes of genes in these viruses? |
|
Definition
Early genes encode three T antigens; late genes encode the structural proteins of the virion |
|
|
Term
What do the early genes that encode 3 T antigens do in Polyoma virus? |
|
Definition
needed to initate DNA replication; responsible for transformation (analogous to E6 and E7 of papilloma virus; small T and large T antigens are necessary to immortalize cells; small T and middle T antigens needed to transform cells) |
|
|
Term
What are the 2 known human polyoma viruses and what do they do in hamsters/mice? |
|
Definition
BK and JC viruses; shown to produce tumors in hamsters/mice (DNA from both can transform many non-human cell lines) |
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Term
Are BK and JC viruses oncogenic in humans? |
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Definition
NOT oncogenic in humans (permissive host); they are ubiquitous |
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Term
What is percentage of adult seropositivity of BK and JC? |
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Definition
> 80% adult seropositivity |
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Term
What is the percentage of seropositivity of BK and JC in US children? |
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Definition
BK: 50% of US children by age 3-4 years; JC: 50% of US children by 10-14 years; infection in healthy children is often subclinical! |
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Term
Where is the site of infection in polyoma virus and what occurs there? |
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Definition
respiratory or GI tract; initial replication |
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Term
What happens after initial replication of polyoma? |
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Definition
followed by viremia and passage to kidney, lung, or brain; viruses persistently infect the kidney |
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Term
Are polyoma viruses a problem in most adults? |
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Definition
no, only in immunodeficient hosts: AIDS and transplant patients |
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Term
Which polyoma virus isfound in urine of AIDS patients? |
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Definition
BK virus is found but no known disease |
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Term
What is the etiologic agent of progressive multifocal leukoencephalopathy (PML)? |
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Definition
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Term
What is PML?/What causes it? |
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Definition
progressive demyelinating disease of the CNS probably due to reactivated JC virus that makes its way to CNS and infects and lyses oligodendrocytes; occurs mid to late life |
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Term
What are symptoms of PML? |
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Definition
clumsiness, progressive weakness or speech problems in a matter of weeks |
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Term
How percentage of AIDS patients develop PML? |
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Definition
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Term
|
Definition
PCR amplification of JC virus DNA from CSF or brain biopsy; detection of white matter lesions by MRI |
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Term
What is the prognosis and treatment of PML? |
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Definition
in transplant patients: alter suppression chemotherapy but still 80% fatality rate within 6 months; in AIDS patients: effective HAART treatment can reduce fatalities to 50% |
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Term
What is the structure of Herpesvirus? |
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Definition
icosahedral capsid surrounded by lipid envelope that contains about a dozen virus-encoded glycoproteins |
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Term
What is the genome of Herpesvirus? |
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Definition
linear, double-stranded DNA (150-250 kilobase pairs) |
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Term
Where does the genome of herpesvirus replicated? Where does the virus assemble? |
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Definition
replicated and assembled in the nucleus |
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Term
Are herpesvirus infections self-limiting or life-threatening? |
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Definition
generally: self-limiting in which primary infection is often asymptomatic; life-threatening: especially in immune compromised hosts |
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Term
What are the alpha herpesvirinae? |
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Definition
neurotropic for latency, aggressive lytic growth; HSV-1, HSV-2, varicella-zoster virus (VZV) |
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Term
What are the beta herpesvirinae? |
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Definition
lymphotropic for latency, more insidious; CMV, human herpesvirus-6 (HHV-6), HHV-7 |
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Term
What are gamma herpesvirinae? |
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Definition
lymphotropic for latency, more insidious; Epstein-Barr, HHV-8 (Kaposi's sarcoma associated herpesvirus) |
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Term
What does a primary infection of varicella zoster virus cause? |
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Definition
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Term
What is the epidemiology/pathogenesis of varicella zoster? |
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Definition
highly communicable, spread by respiratory secretions, primarily spread in late winter and early spring |
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Term
What are the symptoms of varicella zoster? |
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Definition
fever followed within a day by itchy rash starting on scalp and trunk; lesions appear for up to one week (children may return to school on 6th day after onset of rash); children feel fairly well; adult cases can be more serious (result in pneumonia) |
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Term
How is diagnosis of varicella zoster made? |
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Definition
mostly clinical, confirmed by ELISA |
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Term
How do you treat varicella zoster? |
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Definition
treat itchiness and aches with calamine lotion, acetaminophen (AVOID ASPIRIN); oral acyclovir; VZV Ig in adults; vaccine |
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Term
Describe the varicella accine and recommendations for it. |
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Definition
attenuated virus leading to latent infection; recommended as part of MMR childhood regimen |
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Term
What happens when varicella is reactivated? |
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Definition
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Term
How often does shingles occur? |
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Definition
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Term
Describe the onset of shingles. |
|
Definition
sudden onset of pain and varicella-like rash along thoracic dermatome; rash may last 2-4 weeks with pain lasting longer (postherpetic neuralgia) |
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Term
How do you treat shingles? |
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Definition
treat mostly for pain (steroidal); also oral acyclovir |
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Term
Who gets the zoster vaccine? |
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Definition
the new vaccine is for the immunocompetent elderly to reduce incidence/severity of zoster |
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Term
Where is CMV found (in the body)? |
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Definition
saliva, urine, breast milk, semen, cervical secretions, blood (transplanted organs) |
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Term
Describe CMV's contagiouness. |
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Definition
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Term
What is CMV like in low socioeconomic classes? |
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Definition
infection is at 1-2 years of age with up to 80% of adult population CMV+ |
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|
Term
What is CMV like in higher socioeconomic classes? |
|
Definition
usually scquired after 16 yaers of age and only about 50% of adult population is CMV+ |
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|
Term
Which populations are at risk for CMV? |
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Definition
neonates, day care workers, pregnant workers, gay men, immunocompromised patients (especially transplant patients; AIDS patients susceptible to retinitis, colitis, pneumonia) |
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Term
What is the pathogenesis of CMV? |
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Definition
infection through direct contact with secretions, not by aerosol; primary replication is in epithelial cells, followed by spread to lymphoid tissue, CMV latently infects B-cells where it causes large, puffed up lymphocytes |
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Term
What are the symptoms of neonatal CMV? |
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Definition
neonatal infx can occur in utero; most are asymptomatic but can result in retardation and deafness |
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|
Term
What the symptoms of adult CMV? |
|
Definition
asymptomatic though mononucleosis accompanied by fever can occur |
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Term
Who is especially at risk with CMV? |
|
Definition
immunocompromised hosts: most organ transplant patients get CMV infx with pneumonitis (most severe outcome about 1-4 months after transplant, preceded by fever); may be caused by CMV+ donor or by reactivation of CMV+ recipient; if you hear transplant patient, think CMV!!!! Also, AIDS patients prone to CMV retinitis, colitis, pneumonitis |
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|
Term
What can you do to help immunocompromised patients receiving a transplant (in regards to CMV)? |
|
Definition
prophylactic tx with CMV Ig and ganciclovir looks promising for limiting complications |
|
|
Term
|
Definition
ELISA; shell vial assay in which indirect immunofluorescence is used to detect an immediate early protein after 24 h of cell culture infx |
|
|
Term
|
Definition
ganciclovir, a guanosine analog similar to acyclovir, or ciofovir, a deoxycytidine analog |
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|
Term
What does ganciclovir require? |
|
Definition
as with ACV, requires phosphorylation by viral kinase; triphosphate form preferentially inhibits CMV polymerase but is more toxic to host than ACV |
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|
Term
What are the side efects of ganciclovir? |
|
Definition
neutropenia and GI tract bleeding |
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|
Term
For whom is ganciclovir approved? |
|
Definition
treatment of transplant patient infx, CMV retinitis tx in AIDS patients |
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|
Term
What else is approved for CMV retinitis in AIDs patients? |
|
Definition
|
|
Term
What is the MOA for cidofovir? |
|
Definition
competitive inhibitor of CMV (and HSV) DNA polymerase but does not require viral kinase action for activity |
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|
Term
What is cidofovir approved for? |
|
Definition
CMV retinitis tx in AIDS patients |
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|
Term
When does infection of Epstein-Barr occur? |
|
Definition
early age in low socioeconomic setting; adolescence and early adulthood in higher socioeconomic setting (may lead to infectious mononucleosis) |
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|
Term
How much of the adult population contains Ab to EBV? |
|
Definition
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|
Term
What can EBV cause in immunocompromised hosts? |
|
Definition
oral hairy leukoplakia in immunocomprosed hosts |
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|
Term
What is hairy leukoplakia? |
|
Definition
productive infection of tongue epithelial cells; rarely seen except in AIDS patients; treated with ACV |
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|
Term
What does EBV cause in some transplant patients? |
|
Definition
posttransplant lymphoproliferative disease (PTLD) |
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|
Term
With which lymphoma/carcinoma is EBV associated? |
|
Definition
Burkitt's lymphoma and nasopharyngeal carcinoma |
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|
Term
What is the pathogenesis of EBV? |
|
Definition
saliva by kissing with incubation period of 4-7 weeks; initial replication in oropharyngeal epithelium; spreads to lymphocytes then to liver and spleen; EBV remains latent in throat epithelium and B cells; oral shedding of virus occurs for many weeks |
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|
Term
What are the symptoms of EBV? |
|
Definition
most asymptomatic except infectious mononucleosis presents with sore throat, fever for 1-2 weeks, malaise, lymphadenopathy with uneventful recovery |
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|
Term
|
Definition
based on symptoms and presence of at least 50% atypical, large lymphocytes with lobulated nuclei; may also look for heterophil antibodies (Monospot test) |
|
|
Term
Explain the heterophil Ab (Monospot test). |
|
Definition
Ab agglutinate sheep RBC; not present in all patients and origin not understood; if present, will distinguish EBV mono from CMV mono |
|
|
Term
|
Definition
uncontrolled proliferation of B cells due to transformation by EBV and absence of CTLs to control them; highest risk in seronegative transplant recipients in their 1st year; treat by STOPPING immunosuppression (monitor for rejection; ACV not useful b/c infx is latent, virus not replicating) |
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|
Term
EBV and Burkitt's lymphoma |
|
Definition
neoplasm of B cells that affect bones of jaw; endemic in central Africa and New Guinea; associated with 3 factors: early EBV infx leading to latency, activation of c-myc, malaria; early detection allows cure rate of 80%; ouside of Africa, only 20% of BL patients have EBV genomes in tumor |
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|
Term
EBV and nasopharyngeal carcinoma |
|
Definition
neoplasm of epithelial cells; association with EBV is worldwide; high frequency in southern China: high salt diet is likely a cofactor; initial presentation is painless lump in neck; at best, only 60% of patients survive 10 years |
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|
Term
|
Definition
Hodgkin's lymphoma? Multiple sclerosis? |
|
|
Term
What does human herpesvirus-6 (HHV-6) cause? |
|
Definition
roseola (exanthem subitum) and acute febrile illness |
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|
Term
When does HHV-6 usuall infect? |
|
Definition
between ages of 6 months to 3 years |
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|
Term
How much of the US population has Ab to HHV-6? |
|
Definition
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|
Term
When do HHV-6 infections usually occur (what time of year)? |
|
Definition
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|
Term
|
Definition
not well worked out but incubation period is thought to be about 10-15 days |
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|
Term
What is the principal symptom of HHV-6? |
|
Definition
high fever (104°F or higher) |
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|
Term
What are the symptoms like in HHV-6? |
|
Definition
as few as 25% show rash; other symptoms similar to rubella |
|
|
Term
How do you characterize treatment of HHV-6? |
|
Definition
|
|
Term
Is there link between HHV06 and MS patients? |
|
Definition
possibly- increased anti-HHV-6 IgM titers |
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|
Term
|
Definition
|
|
Term
How much of the US population is seropositive to HHV-7 by early childhood? |
|
Definition
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|
Term
What is the relation between HHV-8 and Kaposi's sarcoma? |
|
Definition
the virus is necessary but not sufficient to cause KS |
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|
Term
How is the relation between HHV-8 and KS quantified? |
|
Definition
DNA sequences of HHV-8 recovered from AIDS and non-AIDS KS patients; >80% seropositivity among KS patients, <5% among US blood donors (low risk group) |
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|
Term
Describe the B cell tropism in HHV-8. |
|
Definition
KS tumors occur in lining of lymphatic system; lymphatic channels fill with blood cells, hence bluish, bruised appearnce of lesions |
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|
Term
Where is classical KS seen? |
|
Definition
mediterranean population and Sub-Saharan Africa- not sexually transmitted in these cases |
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|
Term
What are most KS patients in the US? |
|
Definition
AIDS patients- sexually transmitted but virus is absent from semen and vaginal secretions |
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|
Term
Where is HHV-8 virus present in KS/AIDs patients? |
|
Definition
saliva- not understood how it is sexually transmitted |
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|
Term
What is the incubation period for KS after HHV-8 infx? |
|
Definition
10 years- may be relatively mild but if patient is severely compromised, can be life threatening |
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|
Term
What other B cell abnormalities are caused by HHV-8? |
|
Definition
primary effusion lymphoma, Castlemen's disease |
|
|
Term
Is HHV-8 symptomatic in AIDS/Non-AIDS forms? |
|
Definition
95% are ASYMPTOMATIC; infection must be accompanied by loss of immune system for disease symptoms- old age in classical forms and AIDS in gay populations; if symptomatic, treatment in AIDS patients Is tumor-specific (resection, chemotherapy) or targets HIV but not HHV-8 |
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|
Term
Which viruses (from the polyoma/herpesvirus lecture) are ubiquitous (>80% seropositivity) in all US populations? |
|
Definition
|
|
Term
Which viruses (from the polyoma/herpesvirus lecture) are typically acquired in early childhood by essentially all US populations and/or typically symptomatic during primary infx? |
|
Definition
|
|
Term
Which viruses (from the polyoma/herpesvirus lecture) sexually transmitted? |
|
Definition
|
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