10.3 Herpes alpha and beta – Flashcards

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What is the frequency of generalized vaccinia from the small pox vaccine? Who does it generally affect?
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1:5000 cases of vaccine inoculation; healthcare workers and the children of vaccinated
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Name the 7 DNA viruses.
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adenovirus, parvovirus, polyomavirus, papillomavirus, poxvirus, hepadnavirus, herpesvirus
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Describe the virion and genome of herpesvirus.
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large linear dsDNA genome with enveloped icosahedral virion
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Name the alphaherpesvirnae.
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herpes simplex 1, herpes simplex 2, varicella-zoster virus
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Name the gammaherpesvirnae.
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epstein-barr and kaposi's sarcoma
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Name the betaherpesvirdae.
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CMV, herpes lymhoptrophic (HSV6a, HSV6b), human herpes virus 7
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How long ago did the herpesvirus subfamilies diverge?
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over 300 million years ago
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What's the difference between alpha versus gamma and beta herpes viruses?
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alpha viruses replicate well; gamma and beta have poor tc replication
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Where is HSV1 latent?
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trigeminal ganglia
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Where is HSV-2 latent?
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sacral ganglia
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Where is VZV latent?
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dorsal root ganglia
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Where is Epstein-barr virus latent?
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B cells
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here is kaposi's sarcoma latent?
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B cells
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Where is cytomegalovirus latent?
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hematopoietic progenitor cells/monocytes
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Where are herpes lymphotropic viruses latent?
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T cells
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Where is human herpes virus 7 latent?
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T cells
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What is HHV-1?
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HSV-1
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What is HHV-2?
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HSV-2
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What is HHV-3?
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VZV
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Whati s HHV-4?
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EBV
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What is HHV-5?
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CMV
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What is HHV-6?
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Human herpes virus 6
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What is HHV-7?
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human herpes virus 7
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What is HHV-8?
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kaposi's sarcoma associated herpesvirus
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How is HHV-1 transmitted, what is the primary infection site, and what disease does it cause?
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close contact; mucoepithelial cells; oral (fever blisters), ocular lesions, encephalitis
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How is HHV-2 transmitted, what is the primary infection site, and what disease does it cause?
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close contact/sexual contact; mucoepithelial cells; genital, anal lesions, severe neonatal infections, meningitis
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How is HHV-3 transmitted, what is the primary infection site, and what disease does it cause?
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respiratory route/inhalation/close contact
mucoepithelial cells
chickenpox, shingles
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How is HHV-4 transmitted, what is the primary infection site, and what disease does it cause?
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saliva/kissing
B cell
infectious mono; tumors (Burkitt's, immunoblastic lymphomas), nasopharyngeal carcinoma, some T cell tumors
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How is HHV-5 transmitted, what is the primary infection site, and what disease does it cause?
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close contact/sexual, congenital, blood to blood, transplant
lymphocytes, monocytes
mono, severe congenital infections, infections in immunocompromised (gastroenteritis, retinitis, and pneumonia)
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How is HHV-6 transmitted, what is the primary infection site, and what disease does it cause?
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close contact/respiratory
T lymphocytes
roseola in infants; infections in allograft recipients
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How is HHV-7 transmitted, what is the primary infection site, and what disease does it cause?
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saliva, close contact
T lymphocytes
some cases of roseola
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How is HHV-8 transmitted, what is the primary infection site, and what disease does it cause?
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sexual transmission
B lymphocytes, peripheral blood mononuclear cells
tumors including kaposi's sarcoma; some B cell lymphomas
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What is the tropism of alpha herpesvirus?
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epithelial cells, multiple cell types, neurons
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What is the transmission for alpha herpesviruses?
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contact, kissing, sexual, for VZV-aerogenically
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What is the pathogenesis of alpha herpesviruses?
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HSV-vesicular exanthem (fever blisters, labialis, genitalis); VSV- primary chicken pox reactivates to shingles/zoster
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Alphaherpesvirus infections can be severe for which populations?
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neonates and immunocompromised patients
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How do you diagnose alpha herpesvirus?
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cultivation, serology (problematic), PCR
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How do you treat/vaccinate against herpes simplex virus?
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no vaccine. tx with nucleoside analog prodrugs: acyclovir, valacyclovir (valtrex), trifuridine (ocular)
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What is the leading cause of infectious corneal blindness?
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HSV-1
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Where can HSV-1 cause disease?
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encephalitis, keratoconjunctivitis, oral (gingivostomatitis, tonsiliits, labialis), pharyngitis, esophagitis, tracheobronchitis, gladiatorum, genital Whitlow
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HSV infection on the hand is termed ______.
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herpes whitlow
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Where can HSV-2 cause disease?
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encephalitis, oral, pharygitis, genital, perianal, whitlow
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T/F IgM antibodies can be detected during the primary or lytic infection with HSV.
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false, there is absence of detectable antibodies.
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Herpesviruses are latent in cells like nerve cells or B cells because they are _______.
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immunopriveledged
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Recurrent infection is aka ________.
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recrudescence
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What test do you use to diagnose a herpes simplex virus from a cold sore?
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tzanck test--> histological determination of HSV-1 and HSV 2 infection (also works for VZV)
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How do you diagnose HSV encephalitis?
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PCR on CSF (replaces brain biopsy)
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How do you determine whether a HSV infection is HSV-1 or HSV-2?
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IFA/ELISA antibody type specific assays against glycoprotein G (gG)
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What percent of heterosexual women have HSV-2?
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1 partner= <10%
2-10 partners= 40%
11-50= 62%
>50= >80%
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What is the liklihood that a heterosexual man has HSV-2?
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1 partner= 0%
2-10= 20%
11-50= 35%
>50%= >80%
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How many people in the US have HSV-2?
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50 million (more common in women; approx 20% of women have HSV-2)
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How prevalent is neonatal herpes simplex and how do you prevent it?
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1:6000 births; C-section or antivirals late in pregnancy
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How/when do babies get HSV-1 and 2?
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in utero (5% of neonatal infections, HSV-2, ascending or transplacental)
intrapartum (75-80% of neonatal infections)
post-natal (HSV-1 mother/father kissing child)
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Name the neuronal herpesviruses.
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alphaherpesviruses, herpes B/monkey B
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During the HSV latent period, the viral DNA exists as __________ within the neuron cell body.
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in its genomic form as an episome
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What part of the HSV genome is expressed during latency?
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only a stable intron called LAT transcript is expressed
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T/F No virus or virion proteins are produced during the HSV latent infection.
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true (?) according to slide 37
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What are common triggers that reactivate latent HSV?
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sunburn, fever, "exam stress," "hormonal stress"
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Are the symptoms of HSV recurrent infection identical to the primary infection?
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pretty much only symptoms of recurrent infection are usually a milder form of priamry infection
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What percent of americans are seropositive for HSV-1 infection?
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70% (175 million americans) (up to 90% positive by other means of detection)
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What percent of people positive for HSV-1 recurrent infections acquire it before the age of 6?
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50%
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What percent of seropositive individuals exhibit reccurrent HSV-1 infection?
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5% have 1/month
34% have 1/2-11 months
61% have recurrences of 1 or less per year
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What percent of HSV-1 infected people don't know they are infected?
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80%
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How does HSV cause enchephalitis?
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virus transported from peripheral nerves to olfactory bulb and finally into brain. Classically HSV-1 affects the temporal lobe causing focal neurologic signs and cerebral edema
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Herpes simplex encephalitis can clinically resemble...
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brain abscesses, tumors, intracerebral hemorrhage
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How do you treat herpes simplex encephalitis?
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i.v. acyclovir
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What is the mortality of herpes simplex encephalitis?
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70%
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What percent of Americans adults ahve HSV-2?
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30%
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With what frequency does HSV-2 cause a recurrent infection?
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33%= >8-9/year
33%= 4-7
33%= 2-3
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Almost half of all HIV transmission can be contributed to _______.
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HSV-2 infection; persistent inflammation targeted against subclinical recurrence of HSV-2 contributes to high levels of HIV infection
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What is the tropism of VZV?
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epithelial cells, T cells, neurons
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How big is VZV genome?
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120-160 kp dsDNA
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When are you most likely to transmit VZV?
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just prior to rash onset (virus rarely isolated from crusted lesions)
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What is the pathogenesis of VZV?
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URT to regional LNs to primary viremia; enters reticuloendothelial systems and initiates secondary viremia that infects T cells and skin
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Pain along the affected dermatome after a shingles infection is termed...
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post-herpetic neuralgia
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What is the therapy for VZV?
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live attenuated vaccine/ nucleoside analog. prodrugs for treatment (famiciclovir/Valacyclovir)
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T/F Herpes zoster/shingles is generally bilateral.
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false, unilateral
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What is the singles vaccine and for whom is it recommended?
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zostavax= live attenuated (adults > 60 yrs old)
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What are the symptoms of chickenpox?
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crops of vesicular lesion son neck and trunk, highly pruritic, high fever typical, progress to pustular; usually no scarring from virus
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What are the complications of VZV infections?
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pneumonia, severe infection in immunocompromised, bacterial superinfection (e.g. group A strep)
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What is the pathogenesis of shingles/zoster?
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virus travels down the sensory nerve fiber and infects epithelial cells innervated by the fiber: usually stays isolated to a single dermatome
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How long does post herpetic neuralgia last and how do you treat it?
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months after zoster resolves
doesn't respond to antiviral txs
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In what season is varicella prevalent?
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springtime
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Highrisk patients like leukemics could be treated for varicella with...
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passive immunization adminstered within 96 hours of exposure
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What is a relatively common side effect of the live attenuated varicella vaccine?
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5% of healthy children get a mild rash
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When do you give doses of varicella vaccine?
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1st= 12-15 months
2nd= 4-6 years
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When do you give doses of varicella vaccine?
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1st= 12-15 months
2nd= 4-6 years
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Do you give a person over 60 who has already had a case of shingles the zostavax vaccine?
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yes; lessens probability of post-herpetic neuralgia
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When is the varicella vaccine or zostavax contraindicated?
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immunosuppressed patients
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How do you treat herpes virus?
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acyclovir related drugs (acyclovir, famcyclovir, valacyclovir, gancyclovir)
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How do acylcovir related antiviral drugs work?
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virus encoded thymidine kinase phophorylates prodrug into active form- nucleotide triphosphate. This allows incorporatio of cyclovir-triphosphate into elongating viral DNA chain which terminates virus genome replicatoin
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Valacyclovir, acyclovir and famcyclovir are used against...
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HSV1, HSV2, and VZV
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Gancyclovir is used against...
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CMV
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What is the natural host of monkey B virus?
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macaques
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What is the tropism of monkey B?
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epithelial cells, multiple cell types, neurongs, CNS
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How is monkey B transmitted?
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needle stick; scratch; bite; spit in eyes
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What is the incubation of monkey B?
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5-30 days
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What is the pathogenesis of monkey B?
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inital systemic: prodrone of "flu-like" symptoms
early neruological: paresthesias; disorientation; dysphagia
late neurological: rapidly progressive ascending paralysis; encephomyelitis; coma; death
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What is the fatality of monkey b?
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75-80% Severe residual neurological disorders for those who survive.
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T/F there is no evidence of subclinical infections of Monkey B virus in humnas.
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true
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How do you diagnose monkey B virus?
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cultivation; PCR; histology; testing of animal
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How do you treat monkey B infection?
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no vaccine; post exposure: wound cleansing/disinfection;prophylactic acyclovir/gancyclovir; potential reactivation with cessation of treatment
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How big is the CMV genome?
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230 kb ds DNA: largest genome of human DNA viruses!
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What is the tropism of CMV?
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endothelial cells, leukocytes, lymphocytes, monocytes
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How is CMV transmitted?
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contact, kissing, sexual, congenital, transplant, blood
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What are the associated disease of CMV?
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mono, severe congenital infections, transplant rejection
in immunocompromised: retinitis, gastroenteritis, pneumonia
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How do you diagnose CMV?
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differentiation between CMV and EBV mono; CMV antigen; serology; PCR; histology
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How do you treat CMV?
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no vaccine; nucleoside analog prodrugs: ganciclovir, valganciclovir, hyperimmunoglobulin; foscarnet
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Where is CMV latent?
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within monocytes
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Upon reactivation, CMV infectious virions appear in the _______ and the ______.
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urine; saliva
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What is the prevalence of CMV in developed countries? developing countries?
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developed: 40% of adolescents; 70% of adults
developing: over 90%
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T/F CMV infection is often asymptomatic.
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true
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What are the two periods during a persons lifetime when CMV infections increase:
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perinatal period and reproductive years (when individual is sexually active)
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Congenital CMV infection may result in...
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cytomegalic inclusion disease
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Perinatal CMV infection results in..
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asymptomatic infection
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Post natal CMV infection is...
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usually asymptomatic. infectious mononucleosis may develop which consists of fever, lymphadenopathy, and splenomegaly
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What is the course of CMV in immunocompromised patients (transplant recipients and AIDS patients)?
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pneumonitis, ritinitis, colitis, encephalopathy
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T/F Reactivation or reinfection with CMV is usually asymptomatic.
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true, except in immunocompromised patients
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How do you diagnose Cytomegalic inclusion disease?
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isiolation of CMV from the saliva or urine within 3 weeks of birth
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What is the most common congenital viral infection?
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CMV, affects .3-1% of all live births
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Which is responsible for more cases of congenital damage, rubella or CMV?
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CMV
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What is the second most common cause of mental handicap after Down's syndrome?
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CMV (cytomegalic inclusion disease)
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What is the percent chance of transmitting CMV to a fetus following a primary infection?
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40%
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T/F CMV can be transmitted to the fetus only during the first trimester.
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FALSE, can be transmitted during all stages of pregnancy
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What are the CNS symptoms of congenital CMV infection?
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microcephaly, MR, spasticity, epilepsy, periventricular calcification
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5-10% of infants who are infected with CMV but without symptoms at birth will subsquently have...
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varying degrees of hearing and mental or coordination problems
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What are the ocular symptoms of congenital CMV infection?
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choroidretinitis and optic atrophy
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What are the otic symptoms of congenital CMV infection?
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sensorineural deafness
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What are the pulmonary symptoms of congenital CMV infection?
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pneumonitis
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What are the cardiac symptoms of congenital CMV infection?
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myocarditis
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T/F Some children with microcephaly will be of normal intelligence and development, even though their heads will always be small for their age and sex.
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true
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What are the complications of microcephaly?
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developmental delays (speech, movement)
difficulties with coordination and balance, dwarfism/short statures, facial distortion, hyperactivity, mental retardation, seizures
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Postnatal CMV infection mainly occurs through the ______.
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saliva
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What type of sex is a risk factor for increased CMV transmission?
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anal
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___% of blood taken from CMV seropositive donors leads to infection of seronegative recipients.
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3-5
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What type of organ transplant increases your risk of CMV transmission?
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renal (usually 5% chance of transmission, renal is 70-80% chance of transmission)
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CMV mononucleosis is aka_____ and normally infections individuals ages ___.
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kissing disease
ages 14-25
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How long does CMV mono last?
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8 weeks or more
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What are the symptoms of CMV mono?
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chronic fatigue, sore throat/swollen tonsils, chills/fever, loss of appetite, nausea/vomiting occasionally
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T/F Infectious mononucleosis can cause photophobia.
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true!
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What do you tonsils look like if you have mono?
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swollen with a whitish-yellow (exudate) covering
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T/F You can get a swollen spleen and sometimes jaundice from CMV mononucleosis.
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true
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What is the fatality rate of mono?
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1%
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What is the most common cause of death from mono?
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ruptured spleen: recommend avoiding contact sports during and two weeks after infection symptoms subside
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EBV mono is characterized by..
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production of heterophile antibodies
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What test do you use for EBV mono?
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monospot test (heterophil antibody test)
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WHen during the course of infection can you use the monospot test?
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2-9 weeks after a person is infected. Generally not used to diagnose mono that started more than 6 months earlier
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CMV is named after...
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its histological appearnce: enlarged cytomegaly. Infected cells have pronuclear inclusions that appear as "owl-eyes" on histology
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What treatment used on AIDS patients will increase their risk of developing active CMV infection?
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corticosteroids
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In cases of CMV infecting immunocompromised patients, what percent of cases involve the eye? what are the symptoms?
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30% blurred vision, eye pain, photophobia, redness, and blindnes
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What is cytomegalovirus retinitis?
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aka CMV retinitis; inflammation of the eye's retina that can lead to blindness
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What are the two major causes of serious morbidity and mortality after blood and marrow transplantation?
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CMV and graft versus host disease account for 2/3rds of all deaths after transplanation
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What is the most common presentation of CMV in post transplant patients? What percent die from it?
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pneumonitis; 85% die within 2 to 3 weeks
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What are strategies to control CMV infection post transplant?
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get a CMV seronegative graft donor (immunoprophylaxis, blood product filters) or use ganciclovir treatment
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How big are the roseolaviruses (HHV-6 adn 7)?
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170 kb dsDNA
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What is the tropism of HHV 6 and 7?
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T and B lymphocytes, neurons
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How is HHV6 and 7 transmitted?
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saliva; blood; HHV7 breast milk
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What are the associated disease of HHV6 and 7?
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ubiquitous childhood disease (roseola infantum: 6th disease) rarely encephalitis; possibly links with MS and also with myocarditis
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What are the associated disease of HHV6 and 7?
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ubiquitous childhood disease (roseola infantum: 6th disease) rarely encephalitis; possibly links with MS and also with myocarditis
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What is the vaccine/therapy for HHV6 and 7?
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no vaccine; not FDA approved but clinicians utilize nucleoside analog prodrugs; ganciclovir; valganciclovir. Also, foscarnet and cidofivir
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What is exanthema subitum?
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"sudden rash" aka roseola infantum (rose rase of infants) aka sixth disease. Disease of children generally under 2 years old that presents with 3 days of fever followed by a transient rash
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Which viruses cause roseola infantum/exanthema subitum?
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HHV6A and HHV6B and HHV7
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What percent of the population has been infected by roseolavirus?
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90% by age 2. 100% by adulthood
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T/F Roseolavirus cause a pruritic rash that occurs after a three day high fever.
answer
False, the rash isn't itchy
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