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. |
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False, the rash isn't itchy |