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512 Cards in this Set
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3 year old girl with "cold sores" previously and now a cluster of small vesicles with a faint area of surrounding erythema on the thumb
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this description is consistent with herpetic whitlow
most likely diagnosis is HSV-1 |
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how can HSV-1 be transferred from the mouth of a three-year-old to the thumb?
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self-inoculation by sucking on thumb
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what are the two serotypes of herpes simplex virus?
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HSV-1
HSV-2 both cause vesicular lesions via infection of mucosal membranes and or compromised epithelial cells |
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where does HSV replicate?
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basal epithelium of vesicular lesions, and then establish latent and recurring infections within the innervating neurons of the cells
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though there is some overlap, where do the different serotypes of HSV cause disease?
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HSV-1 tends to affect areas above the waist
HSV-2 tends to affect areas below the waist |
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what are vesicular lesions?
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small, blister-like lesions filled with clear fluid
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what are syncytia?
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fusion of neighboring cells infected with virus, resulting in multinucleated giant cells
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what is gingivostomatitis?
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localized inflammation and/or ulcerative lesions in the mucous membranes of the oral cavity
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what is prodrome?
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early symptoms of HSV infection, including itching and tingling of skin 12-24 hours prior to lesion formation
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to what family and subfamily do the herpes simplex viruses belong?
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alphavirinae subfamily
herpesviridae family |
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is HSV enveloped or not?
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enveloped
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what type of nucleic acid is contained within HSV?
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linear, double-stranded DNA
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what is the shape of the capsid of HSV?
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icosadeltahedral
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approximately how much homology is shared by the HSV-1 and HSV-2 viruses?
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50 percent homology
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where does HSV typically replicate?
where does it create a latent infection? |
replication/lytic infection - fibroblast and epithelial cells
latent infections - neurons |
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by what mechanism does HSV enter host cells?
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fusion at the cell membrane and release of gene transcription proteins, protein kinases, and proteins that are cytotoxic to host cell
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what replication machinery is utilized by HSV viruses?
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host transcription/translation machinery
viral-encoded DNA polymerase to replicate the genome |
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by what mechanisms are newly formed enveloped virions released from host cells?
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exocytosis
cell lysis |
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how does HSV enter the body?
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mucosal membranes
breaks in the skin replicates in cells at infection site and then establishes latent infection of neuron innervating the primary infection site via retrograde transport |
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how is retrograde transport important to HSV?
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HSV uses retrograde transport along neuronal axon to establish latent infection in the neuron innervating the primary infection site
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how does HSV avoid antibody-mediated defenses?
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cell-to-cell spread by the formation of syncytia
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why is the latent infection of neurons important for HSV?
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allows virus to avoid host defenses
provides potential for recurrent disease |
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what is herpetic whitlow?
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infection of the finger with HSV-1, resulting from direct contact with herpes lesions
most commonly seen in children who suck their fingers and in health care workers |
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what are the clinical signs of HSV infections?
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oropharyngeal disease, with symptoms of fever, sore throat, gingivostomatitis, and submandibular lymphadenopathy
keratoconjunctivitis, with recurrent lesions of the eye and eyelid cutaneous infections, with vesicular lesions of the mouth, fingers, and genital tract encephalitis |
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when do neonatal infections of HSV most commonly occur?
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during vaginal delivery in pregnant mothers with primary or recurrent genital lesions
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why are neonatal HSV infections important?
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nearly always symptomatic
high mortality rates if not promptly diagnosed and treated |
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what are the signs of neonatal HSV infection?
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localized vesicular lesions of the skin, eye or mouth
encephalitis disseminated disease |
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what is a Tzanck smear?
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scraping of a vesicular lesion (ulcer) to look for Tzanck (multinucleated, giant) cells
used for diagnosis of herpes |
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what are the limitations to the Tzanck smear?
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lacks sensitivity and specificity
doesn't distinguish among HSV-1, HSV-2, and varicella-zoster virus infections |
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what is the definitive diagnostic approach for HSV?
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isolation of virus from herpetic lesions, cerebral spinal fluid, or stool speciments, where the appearance of characteristic HSV cytopathic effects on cells can be observed
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what are the rapid diagnostic tests for HSV?
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detecting viral antigen (via immunofluorescence) or DNA (via PCR) in tissue samples or vesicle fluid
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what is the most widely used analysis in current clinical practice for serotyping HSV?
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DNA probe
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what drugs can be used to treat HSV infections?
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acyclovir
valacyclovir famciclovir all inhibitors of viral DNA synthesis , thereby shortening duration of clinical symptoms and suppressing viral reactivation |
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how can HSV infection be prevented?
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avoiding direct contact with virus or viral lesions
avoiding saliva, urethral, and cervical secretions safe sex practices cesarean delivery of neonates |
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what is asymptomatic shedding?
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HSV viruses can be found in saliva, urethral and cervical secretions in individuals infected with HSV, even if no sores/symptoms
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42 year old woman has high-grade squamous intraepithelial neoplasia on a Pap smear
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most likely cause is human papillomavirus (HPV)-related infection
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what specific types of HPV confer a high risk of cervical neoplasia?
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HPV types 16 and 18 are most commonly associated with anogenital neoplasias
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where, on a cellular level does HPV tend to replicate in benign diseases?
in malignancies? |
benign - host neoplasm where viral DNA remains extrachromosomal
malignancy - integrated into host genome |
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what parts of the bodies are preferentially infected by HPV?
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squamous epithelium of skin and mucous membranes
causes epithelial proliferation and development of cutaneous warts and genital, oral, and conjunctival papillomas |
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what are the major risk factors for HPV infection and progression to carcinomas?
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multiple sexual partners
smoking immunosuppression |
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what types of HPV are associated with cutaneous warts?
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Plantar wart - 1
Common Wart - 2,4 Flat Wart - 3,10 |
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what types of HPV are associated with benign head and neck tumors?
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laryngeal papilloma - 6,11
oral papilloma - 6,11 conjunctival papilloma - 11 |
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what types of HPV are associated with anogenital warts?
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condyloma acuminatum - 6,11
cervical intraepithelial neoplasia - 16,18 |
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what are koilocytes?
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enlarged keratinocytes with shrunken nuclei
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what is poikilocytosis?
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presence of perinuclear cytoplasmic vacuolization and nuclear enlargement of epithelial cells
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what are papillomas?
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epithelial neoplasms producing finger-like projections from the epithelial surface
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what are condylomas?
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epithelial neoplasms and hyperplasias of the skin, resulting in the formation of a large cauliflower-like mass
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to what virus family does HPV belong?
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papillomaviridae family
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what type of genome does HPV have?
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circular, double-stranded DNA
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is HPV enveloped or not?
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not
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why is it important whether a virus is enveloped or not?
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enveloped viruses are susceptible to acids, detergents, and dessication, whereas non-enveloped viruses are able to withstand these (allowing them to survive on fomites)
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what are the methods of transmission of HPV?
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direct contact
sexual intercourse delivery through an infected birth canal |
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how does HPV enter the body?
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enters through breaks in the skin and replicates in basal cell layer of epithelium
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how does HPV replicate?
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DNA is replicated and viral particles are assembled in the nucleus
late viral gene expression occurs in the upper layers of differentiated keratinocytes |
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what has been found in over 95% of cervical carcinoma specimens?
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HPV DNA, primarily types 16 and 18
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what are high-risk vs. low-risk HPV strains?
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high risk - 16, 18
low risk - 6, 11 |
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what are the symptoms of HPV infection?
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variety of cutaneous warts and papillomas
presence of koilocytotic squamous epithelial cells in a Pap smear |
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what causes warts?
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HPV replication stimulating excessive growth of epidermal layers above the basal layer
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what causes laryngeal papillomas in infants?
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infection of larynx in infant from active HPV genital lesions on mother
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what are the stages of cervical cancer development?
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cellular atypia
low-grade intraepithelial lesion high-grade intraepithelial lesion carcinoma |
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what are the treatments for HPV?
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physical removal of lesions/warts via cellular destruction by cryotherapy, acid application, or electrocautery
Immune stimulant therapy using injection of interferon or topical applications of imiquimod |
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what are the preventative measures against HPV?
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routine screening of women with Pap smears
quadrivalent HPV vaccine, Gardasil avoiding direct contact with infected skin lesions safe sex practices |
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what is the vaccine Gardasil composed of?
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major capsid proteins from HPV virus assembled into virus-like particles
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4 year old girl with multiple discrete 1-2mm papules on her upper chest and lower neck that are flesh colored, have a central umbilication
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most likely molluscum contagiosum
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to what family of viruses does molluscum contagiosum belong?
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poxviridae
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how is molluscum contagiosum transmitted?
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direct contact with infected cells or with objects contaminated with virust particles
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in what population is molluscum contagiosum more frequent?
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children
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what are molluscum bodies?
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eosinophilic cytoplasmic inclusions seen in epidermal cells infected with Molluscum contagiosum
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what are umbilicated lesions?
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lesions with cup-shaped crater and a white core
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what are papules?
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lesions that are raised and well circumscribed
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what family of viruses are among the largest, most complex viruses known?
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poxviridae
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what type of genome do pox viruses have?
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linear, double-stranded DNA
(fused at both ends) |
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how do pox viruses enter target cells?
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bind to surface receptor
outer envelope fuses with target cell membrane and enters target cell |
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where does replication of pox viruses happen?
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entirely in host cell cytoplasm
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what is important about a DNA virus that replicates entirely in host cell cytoplasm?
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unique to pox viruses
must provide all enzymes necessary for viral replication |
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what are Guarnieri inclusions?
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cytoplasmic inclusions in cells infected with pox virus, in which viral DNA replication and virion assembly occurs
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how are newly formed pox viruses released from cells?
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released on cell lysis
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what is the only poxvirus specific for humans?
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molluscum contagiosum
(since smallpox has been eradicated) |
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how is molluscum contagiosum transmitted?
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through small skin abrasions from direct contact with infectious particles or via contaminated fomites
wrestling matches, swimming pools, sharing towels, SEXUAL CONTACT |
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how long is the incubation period for Molluscum contagiosum infection?
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2 weeks - 6 months
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what is the presentation of Molluscum contagiosum in immunocompromised patients?
who is at greatest risk for this presentation? |
hundreds of lesions all over the body
patients with late-stage AIDS, with CD4 count <200 cells/uL |
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what is clinically caused by molluscum contagiosum?
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discrete, flesh-colored papules with a central umbilication (most commonly groups of 5-25 on trunk, genitalia, and extremities)
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what is a kissing lesion?
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lesion caused by direct contact of a lesion with an uninfected area of skin on the same host
ex. Molluscum contagiosum lesion on lateral ches may cause a kissing lesion on inner arm |
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how is Molluscum contagiosum treated and/or prevented?
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lesions generally develop within 2-3 months of contact and resolve in 1-2 years
lesions can be removed by curettage, electrocautery, or liquid nitrogen applications |
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8 year old boy with fever and "slapped cheek appearance.
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erythema infectiosum
fifth disease infection with parvovirus B19 |
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in what human cells does parvovirus B19 cause lytic infections?
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mitotically active erythroid precursor cells
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what is the only parvovirus known to cause disease in humans?
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parvovirus B19
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what is the typical presentation of a parvovirus B19 infection?
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typically school-aged child - mild febrile upper respiratory illness, followed by exanthematous rash on face or "slapped cheek" appearance, which later spreads to extremities
adults primarily present with polyarthritis of hands, knees, and ankles (with or without rash) immunodeficient patients could experience severe anemia and aplastic crisis pregnant, seronegative mothers, infection can lead to serious infection and fetal death |
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why is parvovirus B19 infection also called fifth disease?
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it was the fifth childhood exanthem to be described after varicella, rubella, roseola, and measles
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what is an exanthem?
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an eruptive disease or eruptive fever appearing on the skin
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what is an enanthem?
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eruptive disease appearing on mucous membranes
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what are petechiae?
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tiny reddish or purplish spots containing blood and appearing on the skin or mucous membranes
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are parvoviruses enveloped or not?
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not enveloped
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what type of genome do parvoviruses have?
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linear, single-stranded DNA
(contain either positive- or negative-sense copy of the viral genome) |
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what are the smallest of the DNA animal viruses?
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parvoviruses
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to which family does parvovirus B19 belong?
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parvoviridae
only known member to cause human disease |
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how is parvovirus B19 transmitted?
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respiratory and oral secretions
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where does parvovirus B19 replicate first?
where does it move? how? |
nasopharynx
then spreads by viremia to the bone marrow |
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how is parvovirus B19 taken into target cells?
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binds erythrocyte blood group P antigen on erythroid precursor cells
internalized through coated pits uncoated and transported to the nucleus |
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what forms the primer for the initiation of DNA replication?
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inverted repeat sequences on the 5' and 3' ends of the viral DNA genome fold back and hybridize
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where are virions of parvovirus B19 assembled?
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nucleus
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factors from which phase of mitosis are required for parvoviral replication?
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S phase
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how are parvovirus B19 virions released from the host cell?
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lysis of nuclear and cytoplasmic membranes, resulting in cell death
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why does anemia result from parvovirus B19 infection?
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mainly replicates in adult bone marrow and fetal liver cells, disrupting red blood cell production
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what are the symptoms of fifth disease?
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biphasic infection
initial phase (one week) - mild upper respiratory symptoms; low-grade or no fever; rash second phase - immune-mediated, with formation of host antibody-virus immune complexes, reduction of viremia, and emergence of spreading lacy skin rash and/or anthralgias |
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which stage is the infectious stage of fifth disease?
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first stage (first week)
produces flu-like symptoms with mild fever and upper-respiratory symptoms |
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what causes the lacy rash, arthralgias, and arthritis in fifth disease patients?
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circulating antibody-virus immune complexes
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who is at risk for aplastic crisis in fifth disease patients?
why? |
those with chronic hemolytic anemia, such as sickle cell disease
combination of viral replication in red cell precursors along with reduced circulatory life span of existing red cells |
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what is the effect of parvovirus B19 infection on pregnant women and their fetuses?
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primary infection - can result in hydrops fetalis, severe anemia, and fetal death before 3rd trimester
recurrent infection - fetus is protected by maternal circulating antibodies |
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how is diagnosis of parvovirus B19 made?
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clinical presentation
detection of viral DNA via PCR or DNA hybridization assays serologic detection of viral IgM or IgG antibodies via ELISA |
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what are the treatment/prevention options for parvovirus B19?
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no specific treatment
rigorous hand washing isolation of infected patients |
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what virus is used as the smallpox vaccine?
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vaccinia (a form of the cowpox virus)
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why must variola produce its own enzymes for DNA and mRNA synthesis?
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viral replication occurs entirely in host cell cytoplasm, therefore it cannot use enzymes located in host nucleus
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what is the virus that causes smallpox?
to what family does it belong? |
variola
poxviridae |
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what factors allowed smallpox to be eradicated?
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discovery that cowpox could be used to vaccinate against smallpox
humans are only reservoir for variola |
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how does vaccinia (cowpox) act as a live vaccine for variola (smallpox)?
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shares antigenic determinants with variola but primarily causes clinical disease in nonhuman animals
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what are the potentially severe side effects of smallpox vaccination?
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postvaccinial encephalitis
progressive vaccinia necrosum fetal vaccinia primarily in immunosuppressed individuals, those with severe allergies, eczema, or pregnant women |
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when was the smallpox vaccine last used routinely? why?
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1980
WHO declared that smallpox was eradicated and that the risk of vaccination was thought to outweigh the risk of acquiring smallpox |
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where have smallpox vaccinations been reinstituted? why?
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military
public health and safety workers concerns about the risk of smallpox being used as a bioterror weapon |
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what does maculopapular mean?
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clinical presentation combination of both macules (rash) with papules (lesions)
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how do Guarnieri's inclusion bodies relate to smallpox?
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they are the electron-dense intracytoplasmic acidophilic inclusions within infected cells which serve as assembly sites for new smallpox virions
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what virus is responsible for smallpox?
to what family does it belong? to what genera does it belong? |
variola
poxviridae orthopoxvirus |
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what are the largest and most complex viruses known?
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poxviruses
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are poxviruses enveloped or not?
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yes
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what type of genome is contained by poxviruses?
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linear, double-stranded DNA genome
(fused at both ends) |
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what is the mode of transmission for smallpox viruses?
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inhalation of infected respiratory droplets
exposure to infectious skin lesions contact with contaminated fomites |
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what is the path of the smallpox virus after being inhaled?
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initial replication in respiratory tract, where virus binds to a target cell surface receptor and the envelope fuses with the cell membrane; core of the virus is then released into cellular cytoplasm where DNA replication and transcription take place
spread through lymphatic channels causing primary viremia and infection of reticuloendothelial cells |
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from where do poxviruses acquire cell membrane for their envelope?
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unlike other enveloped viruses, they produce their own instead of acquiring host cell membrane
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in smallpox, viral replication in what cells causes secondary viremia and results in the clinical manifestations of the skin and internal organs?
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reticuloendothelial cells
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what causes primary viremia in smallpox?
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spread of virus through lymphatic channels after release from respiratory cells
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what are the two strains of variola virus? how are they important?
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variola major - associated with high mortality rates (20-50%)
variola minor - associated with very low mortality rate (<1%) |
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how is diagnosis of smallpox made?
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clinical presentation
incubation period of two weeks followed by abrupt onset of malaise, fever, chills and myalgia a few days post-onset, a characteristic maculopapular rash begins to develop and progresses in a centrifugal pattern over the head and extremities |
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describe the rash that accompanies smallpox.
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a few days post-onset of symptoms, the characteristic maculopapular rash begins to develop and progresses in a centrifugal pattern over the head and extremities
over two weeks, the rash progresses to a single crop of maculopapular lesions to firm vesicles, then to pustules that scab and slowly heal |
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what causes high mortality of smallpox?
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overwhelming primary infection
or secondary bacterial superinfection |
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what should be done with highly suspected cases of smallpox?
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referred immediately to the CDC, where new variola and orthopox PCR tests are available
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how is smallpox treated?
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no treatments for use in established smallpox disease
prophylaxis includes chemotherapeutic agents such as methisazone or cidofovir |
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65 year old man with left lower back pain (sharp, burning) that radiates to the flank and abdomen; with NSAIDs, develops a rash in same distribution, consisting of patches of erythema with clusters of vesicles
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reactivation of varicella-zoster virus, causing the appearance of shingles
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what is the causative agent of both chickenpox and shingles?
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varicella-zoster virus
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what is the life cycle of varicella zoster virus?
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primary infection by age ten (usually)
latent infection in dorsal root ganglia sometimes reactivated later in patient's life |
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to what family and subfamily does varicella-zoster virus belong?
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family - herpesviridae
subfamily - Alphaherpesvirinae |
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is varicella-zoster virus enveloped?
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yes
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what type of genome does varicella-zoster virus contain?
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double-stranded DNA
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what is a dermatome?
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an area of skin served by one sensory spinal nerve
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what is neuropathic pain?
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pain disseminating from the peripheral nervous system
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how is varicella-zoster virus transmitted?
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respiratory droplets
direct contact with skin lesions |
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where does infection and replication by varicella-zoster virus occur?
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initially - respiratory tract epithelium
spreads to skin by viremia |
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where do transcription and translation of varicella-zoster virus occur?
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host cell nucleus
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what happens in a lytic infection with varicella-zoster virus?
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new virions are assembled in host nucleus, acquire an envelope from the nuclear or Golgi membrane, and are released by exocytosis or lysis of the host cell
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what happens in a latent infection with varicella-zoster virus?
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viral genome is not replicated, and only certain viral genes are transcribed
latent infection of dorsal root or cranial nerve ganglia can occur during initial infection |
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how does varicella-zoster virus spread within a host?
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primary viremia or lymphatic dissemination to the reticuloendothelial system
secondary viremia to the skin and other organs syncytia to spread from cell to cell |
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what is the presentation of chickenpox?
|
crops of vesicles and pustules form on erythematous bases, starting on the head and trunk and progressing centripetally to the extremities
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what are the causes of reactivation of latent varicella zoster infection?
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unknown, but tends to be more common in older persons as cellular immunity decreases, in immunosuppressed patients, and in immunocompetent patients under emotional stress
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what is the typical presentation of shingles?
|
unilateral vesicular eruption of shingles along dermatomal distribution
rash is frequently preceded by pain along the course of the nerve days-weeks before it appears neuropathic pain could persist weeks or months after rash clears (this indicates damage to the nerve root) |
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what is the most rapid, sensitive, and specific assay for diagnosing VZV infections?
|
direct fluorescent-antibody staining of vesicular lesion scrapings
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what viral DNA polymerase inhibitors are available for treating VZV infections?
|
acyclovir
famciclovir valacyclovir |
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how is VZV treated?
|
DNA polymerase inhibitors (acyclovir, famciclovir, valacyclovir) to reduce fever and skin lesions given within 3 days of onset of infection, prior to eruption of lesions; also reduce dissemination to immunocompromised patients
analgesics and other pain killers for neuralgia |
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how is VZV prevented?
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respiratory and contact isolation of infected patients
passive immunization of high-titer varicilla-zoster immunoglobulin (VZIg) for immunocompromised patients if given within 3 days of exposure live vaccine for children and adults live-attenuated vaccine (zostavax) for adults over 60 |
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62 year old man with abnormal liver function tests who had a blood transfusion previously, likely caused by an infectious etiology
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most likely Hep C from blood transfusion
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what are the modes of transmission of Hepatitis C?
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**blood transfusions**
**intravenous drug use** sexual contact (rare) |
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is acute or chronic hepatitis more likely with Hepatitis C infection?
|
chronic (50-85% of patients)
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why is acute hepatitis not a major issue for Hepatitis C patients?
|
only 15% of patients develop acute hepatitis syndrome, and recover completely
most appear asymptomatic yet progress to chronic infection |
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what are the complications of chronic Hepatitis?
|
cirrhosis
liver failure hepatocellular carcinoma |
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how has HCV been decreased as a means of posttransfusion hepatitis?
|
routine screening of donated blood supply, started in 1992
|
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what is the most widely used therapy for HCV?
|
recombinant interferon, which induces host antiviral and antiproliferative activity
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what is hepatitis?
|
inflammation of the liver; viral causative agents include hepatitis viruses A, B, C, D, E, and G
clinical presentation can include fever, nausea or vomiting, jaundice, dark urine, pale feces, and elevated liver enzymes (AST and ALT) |
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what is a Dane particle?
|
a 42-nm particle that is the hepatitis B virion
composed of the genome, a viral DNA polymerase, and P protein (attached to the genome) |
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what is fulminant hepatitis?
|
severe acute hepatitis that causes rapid destruction of the liver
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what are the most common and clinically significant infections of the liver?
|
Hepatitis A, B, C, D, and E
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what are the common complaints of hepatitis patients?
|
fever, nausea, fatigue, arthralgias, myalgias, headache, and sometimes pharyngitis and coryza, followed by visible jaundice, with hepatomegaly
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what causes visible jaundice in hepatitis patients?
|
hyperbilirubinemia
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what causes dark urine in hepatitis patients?
|
bilirubinuria
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how is Hepatitis A usually transmitted?
|
fecal-oral route
(usually by contaminated food or water where sanitation is poor and in day care by children) |
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how is Hepatitis E usually transmitted?
|
fecal-oral route
(usually by contaminated food or water where sanitation is poor and in day care by children) |
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what is the most common cause of acute viral hepatitis in the United States?
|
Hepatitis A virus
(it is found worldwide) |
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where is hepatitis E usually found?
|
Asia
Africa Central America |
|
|
why are hepatitis A and E not major concerns?
|
both usually lead to self-limited illnesses and generally resolve within weeks
almost all hepatitis A patients recover completely and have no long-term complications |
|
|
is Hepatitis A enveloped or not?
|
not
|
|
|
to what family does Hepatitis A belong?
|
picornaviridae family
|
|
|
what type of genome does Hepatitis A have?
|
linear, positive-sense, single-stranded RNA
|
|
|
how many serotypes are there of Hepatitis A?
|
only one
|
|
|
what is the average incubation period of Hepatitis A virus?
|
30 days
|
|
|
describe the demographics of Hepatitis A infections
|
25,000 symptomatic cases in US annually
90% of HAV infections in children and 30-50% in adults are asymptomatic infections in children are mostly asymptomatic or present with nonspecific symptoms adults generally have a more severe clinical course only 1-4% of patients develop fulminant liver failure 1% mortality |
|
|
how is HAV diagnosed?
|
ALT levels rise initially with onset of symptoms
anti-HAV IgM antibodies are produced 1-3 weeks later |
|
|
how is HAV prevented?
|
proper hand washing
avoidance of contaminated food and water vaccine for travelers, and children over 1 year |
|
|
how is HAV treated in exposed persons?
|
HAV immunoglobulin intramuscularly within 14 days of exposure
supportive therapy |
|
|
what is the only DNA-type Hepatitis virus?
|
Hepatitis B
|
|
|
to what family does Hepatitis B virus belong?
|
Hepadnavirus family
|
|
|
what makes Hepatitis B unique among the hepatitis viruses?
|
it has a DNA genome
|
|
|
what type of genome does Hepatitis B virus have?
|
circular and partially double-stranded DNA genome
|
|
|
is Hepatitis B virus enveloped or not?
|
yes
|
|
|
why is HBV able to use an RNA intermediate during replication?
|
DNA polymerase also contains reverse transcriptase and ribonuclease H activity
|
|
|
for what does HBV have a specific affinity?
by what is this affinity mediated? |
liver cells
viral glycoproteins |
|
|
what happens with HBV after it has been taken up into the hepatocytes?
|
genome is converted into fully double-stranded DNA which is then delivered to the nucleus
hos cell's transcription and translation machinery are then used to make new HBV virions virions are released from hepatocyte via exocytosis |
|
|
when can HBsAg be detected?
|
when live HBV virions are present in an infection
|
|
|
what is HBeAg?
|
a glycoprotein cleavage product of the HBV core which is shed into the serum
|
|
|
what is indicated by the presence of both the HBeAg and the HBsAg?
|
active HBV infection, and thus active disease
|
|
|
what is indicated by IgM anti-HBc antibodies?
what is indicated by IgG anti-HBc antibodies? |
recent infection
past infection |
|
|
what is the second most common type of viral hepatitis in the United States?
|
Hepatitis B
|
|
|
how is Hepatitis B transmitted?
|
sexual contact
parenterally (IV drug use, during birth) |
|
|
what percent of infected newborns develop chronic hepatitis B infection?
|
90%
|
|
|
how does age relate to risk in Hepatitis B patients?
|
newborns - 90% develop chronic hepatitis, increasing risk of hepatocellular carcinoma
adults - 95% recover w/o sequelae; 5-10% develop chronic hepatitis leading to cirrhosis |
|
|
what is a chronic carrier state?
|
virus continues to replicate but does not cause hepatic damage to the host in Hepatitis B infections
|
|
|
how is Hepatitis B prevented?
|
vaccine of recombinant HBsAg for infants and adolescents
|
|
|
how is Hepatitis B treated?
|
immunoglobulin within 1 week of exposure for nonimmunized patients
reverse transcriptase inhibitors alpha-interferon |
|
|
where are HBV infection rates still high?
|
southeast asia
mediterranean |
|
|
to what family does Hepatitis C belong?
|
flaviviridae
|
|
|
what type of genome does Hepatitis C have?
|
positive sense RNA genome
|
|
|
is Hepatitis C enveloped or not?
|
yes
|
|
|
why is it difficult to produce an effective vaccine against Hepatitis C?
|
there are hundreds of genotypes as a result of a hypervariable region in the envelope genes
the hypervariable region determines the virulence of the virus |
|
|
what receptor does the Hepatitis C virus use to endocytose into cells?
|
CD81 surface receptor
|
|
|
what causes the viral envelope to fuse with the endosomal membrane, resulting in the release of viral RNA into the host cytoplasm?
|
acidity of the endosome
|
|
|
what happens after the HCV is inside a hepatocyte?
|
viral RNA acts as a messenger RNA, directing production of viral polyprotein
polyprotein anchors to the host cell ER and virus remains cell-associated proteins inhibit apoptosis and action of interferon-alpha |
|
|
how does Hepatitis C cause chronic infection and persistent liver disease?
|
remains associated with the cell
inhibits apoptosis |
|
|
what is the incubation period for infection with Hepatitis C?
|
2-26 weeks
average: 6-7 weeks |
|
|
describe the demographics of Hepatitis C
|
15% develop acute hepatitis and recover completely
70% are initially asymptomatic, but progress to chronic hepatitis |
|
|
what are the complications of chronic Hepatitis C?
|
cirrhosis
liver failure hepatocellular carcinoma |
|
|
how is HCV infection diagnosed?
|
demonstrating the presence of circulating IgG antibodies to HCV antigens through enzyme immunoassay
reverse transcriptase PCR diagnoses infection and quantitates circulating HCV RNA in infected person |
|
|
what are the limitations of detecting HCV antigens for diagnosis?
|
antigens may not be detected until up to 4 months post-infection, making acute HCV infection difficult to diagnose
cannot distinguish between acute, chronic, or resolved HCV infections |
|
|
what is the monitor for HCV disease activity and as a measure of response to therapy?
|
reverse transcriptase polymerase chain reaction (RT-PCR)
|
|
|
what is the treatment for HCV?
|
recombinant interferon-alpha (helps induce host antiviral and antiproliferative activity
end-stage chronic HCV hepatitis may require liver transplant |
|
|
what is the limitation to liver transplantation in Hepatitis C patients?
how are people working to overcome this problem? |
risk of graft reinfection is 50% for HCV
routine screening of donated blood and organs |
|
|
which hepatitis virus is defective?
why? |
Hepatitis D
it requires the presence of Hepatitis B virus to replicate (uses its machinery) |
|
|
what is lacked by Hepatitis D?
|
genes for envelope proteins
to replicate, it requires infection with HBV |
|
|
what does a Hepatitis D virion consist of when released, assuming that the cell is also infected with Hepatitis B?
|
envelope (provided by HBV) with HBsAg
delta antigen single-stranded, circular RNA |
|
|
what type of genome does Hepatitis D have?
|
single-stranded, circular RNA genome
|
|
|
what is the difference in presentation if HDV infection happens after a preexisting HBV infection, vs. if it infects at the same time?
|
preexisting HBV - higher risk of chronic liver infection and chronic HDV infection; more likely to lead to fulminant hepatitis and has a 5-15% mortality rate
simultaneous infection - severe acute disease with a low risk of developing chronic liver infection or mortality |
|
|
how is HDV transmitted?
|
percutaneously
mucosally sexual contact |
|
|
how is diagnosis of HDV made?
|
detection of RNA genome (via RT-PCR)
detection of delta antigen (via ELISA) both from blood |
|
|
what is the limitation to detecting HDV antibodies for diagnosis?
|
present only transiently
|
|
|
what are the preventitive measures against HDV?
|
prophylaxis against HBV to prevent superinfection
education of HBV-positive patients on how to reduce risk factors for infection |
|
|
what is the treatment for HDV?
|
alpha-interferon
lessens clinical symptoms |
|
|
what is enteric non-A, non-B hepatitis?
|
Hepatitis E virus
|
|
|
to what family does Hepatitis E belong?
|
caliciviridae family
|
|
|
is Hepatitis E enveloped or not?
|
not enveloped
|
|
|
what type of genome does Hepatitis E have?
|
linear, positive-sense, single-stranded RNA
|
|
|
what is the major mode of transmission of Hepatitis E?
|
fecal-oral transmission
most frequently through contaminated water sources |
|
|
in what population is Hepatitis E most often seen?
|
travelers (not endemic to US)
|
|
|
what is the incubation period of Hepatitis E?
|
40 days
|
|
|
how is Hepatitis E infection diagnosed?
|
exclusion (no laboratory testing available)
|
|
|
what is the mortality rate for Hepatitis E?
|
very low (1-2%), except for infection in pregnancy (15-25%)
no chronic stage |
|
|
how does severity of hepatitis infection change with age?
|
increases with age of patient at infection
|
|
|
what are the preventative measures against HEV?
|
don't drink water (or ice) and don't eat unpeeled fruits or vegetables
no vaccine available immunoglobulin does not prevent infection |
|
|
to what family does Hepatitis G belong?
|
flaviviridae family
|
|
|
what is the most recently identified hepatitis virus?
|
Hepatitis G
|
|
|
what does HGV resemble in its viral structure?
|
HCV (positive-sense RNA genome)
|
|
|
what does HGV resemble in its transmission?
|
HCV (blood-borne)
|
|
|
what is the major risk of Hepatitis G infection?
|
high production of chronic hepatitis disease
|
|
|
how is HGV diagnosed?
|
identifying the HGV genome via RT-PCR
|
|
|
what is the window period?
|
in Hepatitis B infection, the window period is the interval of a few weeks that is often between the disappearance of HBsAg and the appearance of anti-HBsAb
|
|
|
explain the diagnosis Hepatitis B (chronic vs. acute)
|
acute - HBsAg (surface antigen) in clinical context of elevated AST and jaundice; later anti-HBs (antibody against surface antigen)
window period - anti-HBc IgM (antibody to core antigen); HBeAg (pre-core antigen) represents a high level of viral replication chronic - persistence of HBsAg or HBeAg for more than 6 weeks of infection |
|
|
29 year old man has weight loss, whigh plaques on the pharynx, and purple lesions on the abdomen, which on biopsy reveals Kaposi sarcoma; what virus most likely infects this patient?
|
Human Immunodeficiency Virus (HIV)
|
|
|
to what does HIV bind?
what cells does it infect? |
CD4 surface receptor
macrophages, T lymphocytes, glial cells |
|
|
what serologic testing is used to diagnose HIV?
|
HIV ELISA and western-blot analysis or PCR
|
|
|
to what subfamily and family does HIV belong?
|
subfamily - Lentivirinae
family - retroviridae |
|
|
describe the HIV virus
|
spherical, enveloped RNA virus with a cone-shaped capsid that contains two copies of a positive-strand RNA genome
|
|
|
how does HIV enter cells of macrophage and T helper lineage?
|
binds to CD4 surface receptor protein, and then fuses envelope with cellular membrane
|
|
|
what happens once HIV is in the hos cell cytoplasm?
|
RNA-dependent DNA polymerase enzyme (reverse transcriptase), which is present in the viral capsid, uses the viral RNA to synthesize viral DNA
DNA is transported to nucleus and then spliced into host genome integrated DNA acts as a host cellular gene, and is transcribed by host RNA polymerase II to produce new copies of viral RNA and proteins |
|
|
what is the primary cause of immunosuppression by HIV?
|
reduction in the helper and delayed type hypersensitivity responses mediated by CD4 T cells
|
|
|
what serves as a reservoir and means of distribution of HIV?
|
infected macrophages
|
|
|
how does HIV evade the immune system?
|
inactivation of central components of host immune system (T helper cells and macrophages)
high genetic drift of virus, reducing immune system recognition |
|
|
what causes high genetic drift in HIV?
what is the advantage of this to HIV? |
intrinsic genetic instability as a result of errors caused by reverse transcriptase
harder for immune system to recognize it |
|
|
how is Acquired Immune Deficiency Syndrome (AIDS) defined?
|
presence of HIV
reduction of CD4 T cells AND acquisition of characteristic opportunistic infections |
|
|
what is a retrovirus?
|
an RNA virus that has an enzyme called reverse transcriptase that gives them the unique property of transcribing RNA into DNA
|
|
|
HAART
|
Highly Active AntiRetroviral Therapy
treatment for HIV infection that uses a combination of several antiretroviral drugs, which inhibit the ability of the virus to multiply in the body (interfere with actions of reverse transcriptase and block proteases that activate the virion) and slow development of AIDS |
|
|
from what does HIV appear to be derived from?
|
primate (esp. chimpanzee) lentiviruses
|
|
|
when was AIDS first described?
when was the virus first isolated? |
1981
1983 |
|
|
what type of genome does HIV have?
|
two copies of a positive-sense single-stranded RNA genome
|
|
|
what type of RNA is oriented in the same direction as messenger RNA?
|
positive-sense
|
|
|
what retrovirus has the most complex genome?
|
HIV
|
|
|
why is it difficult to develop a vaccine to HIV?
|
lipid envelope contains glycoproteins that undergo antigenic variation
|
|
|
is HIV enveloped or not?
|
yes
|
|
|
what is a provirus?
|
a virus genome that is integrated into the DNA of a host cell
|
|
|
how are HIV virions released from host cells?
|
bud from plasma membrane
|
|
|
what gene is especially heterogeneous in a single individual infected with HIV?
|
env gene
|
|
|
what is important about the gp120 viral receptor?
|
binding domains responsible for viral attachment to the CD4 molecule and coreceptors
also determines cell tropisms (lymphocyte vs. macrophage) cause antibodies to be formed by host that are only weakly neutralizing to the virus |
|
|
what is important about the gp41 product of HIV?
|
contains a transmembrane domain that anchors glycoproteins to the viral envelope
contains a fusion domain that facilitates viral entry into host cells |
|
|
by what treatments (for 10 minutes at room temperature) can HIV be inactivated?
|
10% bleach
50% ethanol 35% isopropanol 0.5% paraformaldehyde 0.3% hydrogen peroxide |
|
|
by what is HIV inactivated when it's in blood in a needle or syringe?
|
exposure to undiluted bleach for 30-60 seconds
|
|
|
how can HIV in 10% serum be inactivated?
what is the limitation to this method? |
heating at 56degC (133degF) for 10 minutes (same as complement inactivation)
HIV in dried protein-containing mixtures is protected |
|
|
what must be done to lyophilized blood products to ensure inactivation of contaminating HIV viruses?
|
heated at 68degC (154degF) for 72 hours
|
|
|
what is lyophilization?
|
freeze-drying
|
|
|
how is HIV diagnosed?
|
virus isolation (usually considered a research technique)
**detection of antiviral antibodies** **measurement of viral nucleic acid or antigen** |
|
|
what is an excellent correlate of the clinical stage of HIV infection?
|
magnitude of plasma viremia
(compared to presence of antibodies) |
|
|
when do most HIV-infected individuals become seropositive?
|
6-12 weeks after infection
essentially all will be antibody positive in 6 months |
|
|
what is usually detected by Western blot tests for HIV?
|
viral core protein p24, envelope glycoproteins gp41, gp120, gp160
|
|
|
what is the limitation to HAART?
|
large numbers of HIV-infected patients worldwide do not have access to the drugs
|
|
|
what pathogen is commonly responsible for blindness in advanced HIV infections?
|
cytomegalovirus
|
|
|
6-year-old boy has tender inflammation of the parotid glands and fever; what is most likely infecting him?
|
mumps virus
|
|
|
what has mumps been decreased by over 99 percent in the United States?
|
routine vaccination with live, attenuated mumps virus (MMR vaccine)
|
|
|
how many known serotypes of mumps are there?
|
only one
|
|
|
what age are 90% of children typically infected by?
|
15 years old
|
|
|
what is parotitis?
|
inflammation of the parotid glands; large salivary glands located on each side of the face below and in front of the ear
|
|
|
hemagglutinin-neuraminidase protein
|
viral capsid glycoprotein involved with viral attachment, fusion, and enzymatic hydrolysis of various proteins; also produces nonspecific agglutination of red blood cells used for diagnostic assay of mumps virus
|
|
|
what is orchitis?
|
inflammation of the testes
|
|
|
what is oophoritis?
|
inflammation of one or both ovaries
|
|
|
to what family does the mumps virus belong?
|
paramyxoviridae
|
|
|
what are the characteristics of paramyxoviridae viruses?
|
enveloped viruses, with single-stranded, negative-sense RNA genome
|
|
|
what are the two glycoproteins contained in the envelope of the paramyxoviridae viruses?
|
hemagglutinin-neuraminidase protein (attachment)
membrane fusion protein (entry) |
|
|
how is the mumps virus transmitted?
|
direct contact with contaminated respiratory droplets or saliva or via fomites
|
|
|
what cells does the mumps virus infect?
|
epithelial cells of the mouth or nose
|
|
|
to what does the mumps virus bind on the target cell membrane?
|
sialic acid
results from virus fusing with the host cell membrane via the specific viral attachment and surface fusion proteins |
|
|
where do transcription, replication, protein synthesis and assembly of mumps viruses take place?
|
cytoplasm of the host cell
|
|
|
how do newly formed mumps virions acquire their outer envelope?
|
budding through the host cell membrane
|
|
|
describe the path of infection of the mumps virus
|
initial infection in epithelial cells of mouth or nose
infection spreads to salivary glands (parotids or others) either by ascending infection into the gland through Stensen duct or by viremia |
|
|
what is Stensen duct?
|
parotid duct
|
|
|
what most often causes the symptoms of mumps?
|
inflammatory response of the host immune system
|
|
|
what factors promote person-to-person spread of mumps?
|
many mumps infections are subclinical, but still contagious
infected persons are contagious even 1-2 weeks prior to developing symptoms |
|
|
why is mumps infection rarely seen in infants less than 6 months old?
|
passive immunity is transferred from mothers to newborns
|
|
|
how is mumps diagnosed?
|
clinical presentation alon with a patient history that lacks MMR vaccine
|
|
|
what are the clinical symptoms of mumps?
|
acute onset of fever and malaise, followed by painful bilateral or unilateral swelling of the parotid or other salivary glands
10-20% of cases progress to more severe infections with CNS involvement (aseptic meningitis or meningoencephalitis) in adolescent children and adults additional complications may include orchitis, oophoritis, and pancreatitis (rarer and primarily in immunocompromised hosts) |
|
|
how can rapid confirmation of mumps be obtained?
|
direct viral antigen detection via immunofluorescence analysis from saliva, CSF, or urine
|
|
|
what are the cytopathic effects of mumps virus?
|
cell rounding
syncytia formation |
|
|
what is the treatment for mumps?
|
usually self-limiting, but treated with supportive care (fluid, rest, anti-inflammatories)
isolation for a week after symptoms begin |
|
|
62 year old man with flaccid paralysis of right leg; lives with grandchildren who were recently given an oral vaccine; what is the most likely infectious cause of his symptoms?
|
poliomyelititis, caused by poliovirus
most likely from fecal-oral transmission from one of his grandchildrent (recently vaccinated with live-attenuated poliovirus vaccine) |
|
|
what animals can polio infect?
|
exclusively humans
|
|
|
how does poliovirus infection result in flaccid paralysis?
|
destroys motor neurons of the spinal cord
|
|
|
what are the two polio vaccines?
|
live-attenuated - Sabin - administered orally
inactivated - Salk - injected |
|
|
what is the danger which accompanies the Sabin vaccine?
|
since the virus is live-attenuated, it can be passed to close contacts
|
|
|
what is poliomyelitis?
|
inflammation and destruction of the gray matter of the spinal cord, which can result in paralysis
|
|
|
what is in the Sabin vaccine?
|
attenuated live poliovirus, obtained by multiple passages of three types of poliovirus through tissue culture cells
|
|
|
what is in the Salk vaccine?
|
large dose of poliovirus antigen that will elicit a protective antibody response without risk of spreading infection
|
|
|
to what genus and family does poliovirus belong?
|
genus - enterovirus
family - picornaviridae |
|
|
describe the characteristics of poliovirus
|
small, nonenveloped virus with single-stranded, positive-sense RNA genome
|
|
|
is poliovirus enveloped or not?
|
not enveloped
|
|
|
what type of genome does poliovirus have?
|
single-stranded, positive sense RNA genome
at 5' end, a small protein called VPg at 3' end, polyadenylation |
|
|
what is the shape of the capsid of poliovirus?
|
icosahedral capsid composed of four polypeptides (VP1-VP4) that are necessary for maintaining virion structure, attachment to specific host cell receptors, and entry into cells
|
|
|
what is VPg?
what is its function? |
small protein at the 5' end of the poliovirus genome (RNA)
promotes cap-independent association of the poliovirus genome with host cell ribosomes and allows translation of viral proteins to occur |
|
|
how are poliovirus proteins produced?
|
entire genome is transcribed into a single polyprotein that is proteolytically cleaved to produce all of the virally encoded proteins
|
|
|
what is the function of the viral protease produced by poliovirus?
|
specifically degrades the 5' cap proteins from cellular mRNAs and thus preferentially inhibits translation of host mRNA
|
|
|
how do poliovirus virions exit cells?
|
lyse the membrane and cause direct damage to infected cells
|
|
|
what is the main mode of transmission of poliovirus?
|
fecal-oral transmission
|
|
|
what is the main mode of transmission of enteroviruses?
|
fecal-oral transmission
|
|
|
describe the infectious cycle of poliovirus
|
viral particles enter through the mouth and primary replication occurs in oropharynx, tonsils, and lymph nodes or in the intestinal epithelium and adjacent lymphoid tissue
in immune-competent individuals, infection stops here and is asymptomatic in immunodeficient individuals or unvaccinated individuals, spreads via minor viremia to anterior horn cells of the spinal cord, dorsal root ganglia, motor neurons, skeletal muscle cells, and lymphoid cells |
|
|
how can poliovirus survive the stomach?
|
it is resistant to a wide range of pH levels
|
|
|
what limits the specificity of poliovirus for cells?
|
specific receptor recognized by the capsid VP proteins
|
|
|
how does poliovirus enter host cells?
|
binds to receptor
RNA genome is inserted into the host cytoplasm through a channel created in the membrane |
|
|
where do transcription and replication of poliovirus genome take place?
|
host cell cytoplasm
|
|
|
what are the four types of infection caused by poliovirus?
|
asymptomatic illness
abortive poliomyelitis nonparalytic poliomyelitis paralytic poliomyelitis |
|
|
what is asymptomatic illness (in reference to poliovirus)?
|
poliovirus infects oropharynx or intestinal epithelium, but host immune system (antibodies) keep it from spreading to other sites, so there are no symptoms
|
|
|
what is abortive poliomyelitis?
|
poliovirus infects oropharynx or intestinal epithelium and then spreads via minor viremia to the anterior horn cells of the spinal cord, etc.; from these cells, replication leads to a major viremia; at this point, the condition is abortive poliomyelitis if it is controlled by host antibody response
patient has nonspecific symptoms that include fever, sore throat, and headache, and rarely spreads to CNS or meninges |
|
|
what is non-paralytic poliomyelitis?
|
poliovirus spreads via major viremia or via ascending infection through peripheral nerves to the CNS, but does not cause cytolytic damage/paralyze
|
|
|
what causes paralytic poliomyelitis?
|
cytolytic damage caused by virus, not immune response
|
|
|
how is poliovirus diagnosed?
|
clinical presentation
recovery and culture of virus from clinical samples (throat swabs shortly after infection; rectal swabs and stool specimens up to 30 days post onset) |
|
|
why is poliovirus not diagnosed from CNS fluid?
|
even when there is CNS and meningeal involvement, poliovirus is rarely recovered from CNS fluid
|
|
|
how is poliovirus infection prevented?
|
universal vaccination
|
|
|
what are the advantages to the Sabin vaccine?
|
creates a secretory antibody (IgA) in the GI tract
easily administered (oral) |
|
|
what polio vaccination is recommended in the United States?
what is the schedule for vaccination? |
inactivated (Salk) vaccine, which induces humoral antibodies, but does not carry the risk of vaccine-induced disease
primary series of four inoculations within a 1-2 year period, with periodic boosters administered as necessary later in life |
|
|
a 3 year old boy who attends day care develops gastroenteritis in the winter; what is the most likely cause of the child's illness?
|
rotavirus
|
|
|
how is rotavirus activated to form an infectious particle?
|
outer capsid layer must be lysed by gastrointestinal proteases to create an infectious subviral particle
|
|
|
what is reassortment?
|
the formation of new virions with hybrid genomes assembled in cells with mixed viral infections; it occurs among viruses containing segmented genomes (i.e. influenza viruses and reoviruses) resulting in high genetic variation
|
|
|
what is intussusception?
|
blockage of the intestines as a result of the bowel telescoping into itself
|
|
|
what worldwide ubiquitous virus is estimated to cause more than 50 percent of gastroenteritis cases in children less than 2-3 years of age?
|
rotaviruses
|
|
|
when do rotavirus infections typically happen?
|
cold months
|
|
|
what are the symptoms of rotavirus infections?
|
abrupt onset of vomiting followed by frequent watery diarrhea
|
|
|
in what populations are rotavirus outbreaks common?
|
children that attend day care
children in preschool people in hospital settings |
|
|
rotavirus is a genera of what family?
|
Reoviridae
|
|
|
describe a rotavirus
|
double-layered protein capsid that contains a genome made of 11 segments of double-stranded, negative-sense RNA
double capsid looks like a wheel with short spokes connecting the outer capsid with the inner capsid and core |
|
|
what gives the rotavirus its name?
|
its double layered protein capsid looks like a wheel with short spokes connecting the outer capsid to the inner capsid and core
|
|
|
what type of genome does rotavirus have?
|
11 segments of double-stranded, negative sense RNA
|
|
|
how many genera are there within the family Reoviridae?
|
four genera
|
|
|
are rotaviruses enveloped or not?
|
not enveloped
|
|
|
what allows rotaviruses to retain infectivity through a wide range of pH, temperature, and many detergents?
|
being nonenveloped
would be inactivated by an empty stomach, but not in a buffered stomach or in the gastric environment following a meal |
|
|
how are rotaviruses transmitted?
|
**fecal-oral transmission**
fomite transmission |
|
|
why are GI proteolytic enzymes important to rotaviruses?
|
they partially digest the outer capsid, creating an infectious subviral particle (ISVP)
cleaves VP4, a surface protein of the rotaviruses, allowing it to bind to the surface of intestinal epithelial cells and allow the ISVP to enter by direct penetration |
|
|
what happens when rotaviruses enter an intestinal epithelial cell?
|
RNA genome remains in the viral core and is transcribed into mRNA by a viral polymerase
mRNA is transported to the cytoplasm, where it is translated and assembled into new virions initially assembled like an enveloped virus, budding through the ER and taking a part of the membrane as an "envelope" which is soon lost as the virions travel through the ER released from the host cell by cell lysis |
|
|
by what are rotaviruses classified?
|
antigenic epitopes of VP6, an inner capsid protein
classified into at least 3 major subgroups and nine different serotypes |
|
|
what allows rotaviruses to have such high genetic variation?
|
segmented nature of genome, allowing reassortment of genome sequences in mixed infections
results in high numbers of serotypes for viral group and allows for reinfection of persons previously exposed to one rotaviral serotype |
|
|
what is the mechanism by which large numbers of rotaviral particles are found in the stool?
|
rotavirus infects cells of small intestinal villi and multiply in the cytoplasm of enterocytes
damaged cells are sloughed off releasing large numbers of viral particles into the stool virus can be excreted for days to weeks after infection |
|
|
what problems are caused by rotavirus infections?
|
prevents absorption of water, sodium, and glucose, causing loss of water and electrolytes
virally encoded nonstructural protein also acts as an enterotoxin |
|
|
what are the typical symptoms of rotaviral infections?
|
fever
vomiting abdominal pain watery diarrhea w/o blood or mucus symptoms last approximately one week, with viral excretion lasting weeks longer |
|
|
in what populations do rotavirus infections become severe and cause prolonged illness?
|
immunodeficient and malnourished children
|
|
|
what is the best means of relative protection from rotavirus infection?
|
high levels of rotavirus IgA in the lumen of the intestine
|
|
|
how is rotavirus diagnosed?
|
detection of viral antigens in stool samples via enzyme immunoassay and latex agglutination
|
|
|
why is viral culture not used diagnosis of rotavirus?
|
it is difficult and unreliable
|
|
|
what is the treatment for rotaviral infection?
|
supportive therapy, including replacement of fluids and electrolytes to restore physiologic balance and prevent dehydration
oral and IV rehydration therapy are effective and which one is used depends on severity of dehydration |
|
|
why was the attenuated recombinant rotavirus vaccine approval withdrawn?
when was the new one released? |
it was associated with intussusception among vaccine users
2006 |
|
|
caliciviruses (summary)
|
nonenveloped RNA viruses that cause watery diarrhea, especially in children
|
|
|
paramyxoviruses (summary)
|
enveloped RNA viruses that cause childhood respiratory and exanthemous infections
|
|
|
parainfluenza viruses (summary)
|
enveloped RNA viruses which cause respiratory infections such as croup, bronchiolitis, and pneumonia in children
|
|
|
coxsackie viruses (summary)
|
nonenveloped RNA viruses that cause nonspecific respiratory tract infections, febrile rashes, and meningitis
|
|
|
10 month old female presents with bronchiolitis. a chest x-ray shows hyperaeration but no infiltrates. what is the most likely infectious cause of her respiratory illness?
|
respiratory syncytial virus (RSV)
|
|
|
after someone has RSV, are they protected from getting it again?
|
immunity developed with an RSV infection is incomplete, and reinfections are common, however the severity of repeat infections appears reduced, esp. in older children and adults
|
|
|
what is the single most common cause of fatal respiratory tract infections in infants under 12 months?
|
respiratory syncytial virus (RSV)
accounts for approx. 25% of pediatric hospitalizations under 12 months, resulting in severe respiratory illnesses such as bronchiolitis, pneumonia, and respiratory failure |
|
|
in what populations is RSV infection most prominent?
|
children who attend day care
(70-95% are infected by 3-4 years of age) |
|
|
what is bronchiolitis?
|
inflammation of the bronchioles or thin-walled branches of the lungs
caused by inflammation and plugging of the bronchi and bronchioles with mucous and necrotic tissue from immune-mediated cellular damage |
|
|
what is otitis media?
|
inflammation of the middle ear marked with pain, fever, dizziness and abnormal hearing
|
|
|
what is pneumonia?
|
respiratory condition in which there is infection of the lung
|
|
|
to what genus and family does RSV belong?
|
genus: pneumovirus
family: paramyxoviridae |
|
|
is RSV enveloped or not?
|
yes
|
|
|
what type of genome does RSV have?
|
single-stranded, negative-sense RNA genome
|
|
|
how is RSV transmitted?
|
inhalation of aerosolized respiratory droplets
survives on nonporous surfaces (countertops) for 3-30 hours but is inactivated by many detergents, changes in temp. or pH |
|
|
what is caused by RSV?
|
common cause of upper and lower respiratory infection in all age groups
severe, lower respiratory disease in infants and young children |
|
|
where do RSV infections remain localized?
|
respiratory tract (epithelial cells)
|
|
|
how does RSV enter respiratory epithelial cells?
|
fusion of its envelope with host cytoplasmic membrane via two viral envelope glycoproteins
|
|
|
how do the envelope glycoproteins of RSV differ from those of influenza virus or parainfluenza virus?
|
RSV glycoproteins don't possess hemagglutinin or neuraminidase activity
|
|
|
where do RNA transcription, protein synthesis, replication, and assembly of RSV occur?
|
cytoplasm
|
|
|
how are newly synthesized RSV virions released from infected cells?
|
budding from infected cells
|
|
|
what cytopathic quality does RSV have?
|
capable of promoting cell-cell fusion, resulting in multinucleated giant cells known as syncytia
(from where it derives its name) |
|
|
what are the symptoms of RSV?
|
adults and older children - mild upper respiratory tract symptoms (runny nose, mild cough) lasting 1-2 weeks
infants or younger children - more serious illness such as bronchiolitis, cough, tachypnea, respiratory distress, wheezing, hypoxia |
|
|
in what population is mortality from RSV high?
|
infants with underlying disease or reduced immune function
typical causes of death are respiratory failure, cor pulmonale (right-sided heart failure), or bacterial superinfection |
|
|
how is RSV diagnosed?
|
clinical symptoms
viral genome (RT-PCR from nasal washings or antigen detection (immunofluorescence analysis on exfoliated epithelial cells or ELISA on nasal secretions) culture (samples inoculated immediately into cell cultures b/c of labile nature of RSV; recognized by formation of syncytia in culture in 1-2 weeks |
|
|
how is RSV treated?
|
supportive care including oxygenation, ventilatory support, IV fluids, and nebulized cold steam
aerosolized ribavirin (antiviral agent) for high risk infants and severe lower respiratory tract illnesses caused by RSV infection |
|
|
how is RSV prevented?
|
passive immunization in premature infants (monoclonal antibodies; called Synagis)
hand washing, isolation of infected infants, changing of gloves, gowns, and masks between patients in neonatal ICU |
|
|
what are the four basic classes of microorganisms?
|
viruses, bacteria, protozoa, fungi
|
|
|
viruses
|
obligate intracellular parasites
non-cellular and require host machinery to replicate |
|
|
what is the component of a virus that replaces a cell wall?
|
capsid (rigid protein coat)
|
|
|
where (on a virus) are antigenic proteins for attachment to host cells found?
|
tail (narrower end of the virus)
|
|
|
how big is the range of virus diameters?
|
15nm-450nm
|
|
|
what are the possible shapes for viruses?
|
spherical
tetrahedral polygonal rod-shaped polyhedral |
|
|
bacteria
|
single-celled prokaryotes
|
|
|
of what does the cell wall of bacteria consist?
|
complex of sugar and amino acids, esp. peptidoglycan
|
|
|
what surrounds the cytoplasm of bacteria?
|
cell wall
& cell membrane |
|
|
what major characteristic makes bacteria like other prokaryotes?
|
unbound nucleus
|
|
|
what are the possible basic shapes for bacteria?
|
cocci (spherical)
bacilli (rod-shaped) vibrio (comma-shaped) spirilla (corkscrew) |
|
|
of what two groups of organisms do parasites usually consist?
|
protozoans
helminthes |
|
|
what are helminthes?
what are the two classes? |
worms
flatworms (platyhelminths) roundworms (nemathelminths) |
|
|
what three phyla of protozoa infect humans?
|
sarcomastigophora (flagellates and amoebas)
ciliophora (ciliates) apicomplexa (sporozoans) |
|
|
in what two basic forms do fungi grow?
|
yeasts
molds |
|
|
are fungi eukaryotic or prokaryotic?
|
eukaryotic
|
|
|
how do molds usually appear?
|
multicellular filamentous colonies, with branching cylinder-like tubules (hyphae)
|
|
|
how do yeasts usually appear?
|
single cells, usually spherical or ellipsoid in shape
|
|
|
how do yeasts reproduce?
|
mostly by budding
|
|
|
what happens when yeast buds fail to break off?
|
form elongated yeast cells (pseudohyphae)
|
|
|
how are fungi classified?
|
ability to produce superficial vs. deep invasive infection
appearance sexual reproduction characteristics |
|
|
what is a clinical database?
|
conglomeration of history, physical, and laboratory tests
|
|
|
what does a gram stain stain?
|
peptidoglycan
useful for most bacteria |
|
|
for what type of bacteria is acid-fast stain useful?
|
mycobacterium
|
|
|
what techniques are useful for detecting dificult-to-culture organisms?
give an example of one such organism |
immunofluorescence techniques
legionella |
|
|
what is the purpose of susceptibility testing?
|
assess the likelihood that certain antimicrobial agents will be effective against the particular strain of pathogen
|
|
|
what is minimum inhibitory concentration (MIC)?
|
lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after incubation
|
|
|
what is minimum bactericidal concentration (MBC)?
|
lowest concentration of antibiotic required to kill a microorganism
|
|
|
5 year old with conjunctivitis of both eyes, with nonpurulent drainage associated with an upper respiratory infection. what is the most likely infectious cause?
|
adenovirus
|
|
|
to what receptor on host cells do adenoviruses bind?
|
coxsackie adenovirus receptor (CAR)
followed by receptor mediated endocytosis |
|
|
where does the replication of adenovirus genome take place?
|
host cell nucleus
uses virally encoded DNA polymerase |
|
|
where are capsid proteins made for adenoviruses?
where does assembly occur? |
cytoplasm
nucleus |
|
|
what is conjunctivitis?
|
inflammation of eye tissue
a normal feature of many childhood infections, however most commonly caused by infection with adenoviruses |
|
|
in what cells do adenoviruses cause lytic infections?
latent infections? |
lytic - epithelial cells
latent - lymphoid tissue |
|
|
how do most adenoviral diseases play out in immune competent individuals?
in immunocompromised individuals? |
mild and self-limiting
viremia is common in immunocompromised individuals |
|
|
what population is infected with adenoviruses most commonly?
|
children, more commonly than adults
|
|
|
what is preauricular adenopathy?
|
enlargement of lymph node(s) anterior to the ear
|
|
|
are adenoviruses enveloped or not?
|
not enveloped
|
|
|
what type of genome do adenoviruses have?
|
linear, double-stranded DNA with terminal protein on both 5' ends of genome
|
|
|
what is the shape of the capsid of adenoviruses?
|
icosadeltahedral with a penton base and fiber at each vertex
|
|
|
what is determined by the fibers at the vertices of adenovirus capsids among serotypes?
|
target cell specificity, via viral attachment proteins
also serves as a hemagglutinin |
|
|
how are the genomes of adenoviruses replicated?
|
from both strands
single cycle takes 32-36 hours and produces about 10,000 new virions |
|
|
what causes the number of infectious particles from adenovirus replication to be much lower than the number of virions produced?
|
errors in replication and assembly are common
|
|
|
what are the target tissues of adenoviruses?
|
epithelial cells of respiratory tract
conjunctiva of eyes enteric organs |
|
|
what are the modes of transmission of adenoviruses?
|
aerosolized respiratory droplets
close contact fecal-oral transmission fomites |
|
|
why can non-enveloped viruses be transmitted by fomites?
|
they are more resistant to detergents and dessication
|
|
|
what are the symptoms of adenovirus infection?
|
fever
cough nonstreptococcal exudative pharyngitis cervical adenitis conjunctivitis gastroenteritis in more severe cases, could cause laryngitis, bronchiolitis, or pneumonia typically found in children under 3, lasting 3-5 days |
|
|
what is adenoviral follicular conjunctivitis?
|
pink eye
|
|
|
what is a common source for outbreaks of pink eye?
|
swimming pools
|
|
|
what adenoviral types are associated with GI disease in infants and hospitalized patients?
|
40, 41, 42
|
|
|
what adenoviral types are associated with acute respiratory infections?
where are vaccines to these types used? |
4,7
military settings |
|
|
what are the tests that can identify adenoviruses?
|
cell culture
ELISA PCR DNA-probe analysis |
|
|
how is adenovirus infection diagnosed?
|
clinical presentation and patient history
|
|
|
why are adenovirus vaccines not available to the general public?
|
some adenoviruses are oncogenic
|
|
|
1 day old male with microcephaly, jaundice, hepatosplenomegaly and deafness caused by a viral infection. what is the most likely cause of this child's illness?
|
congenital infection with cytomegalovirus
|
|
|
how is congenital cytomegalovirus most likely transmitted?
|
transplacentally during a primary CMV infection of the pregnant mother
|
|
|
what is the definitive diagnostic test for CMV?
|
demonstrate presence of CMV in patient's urine
|
|
|
what does lymphotrophic mean?
|
having a specific affinity for lymph cells and their precursors
|
|
|
what is microcephaly?
|
abnormally smaller sized head, which may be associated with mental retardation
|
|
|
what is a subclinical infection?
|
without the presence of noticeable clinical disease
|
|
|
to what family and subfamily does CMV belong?
|
family - Herpesviridae
subfamily - betaherpesvirinae |
|
|
what is the largest known virus that infects humans?
|
cytomegalovirus (CMV)
|
|
|
is CMV enveloped or not?
|
enveloped
|
|
|
what type of genome does CMV have?
|
linear, double-stranded DNA
|
|
|
what shape is the capsid of CMV?
|
icosadeltahedral
|
|
|
what family of viruses have a tegument?
|
herpesviridae
|
|
|
what is a tegument?
|
phosphoprotein-containing matix, between the envelope and the capsid, which plays a role in initiating replication
|
|
|
what are the target tissues for CMV?
|
lymphocytes
leukocytes kidney heart lung |
|
|
what results in reactivation of a latent CMV infection and severe, symptomatic disease?
|
suppression of immune system (by medications or infections)
|
|
|
what population is typically infected with CMV?
|
children (10-15% before 5yo)
immunocompromised individuals |
|
|
how does CMV present?
|
in immunocompetent individuals, infection is usually asymptomatic, though occasionally presents as a mononucleosis-like syndrome
|
|
|
what are the modes of transmission for CMV?
|
contact with blood
oral secretions sexual contact organ transplant congenital infection |
|
|
what is the most common viral cause of congenital disease and infection?
|
CMV
|
|
|
how many infants experience problems with congenital CMV?
|
only 1% are infected in utero or during delivery
of this 1%, 90% are asymptomatic and 10% are symptomatic |
|
|
what is interesting of the 0.1% of infants who present with symptomatic CMV infections?
|
nearly all of them are born of mothers that had primary CMV infections during the pregnancy
|
|
|
what is the link between pregnancy and CMV infection?
|
primary maternal infection with CMV during pregnancy increases risk of fetal infection and severity of symptoms
reactivation of a latent infection has a much lower risk for fetus, because it is protected by maternal immune response |
|
|
what are the symptoms/complications of congenital CMV syndrome?
|
microcephaly
intracerebral calcifications hepatosplenomegaly thrombocytopenia chorioretinitis deafness mental retardation jaundice rash many die and those who survive have persistent neurologic deficits |
|
|
what are the treatments for CMV?
|
ganciclovir (prevents CMV disease in AIDS patients and transplant recipients; also reduces severity of retinitis and GI disease)
immune globulin plus ganciclovir (reduces mortality of CMV pneumonia in bone marrow transplant patients) foscarnet |
|
|
how is CMV infection prevented?
|
ganciclovir (AIDS patients and transplant recipients)
hygiene and handwashing isolation of infected infants seronegative donors for transplants or prophylactics where seronegative donors are unavailable safe sex no vaccines currently available |
|
|
17 year old female with fever, exudative pharyngitis and adenopathy develops a prominent macular-papular rash after ampicillin is instituted; what is the most likely infectious cause of her ailment?
|
infectious mononucleosis caused by Epstein-Barr virus (EBV)
|
|
|
where does EBV preferentially replicate?
where does it cause latent infection? |
replicates - epithelial cells & B cells
latent infection - B cells |
|
|
to what family and subfamily does EBV belong?
|
family - Herpesviridae
subfamily - gammaherpesvirinae |
|
|
what are the natural hosts of EBV?
|
only humans
|
|
|
why is EBV often called the kissing disease?
|
it occurs by repeated close intimate contact or through sharing of items contaminated with saliva, because it is intermittently shed in the saliva of most seropositive individuals
|
|
|
why are secondary attack rates of EBV low with family and household contacts?
|
90-95% of adults have previously been exposed to EBV
|
|
|
though most primary EBV infections are asymptomatic, what are the symptoms of a primary EBV infection?
|
fever
fatigue pharyngitis tender lymphadenitis hepatosplenopathy |
|
|
why do many EBV patients develop allergic rashes to amoxicillin?
|
symptomatic EBV infections are simmilar to, and therefore often misdiagnosed as, streptococcal pharyngitis
treatment for streptococcal pharyngitis is amoxicillin, but as it's inappropriate, it can cause an allergic rash |
|
|
what is lymphocytosis?
|
larger than normal number of T lymphocytes
|
|
|
what are atypical lymphocytes in cases of EBV infections?
|
enlarged T lymphocytes, also referred to as "Downey cells," with eccentric nuclei and a vacuolated cytoplasm
these appear at the onset of EBV infection |
|
|
what are heterophile antibodies?
when and how are they detectable? |
nonspecific B cell antibodies, including an IgM antibody that recognizes the Paul-Bunnell antigen on sheep, horse, and bovine erythrocytes
detectable from 1 week after onset to several months later by monospot test and ELISA |
|
|
is EBV enveloped or not?
|
enveloped
|
|
|
what type of genome does EBV have?
|
double-stranded, linear DNA
(172kb, encoding >70 viral proteins) |
|
|
what is the shape of the capsid of EBV?
|
icosadeltahedral
|
|
|
why are the glycoprotein spikes on the outer membrane of EBV important?
|
important for host cell attachment to human B cells and epithelial cells of the oropharynx and nasopharynx
|
|
|
what receptor is utilized by EBV?
|
complement component C3d receptor
|
|
|
why can enveloped viruses not be transmitted by fomites?
|
they are generally easily disrupted by acids, detergents, and dessication
|
|
|
what are the two infectious subtypes of EBV?
what is different between them? |
EBV-1
EBV-2 closely related except for differences in their nuclear antigens |
|
|
what are early viral antigens?
|
nonstructural proteins expressed at the onset of lytic viral infection
|
|
|
what are late viral antigens?
|
structural components of the viral capsid and viral membrane
|
|
|
what are latent phase antigens in EBV?
|
those proteins expressed in latently infected B cells
include epstein-barr nuclear antigens, latent proteins, and latent membrane proteins |
|
|
in association with what disease was EBV discovered?
|
(African) Burkitt lymphoma
|
|
|
what is the cofactor disease for EBV?
|
malaria
|
|
|
what diseases are related to EBV?
|
malaria
nasopharyngeal carcinoma B-cell lymphoma* interstitial lymphocytic pneumonia* hairy leukoplakia of the tongue* *-in immunocompromised patients |
|
|
why is EBV found in the saliva of infected individuals?
|
lytic infection of epithelial cells promotes virus shedding into the saliva
allows transmission to other hosts and within same host |
|
|
what are the effects of EBV on B cells?
|
promotes cell growth
prevents apoptosis induces production/secretion of heterophile antibody (IgM antibody to Paul-Bunnell antigen) |
|
|
what happens to persons that have inadequate T cell immunity and are infected with EBV?
|
can't suppress EBV infection
progress to lymphproliferative disease, B-cell lymphomas, or Hodgkin disease |
|
|
in what populations is nasopharyngeal carcinoma primarily seen?
with what conditions is this associated? |
asian
aleutian EBV infection genetic component environmental component |
|
|
what are the rarer, but serious complications of EBV infection?
|
laryngeal obstruction
meningitis encephalitis hemolytic anemia thrombocytopenia splenic rupture |
|
|
what are the treatments and prevention of EBV?
|
no effective treatment
no vaccine available speculation that early exposure to EBV may prevent more severe infections and symptomatic disease |
