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B2A5 Micro
STDs
266
Microbiology
Professional
09/01/2011

Additional Microbiology Flashcards

 


 

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Term
What bugs account for 60-80% of STIs with primary symptoms of dysuria and exudation?
Definition
chlamydia trachomatis, neisseria gonorrhoeae, and ureaplasma urelyticum
Term
Dx tests for dysuria and exudation?
Definition
nucleic acid amplification tests (NAAT) on urine and exudates
Term
Number one reportable disease in USA? Cases/year?
Definition
chlamydia, about 1 milion
Term
Number two reportable disease in USA?
Definition
gonorrhea, about 300,000
Term
Sequalae for Ct/GC lower GU infections?
Definition
spread to upper GU causing pelvic inflammatory disease, sterility and ectopic pregnancy
Term
Conditions caused by Ct/GC infection of newborn?
Definition
conjunctivitis (Ct/GC) and/or pneumonia (Ct)
Term
If a pt is positive for GC, whats the likelyhood they also have Ct?
Definition
fifty percent
Term
Describe the chlamydia trachomatis bug?
Definition
G- obligate intracellular parasite that grows in tissue culture but not artificial medium. Has distinctive intracellular developmental cycle. It is the chlamydia trachomatis D-K bugs that cause chlamydia
Term
Describe the lifecycle of Ct
Definition
two alternating forms: metabolically inert but infectious elementary body (EB) and larger dividing reticulate body (RB). RBs grow within membrane bound vacuole (inclusion body) in the cytoplasm of mucosal epithelial cells (compare with Herpes, which forms a nuclear inclusion body). In a productive infection (as opposed to a persistent infection), the host cell dies by lysis, releasing EBs to infect nearby cells or to be sexually transmitted to a new host.
Term
Which antibiotic is ineffective against Ct and why?
Definition
Because chlamydiae reside in an isosmotic intracellular environment, b-lactam antibiotics are ineffective.
Term
Whats the primary virulence factor of Ct?
Definition
Besides the ability to grow inside of eukaryotic cells, the primary virulence factor of chlamydiae is their ability to cause inflammation (thought to be invoked by a heat shock protein; LPS is of low toxicity)
Term
Describe Neisseria gonorrhoeae
Definition
G- Ox+ non-encapsulated diplococci "kissing kidney beans"
Term
Neisseria: Virulence factors
Definition
LPS and antigenic variation
Term
How is LPS pathogenic
Definition
LPS (often referred to a lipoligosaccharide because of short side chains) is shed during infections and invokes an inflammatory response, which is responsible for much of the pathology seen in localized and disseminated infections.
Term
What are the two mechanisms of antigenic variation utilized by Neisseria gonorrhoeae
Definition
Antigenic variation is achieved by at least two mechanisms involving pili and outer membrane surface proteins (both associated with attachment). The pilus variation is the result of insertion of parts of various silent peptide-encoding loci (PilS) locus with no promoter) into an expression locus (PilE) with a promoter), resulting in huge variety of antigens; this variation can occur multiple times during the course of a single infection.
Term
What part of the immune system kills GC?
Definition
GC are considered extracellular parasites, which are killed when phagocytosed by PMNs
Term
What is a virulence factor that helps GC evade antibodies?
Definition
Secretes IgA1 protease, which distroys IgA1
Term
Does a pt mount a protective immunological response after infection with Ct and/or GC?
Definition
No, Neither Ct nor GC invokes a particularly protective immune response
Term
Does GC desseminate? Ct?
Definition
Some strains of GC can disseminate (cause septicemia and rash). Ct (strains that cause urethritis/cervicitis) are restricted to mucosal epithelial cells; they do not disseminate to the blood or lymph.
Term
Treatment for GC?
Definition
ceftriaxone plus azithromycin or doxyxyxline (because with GC is usually Ct)
Term
Discribe ureaplasma?
Definition
lack cell walls completely thus not susceptible to any beta lactams
Term
Disease caused by ureaplasma
Definition
thought to be significant agents of genital tract infections, especially in women, (particularly problematic during pregnancy and thought to be associated with poor birth outcomes)
Term
Diseases caused by GC and Ct in lower GU tract?
Definition
cervicitis and urethritis
Term
Most common diseases caused by GC and Ct in upper GU tract?
Definition
salpingitis and pelvic inflammatory disease
Term
Other diseases caused by GC and Ct in upper GU tract?
Definition
epididymitis, perihepatitis Fitz-Hugh-Curtis syndrome (imflammation of uterus, ovaduct and liver capsule)
Term
Other sites of disease caused by GC and Ct?
Definition
pharyngitis, rectal infections, conjunctivitis in the newborn (ophthalmia neonatorum usually Ct and rarely GC bc of prophylaxis), infant pneumonia (Ct), disseminated sepsis with rash (GC)
Term
What is Reiters' Syndrome?
Definition
Reactive, non-septic arthritis (immune-response related), Ct, occasionally GC, and following some types of bacterial enterocolitis
Term
what are lab Dx tests for vaginal discharge?
Definition
microscopic or other rapid examination of the discharge
Term
what are the common organisms in Vaginitis?
Definition
Candida albicans, & C. glabrata (agents of a vaginitis referred to as candidasis) & Gardnerella vaginalis, Mobiluncus spp. & other anaerobes (agents of bacterial vaginosis [BV]) are opportunistic microorganisms
Term
Are these organisms normally present in the vagina?
Definition
yes, part of normal flora
Term
If these organisms are part of normal flora, how are they pathogenic?
Definition
they possess virulence factors that allow them to over-colonize the female genital tract & cause disease under certain conditions; however, these factors remain poorly understood
Term
what are some factors allowing the overgrowth of normal flora?
Definition
antibiotic treatment, sexual activity, douching, IUDs, onset of menstrual cycle, pregnancy, tight undergarments
Term
what is a pathogen of the vagina that is sexually transmitted and causes vaginitis?
Definition
trichomonas vaginalis
Term
what type of pathogen is trichomonas?
Definition
single cell protozoan
Term
what can trichomonas cause in males?
Definition
non-gonorrheal urethritis
Term
what are some agents that cause BV?
Definition
Gardnerella vaginalis, Mobiluncus, anaerobes, candida albicans, T. vaginalis
Term
Pt with clear/white discharge with pH 4.5 no odor and under microscope see normal epithelial cells and lactobacilli predominate. Dx?
Definition
uninfected- lactobacilli predominate
Term
Pt with scant white clumped adherent discharge, dysuria, vulvar itching, pain, erythemia. Dx?
Definition
vulvovaginal candidasis
Term
Vaginitis: Pathogen?
Definition
candida albicans most common.
Term
What will you see under microscope with vulvovaginal candidasis?
Definition
leukocytes, epithelial cells, mycelia or pseudomycelia
Term
Pt with profuse yellow/green discharge, frothy and pH >4.5 with dysuria and vulvar itching. Dx?
Definition
trichomonas vaginalis
Term
What will you see under microscope with trichomonas vaginalis?
Definition
leukocytes, twitching trichomonas in 50-70% of positive cases
Term
Pt with moderate white/gray adherent malodorous discharge. Dx?
Definition
bacterial vaginitis
Term
What is a common pathogen with BV?
Definition
gardnerella vaginalis
Term
What will you see under microscope with BV?
Definition
clue cells, few leukocytes and lactobacilli outnumbered by mixed flora
Term
Pt with dysuria, suprapubic pain, significant number of bacteria in urine, polys in urine and low fever. Dx?
Definition
cystitis
Term
Pt with dysuria, suprapubic pain, significant number of bacteria in urine, polys in urine and high fever, back pain. Dx?
Definition
pyelonephritis
Term
Pt with dysuria, mucpurulent discharge, with/with fever and abdominal pain
Definition
cervivitis
Term
How many office visits per year due to vulvovaginitis?
Definition
3 million per year
Term
Positive "whiff test"?
Definition
BV or trichomoniasis
Term
Discribe process of whiff test.
Definition
swab vaginal discharge, add KOH, smell. If fishy odor (due to amines) then BV
Term
cottage cheese discharge?
Definition
candidasis
Term
yellow-green discharge?
Definition
trichomoniasis
Term
Treatment of vaginal candidiasis?
Definition
imidasole intravaginal (3-7 days) or fluconazole (1 day)
Term
Candidiasis vaginitis: Do you need to treat sexual partner?
Definition
not if asymptomatic
Term
Treatment of trichomonal vaginitis?
Definition
metronidazole
Term
Trichomonal vaginitis: Do you need to treat sexual partner?
Definition
yes
Term
Treatment of BV?
Definition
metronidazole or clindamycin cream
Term
BV: Do you need to treat sexual partner?
Definition
no
Term
etiologic agent of syphilis?
Definition
Treponema pallidum
Term
What is the microbiological shape of treponema pallidum?
Definition
spirochete - corkscrew
Term
how do you grow T. pallidum?
Definition
cant grow in lab but can propagate in rabbit testes (sucks for him)
Term
Can T. pallidum cross the placenta?
Definition
yes, causes congenital syphilis
Term
what is the main cause of the pathology of syphilis? (tonin, enzyme, or virulence factor, etc.??)
Definition
pathology of syphilis is largely due to the host’s own cellular inflammatory response
Term
what are the four types/levels of syphilis?
Definition
primary, secondary, tertiary and congenital
Term
Hallmark features of primary syphilis?
Definition
hallmark feature of primary syphilis is a non-painful ulcer, a chancre, which develops at the site of entry
Term
Hallmark feature of secondary syphilis?
Definition
a systemic infection, characterized by fever, swollen lymph nodes, mucous membrane lesions (snail track lesions), & sometimes a skin rash that eventually includes soles & palms &/or wart-resembling lesions (condylomata lata) in the perineum & anal regions
Term
What tests are lab diagnostic of syphilis?
Definition
serology and microscopic examination of scrapings
Term
What do you see under microscope with T. pallidum?
Definition
cannot be seen with standard light microscope because they are too thin. Gram stain is useless
Term
What kind of microscope can visualize T. pallidum?
Definition
dark field microscope (indirect light)
Term
What is the cell structure of spirochetes?
Definition
similar to G- bacteria, have an inner membrane, a periplasm w/ peptidoglycan & an outer sheath/membrane, outer sheath is different from other gram-negative outer membranes; it’s proteins are mainly lipoproteins & lipids (not LPS) that probably contribute to the pathogenic inflammatory process.
Term
What kind of motility do T. pallidum have?
Definition
motile by flagella-like organelles in the periplasm, called axial filaments
Term
Untreated syphilis, what occurs after secondary phase?
Definition
latent phase that can last for years. Can progress to tertiaty
Term
Pt. with a painless ulcer on penis. When did he contract syphilis?
Definition
2-3 weeks ago due to incubation period
Term
Pt. with a painless ulcer on penis. When will this ulcer resolve without treatment (you should treat them but if you don’t)?
Definition
3-6 weeks
Term
When does secondary syphilis appear?
Definition
1-2 mo after initial infection.
Term
When is the early latent period of untreated syphilis?
Definition
1-2 years following resolution of secondary syphilis.
Term
When is the late latent period of untreated syphilis?
Definition
1-2 years post infection lasting until tertiary syphilis presents.
Term
Organ systems affected in tertiary syphilis?
Definition
almost all - CNS, heart, skin, bone
Term
Describe a primary syphilis ulcer?
Definition
painless ulcer with indurated ridges (hard chancre)
Term
Describe the symptoms of secondary syphilis?
Definition
rash, lesions on mucous membranes, wart-like lesions, feverm lymphadenopathy, alopecia, CNS and liver involvement
Term
Describe the rash of secondary syphilis?
Definition
hyperpigmented maculopapular rash over entire body that w/ time extends to palms & soles
Term
What other conditions can present with rash on palms and soles?
Definition
rocky mountain spotted fever, foot hand & mouth disease, & rarely meningococcemia
Term
What is another name for the muscous membrane lesions in syphilis?
Definition
snail track lesions
Term
What is the name of the wart-like lesions in syphilis?
Definition
condylomata lata
Term
Where are condylomata lata located
Definition
moist folds in perineum and anal regions
Term
When in course of syphilis is the patient able to transfer infection to fetus?
Definition
early latent
Term
Is which phases of syphilis is a patient not infectious?
Definition
late latent and tertiary
Term
Tertiary syphilis is a disease of…
Definition
the inner lining of arteries - endarteritis
Term
What is a gumma?
Definition
soft, non-cancerous growth resulting from tertiary syphilis. It’s a form of a granuloma
Term
Cardiovascular syphilis affects which structures?
Definition
ascending aorta and aortic valves (regurg)
Term
CNS syphilis has multiple forms including:
Definition
asymptomatic meningitis, acute syphilitic meningitis, meningovascular syphilis, paresis, tabes dorsalis
Term
What is paresis?
Definition
In this form of tertiary syphilis, many spirochetes found in cerebral cortex & Meninges; progressive change in personality, insanity, paranoia
Term
What is tabes dorsalis?
Definition
demyelization of posterior columns & dorsal roots; pt shuffles when walking; lightening pains
Term
What is a common result of congenital syphilis?
Definition
still birth and spontaneous abortion
Term
When during pregmancy is syphilis transmitted?
Definition
after 1st trimester transplacentally
Term
What are early signs of congenital syphilis in a live birth?
Definition
snuffles (very runny nose), bullous rash, snail track lesions, condyloma lata at birth, enlarged live and spleen
Term
What are late signs of congenital syphilis?
Definition
bone abnormalities (sabre shins, frontal bossing, saddle nose), vision defects (gun barrel sight) and hutchinson's triad
Term
What is Hutchinson's triad?
Definition
notched incisors or screwdriver teeth, keratitis, deafness
Term
Syphilis is an STD but can be transmitted a few other ways. How?
Definition
It can be transmitted by biting or through a crack in skin by touching a chancre or snail track lesion or handling a contaminated catheter
Term
What is the trend in epidemiology of syphilis?
Definition
rates have plummeted in last 20 years.
Term
Risk factors and lifestyles associated with syphilis?
Definition
concentrated in urban populations, memphis, much higher rates in african americans, higher in men having sex with men (MSM)
Term
Wht are two ways of Dx syphilis?
Definition
serology and microscopic examination of scrapings
Term
What are the serology tests for syphilis?
Definition
non-treponemal serology tests- non specific tests. Ag is not T. pallidum but rather beef heart mitochondrial cardiolipin
Term
non-treponemal serology tests for syphilis
Definition
Rapid Plasma Reagin (RPR) yeast test and Venereal Disease Research Laboratory (VDRL) test
Term
Describe the process of the rapid plasma reagin yeast test.
Definition
carbon particles coated with cardiolipin and mixed with diluted pt serum. If you observe agglutination, positive test. No agglutination, negative test.
Term
What are the positives and negatives about the non-treponemal tests?
Definition
Positives: cheap, relatively sensitive Nagatives: false positives (viral epatitis, mono, lupus, & rarely pregnancy)
Term
What do you do if you get a positive RPR test?
Definition
Do a specific test
Term
What is the treponemal tests (specific)?
Definition
antigen is T. pallidum and test is Fluorescent Treponemal Antigen-Absorbed test (FTA-ABS)
Term
Describe the FTA-ABS test.
Definition
T. pallidum is commercially prepared and fixed on microscope slide. Pt serum first a. bsorbed w/ non=pathogenic treponems to remove cross-reacting Abs against normal spirochetal flora. Next, mix absorbed serum with antigen attached to slide. Add fluorescent dye-tagged goat anti-human immunoglobulin. observe staining of spirochetes using fluorescent microscope in the dark. (fluorescence = positive test)
Term
Negatives to the FTA-ABS test?
Definition
expensive, cumbersome, titers tend to remain positive for months after pt is cured
Term
Pt has primary syphilis and has a chancre. Will they have positive serology?
Definition
not necessarily. Pt may not be positive when chancres first appear
Term
Differential Dx for syphilis?
Definition
any ulcer forming STD (herpes, LGV, haemophilis ducreyi), genital warts, any rash disorder, flu, mono
Term
Treatment for syphilis?
Definition
large single IM dose of Pen G
Term
Other treatments to syphilis?
Definition
macrolides, azithro
Term
Is there a vaccine for syphilis?
Definition
no
Term
Describe the characteristics of herpes simplex virus.
Definition
large double stranded DNA virus with an icosahedral capsid surrounded by lipid envelope
Term
Herpes is a complex virus. What does its DNA encode?
Definition
over 90 proteins that supply attachment & fusion glycoproteins of the envelope, transcriptional regulators that redirect host RNA polymerase to viral genes, viral DNA polymerase & associated enzymes for replication of the virus genome, capsomeres, & other envelope glycoproteins required for virus spread from cell to cell
Term
How does the complexity of herpes actually act as its downfall?
Definition
several effective anti-herpetic drugs target unique features of the virus. These limit toxicity to humans, but none are curative
Term
What are the hallmarks of herpes?
Definition
ability to establish latent infections
Term
What is latency?
Definition
the virus genome, but not progeny, is maintained in a quiescent state for the remainder of host’s life
Term
What does the 1 and 2 refer to in herpes?
Definition
different serotypes
Term
What is the old adage about Herpes? what is incorrect about this saying?
Definition
Herpes I infects above the belt and Herpes II infects below the belt. Incorrect because HSV1 can also cause genital lesions.
Term
What are two other sexually transmitted viruses that do not cause genital lesions?
Definition
CMV and Kaposi's associated herpes virus
Term
Describe the replication cycle of herpes.
Definition
viral attachement and surface proteins attach to epithelial surface, HSV directly fuses with plasma membrane in pH INDEPENDENT manner. Nucleocapsid is released and migrates to cell nucleus where genome is released. Initial transcription/translation (immediate early expression) produces proteins that act as transcriptional regulatios modifying the host RNA polymerase to it preferentially transcribes viral genes.
Term
Why is thymidine kinase important? Two ways
Definition
1. required to phosphorylate and activate acyclovir and its derivatives 2. Thymidine kinase mutants occur spontaneously and render HSV resistant t acyclovir
Term
What is the ultimate target on many anti-herpes drugs?
Definition
components of the viral-encoded DNA polymerase are important clinically because they are targets of mant anti-herpes drugs like acyclovir
Term
Herpes: What are the late proteins produced during reproduction?
Definition
encoded capsomeres, enveloped glycoproteins, other structural proteins
Term
Where does herpes virus assembly occur?
Definition
in the nucleus
Term
How is the herpes virus released?
Definition
buds from the plasma membrane
Term
What is a syncitia and how does it form?
Definition
syncitia: giant cells w/ more than one nucleus. Important because the same viral glycoproteins responsible for the initial fusion (entry) event are also present in the plasma membrane of infected cells late in infection → infected cells may fuse w/ adjacent, uninfected cells.
Term
How are syncitia important for diagnosis of HSV?
Definition
syncitium formation are the basis of a diagnostic test for HSV: the Tzanck smear
Term
How are syncitia important for spread of HSV?
Definition
spread from cell to cell w/o release of progeny
Term
What is the Tzanck smear?
Definition
scraping of an ulcer base to look for Tzanck cells (multinucleated giant cells with nuclear inclusion bodies)
Term
Where does HSV reside during latency period?
Definition
in peripherial sensory neurons, the entire genome is maintained extra chromosomally in neurons (like plasmid in bacteria)
Term
How does HSV maintain itself during latency and avoid being destroyed?
Definition
Only HSV gene expressed during latency is called LAT (latency-associated transcript) whose product is an RNA species that silences a subset of cellular genes to prevent apoptosis of the infected neuron
Term
What are the HSV1 diseases:
Definition
fever blisters, keratitis, encephalitis, herpes whitlow, gingivostomatitis, conjunctivitis, blepharitis MAKE SURE YOU KNOW THE FIRST THREE
Term
What are the HSV2 diseases:
Definition
cervicitis, vulvular vesicles, penile vesicles, meningitis, vaginal vesicles, urethritis, perianal vesicles, encephalitis MAKE SURE YOU KNOW THE FIRST FOUR
Term
What is the outcome of most herpes infections?
Definition
mostly self limiting
Term
in which herpes pt population is disseminated disease a problem?
Definition
immunocompromised patients, including neonates
Term
When do blisters appear after HSV infection?
Definition
2-3 weeks post infection
Term
When do blisters tend to reappear in HSV?
Definition
during lapses in cell mediated immunity
Term
HSV: A symptomatic oral infection: primary infection. Name of disease, location.
Definition
gingivostomatitis, lips, tongue, facial skin around mouth
Term
HSV: A symptomatic oral infection: secondary infection. Name of disease, location.
Definition
herpes labialis, sometime same site as primary infection, blisters may itch and burn.
Term
Can somone transmit HSV while they do not have a lesion?
Definition
yes, virus shedding occurs in the absence of recurrent vesicles and well after lesions are healed.
Term
Which HSV serotype recur more frequently
Definition
HSV2
Term
What are the ocular infections of HSV?
Definition
Blephartis & conjunctivitis
Term
Symptoms of Blephartis & conjunctivitis ?
Definition
blisters around eye lid
Term
What is a recurrent ocular HSV infection?
Definition
keratitis- can result in significant corneal scaring; characterized by red painful eye, blurred vision, & photophobia
Term
Is encephalitis primary or recurrent in adults? Neonates?
Definition
recurrent HSV 1 infections in adults; 1° HSV 2 infections in neonates
Term
Pt with headache, fever, confusion and seizures. Dx?
Definition
encephalitis- can be due to HSV
Term
What is the outcome of HSV encephalitis?
Definition
70% mortality if untreated and 20-25% if treated early
Term
If neonate has HSV encephalitis, which serotype usually?
Definition
HSV2
Term
If adult has HSV encephalitis, which serotype usually?
Definition
recurrant HSV1
Term
What is another CNS disease that can be caused by HSV?
Definition
meningitis
Term
what serotype of HSV can cause meningitis?
Definition
HSV2
Term
If you have a neonate with HSV, what symptoms will you observe?
Definition
eyes, skin and mouth have "zoster-form" rash
Term
What is the outcome of neonates with CNS involvement or disseminated HSV?
Definition
75% of severe infection pt will die or have significant sequelas
Term
At what age are most HSV2 infections diagnosed?
Definition
between 20 and 29
Term
what are the current rates of HSV in adult males? Adult females? Young adults?
Definition
10% in adult males, 20% in adult females, & 10% in young adults
Term
What percent of neonatal HSV is transplacental?
Definition
5%
Term
what is risk of transmission to newborn if mother is undergoing primary HSV infection?
Definition
30%
Term
what is risk of transmission to newborn if mother is undergoinga recurrent HSV infection?
Definition
2-3%
Term
how do you deliver if mother has herpes lesions?
Definition
c section
Term
Dianostic tools for Dx genitcal herpes?
Definition
culture virus from lesion to look for characteristic cytopathic effect, fluorescent Ab screening PCR screening from vesicle swab, Tzank smear
Term
What is the characteristic cytopathic effect seen in HSV?
Definition
HSV infected cells become rounded and clumped
Term
How can you distinguish between serotypes of HSV?
Definition
PRC screening from vesicle swabs and serology to detect Abs to glycoprotein G (virus envelope protein)
Term
what is the limitation of serology testing for Ab to glycoprotein G?
Definition
can only determine past infections (need time for Ab development)
Term
How do ou Dx keratitis due to HSV?
Definition
slit lamp exam to look for corneal infected cells
Term
How to Dx viral meningitis?
Definition
spinal tap to rule out bacterial causes and culture of CSF to look for cytopathic effect indicating a viral origin
Term
Course of disease with viral meningitis?
Definition
self-limiting in 7-10 days
Term
How to Dx encephalitis? Discuss tests that arent as helpful, tests that are helpful. A test that rules out HSV. How to confirm HSV.
Definition
1. cultures from CSF are RARELY positive 2. AB titers rise after 1-2 weeks thus its too late for tx in severe disease. 3. EEG - normal EEG rules out herpes encephalitis 4. PCR of CSF in Southern blot format to reveal characteristic HSV pattern. Good test because gives results in 24 hours.
Term
How do you check for disseminated HSV disease in a neonate?
Definition
check liver enzymes
Term
Any cure for HSV?
Definition
no
Term
Drug of choice to lessen disease episodes in HSV?
Definition
acyclovir
Term
How does acyclovir function to lessen disease episodes in HSV?
Definition
Deoxyguanosine analogs that prevent viral genome replication by inhibiting the viral DNA polymerase
Term
What is an important limitation to acyclovir?
Definition
progrug thus needs phosphporylation before active (must add three phosphates). 1st P added by viral kinase (HSV thymidine kinase) and subsequent Ps added by cellular kinases. The first P MUST be added by the viral kinase thus if acyclovir enters uninfected cel it is never activated. BIG POINT: HSV thymidine kinase mutants that dont phosphorylate acyclovir can arise making that HSV insensitive to Acyclovir.
Term
What patient population has a problem with acyclovir insensitivity?
Definition
AIDS patients
Term
Side effects of Acyclovir therapy?
Definition
nausea, skin rash, diarrhea and with high doses: nephrotoxicity, seizures, disorientation
Term
What is another HSV therapy that inhibits viral DNA polymerase and is used systemically and has low toxicity?
Definition
vidarabine and trifluoridine
Term
What is the back up therapy when acyclovir fails?
Definition
foscarnet
Term
What is the mechanism of foscarnet?
Definition
it’s a pyrophosphate analog that blocks viral DNA polymerase preventing viral genome replication. It doesn’t require phosphorylation like acyclovir
Term
What is an over-the-counter medication for HSV cold sores?
Definition
docosanol (abreva)
Term
What is the mechanism for docosanol?
Definition
modifies the host cell membrane so tha the virus envelope cannot fuse with the plasma membrane thus limiting the spread of the reactivated virus.
Term
Treatment regeme for oral herpes?
Definition
docosanol (abreva) and acyclovir oral or cream if outbreaks are frequent
Term
Treatment regeme for herpes keratitis?
Definition
vidarabine or trifluorodine drops
Term
Treatment regeme for genital herpes?
Definition
low dose acyclovir from first sign of outbreak until completed. Single dose high dose famciclovir is FDA-approved if taken within 6 hours of symptoms
Term
What is the treatment for expectant mothers with genital herpes?
Definition
daily suppressive therapy with acyclovir
Term
Treatment regeme for herpes meningitis?
Definition
resolve without treatment, but can give IV acyclovir
Term
Treatment regeme for herpes encephalitis?
Definition
IV high dose acyclovir for 10 d - 3 weeks at first suspicion of illness
Term
Treatment regeme for neonatal/congenital HSV?
Definition
IV high dose acyclovir for 14 day (skin, eye, mouth infections) and 21 days (CNS or disseminated disease)
Term
Treatment regeme for herpes in immunocompromised patients?
Definition
treat aggressively with acyclovir to limit spread
Term
Trend in the epidemiology of HSV in US adolescent and adult population?
Definition
decline in recent years
Term
Which cells type are infected with HPV?
Definition
epithelial cells of the skin and mucosa
Term
What disease is HPV linked with due to the pathology of HPV?
Definition
cancer - mostly cervical also penile anal oral and neck
Term
Where are HPV warts on children?
Definition
hands and face
Term
Where are HPV wards on young adults and adolescents?
Definition
anogenital
Term
What is the name given to anogenital warts?
Definition
condylomas
Term
What serotypes of HPV cause prominent anogenital warts -condylomas?
Definition
HPV 6 and 11
Term
What is the association of HPV 6 and II and cancer?
Definition
low risk of cancer
Term
What HPV serotypes are required for development of cervical cancer?
Definition
HPV 16 and 18
Term
Do HPV 16 and 18 produce prominent warts?
Definition
no, they are associated with sub-clinical papilloma infections.
Term
How do HPV 16 and 18 cause cancer?
Definition
produce early viral proteins E6 and E7 which bind to and remove/inactivate tumor supressor proteins p53 and Rb
Term
How is HPV spread?
Definition
direct contact with worts or contaminated fomites (inanimate objects contaminated with HPV)
Term
Do most people with HPV have warts? Why or why not?
Definition
Because the innate immunity keeps the infections in check
Term
Treatment of warts?
Definition
physical destruction of the wart
Term
Do warts reoccur?
Definition
yes because virus remains in the basal layer of the skin
Term
Describe the physical characteristics of HPV?
Definition
small circular double-stranded DNA virus with an icosahedral capsid and no envelope
Term
What makes the capsid of HPV?
Definition
two proteins L1 and L2 as these are products of genes transcribed after DNA replication that self-assemble to form capsids.
Term
Does HPV have an envelope? How does this affect stability?
Definition
The capsid is not enveloped and this contributes to the stability of virus particles on the skin and fomites.
Term
How does HPV replicate in permissive cells? Where? How is it released?
Definition
, the virus replicates and assembles in the nucleus and is released by lysing cells.
Term
How does HPV replicate in nonpermissive cells?
Definition
In non-permissive cells, late gene expression does not occur and instead of virus production, infection leads to the formation of transformed cells: cells capable of producing tumors.
Term
How is the HPV genome maintained in benign tumor cells?
Definition
In benign tumor cells (such as warts), the genome is maintained extra-chromosomally (similar to a bacterial plasmid) in 40-50 copies.
Term
How is the HPV genome maintained in malignant tumor cells?
Definition
in malignant tumor cells (such as cervical carcinomas), a portion of the virus genome is integrated into the host chromosome
Term
What are the features of transformed cells?
Definition
immortal, no longer contact inhibited in cell culture, no longer require serum-derived growth factors in cell culture, no longer anchorage-dependent for growth in cell culture, can lead to tumor formation in syngenetic animals
Term
What do the late genes and early genes code for in HPV?
Definition
the late genes encode capsid proteins, the early (E) genes of papilloma viruses encode proteins needed for replication and transformation
Term
Describe the importance of proteins E6 and E7?
Definition
E6 binds to the tumor suppressor protein p53 and leads to its degradation, while E7 binds to another tumor suppressor protein, Rb (retinoblastoma protein), and inactivates it. This combined effort leads to uncontrolled growth of the cells, and hence, tumor formation
Term
What is the different in benign and malignant tumor cells in terms of E6 and E7?
Definition
In malignant cells, where only a portion of the virus genome is integrated into the host chromosome, the E6 and E7 genes are always intact. Because a viral regulatory protein is disrupted during such integrations, the E6 and E7 proteins are expressed at elevated levels compared to expression from the extra-chromosomally maintained copies of the genome found in benign tumor cells. The elevated expression of E6 and E7 from integrated genomes is believed to be a major reason why the tumor cells become malignant rather than remain benign.
Term
What epithelial cells are first infected in HPV?
Definition
The viruses initially infect the germinal cells in the basal layer of the skin
Term
Are germinal cells permissive or nonpermissive of HPV?
Definition
these are non-permissive cells, so virus particles are not produced and the cells are transformed.
Term
What happens to the germinal cells infected with HPV?
Definition
infected germinal cells mature and migrate to the skin surface. As they differentiate into keratinized epithelia, the cells become permissive and produce virus progeny
Term
What is the result of HPV-infected germinal cell migration and differentiation?
Definition
The result is a benign tumor (wart), due to proliferation of the transformed germinal cells.
Term
How is it that direct contact with a wart will spread HPV?
Definition
The transformed and differentiated infected cells of the wart shed virus particles because they are permissive and produce virus progeny
Term
Why do warts tend to cluster in formation?
Definition
shed virus infects surrounding basal layer cells and the process begins anew
Term
Why does wart treatment not prevent warts from returning?
Definition
treatment destroys the wart but does not eliminate the virus genome from the non-permissive germinal cells which serve as a renewable source of infected keratinocytes.
Term
What is the shape, type and size of the HPV genome?
Definition
circular ds DNA genome of 8 kbp
Term
What is the outer HPV virus composed of (capsid? envelope?)
Definition
non-enveloped icosahedral capsid composed of L1 and L2 proteins
Term
What is the replication and release process of HPV?
Definition
replication and assembly in the nucleus of permissive cells followed by cell lysis for release
Term
What occurs in nonpermissive cells infected with HPV?
Definition
no virus production in non-permissive cells but virus genome is maintained and cells are transformed
Term
E6 protein leads to degradation of which tumor supressor protein?
Definition
E6 leads to the degradation of p53
Term
E7 protein leads to inactivation of which tumor supressor protein?
Definition
E7 leads to the inactivation of Rb protein
Term
What are the levels of E6 and E7 in malignant tumors compared to benign?
Definition
overexpressed in malignant tumors
Term
Which cells maintain the HPV genome? Are these cells permissive or nonpermissive?
Definition
Germinal cells in basal layer of skin are non-permissive and when infected maintain the virus genome (which can be for life)
Term
Which cells lead to the high contagious nature of HPV warts?
Definition
Differentiated keratinocytes are permissive and produce virus leading to the highly contagious nature of warts and the clustering of warts
Term
What cells lead to the recurrances of warts?
Definition
maintenance of the virus genome in germinal cells leads to wart recurrences in many instances
Term
What is the name of common and plantar warts?
Definition
verruca vulgaris
Term
What is the name of flat warts?
Definition
verruca plana
Term
What is the name of anogenital warts?
Definition
condyloma accuminata and condyloma plana
Term
What HPV serotypes cause anogenital warts?
Definition
HPV 6 and 11
Term
What HPV serotypes cause sub-clinacal palilloma infections?
Definition
HPV 16, 18 and 31
Term
What HPV serotypes cause cervical, penile, anal, oral and neck cancers?
Definition
HPV 16, 18 and 31
Term
What HPV serotypes cause infantile laryngeal papillomas?
Definition
HPV 6 and 11
Term
What is epidermodysplasia verruciformis?
Definition
an extremely rareautosomal recessive genetic hereditary skin disorder associated with a high risk of carcinoma of the skin. It is characterized by abnormal susceptibility to human papillomaviruses (HPVs) of the skin
Term
What is the course of most warts?
Definition
most warts are benign neoplasms that will disappear untreated within 2 years
Term
What are laryngeal papillomas?
Definition
chronic, benign warts in the respiratory tract that generally first appear before the age of 5; thankfully, the disease is relatively rare. Because of the associated respiratory distress, up to 3% of patients die annually.
Term
What does a condyloma acuminata look like?
Definition
more elevated and flap-like. Like a scale.
Term
What does condyloma plana look like?
Definition
more typical wart-like. Rounded in shape.
Term
What solution turns warts white and can be used to identify warts?
Definition
a 5% acetic acid solution
Term
What evidence on a Pap smear is indicative of HPV?
Definition
A Pap smear can detect koilocytotic (vacuolated cytoplasm) squamous epithelial cells (Fig. 9) which are indicative of HPV infection.
Term
Most cervical dysplasias are caused by HPV. Will most of these lead to invasive cervical cancer?
Definition
no
Term
What is the incidence of HPV in US women?
Definition
15-60%
Term
HPV 16 and 18 account for what percent of cervical cancers?
Definition
HPV 16 and 18 lead to SPI and account for 70% of cervical cancers
Term
How effective is the immune system at eliminating most infections?
Definition
most infections are eradicated
Term
What are some co-factors for developing cervical cancer?
Definition
smoking and co-infection with Herpes
Term
If a pregnant pt has genital warts should you remove them during pregnancy or wait until parturition?
Definition
remove during pregnancy to prevent spread to neonate
Term
What is a difficulty for diagnosis of HPV?
Definition
HPV cannot be routinely grown in cell culture
Term
What tests can dx HPV and cervical cancer?
Definition
adnormal pap smear followed by colposcopy to look for dysplasia. There is an FDA-approved test for detecting HPV DNA in cells
Term
Are condoms effective for prevention of HPV spread?
Definition
no because they do not cover all areas of the skin that come in contact during intercourse
Term
What is the HPV vaccine? What types of HPV does it cover?
Definition
HPV 6, 11, 16 and 18
Term
Who should receive gardasil?
Definition
males and females age 9-26
Term
What are some methods for wart removal?
Definition
acid, freezing, electrically burning and creams that inhibit cellular reproduction
Term
What acids are used in wart removal? What do they do?
Definition
BCA and TCA - denature proteins
Term
What is LEEP? What is it used for?
Definition
(loop electrosurgical excision procedure) removes cells involved in cervical dysplasia
Term
What is podofilox?
Definition
a gel whose active ingredient is an anti-mitotic agent. It is not recommended for use during pregnancy
Term
What is imiquimod?
Definition
a topical agent that stimulates localized interferon and cytokine production. It is not recommended for use during pregnancy
Term
How many cervical cancer deaths in US per year?
Definition
deaths - 4000
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