B2A5 Micro – Flashcards
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| What bugs account for 60-80% of STIs with primary symptoms of dysuria and exudation? |
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| chlamydia trachomatis, neisseria gonorrhoeae, and ureaplasma urelyticum |
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| Dx tests for dysuria and exudation? |
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| nucleic acid amplification tests (NAAT) on urine and exudates |
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| Number one reportable disease in USA? Cases/year? |
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| chlamydia, about 1 milion |
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| Number two reportable disease in USA? |
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| gonorrhea, about 300,000 |
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| Sequalae for Ct/GC lower GU infections? |
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| spread to upper GU causing pelvic inflammatory disease, sterility and ectopic pregnancy |
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| Conditions caused by Ct/GC infection of newborn? |
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| conjunctivitis (Ct/GC) and/or pneumonia (Ct) |
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| If a pt is positive for GC, whats the likelyhood they also have Ct? |
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| fifty percent |
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| Describe the chlamydia trachomatis bug? |
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| 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 |
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| Describe the lifecycle of Ct |
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| 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. |
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| Which antibiotic is ineffective against Ct and why? |
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| Because chlamydiae reside in an isosmotic intracellular environment, b-lactam antibiotics are ineffective. |
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| Whats the primary virulence factor of Ct? |
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| 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) |
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| Describe Neisseria gonorrhoeae |
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| G- Ox+ non-encapsulated diplococci "kissing kidney beans" |
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| Neisseria: Virulence factors |
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| LPS and antigenic variation |
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| How is LPS pathogenic |
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| 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. |
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| What are the two mechanisms of antigenic variation utilized by Neisseria gonorrhoeae |
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| 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. |
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| What part of the immune system kills GC? |
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| GC are considered extracellular parasites, which are killed when phagocytosed by PMNs |
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| What is a virulence factor that helps GC evade antibodies? |
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| Secretes IgA1 protease, which distroys IgA1 |
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| Does a pt mount a protective immunological response after infection with Ct and/or GC? |
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| No, Neither Ct nor GC invokes a particularly protective immune response |
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| Does GC desseminate? Ct? |
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| 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. |
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| Treatment for GC? |
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| ceftriaxone plus azithromycin or doxyxyxline (because with GC is usually Ct) |
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| Discribe ureaplasma? |
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| lack cell walls completely thus not susceptible to any beta lactams |
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| Disease caused by ureaplasma |
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| 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) |
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| Diseases caused by GC and Ct in lower GU tract? |
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| cervicitis and urethritis |
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| Most common diseases caused by GC and Ct in upper GU tract? |
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| salpingitis and pelvic inflammatory disease |
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| Other diseases caused by GC and Ct in upper GU tract? |
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| epididymitis, perihepatitis Fitz-Hugh-Curtis syndrome (imflammation of uterus, ovaduct and liver capsule) |
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| Other sites of disease caused by GC and Ct? |
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| 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) |
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| What is Reiters' Syndrome? |
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| Reactive, non-septic arthritis (immune-response related), Ct, occasionally GC, and following some types of bacterial enterocolitis |
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| what are lab Dx tests for vaginal discharge? |
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| microscopic or other rapid examination of the discharge |
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| what are the common organisms in Vaginitis? |
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| 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 |
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| Are these organisms normally present in the vagina? |
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| yes, part of normal flora |
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| If these organisms are part of normal flora, how are they pathogenic? |
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| 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 |
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| what are some factors allowing the overgrowth of normal flora? |
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| antibiotic treatment, sexual activity, douching, IUDs, onset of menstrual cycle, pregnancy, tight undergarments |
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| what is a pathogen of the vagina that is sexually transmitted and causes vaginitis? |
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| trichomonas vaginalis |
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| what type of pathogen is trichomonas? |
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| single cell protozoan |
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| what can trichomonas cause in males? |
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| non-gonorrheal urethritis |
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| what are some agents that cause BV? |
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| Gardnerella vaginalis, Mobiluncus, anaerobes, candida albicans, T. vaginalis |
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| Pt with clear/white discharge with pH 4.5 no odor and under microscope see normal epithelial cells and lactobacilli predominate. Dx? |
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| uninfected- lactobacilli predominate |
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| Pt with scant white clumped adherent discharge, dysuria, vulvar itching, pain, erythemia. Dx? |
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| vulvovaginal candidasis |
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| Vaginitis: Pathogen? |
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| candida albicans most common. |
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| What will you see under microscope with vulvovaginal candidasis? |
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| leukocytes, epithelial cells, mycelia or pseudomycelia |
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| Pt with profuse yellow/green discharge, frothy and pH >4.5 with dysuria and vulvar itching. Dx? |
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| trichomonas vaginalis |
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| What will you see under microscope with trichomonas vaginalis? |
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| leukocytes, twitching trichomonas in 50-70% of positive cases |
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| Pt with moderate white/gray adherent malodorous discharge. Dx? |
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| bacterial vaginitis |
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| What is a common pathogen with BV? |
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| gardnerella vaginalis |
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| What will you see under microscope with BV? |
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| clue cells, few leukocytes and lactobacilli outnumbered by mixed flora |
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| Pt with dysuria, suprapubic pain, significant number of bacteria in urine, polys in urine and low fever. Dx? |
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| cystitis |
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| Pt with dysuria, suprapubic pain, significant number of bacteria in urine, polys in urine and high fever, back pain. Dx? |
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| pyelonephritis |
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| Pt with dysuria, mucpurulent discharge, with/with fever and abdominal pain |
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| cervivitis |
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| How many office visits per year due to vulvovaginitis? |
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| 3 million per year |
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| Positive "whiff test"? |
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| BV or trichomoniasis |
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| Discribe process of whiff test. |
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| swab vaginal discharge, add KOH, smell. If fishy odor (due to amines) then BV |
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| cottage cheese discharge? |
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| candidasis |
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| yellow-green discharge? |
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| trichomoniasis |
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| Treatment of vaginal candidiasis? |
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| imidasole intravaginal (3-7 days) or fluconazole (1 day) |
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| Candidiasis vaginitis: Do you need to treat sexual partner? |
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| not if asymptomatic |
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| Treatment of trichomonal vaginitis? |
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| metronidazole |
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| Trichomonal vaginitis: Do you need to treat sexual partner? |
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| yes |
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| Treatment of BV? |
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| metronidazole or clindamycin cream |
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| BV: Do you need to treat sexual partner? |
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| no |
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| etiologic agent of syphilis? |
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| Treponema pallidum |
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| What is the microbiological shape of treponema pallidum? |
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| spirochete - corkscrew |
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| how do you grow T. pallidum? |
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| cant grow in lab but can propagate in rabbit testes (sucks for him) |
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| Can T. pallidum cross the placenta? |
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| yes, causes congenital syphilis |
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| what is the main cause of the pathology of syphilis? (tonin, enzyme, or virulence factor, etc.??) |
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| pathology of syphilis is largely due to the host’s own cellular inflammatory response |
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| what are the four types/levels of syphilis? |
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| primary, secondary, tertiary and congenital |
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| Hallmark features of primary syphilis? |
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| hallmark feature of primary syphilis is a non-painful ulcer, a chancre, which develops at the site of entry |
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| Hallmark feature of secondary syphilis? |
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| 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 |
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| What tests are lab diagnostic of syphilis? |
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| serology and microscopic examination of scrapings |
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| What do you see under microscope with T. pallidum? |
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| cannot be seen with standard light microscope because they are too thin. Gram stain is useless |
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| What kind of microscope can visualize T. pallidum? |
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| dark field microscope (indirect light) |
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| What is the cell structure of spirochetes? |
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| 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. |
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| What kind of motility do T. pallidum have? |
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| motile by flagella-like organelles in the periplasm, called axial filaments |
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| Untreated syphilis, what occurs after secondary phase? |
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| latent phase that can last for years. Can progress to tertiaty |
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| Pt. with a painless ulcer on penis. When did he contract syphilis? |
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| 2-3 weeks ago due to incubation period |
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| Pt. with a painless ulcer on penis. When will this ulcer resolve without treatment (you should treat them but if you don’t)? |
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| 3-6 weeks |
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| When does secondary syphilis appear? |
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| 1-2 mo after initial infection. |
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| When is the early latent period of untreated syphilis? |
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| 1-2 years following resolution of secondary syphilis. |
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| When is the late latent period of untreated syphilis? |
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| 1-2 years post infection lasting until tertiary syphilis presents. |
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| Organ systems affected in tertiary syphilis? |
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| almost all - CNS, heart, skin, bone |
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| Describe a primary syphilis ulcer? |
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| painless ulcer with indurated ridges (hard chancre) |
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| Describe the symptoms of secondary syphilis? |
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| rash, lesions on mucous membranes, wart-like lesions, feverm lymphadenopathy, alopecia, CNS and liver involvement |
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| Describe the rash of secondary syphilis? |
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| hyperpigmented maculopapular rash over entire body that w/ time extends to palms & soles |
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| What other conditions can present with rash on palms and soles? |
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| rocky mountain spotted fever, foot hand & mouth disease, & rarely meningococcemia |
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| What is another name for the muscous membrane lesions in syphilis? |
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| snail track lesions |
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| What is the name of the wart-like lesions in syphilis? |
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| condylomata lata |
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| Where are condylomata lata located |
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| moist folds in perineum and anal regions |
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| When in course of syphilis is the patient able to transfer infection to fetus? |
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| early latent |
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| Is which phases of syphilis is a patient not infectious? |
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| late latent and tertiary |
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| Tertiary syphilis is a disease of… |
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| the inner lining of arteries - endarteritis |
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| What is a gumma? |
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| soft, non-cancerous growth resulting from tertiary syphilis. It’s a form of a granuloma |
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| Cardiovascular syphilis affects which structures? |
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| ascending aorta and aortic valves (regurg) |
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| CNS syphilis has multiple forms including: |
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| asymptomatic meningitis, acute syphilitic meningitis, meningovascular syphilis, paresis, tabes dorsalis |
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| What is paresis? |
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| In this form of tertiary syphilis, many spirochetes found in cerebral cortex & Meninges; progressive change in personality, insanity, paranoia |
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| What is tabes dorsalis? |
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| demyelization of posterior columns & dorsal roots; pt shuffles when walking; lightening pains |
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| What is a common result of congenital syphilis? |
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| still birth and spontaneous abortion |
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| When during pregmancy is syphilis transmitted? |
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| after 1st trimester transplacentally |
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| What are early signs of congenital syphilis in a live birth? |
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| snuffles (very runny nose), bullous rash, snail track lesions, condyloma lata at birth, enlarged live and spleen |
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| What are late signs of congenital syphilis? |
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| bone abnormalities (sabre shins, frontal bossing, saddle nose), vision defects (gun barrel sight) and hutchinson's triad |
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| What is Hutchinson's triad? |
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| notched incisors or screwdriver teeth, keratitis, deafness |
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| Syphilis is an STD but can be transmitted a few other ways. How? |
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| 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 |
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| What is the trend in epidemiology of syphilis? |
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| rates have plummeted in last 20 years. |
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| Risk factors and lifestyles associated with syphilis? |
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| concentrated in urban populations, memphis, much higher rates in african americans, higher in men having sex with men (MSM) |
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| Wht are two ways of Dx syphilis? |
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| serology and microscopic examination of scrapings |
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| What are the serology tests for syphilis? |
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| non-treponemal serology tests- non specific tests. Ag is not T. pallidum but rather beef heart mitochondrial cardiolipin |
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| non-treponemal serology tests for syphilis |
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| Rapid Plasma Reagin (RPR) yeast test and Venereal Disease Research Laboratory (VDRL) test |
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| Describe the process of the rapid plasma reagin yeast test. |
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| carbon particles coated with cardiolipin and mixed with diluted pt serum. If you observe agglutination, positive test. No agglutination, negative test. |
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| What are the positives and negatives about the non-treponemal tests? |
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| Positives: cheap, relatively sensitive Nagatives: false positives (viral epatitis, mono, lupus, & rarely pregnancy) |
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| What do you do if you get a positive RPR test? |
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| Do a specific test |
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| What is the treponemal tests (specific)? |
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| antigen is T. pallidum and test is Fluorescent Treponemal Antigen-Absorbed test (FTA-ABS) |
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| Describe the FTA-ABS test. |
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| 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) |
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| Negatives to the FTA-ABS test? |
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| expensive, cumbersome, titers tend to remain positive for months after pt is cured |
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| Pt has primary syphilis and has a chancre. Will they have positive serology? |
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| not necessarily. Pt may not be positive when chancres first appear |
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| Differential Dx for syphilis? |
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| any ulcer forming STD (herpes, LGV, haemophilis ducreyi), genital warts, any rash disorder, flu, mono |
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| Treatment for syphilis? |
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| large single IM dose of Pen G |
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| Other treatments to syphilis? |
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| macrolides, azithro |
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| Is there a vaccine for syphilis? |
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| no |
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| Describe the characteristics of herpes simplex virus. |
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| large double stranded DNA virus with an icosahedral capsid surrounded by lipid envelope |
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| Herpes is a complex virus. What does its DNA encode? |
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| 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 |
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| How does the complexity of herpes actually act as its downfall? |
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| several effective anti-herpetic drugs target unique features of the virus. These limit toxicity to humans, but none are curative |
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| What are the hallmarks of herpes? |
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| ability to establish latent infections |
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| What is latency? |
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| the virus genome, but not progeny, is maintained in a quiescent state for the remainder of host’s life |
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| What does the 1 and 2 refer to in herpes? |
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| different serotypes |
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| What is the old adage about Herpes? what is incorrect about this saying? |
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| Herpes I infects above the belt and Herpes II infects below the belt. Incorrect because HSV1 can also cause genital lesions. |
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| What are two other sexually transmitted viruses that do not cause genital lesions? |
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| CMV and Kaposi's associated herpes virus |
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| Describe the replication cycle of herpes. |
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| 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. |
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| Why is thymidine kinase important? Two ways |
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| 1. required to phosphorylate and activate acyclovir and its derivatives 2. Thymidine kinase mutants occur spontaneously and render HSV resistant t acyclovir |
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| What is the ultimate target on many anti-herpes drugs? |
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| components of the viral-encoded DNA polymerase are important clinically because they are targets of mant anti-herpes drugs like acyclovir |
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| Herpes: What are the late proteins produced during reproduction? |
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| encoded capsomeres, enveloped glycoproteins, other structural proteins |
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| Where does herpes virus assembly occur? |
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| in the nucleus |
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| How is the herpes virus released? |
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| buds from the plasma membrane |
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| What is a syncitia and how does it form? |
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| 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. |
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| How are syncitia important for diagnosis of HSV? |
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| syncitium formation are the basis of a diagnostic test for HSV: the Tzanck smear |
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| How are syncitia important for spread of HSV? |
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| spread from cell to cell w/o release of progeny |
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| What is the Tzanck smear? |
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| scraping of an ulcer base to look for Tzanck cells (multinucleated giant cells with nuclear inclusion bodies) |
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| Where does HSV reside during latency period? |
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| in peripherial sensory neurons, the entire genome is maintained extra chromosomally in neurons (like plasmid in bacteria) |
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| How does HSV maintain itself during latency and avoid being destroyed? |
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| 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 |
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| What are the HSV1 diseases: |
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| fever blisters, keratitis, encephalitis, herpes whitlow, gingivostomatitis, conjunctivitis, blepharitis MAKE SURE YOU KNOW THE FIRST THREE |
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| What are the HSV2 diseases: |
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| cervicitis, vulvular vesicles, penile vesicles, meningitis, vaginal vesicles, urethritis, perianal vesicles, encephalitis MAKE SURE YOU KNOW THE FIRST FOUR |
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| What is the outcome of most herpes infections? |
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| mostly self limiting |
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| in which herpes pt population is disseminated disease a problem? |
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| immunocompromised patients, including neonates |
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| When do blisters appear after HSV infection? |
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| 2-3 weeks post infection |
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| When do blisters tend to reappear in HSV? |
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| during lapses in cell mediated immunity |
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| HSV: A symptomatic oral infection: primary infection. Name of disease, location. |
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| gingivostomatitis, lips, tongue, facial skin around mouth |
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| HSV: A symptomatic oral infection: secondary infection. Name of disease, location. |
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| herpes labialis, sometime same site as primary infection, blisters may itch and burn. |
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| Can somone transmit HSV while they do not have a lesion? |
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| yes, virus shedding occurs in the absence of recurrent vesicles and well after lesions are healed. |
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| Which HSV serotype recur more frequently |
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| HSV2 |
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| What are the ocular infections of HSV? |
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| Blephartis & conjunctivitis |
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| Symptoms of Blephartis & conjunctivitis ? |
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| blisters around eye lid |
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| What is a recurrent ocular HSV infection? |
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| keratitis- can result in significant corneal scaring; characterized by red painful eye, blurred vision, & photophobia |
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| Is encephalitis primary or recurrent in adults? Neonates? |
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| recurrent HSV 1 infections in adults; 1° HSV 2 infections in neonates |
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| Pt with headache, fever, confusion and seizures. Dx? |
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| encephalitis- can be due to HSV |
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| What is the outcome of HSV encephalitis? |
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| 70% mortality if untreated and 20-25% if treated early |
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| If neonate has HSV encephalitis, which serotype usually? |
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| HSV2 |
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| If adult has HSV encephalitis, which serotype usually? |
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| recurrant HSV1 |
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| What is another CNS disease that can be caused by HSV? |
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| meningitis |
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| what serotype of HSV can cause meningitis? |
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| HSV2 |
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| If you have a neonate with HSV, what symptoms will you observe? |
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| eyes, skin and mouth have "zoster-form" rash |
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| What is the outcome of neonates with CNS involvement or disseminated HSV? |
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| 75% of severe infection pt will die or have significant sequelas |
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| At what age are most HSV2 infections diagnosed? |
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| between 20 and 29 |
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| what are the current rates of HSV in adult males? Adult females? Young adults? |
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| 10% in adult males, 20% in adult females, & 10% in young adults |
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| What percent of neonatal HSV is transplacental? |
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| 5% |
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| what is risk of transmission to newborn if mother is undergoing primary HSV infection? |
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| 30% |
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| what is risk of transmission to newborn if mother is undergoinga recurrent HSV infection? |
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| 2-3% |
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| how do you deliver if mother has herpes lesions? |
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| c section |
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| Dianostic tools for Dx genitcal herpes? |
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| culture virus from lesion to look for characteristic cytopathic effect, fluorescent Ab screening PCR screening from vesicle swab, Tzank smear |
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| What is the characteristic cytopathic effect seen in HSV? |
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| HSV infected cells become rounded and clumped |
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| How can you distinguish between serotypes of HSV? |
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| PRC screening from vesicle swabs and serology to detect Abs to glycoprotein G (virus envelope protein) |
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| what is the limitation of serology testing for Ab to glycoprotein G? |
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| can only determine past infections (need time for Ab development) |
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| How do ou Dx keratitis due to HSV? |
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| slit lamp exam to look for corneal infected cells |
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| How to Dx viral meningitis? |
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| spinal tap to rule out bacterial causes and culture of CSF to look for cytopathic effect indicating a viral origin |
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| Course of disease with viral meningitis? |
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| self-limiting in 7-10 days |
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| How to Dx encephalitis? Discuss tests that arent as helpful, tests that are helpful. A test that rules out HSV. How to confirm HSV. |
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| 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. |
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| How do you check for disseminated HSV disease in a neonate? |
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| check liver enzymes |
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| Any cure for HSV? |
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| no |
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| Drug of choice to lessen disease episodes in HSV? |
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| acyclovir |
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| How does acyclovir function to lessen disease episodes in HSV? |
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| Deoxyguanosine analogs that prevent viral genome replication by inhibiting the viral DNA polymerase |
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| What is an important limitation to acyclovir? |
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| 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. |
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| What patient population has a problem with acyclovir insensitivity? |
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| AIDS patients |
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| Side effects of Acyclovir therapy? |
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| nausea, skin rash, diarrhea and with high doses: nephrotoxicity, seizures, disorientation |
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| What is another HSV therapy that inhibits viral DNA polymerase and is used systemically and has low toxicity? |
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| vidarabine and trifluoridine |
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| What is the back up therapy when acyclovir fails? |
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| foscarnet |
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| What is the mechanism of foscarnet? |
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| it’s a pyrophosphate analog that blocks viral DNA polymerase preventing viral genome replication. It doesn’t require phosphorylation like acyclovir |
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| What is an over-the-counter medication for HSV cold sores? |
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| docosanol (abreva) |
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| What is the mechanism for docosanol? |
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| modifies the host cell membrane so tha the virus envelope cannot fuse with the plasma membrane thus limiting the spread of the reactivated virus. |
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| Treatment regeme for oral herpes? |
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| docosanol (abreva) and acyclovir oral or cream if outbreaks are frequent |
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| Treatment regeme for herpes keratitis? |
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| vidarabine or trifluorodine drops |
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| Treatment regeme for genital herpes? |
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| 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 |
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| What is the treatment for expectant mothers with genital herpes? |
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| daily suppressive therapy with acyclovir |
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| Treatment regeme for herpes meningitis? |
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| resolve without treatment, but can give IV acyclovir |
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| Treatment regeme for herpes encephalitis? |
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| IV high dose acyclovir for 10 d - 3 weeks at first suspicion of illness |
question
| Treatment regeme for neonatal/congenital HSV? |
answer
| IV high dose acyclovir for 14 day (skin, eye, mouth infections) and 21 days (CNS or disseminated disease) |
question
| Treatment regeme for herpes in immunocompromised patients? |
answer
| treat aggressively with acyclovir to limit spread |
question
| Trend in the epidemiology of HSV in US adolescent and adult population? |
answer
| decline in recent years |
question
| Which cells type are infected with HPV? |
answer
| epithelial cells of the skin and mucosa |
question
| What disease is HPV linked with due to the pathology of HPV? |
answer
| cancer - mostly cervical also penile anal oral and neck |
question
| Where are HPV warts on children? |
answer
| hands and face |
question
| Where are HPV wards on young adults and adolescents? |
answer
| anogenital |
question
| What is the name given to anogenital warts? |
answer
| condylomas |
question
| What serotypes of HPV cause prominent anogenital warts -condylomas? |
answer
| HPV 6 and 11 |
question
| What is the association of HPV 6 and II and cancer? |
answer
| low risk of cancer |
question
| What HPV serotypes are required for development of cervical cancer? |
answer
| HPV 16 and 18 |
question
| Do HPV 16 and 18 produce prominent warts? |
answer
| no, they are associated with sub-clinical papilloma infections. |
question
| How do HPV 16 and 18 cause cancer? |
answer
| produce early viral proteins E6 and E7 which bind to and remove/inactivate tumor supressor proteins p53 and Rb |
question
| How is HPV spread? |
answer
| direct contact with worts or contaminated fomites (inanimate objects contaminated with HPV) |
question
| Do most people with HPV have warts? Why or why not? |
answer
| Because the innate immunity keeps the infections in check |
question
| Treatment of warts? |
answer
| physical destruction of the wart |
question
| Do warts reoccur? |
answer
| yes because virus remains in the basal layer of the skin |
question
| Describe the physical characteristics of HPV? |
answer
| small circular double-stranded DNA virus with an icosahedral capsid and no envelope |
question
| What makes the capsid of HPV? |
answer
| two proteins L1 and L2 as these are products of genes transcribed after DNA replication that self-assemble to form capsids. |
question
| Does HPV have an envelope? How does this affect stability? |
answer
| The capsid is not enveloped and this contributes to the stability of virus particles on the skin and fomites. |
question
| How does HPV replicate in permissive cells? Where? How is it released? |
answer
| , the virus replicates and assembles in the nucleus and is released by lysing cells. |
question
| How does HPV replicate in nonpermissive cells? |
answer
| 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. |
question
| How is the HPV genome maintained in benign tumor cells? |
answer
| In benign tumor cells (such as warts), the genome is maintained extra-chromosomally (similar to a bacterial plasmid) in 40-50 copies. |
question
| How is the HPV genome maintained in malignant tumor cells? |
answer
| in malignant tumor cells (such as cervical carcinomas), a portion of the virus genome is integrated into the host chromosome |
question
| What are the features of transformed cells? |
answer
| 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 |
question
| What do the late genes and early genes code for in HPV? |
answer
| the late genes encode capsid proteins, the early (E) genes of papilloma viruses encode proteins needed for replication and transformation |
question
| Describe the importance of proteins E6 and E7? |
answer
| 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 |
question
| What is the different in benign and malignant tumor cells in terms of E6 and E7? |
answer
| 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. |
question
| What epithelial cells are first infected in HPV? |
answer
| The viruses initially infect the germinal cells in the basal layer of the skin |
question
| Are germinal cells permissive or nonpermissive of HPV? |
answer
| these are non-permissive cells, so virus particles are not produced and the cells are transformed. |
question
| What happens to the germinal cells infected with HPV? |
answer
| infected germinal cells mature and migrate to the skin surface. As they differentiate into keratinized epithelia, the cells become permissive and produce virus progeny |
question
| What is the result of HPV-infected germinal cell migration and differentiation? |
answer
| The result is a benign tumor (wart), due to proliferation of the transformed germinal cells. |
question
| How is it that direct contact with a wart will spread HPV? |
answer
| The transformed and differentiated infected cells of the wart shed virus particles because they are permissive and produce virus progeny |
question
| Why do warts tend to cluster in formation? |
answer
| shed virus infects surrounding basal layer cells and the process begins anew |
question
| Why does wart treatment not prevent warts from returning? |
answer
| 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. |
question
| What is the shape, type and size of the HPV genome? |
answer
| circular ds DNA genome of 8 kbp |
question
| What is the outer HPV virus composed of (capsid? envelope?) |
answer
| non-enveloped icosahedral capsid composed of L1 and L2 proteins |
question
| What is the replication and release process of HPV? |
answer
| replication and assembly in the nucleus of permissive cells followed by cell lysis for release |
question
| What occurs in nonpermissive cells infected with HPV? |
answer
| no virus production in non-permissive cells but virus genome is maintained and cells are transformed |
question
| E6 protein leads to degradation of which tumor supressor protein? |
answer
| E6 leads to the degradation of p53 |
question
| E7 protein leads to inactivation of which tumor supressor protein? |
answer
| E7 leads to the inactivation of Rb protein |
question
| What are the levels of E6 and E7 in malignant tumors compared to benign? |
answer
| overexpressed in malignant tumors |
question
| Which cells maintain the HPV genome? Are these cells permissive or nonpermissive? |
answer
| Germinal cells in basal layer of skin are non-permissive and when infected maintain the virus genome (which can be for life) |
question
| Which cells lead to the high contagious nature of HPV warts? |
answer
| Differentiated keratinocytes are permissive and produce virus leading to the highly contagious nature of warts and the clustering of warts |
question
| What cells lead to the recurrances of warts? |
answer
| maintenance of the virus genome in germinal cells leads to wart recurrences in many instances |
question
| What is the name of common and plantar warts? |
answer
| verruca vulgaris |
question
| What is the name of flat warts? |
answer
| verruca plana |
question
| What is the name of anogenital warts? |
answer
| condyloma accuminata and condyloma plana |
question
| What HPV serotypes cause anogenital warts? |
answer
| HPV 6 and 11 |
question
| What HPV serotypes cause sub-clinacal palilloma infections? |
answer
| HPV 16, 18 and 31 |
question
| What HPV serotypes cause cervical, penile, anal, oral and neck cancers? |
answer
| HPV 16, 18 and 31 |
question
| What HPV serotypes cause infantile laryngeal papillomas? |
answer
| HPV 6 and 11 |
question
| What is epidermodysplasia verruciformis? |
answer
| 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 |
question
| What is the course of most warts? |
answer
| most warts are benign neoplasms that will disappear untreated within 2 years |
question
| What are laryngeal papillomas? |
answer
| 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. |
question
| What does a condyloma acuminata look like? |
answer
| more elevated and flap-like. Like a scale. |
question
| What does condyloma plana look like? |
answer
| more typical wart-like. Rounded in shape. |
question
| What solution turns warts white and can be used to identify warts? |
answer
| a 5% acetic acid solution |
question
| What evidence on a Pap smear is indicative of HPV? |
answer
| A Pap smear can detect koilocytotic (vacuolated cytoplasm) squamous epithelial cells (Fig. 9) which are indicative of HPV infection. |
question
| Most cervical dysplasias are caused by HPV. Will most of these lead to invasive cervical cancer? |
answer
| no |
question
| What is the incidence of HPV in US women? |
answer
| 15-60% |
question
| HPV 16 and 18 account for what percent of cervical cancers? |
answer
| HPV 16 and 18 lead to SPI and account for 70% of cervical cancers |
question
| How effective is the immune system at eliminating most infections? |
answer
| most infections are eradicated |
question
| What are some co-factors for developing cervical cancer? |
answer
| smoking and co-infection with Herpes |
question
| If a pregnant pt has genital warts should you remove them during pregnancy or wait until parturition? |
answer
| remove during pregnancy to prevent spread to neonate |
question
| What is a difficulty for diagnosis of HPV? |
answer
| HPV cannot be routinely grown in cell culture |
question
| What tests can dx HPV and cervical cancer? |
answer
| adnormal pap smear followed by colposcopy to look for dysplasia. There is an FDA-approved test for detecting HPV DNA in cells |
question
| Are condoms effective for prevention of HPV spread? |
answer
| no because they do not cover all areas of the skin that come in contact during intercourse |
question
| What is the HPV vaccine? What types of HPV does it cover? |
answer
| HPV 6, 11, 16 and 18 |
question
| Who should receive gardasil? |
answer
| males and females age 9-26 |
question
| What are some methods for wart removal? |
answer
| acid, freezing, electrically burning and creams that inhibit cellular reproduction |
question
| What acids are used in wart removal? What do they do? |
answer
| BCA and TCA - denature proteins |
question
| What is LEEP? What is it used for? |
answer
| (loop electrosurgical excision procedure) removes cells involved in cervical dysplasia |
question
| What is podofilox? |
answer
| a gel whose active ingredient is an anti-mitotic agent. It is not recommended for use during pregnancy |
question
| What is imiquimod? |
answer
| a topical agent that stimulates localized interferon and cytokine production. It is not recommended for use during pregnancy |
question
| How many cervical cancer deaths in US per year? |
answer
| deaths - 4000 |
