STIs and STI treatment Flashcards
HPV structure, transmission, genome maintenance in host cell?
- circular dsDN, icosahedral capsid composed of L1 and L2 “late” proteins that self assemble (Vaccine basis!)
- Non enveloped = more stable, can survive on skin/fomites
– transmitted via skin-skin contact /fomites
- Benign tumor cells (warts) –> extrachromosomal genome
- Malignant tumor (cervical carcinomas) –> integrated into host genome (E6 and 7, with E2 disruption - loss of regulation)
how do papilloma viruses grow in permissive vs non - permissive cells? how does this effect tx?
- initially infect germinal cells (non permissive = no viruses produced) and transform them
- germinal cells mature/migrate to skin surface –> become permissive /produce virus progeny
- tx: difficult to completely eradicate infection while virus remains in germinal cell layer
- proliferating cells also shed virus ie spread via direct contact and tend to cluster
HPV Subtypes for:
- common warts (verruca vulgaris or plana),
- Anogenital (condyloma acuminata vs condyloma plana),
- sub clinical papilloma infection (SPI) / cervical / penile / oral / neck cancers, laryngeal papilloma
– common warts - don’t know
– anogential:
acuminata = 6 and 11
plana = 16, 18
– SPI and carcinomas = 16, 11, 31, 33
Koilocyte
– squamous epithelial cells that are indicative of HPV infection
Histo: vacuolated cytoplasm
SPI
Sub Clinical Papilloma Infection: not readily detected, more of a concern than condyloma plana or acuminata bc of link to cervical cancer
Laryngeal Papilloma
- chronic, benign warts in respiratory tract that generally appear < 5 yo (Genotypes 6 and 11)
- due to maternal HPV infection intrapartum
**Associated with respiratory distress –> 3% = deaths
Epidermodysplasia
– inherited immune deficiency = can’t fight off HPV = numerous lesions throughout lifetime
co-factors for risk of cervical cancer development?
Smoking and concomitant HSV or HIV infection
HPV Dx? tx?
Dx: Routine Pap smears –> colposcopy for abnormal results to look for dyspolasia
**cannot be grown in culture! – use PCR to dx genotype?
Tx:
- wart removal: Bi or trichloroacetic acid brushed on denatures proteins, cryotherapy, LEEP (loop electrosx excision), Podofilox (anti mitotic), Imiquimod (TLR 7 = inc T cell response),
- Vaccine: gardasil (L1 capsid protein = 16, 18, 6, 11) and cervarix (16, 18 only)
Common urethritis/cervicitis (PID) agents?
Chlamydia trachomatis, Neisseria gonorrhoeae, ureaplasma urelyticum (mycoplasma)
Primary symptoms of Ct and GC? laboratory dx?
Presentation: dysuria, penile/vaginal exudation
DX: NAAT (nuc acid amp) on urine or exudate – bc they typically occur together!
- -> GC = Oxidase+, G- stain + PMNs or Thayer Martin / chocolate agar medium (+ vanc/nystatin/colistin to xNormal flora)
- -> Ct = no cocci on G stain, no polys
Can you use flouroquinolones for GC?
NO – no longer recommended due to resistance
How do you treat sexual contacts of GC/Ct infected pts?
??
Lymphogranuloma venereum (LGV) and Trachoma and C. Pneumoniae
LGV = more invasive strain of Ct –> invades inguinal LNs and causes ulceration at site of entry
— may have CHANCROID (painful, no hard rim)
Trachoma = Ct Strain that is potentially BLINDING chronic dz, prevelant in Asia, Middle East, Africa (do not cause urethritis)
Chlamydia Pneumoniae = Resp infections / PNA
High risk populations for GC, Ct (and ureaplasma)? are infections always clinically apparent?
Risk: sexually active, multiple partners, a partner w/ multiple partners, inner city, African American, 15-24 yo age groups
UNAPPARENT INFECTIONS ARE COMMON!!!
GC and Ct treatment
Tx: Ceftriaxone + Azithromycin or Doxy
GC (beta lactam resistant) = Ceftriaxone (IM) +/-
Ct (intracellular) = Axithromycin / Doxycyclin
GC, Ct, ureaplasma virulence factors
GC: No capsule, LOS shedding (not classic LPS!) = inflammatory response, IgA1ase,
+ ANTIGENIC VARIATION (pilS –> pilE – silent inserts into expression locus) = no vaccine / reinfection common!
+ can DISSEMINATE = septicemia or rash
Ct: Obligate INTRACELLULAR parasite (G- Ish, deficient peptidoglycan), heat shock protein/low tox LPS –> inflammatory response!
+ distinct development cycle: Elementary Bodies (EB) = inert/ non infectious –> Reticulate bodies (RB) = grow in membrane vacuole
**Damage to human host = mainly result of inflammatory response
Ureaplasma: lack cell wall (not b-lactam susceptible),
Lower GU, upper GU, and other infections caused by GC and Ct?
- Lower UG: cervicitis / urethritis
- Upper UG: PID / salpingitis / epididymitis / prostatitis
– Other:
> Rectal infection (MSM),
> pharyngitis (Oral sex - GC only),
> Conjunctivitis in newborn “ophthalmia neonatorum” (Ct usually), Infant PNA (Ct only),
> Disseminated dz (GC only) = sepsis / rash / aseptic arthritis (Reiter’s syndrome) /endocarditis / meningitis
Urethritis discharge in GC vs Ct?
GC – “the clap” - thick, purulent
Ct – less purulent, milky
symptoms of infant Ct pneumonia?
- Repetitive staccato cough w/ tychypnea (wheezing is rare!)
- Afebrile, hyperinflation/bilateral infiltrates on CXR, preceding/concurrent conjunctivitis hx possible
– vertical transmission!
– raised IgM levels
Diff dx: RSV, ureaplasma, CMV, adenovirus, influenza, pertussis
Def, Symptoms, and consequences of PID?
PID: inflammatory process involving a variable combo of endometritis, salpingitis, tubo-ovarian abscess, and pelvic peritonitis
- dull to severe lower abdominal pain (often starting w/ onset of menstrual cycle)
- fever
- Cervical motion tenderness + adnexal tenderness
Consequences: sterility, ectopic pregnancy, chronic pelvic pain, hospitalization, tubo-ovarian abscess,
**overt symptoms less common w/ Ct, but damage worse with Ct!
HSV structure? Hallmark? replication cycle?
Structure:
- large dsDNA virus w/ icosohedral capsid + lipid envelope
- COMPLEX = 90+ Proteins = several anti herpetic Rx’s
Hallmark:
– LATENCY = quiescent virus genome in dorsal root ganglia = recurrent infections
Rep cycle:
- fuses w/ plasma membrane in pH Independent manner
- nucleocapsid released –> migrates to nucleus
- immediate early expression (transcriptional regulator proteins / modify host RNA polymerase)
- Replicate viral genome
- “late” class proteins produced (structural)
- viral assembly in nucleus
- virus buds from plasma membrane
Important “early” proteins in HSV replication? Why?
1) DNA polymerase = ultimate target of acyclovir and famciclovir
2) Thymidine kinase = required for phosphorylation / activation of acyclovir (increases cell specificity of ACV)
** Thymidine kinase mutations = resistance to ACV – particularly important w/ AIDS patients
How does HSV form multinucleated giant cells? how is this diagnostically important?
– viral glycoproteins respsonsible for fusion (entry) = same as those present in plasma membrane of infected cell late in replication –> adjacent infected / uninfected cells can fuse and form giant cells
** Virus can spread cell to cell w/out progeny release!
** TZANCK SMEAR = diagnostic test taking cells from ulcerous lesion, looking for giant cells w/ nuclear inclusion bodies
LAT
Latency Associated Transcript: HSV gene whose product is an RNA species that silences subset of cellular gene to prevent apoptosis in infected neuron – NO VIRUS PARTICLES PRODUCED during maintenence period
**Decline in cell mediated immunity (stress, etc) –> virus reactivation –> recurrent infection in epithelial cells innervated by latent infected neuron
Diseases caused by HSV1 vs. HSV2
HSV1: herpes labialis/fever blister, gingivostomatitis, keratitis, ENCEPHALITIS (+ conjunctivitis, blepharitis, urogential lesions)
HSV2: Cervicitis, vulvular and penile vesicles, MENINGITIS, (SEM dz possible, urethritis - rare, perianal and vaginal vesicles, encephalitis)
- *Generally self-limiting!
- *Disseminated disease – immunocompromised and neonates! = can be severe/fatal!
Primary vs. Recurrent HSV infection
**1o = generally worse symptoms/longer duration
Oral:
- 1o = gingivostomatitis,
- recur = fever blister(s), both +/- fever/HA
Ocular:
- 1o = blepharitis/conjunctivitis, usually children
- recur keratitis = corneal scarring if not treated
Genital:
- 1o males = penile vesicles, 1o females = ext/int vesicles
- recur = generally fewer lesions / heal more quickly, frequency diminishes w/ time
- *both = +/- prodromal/flu-like symptoms = tip off to recurrence
CNS:
- 1o HSV2 = Aseptic Meningitis / Encephalitis in neonates
- recur HSV1 = Encephalitis in Adults (trigeminal N)
- *70% mortality w/out treatment
Neonatal HSV infections: symptoms/progression, chance of maternal transmission / delivery options
Symptoms:
- -> develop 1-2 week postpartum,
- -> can be limited to skin / eyes / mouth (SEM) w/ “zoster like” rash
- -> or be more severe w/ CNS involvement (encephalitis: seizures, irritability, coma)
- -> or disseminate to multiple organs
**75% severe infections = death, significant sequelae
- *1o maternal infection = 30% chance transmission vs. recurrance = 2-3% chance – maternal Abs may be protective
- DO A C-SECTION if mother presents with herpetic lesions!!
HSV dx – genital, meningitis, encephalitis, neonatal
Genital:
- Gold standard = PCR screening of vesicle swab (can distinguish serotypes!)
- historically = virus was cultured or TZANCK SMEAR done
Meningitis:
– RULE OUT BACTERIAL SOURCE! = CSF used for PCR / culture
Encephalitis:
– CSF rarely positive, can do EEG followed by PCR amplification and southern blot confirmation
Neonatal/congenital:
– PCR / culture –> CHECK LFTs/Liver enzymes for disseminated disease!
What Ag is used to serotype HSV?
Abs to Glycoprotein G – virus envelope component
**Only indicates PAST INFECTION unless you monitor for IgM vs. IgG
HSV treatment
**NO CURE – infected? = infected for life due to latency
AntiHSV — lessens disease episode:
1) Acyclovir (dGuanine analog = xViral DNA polymerase)
2) Vidarabine and triflouridne (base analog, used in keratitis)
3) Foscarnet (pyrophosphate analog blocks pyrophosphate exchange)
4) Docosonal (Over the counter cold sore med, host membrane modifier =xFusion)
- Neonatal/congenital herpes = IV, high dose ACV for 14 - 21 days
- Herpes encephalitis = high dose IV ACV for 10 days - 3 wks
- immunocompromised = aggressive ACV tx
Most common agents causing BV/vaginitis? transmission/cause?
Candida albicans and C. glabrata – aka candidiasis
Gardnerella vaginalis, Mobiluncus spp. and other ANAEROBES
Trichomonas Vaginalis – single cell protozoan! = frank pathogen/sexually transmitted
- *Candididasis and anaerobes = Opportunistic! – overgrowth of normal flora, not sexually transmitted due to disruption of other normal flora, especially G+ lactobacilli which maintain low pH by H2O2 production
ex) sex, douching, IUDs, menstrual cycle, preg, antibiotics
Is BV generally a single agent disease?
NO, usually a combination of various anearobes
Vulvovaginal Discharge character in: normal vs. candidiasis, trichomonal, bacterial vaginitis
Normal: variable, clear/white, non-homogenous/patchy
Candidiasis: scant, white, clumped
“cottage cheese”, pH < 4.5
Bacterial: moderate, white/grey, adherent/coats vagina, homogenous, MALODOROUS (anaerobes), pH > 4.5
Trichomonas: PROFUSE, yellow/green, frothy, homogenous, pH > 4.5
Microscopy of vaginal epithelial cell culture in: normal vs. candidiasis, trichomonal, bacterial vaginitis
normal: normal epithelial cells + G+ lactobacilli predominate
Candidiasis: leukocytes, epithelial cells, mycelia or pseudomycelia + yeast/branching hyphea on KOH wet mount
BV: CLUE CELLS (vaginal epithelial cells w/ adherent bacteria), a few leukocytes, lactobacilli outnumbered by mixed flora
Trich: leukocytes/PMNs, trichomonads (size of PMNs w/ TWITCHING MOTILITY!)
Symptoms of cystitis, pylonephritis, cervicitis
cystitis: dysuria, suprapubic pain, leukocytes/polys in urine, ^bacteria in urine
Pylonephritis: cystitis signs/symp + Significant fever, flank pain, WBC and RBC casts in urine
Cervicitis: dysruia, mucopurulent discharge (from cervix), +/- fever/abdominal pain/pruritis
TX: candidiasis, BV, trich
Candidiasis: intravaginal Imidazole, oral fluconazole
– partner = nothing if asymptomatic / tx for contact dermatitis
BV: Metronidazole or Clindamycine (intravagnially)
– partner: none
Trich: Metronidazole
– partner = metronidazole
DM /immunodeficient and Vaginitis?
Can suffer from CHRONIC CANDIDIASIS (genital and oral)
Syphilis/Treponema pallidum: structure? Hallmark? dev/proliferation?
Structure: spirochete (spiral bacterium) = inner periplasm w/ peptidoglycan + outer sheath (no LPS), axial filaments = motile
**too thin to see on G stain/direct light transmission microscopy
Hallmarks:
1o = non painful chancre/ulcer @ site of entry,
2o = systemic infection w/ snail track lesions +/- palmar and sole rash/condylomata lata
Proliferation: distinct sequential phases, including latent phase that can last for years (continue for life/3o dz)
Syphilis Immune Response
- Rigorous humoral / cellular response that DOES NOT eliminate infection
- *host cellular immune response controls infection but ALSO PATHOLOGY (esp tertiary syphilis)
1o, 2o, 3o syphilis
1o = 2-3 wk incubation, painless chancre/non tender inguinal lymphadenopathy, resolves in 3-6 wks
2o = 1-2 months following infections, disseminated infection (blood and lymph):
- hyperpigmented/maculopapular rash +/- palms and soles
- SNAIL TRACK LESIONS on mucous membranes
- Condylomata lata (wart like lesions @ moist skin folds)
3o = almost any organ can be affected (heart, CNS, skin, bone)
Congenital syphilis: symptoms at birth? transmission? early/late symptoms? tx?
- may or may not have symptoms at birth
- disseminated infection transmitted transplacentally after 1st trimester via blood
- early = snuffles, bullous rash, snail track lesions, condylomata lata, enlarged liver/spleen
- late (~2 years) = stigmata may develop, bone abnormalities (saber shins / frontal bossing), vision defects, Hutchinson’s triad
Tx: 10 day course crystalline Pen G or Procaine Pen G
Hutchinson’s triad?
CONGENITAL SYPHILIS - late symptom possibility
- notched incisors/screwdriver teeth
- Keratitis
- deafness
Syphilis dx
1st: NON TREPONEMAL SEROLOGIC TEST – RPR (rapid plasma reagin) or VDRL (venereal disease research lab test)
* sensitive, but not specific
Next: Treponemal test – FTA-ABS (flourescent treponemal Ag absorbed…have to remove cross reacting Abs against normal spirochetal flora)
* specific
**non treponemal = Ag is NOT T. PALLIDUM – beef heart cardiolipin instead = cheaper, relatively sensitive, good to monitor antibiotic efficacy!
How long will T pallidum titers remain high?
Can remain high for months after patient is cured of syphilis!
Darkfield Microscopy
Historical method of diagnosing T. pallidum/syphilis
(or useful early on – titers are not high enough)
– light projected at oblique angle –> light refracted through objective lens if spirochete is present
Treatment for syphilis/T pallidum?
Large, single dose of Pen G
Macrolides, azithromycin as alternatives
Which STIs are reportable to health department?
- Syphilis
- GC
- Ct
E6, E7, E2
E6 = binds/inactivates p53 E7 = binds/inactivates RB
E2 = regulates E6 and E7 expression – get’s disrupted when viral DNA is inserted into host DNA
Do acyclovir/valacyclovir and famciclovir cause DNA chain termination? how are they metabolized/prodruging? toxicity?
NO - competitively inhibit viral DNA polymerase by competing w/ dGTP for incorporation into viral DNA
Valacyclovir –> acyclovir (better bioavailability)
Famciclovir – deacetylated–> Penciclovir
Toxicity:
acyclovir /valACV = neurotoxicity/seizures
Famaciclovir = n/a
Benzathine Pen G: uses, special?, limitations
Uses: syphilis, latent syphilis
Special bc: IM administration = drug depot that liberates drug for 2 weeks – good for non compliant pts
Limitations: poor penetration of CSF, not good for neurosyphilis
Jarisch Herxheimer Reaction
– chills, fever, HA, myalgias, arthralgias +/- cutaneous lesions may become more prominent
- common w/ secondary syphilis after Pen G administration -DO NOT STOP DRUG!
