STIs 2 Flashcards
ddx for genital ulcer disease
1. Herpes Simplex Virus (type 2 > type 1)
2. Syphilis (Treponema pallidum)
3. Chancroid (Haemophilus ducreyi)
4. Lymphogranuloma venerium (LGV), caused by C. trachomatis
Herpesviridae - species
- Human virus:
-HSV1 (human herpesvirus 1)
-HSV2 (human herpesvirus 2)
-Varicella zoster virus (HHV-3)
-Epstein Barr virus (HHV-4)
-CMV (HHV-5)
-HHV6
-HHV7
-HHV8 (Kaposi’s sarcoma herpesvirus) - Simian virus:
-Herpes B virus
human herpesviruses - overview
*establish latent infection in specific target cells
*infection persists despite the host immune response, often with recurrent disease
*HSV1, HSV2, VZV, EBV, CMV, etc
herpes simplex virus (HSV) - epidemiology
*most common cause of genital ulcer disease worldwide
*genital herpes most often due to HSV2, but HSV1 becoming more common
*most cases are asymptomatic
*risk related to lifetime number of sex partners, age of sexual debut, and history of other STIs
HSV - transmission
*close contact with person shedding virus:
-inoculation of HSV2 on susceptible mucosal surface or crack in skin
-vertical transmission from mother to fetus during pregnancy/birth
*majority of genital herpes infections are transmitted by persons who are unaware they are infected or aysmptomatic
*incubation period = 2 to 12 days
*drying and soap&water readily inactivate HSV; fomite transmission unlikely
HSV pathogenesis
- exposure to virus → viral replication in epidermis →
- infection of sensory/autonomic nerves →
- intra-axonal transport to nerve cell bodies →
- HSV1 (trigeminal), HSV2 (sacral ganglia) →
- latent virus in sensory ganglion, which then reactivates (recurrent infection):
-triggers: trauma, UV light, immunosuppression
HSV1 - latent cell
*latency in trigeminal nerve
HSV2 - latent cell
*latency in sacral ganglia
HSV clinical manifestations: primary episode
*characterized by multiple lesions that are more severe, last longer, and have higher titers of virus than recurrent infections
*typical lesion progression: papules → vesicles → pustules → ulcers → crusts → healed
*often associated with systemic sx including: fever, headache, malaise, myalgia
*cervicitis, urethritis, perianal infection, proctitis
*illness lasts 2-4 weeks
HSV clinical manifestations: recurrent disease
*usually localized to defined mucocutaneous site
*symptoms more mild, duration shorter
*frequency and number of recurrences decreases over time
*prodromal symptoms
*“atypical” syndromes common (fissures)
genital herpes - diagnosis
*patient history and clinical presentation
*laboratory tests:
-virus detection tests (culture, PCR of lesion)
-serology
HSV treatment
ACYCLOVIR
other options: valacyclovir, famciclovir
*generally treat for 7-10 days
*MOA: all phosphorylated by cellular and herpesvirus THYMIDINE KINASES that inhibit viral DNA synthesis (requires the virus for the treatment to work)
HSV prevention
*antivirals - decrease transmission by 55%
*condoms - decrease transmission by 30%
HSV - treatment approaches of recurrences
- episodic treatment
- suppressive treatment:
-reduces frequency of recurrences
-reduces but does not eliminate subclinical viral shedding
-periodically, reassess need for continued suppressive therapy
HSV2 - complications
*urinary retention
*sacral radiculopathy
*aseptic meningitis
*pneumonia
*hepatitis
*transverse myelitis, autonomic sx, decreased reflexes/motor strength
syphilis - microbiology
*etiologic agent = Treponema pallidum
*corkscrew-shaped, motile microaerophilic bacterium
*cannot be cultured in vitro; cannot be viewed by normal light microscopy
syphilis - pathophysiology
- penetration: T. pallidum enters the body via skin and mucous membranes through abrasions during sexual contact
- dissemination: travels via the lymphatic system to regional lymph nodes and then throughout the body via the bloodstream
*vertical transmission: transplanted transplacentally from mother to fetus during pregnancy
primary syphilis - clinical presentation
*primary lesion or “chancre” develops at the site of inoculation
*chancre: progresses from macule → papule → ulcer
-typically PAINLESS, indurated, and has a clean base
-highly infectious
-heals spontaneously in 1-6 weeks
-25% present with multiple lesions
*regional lymphadenopathy: classically rubbery, painless, bilateral
*note - serologic tests for syphilis may not be positive during early primary syphilis
secondary syphilis - clinical presentation
*secondary lesions occur 3-6 weeks after the primary chancre appears; may persist for weeks to months
*primary and secondary stages may overlap
*manifestations: rash (maculopapular, can involves palms + soles), lymphadenopathy, malaise, MUCOUS PATCHES, CONDYLOMATA LATA, alopecia
*serologic tests are usually highest in titer during this stage
latent syphilis - overview
*host suppresses infection (no lesions are clinically apparent)
*only evidence is positive serologic test
*may occur between primary and secondary stages, between secondary relapses, and after secondary stage
*categories:
-early latent = < 1 year duration
-late latent = 1+ year duration
tertiary (late) syphilis - clinical manifestations
*approx 30% of untreated pts progress to tertiary stage within 1-20 years
*rare d/t widespread availability and use of antibiotics
*manifestations:
1. gummatous lesions
2. CARDIOVASCULAR SYPHILIS (ascending thoracic aortic aneurysm)
3. TABES DORSALIS
neurosyphilis - overview
*occurs when T. pallidum invades the CNS
*may occur at any stage of syphilis
*clinical manifestations:
-asymptomatic; psychiatric changes
-acute syphilitic meningitis
-meningovascular (strokes classically in middle cerebral artery distribution)
-ocular syphilis (uveitis)
-general paresis (progressive dementia & generalized paralysis)
-TABES DORSALIS
neurosyphilis: tabes dorsalis
*demyelination of sensory neurons in posterior (dorsal) columns:
-paresthesias
-locomotor ataxia (high-stepping gait with foot slap due to lack of proprioception)
syphilis - diagnosis
- primary: clinical + serology
- secondary: serology
- tertiary: clinical + serology
- neurosyphilis: serology on serum + CSF
syphilis serology - nontreponemal
*traditional screening
*not specific for T. pallidum (can be positive with other syndromes)
*purified cardiolipin with TITER
*tests:
-RPR (rapid plasma reagin) = most common
-VDRL (venereal disease research laboratory) = on CSF
syphilis serology - treponemal
*cannot distinguish active vs past infection
*performed when nontreponemal test (RPR, VDRL) is positive
*automated screening and confirmation
*tests:
-FTA-ABS
-MHA-TP
syphilis - treatment
TREATMENT OF CHOICE IS ALWAYS PENICILLIN
*primary, secondary, and early latent: benzathine PENICILLIN G injection
*late latent and tertiary: 3 injections (1 per week) if benzathine PENICILLIN G
*neurosyphilis: aqueous crystalline penicillin G IV for 10-14 days (DOES NOT MATTER IF ALLERGIC TO PENICILLIN)
syphilis treatment - penicillin allergy
*must DESENSITIZE pt to penicillin (give small doses in escalating levels)
*this is required if pt is pregnant or has neurosyphilis
Jarish-Herxheimer reaction
*acute febrile reaction with headache, myalgia, fever within 24 hours of syphilis therapy
*transient, cytokine-mediated reaction to rapid killing of circulating spirochetes
chancroid (Haemophilus ducreyi)
*declining prevalence in US and worldwide (sporadic outbreaks)
*clinical dx: PAINFUL ulcer, regional LAD
*treatment: azithromycin or ceftriaxone
Lymphogranuloma venereum (LGV) - overview
*classic Chlamydia trachomatis genital ulcer disease
*self-limited, tender papule → ulcer; LAD
*serovars L1, L2, and L3
*most frequently in tropical and subtropical areas
*more common in men than women
Lymphogranuloma venereum (LGV) - diagnosis
clinical dx:
*genital ulcer disease with lymphadenopathy (groove sign)
*proctitis (in MSM)
dx = SEROLOGY
Lymphogranuloma venereum (LGV) - treatment
doxycycline
condyloma acuminata - overview
*human papillomavirus (HPV types 6 or 11)
contrast to condyloma lata associated with syphilis; syphilitic lesions are broader, flatter, and paler than HPV lesions
human papillomavirus (HPV) - epidemiology
*90% of adults in the US will become infection with HPV
*after exposure, infection with HPV often clears spontaneously
human papillomavirus (HPV) - microbiology
*nonenveloped double-stranded DNA virus
*more than 400 types identified
*ONCOGENIC strains = 16 and 18
*NONONCOGENIC strains = 6 and 11
HPV-related squamous cell dysplasias
*cervical
*vulvar/vaginal
*penile
*anal
*oropharyngeal
HPV - diagnosis
*clinical
*pap smear (cervical, anal in high-risk pts)
*culture (not reliable)
*molecular techniques = nucleic acid probe tests, amplification
HPV vaccines
*Gardasil 9 (9vHPV) vaccine: protection against HPV types: 6, 11, 16, 18, 31, 33, 45, 52, 58
*noninfectious core proteins
*3 doses or 2 doses if < age 15
HPV vaccine - considerations
*vaccine is still recommended if:
-history of genital warts
-abnormal pap test
-positive HPV DNA test
*routine pap smears should still be performed after vaccination
prevention of STIs - overview
*limit sexual partners
*condom use (correct & consistent)
*screening of asymptomatic populations
*pt counseling: abstain from sexual intercourse until partners are treated and for 7 days after tx
*partner treatment: most recent partner & all partners in past 90 days
