STD: Syphilis, Herpes Flashcards
what is syphilis caused by?
Treponema pallidum (bacteria)
what are the transmission routes of syphilis?
- sexual contact
2. mother-to-child (transplacental during pregnancy)
how do we diagnose syphilis?
- Darkfield microscopy of exudates from lesions
- TWO serological tests needs to be conducted:
a. Treponemal test (for confirmatory)
b. non-treponemal test (for monitoring)
what is presentation for primary syphilis?
- heals spontaneously in 1-8 weeks
- site of infection: external genitalia, perianal region, mouth, throat
Signs and sx:
- single painless ulcer or chancre at the site of infection but can also present with multiple, atypical or painful lesions
what is the presentation for secondary syphilis?
- develops 2-8 weeks after the initial infection in untreated or inadequately treated individual
- disappears in 4-10 weeks if untreated
- Site of infection: multisystem due to hematogenous and lymphatic spread
- Signs and sx:
- includes skin rash, mucocutaneous lesions, and lymphadenopathy (swollen and painful lymph node)
what is presentation for latent syphilis?
definition:
~ early <1yr
~ late >1yr
- develops 4-10 weeks after secondary stage in untreated or inadequately treated individual
site of infection: possible multisystem involvement
- signs and symptoms:
- asymptomatic but picked up by serology testing
- internal organs continue to be affected by infection
note: as asymptomatic –> untreated can go to tertiary wo the person knowing
what is the presentation for tertiary syphilis
- develops in ~30% of untreated or inadequately treated individual 10-30yrs after initial infection
site of infection: possible multisystem heart, eyes, bones, joint
signs and symptoms:
- gummatous lesions in joints leading to impaired movement
- cardiac involvement leading to heart-aortic insufficiency
what is the presentation for neurosyphilis
- CNS involvement occurring at ANY stage of syphilis
- site of infection: CNS
- signs and symptoms:
- -> cognitive dysfunction, motor or sensory deficits, –> ophthalmic or auditory symptoms,
- -> signs and sx of meningitis, stroke
what is the purpose of treponemal serology test for diagnosing syphilis?
- uses treponemal antigen to detect treponemal antibody
1st type of test: T. pallidum Hemagglutination test (TPHA)
2nd type of test: T. pallidum passive particle agglutination assay (TPPA)
- these treponemal tests are more sensitive and specific than non-treponemal test, thus used as CONFIRMATORY tests
- may remain reactive for life, thus NOT for monitoring response to treatment
what is the purpose of non-treponemal serology test for diagnosing syphilis?
- uses nontreponemal antigen (cardiolipin) to detect treponemal antibodies
1st type of test: venereal disease research laboratory (VDRL) slide test
2nd type of test: rapid plasma reagin (RPR) card test
results: a positive test can indicate presence of ANY stage of syphilis
results reported in quantitative manner = the most dilute serum conc with a positive reaction
e. g.
1: 16 positive means at 1:32 no reaction is seen
(note: 1:16 means that easier to clear the bacteria out of the body compared to 1:32)
- used as a tool to monitor response to treatment
(note VDRL/RPR are NOT interchangeable) - titres usually declines after treatment and can become non-reactive with time
- less specific, thus if positive is seen in this nontreponemal test, it needs to be confirmed with a treponemal test
syphilis treatment for primary, secondary, or early latent (<1yr)
- IM benzathine penicillin G 2.4 million units x 1 dose
for pencillin-allergic:
2. PO doxycycline 100mg BID x 14 days
(counselling: take w food to reduce GI upset.
take with water and remain upright for at least 30min to prevent heartburn.
don’t take with milk, Ca, Fe, take 2 hours apart.
SEL GI, photosensitivity)
syphilis treatment for late latent (>1yr) or unknown duration or tertiary
- IM benzathine penicillin G 2.4 million units once a week x 3 doses
for penicillin-allergic:
2. PO doxycyline 100mg BID x 28 days
syphilis treatment for neurosyphilis
- IV crystalline penicillin G 3-4 million units q4h OR 18-24 million units/day as continuous infusion x 10-14 days
OR
- IM procaine penicillin G 2.4 million units daily + PO probenecid 500mg QID x 10-14 days
for penicillin allergic:
3. IV/IM ceftriaxone 2g daily x 10-14 days (note: cross-reactivity of penicillin with cephalosporins v low)
(if concern for cross-sensitivity - skin test to confirm pencillin allergy, desensitize if necessary)
what are the monitoring parameters for syphilis?
- Jarisch-Herxheimer rxn: acute febrile rxn accompanied w headache, myalgia, and other symptoms
- appears within the first 24 hours after any therapy for syphilis
- note: antipyretics will help but NOT prevent - for primary/secondary syphilis:
- VDRL or RPR at 6 and 12 months
- treatment success = decrease of VDRL or RPR titre by at least fourfold (e.g. 1:64 to 1:16) - for latent/tertiary syphilis: VDRL or RPR at 6, 12 and 24 months
- for neurosyphilis: CSF examination every 6 month until CSF normal
- Treatment failure at 6 months:
a. shows signs and symptoms of disease OR
b. fail to decrease VDRL or RPR titre by fourfold OR increases (1:16 to 1:64)
c. retreat and re-evaluate for unrecognized neurosyphilis
what are some management protocols of the sexual partners for syphilis?
- sexual partners should be evaluated for STIs and treated if tested positive
- abstinence for 7 days after single-dose regimen OR
- abstinence during the 10-14/28-day regimen and resolution of symptoms, if present
what is the herpes virus
- is an enveloped virus with double-stranded DNA
- lacks a cell wall, cell membrane, and ribosomal structures
- replicate in host cell nucleus
- persist indefinitely (life-long) in infected host (latent infection)
- periodic reactivations, esp in immunocompromised hosts
how is herpes virus replication inhibited
- acyclovir/ valacyclovir inhibits viral DNA polymerase –> inhibits DNA synthesis and replication
3 common types of herpes viruses and what are their common names?
- Human herpesvirus 1 = Herpes simplex virus 1
- Human herpesvirus 2 = Herpes simplex virus 2
- human herpesvirus 3 = varicella-zoster virus
difference between HSV-1 and HSV-2
HSV-1:
- young children
- contact (often saliva) transmission
- diseases: herpes gingivostomatitis, herpes labialis (cold sore)
- management = self-limiting usually; PO acyclovir or valacyclovir; topical acyclovir (modest benefit)
HSV-2:
- young adults
- sexual*
- disease = genital herpes
management = usually self limiting; PO acyclovir or valacyclovir
For BOTH HSV-1 and HSV-2:
reactivation (relapse/ recurrence/flares) =
- stimuli e.g. fever, menstruation, sunlight, stress etc can reactivate the virus
- reactivation may be clinically asymptomatic, or it may produce life-threatening disease
varicella zoster virus; what two form of diseases it can cause?
- primary VZV = diffuse vesicular rash of varicella, or chicken pox
- reactivation of latent VZV = herpes zoster, or shingles
- virus persisting in the nerve ganglia reactivated
what are the characteristics of varicella (chickenpox)?
- benign self-limiting
- but can be severe disease in immunocompromised individuals
- fever starts 1-2 days before rash appears and lasts for 4-5 days;
- fever is gone once the rash has completely appeared
- groups of new lesions appear over 4-7 days
- pox/rash on most parts of the body
- -> got papules (no pus), vesicles (clear fluid), pustules (pus), scabs
what are the characteristics of herpes zoster (shingles)
- increase risk: increasing age and immunosuppression
- rash begins as papules, evolves into vesicles, and onto pustules
- new lesions appear for 3-5 days, usually dries with crusting in 7-10 days
- rash usually precedes by tingling, itching, or pain (or combination of these) for 2-3 days, and these symptoms can be continuous or episodic
- post-herpetic neuralgia occurs in 10-50% of patients
- pain that persist after the rash has resolved
- pain may persist for many months
treatment for varicella/shingles (human herpesvirus 3)
Acyclovir and valacyclovir (to start within 24-48 hours of rash) to reduce duration and severity of symptoms
- Acyclovir dose: PO 800mg 5 times daily x 7 days
- Valacyclovir dose: PO 1g 3 times daily x 7 days (vala preferred over acyclovir)
- vaccines available to PREVENT chicken pox and shingles
which herpes virus causes genital herpes?
HSV-2
HSV-1 causes cold sore, not a STI
HSV-3 causes (varicella) chickenpox/ (herpes zoster) shingles not a STI
characteristics of genital herpes
- HSV-1 & HSV-2 but
- HSV-2: most recurrent genital herpes
- 5 stages of a HSV infection:
a. primary mucocutaneous infection
b. infection of the nerve ganglia
c. establish latency
d. reactivation
e. recurrent outbreaks/flairs - vesicles develop over 7-10 days, heal in 2-4 weeks
- intermittent viral shedding from epithelial cells –> person can be asymptomatically transferring herpes to their sexual partners
- chronic and life-long viral infection
- may not be symptomatic while shedding and transmission occurs
how is genital herpes transmitted?
transfer of body fluids and intimate skin-to-skin contact
how is HSV-3 transmitted (chickenpox and shingles)
virus can be inhaled
how do we diagnose genital herpes?
- patient history: previous lesion/ sexual contact with similar lesions
- Presentation/symptoms:
- classical painful multiple vesicular or ulcerative lesions
- local itching, pain, tender inguinal lymphadenopathy
- flu-like symptoms (e.g. fever, headache, malaise) during the first few days after appearance of lesions
- prodromal symptoms (before the lesions): mild burning, itching, tingling seen in ~50% of patients prior to appearance of recurrent lesions (seen in the recurrent disease)
- symptoms are less severe in recurrent disease (less lesions, heal faster, milder symptoms)
(as ab from the first infection)
what are 2 test can be done to diagnose genital herpes
- Virologic test
- viral cell culture and NAAT/PCR for HSV DNA from genital lesions - Type-specific serologic tests (send blood to look for ab)
- Ab to HSV develop during the first several weeks after infection and persist indefinitely
- serology is NOT useful for first episode infection as it takes bet 6-8 weeks for serological detection after the first episode
- presence of HSV-2 Ab implies anogenital infection
what is the goal for the treatment of genital herpes?
- relieve symptoms, shorten clinical course, prevent complications and recurrences, decreases transmission
what are the supportive care (non-pharmacological) for genital herpes?
- warm saline bath relieves discomfort
- good genital hygiene to prevent superinfection
- counselling regarding natural history
what are the antiviral treatment for FIRST episode of genital herpes?
- Acyclovir
- 400mg TDS x 7-10days
OR
- IV 5-10mg/kg q8h x 2-7 days, complete with PO for total 10 days (for severe disease or complications that requires hospitalisation) - Valacyclovir 1g BD for 7-10 days
Treatment can be extended if healing is incomplete after 10 days of therapy
why use acyclovir and valacyclovir as the anti-viral treatment for genital herpes?
proven to:
- reduce viral shedding by 7 days
- reduce duration of symptoms by 2 days
- reduce time to healing of FIRST episode by 4 days
- both drugs have comparable efficacy and tolerability; thus the choice of drug is dependent on patient compliance and cost (valacyclovir BD vs acyclovir TDS)
- maximum benefit when initiated at the earliest stage of disease (within 72hours)
- DOES NOT prevent latency or affect frequency and severity of recurrent disease after drug is discontinued
- topical antiviral offers minimal clinical benefit, also can cause local irritation; thus use of it is discouraged
acyclovir and valacyclovir; their route of inhibition (MOA)
- acyclovir inhibits viral DNA polymerase –> inhibits DNA synthesis and replication
- valacyclovir is a L-valine ester of acyclovir
valacyclovir –> acyclovir + valine
acyclovir’s F: 10-20%, t1/2 = ~3hrs
valacyclovir’s F: 55%, t1/2 = ~3hrs
counselling when administering acyclovir and valacyclovir
acyclovir: take wo regards to food, after food is possible if GI upset is present
SE: Malaise, headache, N/V/D
- maintain adequate hydration to prevent crystallisation in renal tubules (more common in IV)
valacyclovir:
as per acyclovir hydration
- main SE: headache
definition of recurrent genital herpes
median of 4 recurrence the year after their first symptomatic episode
- recurrent flares are common
what are the pharmacological management for recurrent genital herpes
Chronic suppressive or episodic therapy
- choice based on patient’s preference
what are the advantages and disadvantages of chronic suppressive therapy
advantages:
- reduces freq of recurrence by 70-80% in patient who have freq recurrence (i.e. >6 recurrences per year)
- many pts report no symptomatic outbreaks
- improved QOL
- established long term safety and efficacy
- decrease risk of transmission (in combi with consistent condom use and abstinence during recurrence)
- -> reduces viral shedding, including asymptomatic shedding
disadvantages:
- cost and
- compliance
the treatment regimen for chronic suppressive therapy
- *acyclovir 400mg PO BD
OR
2. valacyclovir 500mg PO OD (this many not effective for those that have >=10 episodes/year)
- *valacyclovir 1g PO OD
- famciclovir (not found in SG): 250mg PO BD
duration: dependent on patient and disease
- patient with complicated disease e.g disseminated disease (encephalitis, meningitis, keratitis), usually in immunocompromised host, may need indefinite suppression
advantages and disadvantages of episodic therapy
advantages:
- shorten duration and severity of symptoms
- less costly vs chronic suppression therapy
- patients more likely to be compliant
disadvantages:
- requires initiation of therapy WITHIN 1 day of lesion onset or during prodrome that precedes some outbreaks
- does not reduce the risk of transmission (doesnt reduce viral shedding)
the treatment regimen for episodic therapy
- acyclovir 800mg PO BD x 5 days
(400mg TDS x 5 days also can but not recommended bcos of freq of dosing)
or
- acyclovir 800mg PO TDS x 2 days
or
- valacyclovir 500mg PO BD x 3 days
or
- valacyclovir 1g OD x 5 days
or
5. Famciclovir 1g PO BD X 1 day or 6. Famciclovir 500mg PO once, followed by 250mg BD x 2days or 7. Famciclovir 125mg PO BD x 5 days
counselling of persons with HSV infection
- educate concerning the natural hx of the disease
- encourage to inform their current and future sex partners
- sexual transmission of HSV can occur during asymptomatic periods
- those w genital herpes should remain abstinent from sexual activity with uninfected partner when lesions or prodromal symptoms are present
- risk of HSV sexual transmission can be decreased by daily use of acyclovir/valacyclovir by the infected person
- latex condoms when used consistently and correctly, might reduce risk of genital herpes transmission
- risk of neonatal HSV infection (during labour process)
- increase risk for HIV acquisition (2x more likely)
management of sex partners for genital herpes
- symptomatic sex partners should be evaluated and treated in the same manner as pts who have genital lesions
- asymptomatic sex partners of patients who have genital herpes should be questioned concerning hx of genital lesions and offered type-specific serologic testing for HSV-2 (as HSV-2 causes genital herpes)
