STD: Syphilis, Herpes

Question 1

what is syphilis caused by?

Answer 1

Treponema pallidum (bacteria)

Question 2

what are the transmission routes of syphilis?

Answer 2

1. sexual contact

2. mother-to-child (transplacental during pregnancy)

Question 3

how do we diagnose syphilis?

Answer 3

1. Darkfield microscopy of exudates from lesions
2. TWO serological tests needs to be conducted:
   a. Treponemal test (for confirmatory)
   b. non-treponemal test (for monitoring)

Question 4

what is presentation for primary syphilis?

Answer 4

• 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

Question 5

what is the presentation for secondary syphilis?

Answer 5

• 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)

Question 6

what is presentation for latent syphilis?

Answer 6

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

Question 7

what is the presentation for tertiary syphilis

Answer 7

• 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

Question 8

what is the presentation for neurosyphilis

Answer 8

• 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

Question 9

what is the purpose of treponemal serology test for diagnosing syphilis?

Answer 9

• 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

Question 10

what is the purpose of non-treponemal serology test for diagnosing syphilis?

Answer 10

• 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

Question 11

syphilis treatment for primary, secondary, or early latent (<1yr)

Answer 11

1. 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)

Question 12

syphilis treatment for late latent (>1yr) or unknown duration or tertiary

Answer 12

1. 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

Question 13

syphilis treatment for neurosyphilis

Answer 13

1. IV crystalline penicillin G 3-4 million units q4h OR 18-24 million units/day as continuous infusion x 10-14 days

OR

2. 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)

Question 14

what are the monitoring parameters for syphilis?

Answer 14

1. 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
2. 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)
3. for latent/tertiary syphilis: VDRL or RPR at 6, 12 and 24 months
4. for neurosyphilis: CSF examination every 6 month until CSF normal
5. 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

Question 15

what are some management protocols of the sexual partners for syphilis?

Answer 15

• 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

Question 16

what is the herpes virus

Answer 16

• 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

Question 17

how is herpes virus replication inhibited

Answer 17

• acyclovir/ valacyclovir inhibits viral DNA polymerase –> inhibits DNA synthesis and replication

Question 18

3 common types of herpes viruses and what are their common names?

Answer 18

• Human herpesvirus 1 = Herpes simplex virus 1
• Human herpesvirus 2 = Herpes simplex virus 2
• human herpesvirus 3 = varicella-zoster virus

Question 19

difference between HSV-1 and HSV-2

Answer 19

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

Question 20

varicella zoster virus; what two form of diseases it can cause?

Answer 20

1. primary VZV = diffuse vesicular rash of varicella, or chicken pox
2. reactivation of latent VZV = herpes zoster, or shingles
   - virus persisting in the nerve ganglia reactivated

Question 21

what are the characteristics of varicella (chickenpox)?

Answer 21

• 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

Question 22

what are the characteristics of herpes zoster (shingles)

Answer 22

• 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

Question 23

treatment for varicella/shingles (human herpesvirus 3)

Answer 23

Acyclovir and valacyclovir (to start within 24-48 hours of rash) to reduce duration and severity of symptoms

1. Acyclovir dose: PO 800mg 5 times daily x 7 days
2. Valacyclovir dose: PO 1g 3 times daily x 7 days (vala preferred over acyclovir)
3. vaccines available to PREVENT chicken pox and shingles

Question 24

which herpes virus causes genital herpes?

Answer 24

HSV-2

HSV-1 causes cold sore, not a STI

HSV-3 causes (varicella) chickenpox/ (herpes zoster) shingles not a STI

Question 25

characteristics of genital herpes

Answer 25

- 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

Question 26

how is genital herpes transmitted?

Answer 26

transfer of body fluids and intimate skin-to-skin contact

Question 27

how is HSV-3 transmitted (chickenpox and shingles)

Answer 27

virus can be inhaled

Question 28

how do we diagnose genital herpes?

Answer 28

1. patient history: previous lesion/ sexual contact with similar lesions 2. 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)

Question 29

what are 2 test can be done to diagnose genital herpes

Answer 29

1. Virologic test - viral cell culture and NAAT/PCR for HSV DNA from genital lesions 2. 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

Question 30

what is the goal for the treatment of genital herpes?

Answer 30

- relieve symptoms, shorten clinical course, prevent complications and recurrences, decreases transmission

Question 31

what are the supportive care (non-pharmacological) for genital herpes?

Answer 31

- warm saline bath relieves discomfort - good genital hygiene to prevent superinfection - counselling regarding natural history

Question 32

what are the antiviral treatment for FIRST episode of genital herpes?

Answer 32

1. 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) 2. Valacyclovir 1g BD for 7-10 days Treatment can be extended if healing is incomplete after 10 days of therapy

Question 33

why use acyclovir and valacyclovir as the anti-viral treatment for genital herpes?

Answer 33

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

Question 34

acyclovir and valacyclovir; their route of inhibition (MOA)

Answer 34

- 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

Question 35

counselling when administering acyclovir and valacyclovir

Answer 35

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

Question 36

definition of recurrent genital herpes

Answer 36

median of 4 recurrence the year after their first symptomatic episode - recurrent flares are common

Question 37

what are the pharmacological management for recurrent genital herpes

Answer 37

Chronic suppressive or episodic therapy | - choice based on patient's preference

Question 38

what are the advantages and disadvantages of chronic suppressive therapy

Answer 38

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

Question 39

the treatment regimen for chronic suppressive therapy

Answer 39

1. *acyclovir 400mg PO BD OR 2. valacyclovir 500mg PO OD (this many not effective for those that have >=10 episodes/year) 3. *valacyclovir 1g PO OD 4. 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

Question 40

advantages and disadvantages of episodic therapy

Answer 40

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)

Question 41

the treatment regimen for episodic therapy

Answer 41

1. acyclovir 800mg PO BD x 5 days (400mg TDS x 5 days also can but not recommended bcos of freq of dosing) or 2. acyclovir 800mg PO TDS x 2 days or 3. valacyclovir 500mg PO BD x 3 days or 4. 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 ```

Question 42

counselling of persons with HSV infection

Answer 42

- 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)

Question 43

management of sex partners for genital herpes

Answer 43

- 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)