STIs 2 Flashcards
Syphilis: The Great Mimicker/Imitator
Syphilis is a sexually transmitted infection caused
by Treponema pallidum; an incredibly small bacteria
known as a spirochete – discovered in 1905.
It is known as “The Great Imitator” since it difficult
to distinguish clinically on history and patients can
be initially asymptomatic but then develop systemic
or secondary disease that was historically confusing
(i.e., rashes, hair loss) as well as very late
manifestations including chronic skin changes that
mimicked leprosy.
Treponema species also cause other diseases in developing countries known as yaws and pinta.
Syphilis: Treponema pallidum
transmission
PATHOGEN: Treponema pallidum (SPIROCHETE) – only
infects HUMANS
TRANSMISSION:
* Efficient transmission via sexual contact (contact with
chancre, sexual fluids, via oral, vaginal or anal sex)
* A single sexual encounter with someone with active
primary/secondary syphilis has a ~33% risk of
infection!
* Vertical transmission possible!
* Infectious syphilis is associated with increased
transmission of and susceptibility to HIV infection
Spirochetes are often gram-negative but should be classified SEPARATELY due to unique susceptibilities!
Syphilis: Epidemiology & Patterns in Canada
Syphilis is found worldwide (ubiquitous) but
ONLY infects humans (eradicable!)
* 1905 - organism that causes syphilis,
Treponema pallidum, was first described
Syphilis has been notifiable in Canada since
1940 (rates were very high)
* Rates in Alberta over the past six years
have increased 10-15-fold!!
Risk factors: MSM, substance use, sex
workers
Currently congenital syphilis rates are VERY HIGH in Alberta and are of MAJOR public health concern.
Syphilis: Alarming Rise of Congenital Syphilis
With syphilis outbreaks - increase in
congenital syphilis.
Congenital syphilis can lead to long
term health complications and death
of the infants.
Most infants infected during pregnancy
(100% if untreated primary or
secondary).
In 2019, 66 cases (majority in
Edmonton zone).
ALL PREGNANT WOMEN SHOULD BE SCREENED IN FIRST TRIMESTER & RE-SCREENED @ DELIVERY!
Congenital Syphilis: Features & Complications
Congenital syphilis occurs with vertical transmission of Treponema
pallidum from mother to infant usually if active in primary/secondary
stages of syphilis. Patients can be asymptomatic at birth but then
develop problems later in life:
* EARLY Congenital Syphilis (months 0-3 of life)
* Vesiculobullous rashes, petechial lesions
* Generalized lymphadenopathy, failure to thrive
* Meningitis, choroiditis and seizures, intellectually disabled
* Paralysis to limbs with osteochondritis
- LATE Congenital Syphilis (>2 years of life)
- Gummatous ulcers of nose/palate
- Saber shins/frontal bossing (periosteal bone lesions)
- Corneal scarring from interstitial keratitis (blindness)
- Sensorineural hearing loss (deafness)
Treatment with penicillin in newborns may or may not prevent these manifestations of congenital syphilis.
Syphilis: Stages of Infection
Early Latent Phase (< 1 Year)
Contagious during active primary or
secondary, early latent phase
PRIMARY
SYPHILIS
~21 days after
exposure;
resolves on its
own in 4-6/52
MAY DEVELOP
SECONDARY
SYPHILIS
Often 2-12 weeks after
primary syphilis
MAY DEVELOP
TERTIARY SYPHILIS
Often years-decades
after initial infection
Gummatous Syphilis OR Syphilis of
the Bone (~3-10 years after)
Cardiovascular Syphilis – ~10-25 years
Neurosyphilis (can happen EARLY as
well!)
Late Latent Phase (>1 Year)
Non-contagious
Can remain permanently
Lifelong If untreated
Patients may or MAY NOT remember their PRIMARY chancre (or be completely asymptomatic in 30%!)
Secondary Syphilis: Other Features & Complications
Other manifestations include:
* Alopecia (hair loss)
* Condyloma lata (development of wartlike lesions)
* Mucous patches
* Features of constitutional
illness/bacteremia
* Fevers, chills, night sweats, malaise,
lymphadenopathy
* Arthralgias/myalgias
During secondary syphilis – patients have a high-grade bacteremia and can be REACTIVE to penicillin.
Tertiary Syphilis: Gummatous & Cardiovascular Syphilis
The development of gumma and cardiovascular manifestations only occurs in late untreated syphilis.
So on the left is a picture of a gamma. So this is kind of
manifestation of syphilis when it enters the the nerves, and then it causes this inflation and arteries and surrounding tissues, causing these skin lesions.
- And then the picture on the right is the example of cardiovascular
- syphilis, and for some reason syphilis is really attracted to the aorta. I think the most common presentation of cardiovascular syphilis is descending aortic aneurysm
- and it’s been associated with strokes. So one of the pearls that I was taught that to get a patient who presents the stroke with no known cardiovascular risk factors to think about syphilis.
Neurosyphilis: it’s typically, but it can also occur in the early stages of the syphilis infection and patients, and it kind of presents with like focal neurological deficits and patients kind of appear that they have new onset of dementia. Gait changes, ataxia
Syphilis: Recognizing Syphilis & Diagnostic Testing
In Alberta, syphilis testing is done easily – as a syphilis screen
from a blood sample is managed by the laboratory who receive
a request and then proceed independently through a series of
tests if –ve or +ve.
1. Syphilis EIA (Enzyme Immunoassay; remains positive
forever if history of syphilis) > if + proceed to
2. TPPA (treponema pallidum particle agglutination); a
confirmatory test – if +ve
3. Rapid plasma reagin (RPR);
* RPR is most important as gives an idea of if previously
treated or not, current status
Dilutions of RPR/VRDL
1:512
1:256
1:128
1:64
1:32
1:16
1:8
1:4
1:2
1:1
1:1024
Treatment Failure =
LESS THAN 4-fold
decline in RPR after 6-
12 months (primary)
OR 12-24 months if
later
Interpretation of strange discordant EIA/TPPA/RPR is done by infectious diseases/STI services.
Syphilis: Lack of Resistance to Penicillin!
Q: Why has syphilis NOT developed drug-resistance to
penicillin after all these years? Most other organisms
have!
1. Mutations to it’s PBP lead to fatal error mutations
that is incompatible with life
2. Treponema pallidum is INCAPABLE of participating in
horizontal gene transfer (no plasmid, bacteriophages;
or other mobile genetic elements) – VERY SMALL
genome and quite adapted to humans
For the foreseeable future, PCN will remain drug-of-choice for syphilis.
Syphilis: Treatment By STAGE OF INFECTION
Primary, Secondary OR Early Latent
* Benzathine Penicillin G 2.4 MU IM x 1 dose OR
* Doxycycline 100 mg PO BID x 14/7 OR
Late Latent Syphilis (>1 year from infection OR unknown)
* Benzathine Penicillin G 2.4 MU IM wkly x 3 doses
Doxycycline 100 mg PO BID x 28/7 OR
Treatment in late latent syphilis involves a LONGER course due to presumed deep-seated infection.
Syphilis: Treatment in Pregnancy
Pregnant Individuals
EARLY LATENT or PRIMARY/SECONDARY Syphilis
Preferred:
* Benzathine penicillin 2.4 mu IM weekly for 2
consecutive weeks
Alternate (There is no alternate in pregnancy):
* Pregnant individuals who are allergic to penicillin will
require penicillin de-sensitization prior to treatment
Pregnant Individuals
LATE LATENT DISEASE
Preferred:
* Benzathine penicillin 2.4 mu IM weekly for 3
consecutive weeks
Alternate (There is no alternate in pregnancy):
* Pregnant individuals who are allergic to penicillin will
require penicillin de-sensitization prior to treatment
This highlights the CRITICAL DETRIMENTAL IMPACT of penicillin allergy on our patients’ charts!
We extend the benzathine penicillin dose to 2 weeks for them 2 consecutive weeks, just due to their risk of congenital syphilis
changes in pregnancy, such as volume, distribution,
It’s just one thingto note that in pregnancy there is no alternative therapy
Doxy TERATOGENIC FX in fetus
So in these patients we essentially have to them with penicillin allergy or not, and if required, we will go. We will try and desensitize them on prior to their treatment,
Syphilis & The Penicillin Allergy
Desensitization:
Mechanism &
Immunology
Allergen administered at dose/rate sufficient to
cause very limited mast-cell degranulation
until depleted without systemic signs &
symptoms (+ chemokine release)
Potential mechanism involving IgEinternalization or counter-regulation
Desensitization lasts up to 4 half-lives of
antigen (~48 hours for penicillin)
Desensitization is often prescribed UNNECESSARILY in patients who do NOT have penicillin allergy.
Syphilis & The Penicillin Allergy
steps
- Obtain informed consent
- Perform procedure in ICU preferably (although can do PO
not in ICU) - Obtain intravenous access
- PO route is preferable in interval of 20-30 minutes (or IV
15-20 min) - Starting dosage @ 1/10,000 normal dosage -> 1/1,000
- Up to 33% experience mild reactions, treat through
- Stop if patient develops airway compromise, hypotension
refractory - Do NOT pre-treat with antihistamines or corticosteroids
Desensitization is often prescribed UNNECESSARILY in patients who do NOT have penicillin allergy.
Syphilis: Follow-Up Testing & RPR Decline
Follow-up of syphilis cases depends upon the stage of syphilis
infection, RPR result, HIV co-infection and pregnancy.
* Unless the individual is HIV positive, serological follow-up can
stop once the RPR is non-reactive
* Infectious syphilis/HIV negative:
* serology at 1, 3, 6 and 12 months (or until the RPR is nonreactive); the serological response to treatment is reflected
by the RPR which should decline (see Canadian Guidelines
Syphilis Chapter).
* Non-infectious syphilis/HIV negative:
* serology at 12 months and 24 months (unless the RPR is nonreactive)
Patients can be REINFECTED to syphilis later – and are NOT immune. Counsel patients on condom use!
