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!
Patient Case Example: Syphilis – FOLLOW-UP
A 26-year-old male is admitted to the hospital for fever,
chills and generalized malaise found to have
Staphylococcus aureus bacteremia related to injection
drug use (IDU). During his work-up, several screening
tests are sent due to his background, and he is found to
be syphilis EIA+ with an RPR of 8 dils. 4 months ago, you
notice his RPR was 256 dils.
Your team is deciding on treatment strategies for this
patient. Q: what treatment, if any – does this patient
require?
CLINICAL INTERPRETATION:
Patient has persistently positive EIA
(normal) with an RPR of 8 which is >4
dilution difference between 256 since
4 months ago
This indicates successfully treated
syphilis and requires no additional
treatment, expect RPR to continue to
fall until no longer positive.
Syphilis is a common STI found in the hospital setting in patients admitted for other reasons.
Basic Virology of HHVs: Structure & Transmission
Structure & Nucleic Acid
* Group II (dsDNA) virus
* Icosahedral, enveloped (easy to destroy)
Epidemiology
* Ubiquitous (prevalent worldwide)
* Seropositivity (IgG+) ~ equal to age (e.g., ~20% of
people have been exposed @ age 20 years)
Transmission
* Usually shared by direct contact with blood or
bodily fluids (e.g., mainly sexual/oral) M>F more
* Also shared vertically (possible, but not guaranteed
transmission of virus)
Summary of Human Herpesviruses
HHV-1
HSV-1
Herpes Simplex Virus
Wide variety of epithelia including
keratinized epithelium
Local sensory neurons (not DRG or
trigeminal ganglion)
Latency Behavior of Human Herpesviruses
Human herpesviruses are unique in that they always
establish lifelong latency after primary infection. In
this state: the host immune-system never truly
eradicates their presence, and they enter an inactive
state in a specific body location (i.e., tropism).
After primary infection has resolved, herpesviruses
may REACTIVATE later in life, causing a similar or
different syndrome (usually less severe):
* E.g., shingles (reactivation of latent varicella zoster
virus; primary infection = chickenpox)
* E.g., recurrent oral/genital herpes
Antiviral agents can SUPPRESS but NEVER CURE human-herpesvirus infections due to permanent
latency. Goal is control by host immune-system (typically CD8+ T-lymphocytes)
Primary versus Secondary Disease
~7 days
incubation
Primary Infection: WORSE
First exposure, no immune
memory of virus
May cause acute illness
Recovery
And establishment of latency
Most patients asymptomatic in this
stage chronically, still can be contagious
Secondary Disease
Reactivation of latent virus
due to loss of immunesystem control
Reactivation occurs in
~90% of infected
patients, can be
frequent OR infrequent
Primary Herpesvirus Infections
Although HSV-2 and HSV-1 typically cause a mild-severe
genital OR oral herpes infection as the primary infection in
most patients, some patients who are susceptible and are
exposed to high-inoculum OR immunodeficient can
experience severe disseminated herpesvirus disease
(uncommon):
Manifestations could include:
* Viral meningoencephalitis (seizures, altered LOC,
headache)
* Autonomic nervous system dysfunction
* Herpesvirus pneumonia (RARE)
* Viral hepatitis (RARE)
Features of severe primary disease can re-manifest in reactivation in IMMUNOCOMPROMISED patients!
Herpesvirus Life Cycle and Pharmacologic Targets
Attach/Fusion
Transcription/Translation Uncoating
Assembly/Packaging
Egress
As a double-stranded DNA virus, the
herpesviruses need to replicate their DNA
before being able to transcribe into an
mRNA transcript (will use host ribosomes to
translate viral proteins).
This DNA-dependent-DNA polymerase is the
primary pharmacologic target of therapy.
The major class of HHV antivirals mimic
free-floating DNA-base pairs (lack 3’-OH)
and cause chain-termination of DNA
polymerase, halting replication.
Serostatus & Seroconversion: IgG & IgM Testing
IgM
Spikes in primary infection, then
fluctuates in serum due to periodic
release from latency
(even if asymptomatic)
IgG
Slowly rises weeks after primary
infection, remains elevated
lifelong thereafter
IgM is of minimal value in diagnosis/recognition of reactivation, since it fluctuates normally via periodic
latency release. However, IgM+/IgG- serology is confirmatory for primary disease
Herpes Simplex Virus (Primary vs. Secondary/Latent Syndromes)
Primary Syndromes
Due to host site on the local epithelium:
Primary syndromes can include wide variety:
* Orolabial herpes (most often HSV-1)
* Genital herpes (most often HSV-2)
* HSV Encephalitis (e.g., seizures, loss of consciousness)
* Herpes whitlow (fingers), HSV pneumonia (rare)
Secondary Syndromes
Due to local latency in local sensory neurons:
Reactivation often simply leads to less severe recurrence of
primary syndromes, most often orolabial or genital herpes –
at the same original site of primary disease.
Herpes Simplex Virus (HHV-1 & HHV-2)
Orolabial Herpes Genital Herpes
Mostly caused by HSV-1 (some HSV-2)
Pruritic, painful vesicular lesions followed
by rupture, ulceration, and healing over
time (if severe, scarring)
Exacerbated by sunlight, trauma, cold
Also known as “fever blisters”
Mostly caused by HSV-2 (some HSV-1)
vulvovaginal region, anal, or urethral or
inguinal region VESICULAR LESIONS that
ULCERATE with erythematous base > crust.
Prodrome = parasthesia/pain @ site!
(contagious during all these periods)
Last usually ~2 weeks than spontaneously
resolve.
Diagnosis of Herpesvirus Infection
- Diagnosis is often made CLINICALLY
with corroboration with serology +/-
PCR testing if active disease - Serology testing (HSV type-specific
antibody testing) available in Alberta
– Help determine if HSV-1 versus HSV-2
– May be useful for counselling individuals
with genital herpes and their partners
Antiviral Pharmacology for Herpesviruses
Interferes with DNA
polymerase by mimicking
nucleosides (e.g., guanine
[acyclovir, ganciclovir],
cytosine [Cidofovir]),
incorporating into machinery
and causing chain
termination.
Foscarnet acts a
pyrophosphate analog and
disrupts DNA polymerase
see slide 32
acyclovir
vala
Usually very well tolerated. GI
distress.
Rapid IV push acyclovir associated
with precipitation in nephron
tubules
Valacyclovir is often preferred to acyclovir due to better bioavailability and reduced frequency of dosing.
Pharmacologic Management of Herpes Simplex Virus Infections
Treatment
Similar to other acute viral illnesses, EARLY therapy may be better – particularly before crusting over.
* First Episode: Valacyclovir 1 g PO BID x 7-10/7 (genital) START ASAP
* Subsequent Episodes: Valacyclovir 500 mg PO BID x 3/7 OR 1 g PO QD x 5/7
(treatment reduces time-to-resolution by ~2 days (~1 d oral), reduces time-to-healing by 4
days, and reduces duration of viral shedding by 7/7) – if started w/I 72 hours of onset
Prophylaxis/Suppression
* Chronic Suppression (if >6 outbreaks/yr): Valacyclovir 500 mg-1 g PO daily
(chronic suppression reduces frequency by 70-80% in those with frequent recurrence, as
well as decreases the rate of HSV-2 transmission to susceptible partners!)
* Pill-In-Pocket (patient-initiated treatment): treatment regimen prescribed in advance
Suppressive Therapy in Pregnant Patients
Require initiation at 36 weeks until delivery (women
with history of known recurrent genital HSV)
* Reduces recurrent disease and need for C-section
* Appear safe to use in pregnancy (Pasternak, B. and Hviid, A. Use
of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the
risk of birth defects. JAMA 2010;304:859-866.)
* Acyclovir 200 mg 4 x/day or 400 mg 3x/day
* Valacyclovir 500 mg twice daily
If active lesions are present – can be SWABBED for HSV PCR testing (blood/CSF can be sent for viral PCR)
Counseling Patients with Genital Herpes
- Genital HSV is not curable
- Explain natural history of disease
- focus on potential for recurrent episodes,
asymptomatic shedding and sexual
transmission - Should inform sexual partners that they
have genital herpes - Discuss risk of neonatal infection with all
patients, including men. - Women who have genital herpes should be
advised to inform HCP who care for them
during pregnancy
Genital herpes is RECURRENT problem, but it can be managed EFFECTIVELY with antivirals!
Sexually Transmitted Infections: Correct Use of Condoms
Sexually Transmitted Infections: Safer-Sex Counselling
Consistent and correct use of condoms:
* Reduces (but does not eliminate risk of HIV/STI)
* Different level of protection for different STIs
* Inconsistent use can lead to STI acquisition
* Counselling on correct use of condoms
There are some EASY changes people can make to get MUCH more efficacy from condom use.
- STI modes of transmission
- Risks of various sexual activities (oral, genital, rectal)
- Abstinence, mutual monogamy and barrier-method options and availability (male condom,
female condom, dental dam) - Harm-reduction counselling: determining which prevention measures are appropriate and
realistic to implement, given the patient’s personal sexual situation(s) (e.g., if practising receptive
anal intercourse, always use a condom and extra lubrication, and avoid use of spermicidal condoms).
“If you or your partner(s) have ever had another sexual partner, there are a number of options open to you for
safer sex. Always using a condom, or getting tested for STI/HIV with your partner followed by mutual
monogamy are a few of these options. Do you think any of these might work for you and your partner?”
Dispelling myths– like STI’s can be prevented by “pulling out” may improve condom adherence.
Sexually Transmitted Infections: Incorporating into Your Practice
Assessing and discussing STI risk (e.g., females requesting ECP, younger
individuals, vulnerable groups)
* Providing education on signs and symptoms (or lack of signs and
symptoms)
* Helping patients minimize risk (mutually monogamous partners, reducing
number of partners, non-insertive sexual practices)
* Patient-centred counselling
* Promoting vaccines – HAV, HBV, HPV where appropriate
* STI screening and testing (referral if necessary)
* Offer treatment, following up and counselling
NON-JUDGEMENTAL: Counselling should be targeted at giving patients the TOOLS to protect themselves.
