Syphillis

Question 1

What causes the syphilis infection

Answer 1

Treponema pallidum spirochetegram negative bacteria Obligate parasite

Question 2

Transmission

Answer 2

• Acquired: Sexual contact (enters through breaks in the skin) contaminated needles / Direct lesions
• Congenital: (in utero or at delivery)

Question 3

How does primary syphilis present

Answer 3

Primary syph is 1-3 weeks after exposure to infection, syphilitic chancre (painless classically but actually half are painful)
Be solitary or multiple (approximately one third reported as multiple)
Hard base, raised borders, fluid rich in spirochetes,
Chancre can be around external genitialia but if through contact can occur anywhere
Chance will heal on its on over months - can have associated lymphadenopathy
(if through blood may not be )
HIGH risk fetal infection

Question 4

What occurs in secondary syph

Answer 4

Secondary 6-12 weeks after infections - spirochetaemia - Generalised lymphadenopathy
Can affect endothelial cells - causing non itchy maculopapular rash - trunk then travels to palms, soles, Can be pustular or papulosquamous
Can be condyloma lata wart like (smooth white painless gentials, anal, armpits)
Secondary syph is most infectious - lasts weeks to months
Can have constitutional sx
Latent phase - Disease - dormant / asymptomatic - stored in organs
Early phase - within a year, spirochetes can reenter the blood - can have sx of secondary syph
Late phase - after 1 year - will stay within organs

MODERATE rate of fetal infection
If untreated 40% progress to tertiary infection

Question 5

What is Tertiary Syphilis, what happens

Answer 5

1/3 of untreated populations
Type 4 hypersensitive reaction, immune reaction with T cells, pro inflammatory phagocytes and cytokines TNF IL 1 IL 6 leading to Redness warmth systemic sx like fever
Antigen on T Pallidum : group specific antigen
Species specific antigen
Cardiolipid (within spirochetes and cells in our body)
Granulomatous lesions - Gumma - immune cells surrounded by fibroblasts - often no spirochetes in there, Can necrose
Teritiary syph - cardiovascular - endarteritis (inflammatory of the vessels)
Brain and spinal cord - loss posterior spinal cord - loss of proprioception or vibration
Or anterior cord - paralysis
Liver joints and testes
Negligible rate fetal infection

Question 6

How to test for syphilis

Answer 6

Dark field miroscopy to see spirochetes from chancre
Confirmed with serology
Antibodies against T pallidum - not syph specific

Non treponemal tests Antibodies to non specific antigens (VeRy close)
RPR- rapid plasma reagin test
VDRL- Veneral disease research labarotory test
Reagin Anti cardiolipid antibodies
Low sensitivity in early or late disease
Become negative after successful treatment so can be used to monitor response to treatment

Treponemal tests: (specific Antibodies) (T for T)
TPPA (T Pallidum particle agglutination)
FTA ABS fluorescent treponemal antibody
EIA (Enzyme immunoassays)
TPHA
More specific - positive for years despite treatment

Question 7

Screening for syph

Answer 7

Population based setting
Booking bloods and repeat 28 weeks
“Traditional algorithm” High prevalence - use non treponemal (VDRL) and confirm with treponemal specific test (TPPA)

If low prevalence setting use treponemal (TPPA) and confirm with non (VDRL) less work and better sensitivity

Pregnancy RPR - should be used / IgG based test (IgM increases false positive results)

Question 8

Fetal Childhood affects

Early and late

Answer 8

2/3 babies born without sx

Early - IUD jaundice, Hepatosplenomegly, maculopapular rash, palms and soles, pneumonia, coombs negative HA snuffles Mucocutanous lesions of palms and soles peristitis

Later - hutchinsons teeth (notched central teeth) saddle nose, frontal bossing, saber shin deformity, knee synovitis
Hutchinsons triad - hutchinsons teeth, interstitual keratitis, deafness

Question 9

What is the treatment for syph

Answer 9

– Benzathine penicillin 1.8g (= 2.4 million units) IM, as a single dose OR
Can have jarisch - herxheirmer syndrome - as spirochetes are treated then explode and a large inflammatory reaction is activated

Question 10

How to interpret tests 
VDRL + TPPA + 
VDRL + TPPA -
VDRL - TPPA -
VDRL - TPPA +

Answer 10

VDRL + TPPA + Syph - needs treatment
VDRL + TPPA - if repeated and same then biologically false positive
VDRL - TPPA - No syph
VDRL - TPPA + Previous treated

Question 11

How to monitor effectiveness of treatment

Answer 11

Repeat VDRL or RPR monthly until delivery

-ve or >4 fold drop in titre - successful treatment

Question 12

How to monitor neonatal syph

Answer 12

Infant serology (IgM, RPR to be run in parallel
with maternal serology)
Full clinical examination (rash, mucosal lesions, hepatomegaly,nasal discharge, bony tenderness,
eye lesions)
Placental histo and PCR
Bloods and CSF if any of these are abnormal
Repeat infant serology at 3 and 6 months

Question 13

Does timing of treatment in pregnancy matter?

Answer 13

Women and their partners who are tested and receive appropriate treatment during the first two trimesters of pregnancy are 2.24 times more likely to have a healthy baby than those receiving syphilis treatment during the third trimester

Question 14

Is syphilis always symptomatic?

Answer 14

Approximately 50% of women will have no symptoms and will only be diagnosed by serological testing

Question 15

When does vertical transmission occur?

Answer 15

o Treponema pallidum readily crosses the placenta
o Can occur as early as 9–10 weeks gestation
o Can occur at any stage of disease, including during incubation, although risk is greatest in infectious syphilis
o Can occur several years after initial infection in the untreated woman
o More commonly occurs in the last two trimesters

Question 16

What is the incubation period for syphilis ?

Answer 16

· Mean incubation 21 days (range 9–90 days) from contact to the development of a chancre

o Larger infectious dose results in earlier ulcers

Question 17

When are people the most infectious?

Answer 17

· First two years of infection

o If untreated, period of high infectivity is 12 months

o Sexual transmission uncommon after two years of infection

· Infectious cases become non-infectious seven days after one dose of benzathine penicillin, or when all symptoms have resolved, whichever is longer

· Immunity is not conferred by treatment or previous infection—re-infection can occur

Question 18

How does syphilis transmission affect transmission of other infections?

Answer 18

· Maternal syphilis is thought to increase the risk of vertical transmission of HIV and other sexually transmitted infections (STI)

Question 19

What is the risk of untreated syphilis in pregnancy?

Answer 19

· Although estimates vary, approximately 50% of women with syphilis requiring treatment in pregnancy suffer adverse pregnancy outcomes

· In the absence of effective treatment maternal/fetal impacts include:
o 25% of pregnancies result in a second trimester miscarriage or stillbirth
o 11% of pregnancies result in a neonatal death at term
o 13% of pregnancies result in a preterm or low birth weight infant

Question 20

What are rates of transmission for different stages of syphilis ?

Answer 20

· Rates of transmission to babies born to women with untreated syphilis are estimated to be:
o 70% for primary and secondary syphilis
o 40% for early latent syphilis
o 10% for late latent syphilis
· 27% of untreated babies who survive to 30 days are likely to develop symptoms of congenital syphilis, including:
o Neurological and developmental delays
o Musculoskeletal problems

Question 21

Other then congential syphilis that are the other risks of having infection in pregnancy to the fetus?

Answer 21

· Placental infiltration reduces blood flow to the fetus and may lead to growth restriction

Question 22

How to assess ongoing risk in pregnancy?

Answer 22

Ongoing risk assessment
· Maintain awareness of the ongoing risk of infection/re-infection after initial screening and/or treatment for syphilis
· As part of routine antenatal care, assess for changes in risk behaviours/status, for example:
o Change or addition of sexual partner(s)
o Change in risk behaviours (e.g. methamphetamine use)
o High risk sexual activity
· Actively consider if repeat screening is indicated

Question 23

How to prevent syphilis infection

Answer 23

Prevention

· Advise condom use (male or female condoms, dental dams) to help prevent syphilis infection and re-infection during pregnancy (as well as other STIs)

o Condoms reduce the risk of syphilis only when the infected area or site is protected from direct contact

· Encourage communication about change in sexual partners

· Offer information about safe sex practices including:

o Increased risk if sexual partner(s) engage in male to male sex

o Avoiding drug use during pregnancy

o Signs and symptoms of STIs

· If woman or partner treated for syphilis requiring treatment in pregnancy, advise to abstain from sexual activity for seven days (or until symptoms have resolved whichever is longer) after both have received adequate treatment

Question 24

If syphilis in pregnancy

What do you do first?

Answer 24

Assessment
Obstetric and sexual history
Direct question for symptoms of syphilis (e.g. genital rashes, lumps and sores, including if current partner is symptomatic)
· Previous syphilis testing
o Antenatal screening
o Blood donation
o Sexual health screening
· Potential for previous infection with non-venereal Treponema pallidum infection
o Childhood skin infections (e.g. yaws, bejel or pinta)
o Previously resident in endemic country
Obstetric hx
· Previous adverse pregnancy outcomes
· Identify live births and consider if children may now have late congenital disease
o Initiate follow-up as indicated
Clinical examination
· Syphilis requiring treatment in pregnancy y
o Genital examination
o Skin examination including torso, eyes, mouth, scalp, palms and soles
o If neurological symptoms, conduct a neurological examination
· Symptomatic late disease
o Skin
o Musculoskeletal (congenital)
o Cardiovascular system (for signs of aortic regurgitation)
o Nervous system
Investigations
· Dry swab suspicious genital lesions for PCR
· Collect serum and request ‘syphilis serology’ on pathology forms
· Recommend screening for other STIs
· In consultation with an expert practitioner, consider other investigations as relevant to circumstances

Assess previous treatment
· If previous syphilis diagnosis, identify:
o Year and place of diagnosis
o Treatment received (drug, route, duration)
o Serological results
· Consider pregnant women with reactive serology as having syphilis requiring treatment in pregnancy unless an adequate treatment history is available

· Collaborate with QSSS and/or expert practitioner about recommended management

Question 25

Managing a positive syphilis in pregnancy

How to assess for fetal infection?

Answer 25

· Before 18–20 weeks fetal abnormalities are not usually seen because of fetal immunologic immaturity

An abnormal USS is not diagnostic of fetal infection and a normal USS does not exclude fetal infection

If syphilis requiring treatment in pregnancy is diagnosed after 20 weeks gestation, request an USS to evaluate for congenital syphilis

o Do not delay treatment to achieve USS
· Include on request form:
o Relevant history (e.g. serology, gestation, treatment)
· Request assessment of:
o Placental size
o Amniotic fluid volume (single deepest pocket)
o Middle cerebral artery (MCA) Doppler velocity
o Liver size and echodensity

Suspect fetal infection if there are characteristic findings on USS after 20 weeks in a woman with syphilis requiring treatment in pregnancy

· Formulate a plan about ongoing monitoring in collaboration with a maternal fetal medicine specialist

· If presumptive diagnosis of congenital syphilis, consider sequential monitoring to assess fetal well-being and response to treatment

Question 26

Do fetal USS abnormalities improve with treatment?

Answer 26

· With successful treatment:
o MCA abnormalities, ascites and polyhydramnios usually resolve within one month
o Followed by resolution of placentomegaly
o Hepatomegaly can take months to resolve after maternal treatment
· Rarely required intrauterine transfusion for fetal anaemia

Question 27

What are the early and late USS signs of syph fetal infection

Answer 27

Early
Hepatomegaly 80%
assess liver length 
Placentomagaly 30% 
Assess thickness greater then 2 SD above estimated GA 

Later
Anaemia based on MCA doppler 30%
over 1.5 MoM 
Polyhydramnios 12%
SDP over 8cm 
Ascites /hydrops 10%
2 or more cavities with abn  fluid collections

Question 28

How do we treat the syph?

Answer 28

long acting IM benzathine penicillin 1.8 g IM once

seek advice if allergic - may consider desensitisation

Question 29

What is a Jarisch Herxheimer Reaction

How to manage it?

Answer 29

JHR is an acute non-allergic reaction to penicillin that may occur in pregnant women after administration. Symptoms can be acute, or absent, and last up to 24 hours.

Do not delay treatment to avoid potential symptoms of JHR as the risk of adverse outcomes are likely to be higher without treatment

· Thought to result from the rapid killing of spirochetes causing copious release of endotoxins, lipopolysaccharides, prostaglandins, and cytokines, leading to an acute inflammatory response
· More common during treatment for infectious syphilis due to high bacterial burden
· Case studies report JHR occurs in up to 44% of pregnant women treated for syphilis
· Concerns about JHR relevant only to the first dose of treatment
· Onset within 2–12 hours post treatment and lasts several hours
· Usually self-limiting resolving by 24 hours after treatment
· Fever, headaches, rigors, joint pain chills, malaise, transient accentuation of cutaneous lesions, hypotension and tachycardia

May precipitate uterine contractions (56–67%), decreased fetal movements (67%) and abnormal fetal heart rate (FHR) tracings (50%)

· In severely affected pregnancies preterm birth and stillbirth have been reported

· Do not delay treatment due to concerns about adequacy of monitoring

· Offer information to women about JHR

· Advise women to:
o Stay well hydrated, rest and take paracetamol for pain or fever
o Contact their health care provider, or nearest birth unit, if they experience regular cramping or contractions, a change in fetal movements or fever within 24 hours post administration
Recommended increased maternal and fetal surveillance for:
o Women with a known co-infection of HIV o Fetal USS abnormalities
· Consider increased maternal and fetal surveillance if:
o Viable gestation
o Known high syphilis titres
· Consider inpatient management for higher risk groups (as above)
o Supportive management relevant to symptoms (e.g. antipyretics, intravenous fluids, tocolysis)

· If inpatient management not practical (e.g. in a remote setting) consider:
o Outreach follow-up contact in the community (e.g. by phone, text or personal contact)
o Fetal heart rate (FHR) auscultation or cardiotocography pre and post administration

Question 30

FU after penicillin tx

Answer 30

VDRL and RPR monthly until delivery

retreat if rise in titre

Cure if negative titre or 4X drop in titre

Question 31

How to perform contact tracing?

And how to manage contacts?

Answer 31

Of contactable sexual partners of pregnant women with infectious syphilis, 40–60% will also have an infection

· If primary syphilis:
o Duration of symptoms plus three months
o If duration uncertain, six months prior to presentation
· If secondary syphilis:
o Duration of symptoms plus six months
o If duration uncertain 12 months prior to presentation
· If early latent or unknown duration:
o 12 months prior to presentation

· If exposed to infectious syphilis, recommend empirical treatment regardless of syphilis serology results

o Benzathine penicillin 1.8 g (2.4 million units) IM once

o Administer as a divided dose of two injections of 900 mg each (one in each of the ventrogluteal regions or in the upper outer quadrant of each buttock42)

· Obtain sexual history (including symptoms)

· Clinical examination for signs of syphilis and other STIs

o Collect serology for syphilis and other STI tests as indicated

· Inform contacts of their test results at the earliest opportunity

· Do not:

o Record the name of the index case in the contacts’ health record

o Disclose the name of the index case to a contact

· Discuss with contacts:

o Infectious nature of the disease

o Possibility of infection even in the absence of symptoms or reactive serology

o Importance of follow-up and repeat serology testing

o Need to abstain from sexual activity for seven days after treatment or until symptoms (if present) have resolved–whichever is longer

Question 32

How should get syphilis serology at birth?

Answer 32

· Recommend syphilis serology at birth (any of the following):
o Syphilis requiring treatment in pregnancy
o Woman is high risk
o Woman is increased risk AND § Serology NOT collected after 26 weeks
§ Preterm birth with most recent serology more than four weeks before birth
o Indicated following risk assessment

Question 33

If syphilis requiring treatment in pregnancy, request at delivery ?

Answer 33

·placental histopathologic examination of the placenta and/or umbilical cord for PCR

o Not diagnostic but improves detection in both liveborn and stillborn babies

Swab for PCR
Store fresh

)

Question 34

What are typical placental syph findings?

Answer 34

· Placenta often large, thick, and pale—characteristic findings:
o Hydrops placentalis, chronic villitis (plasma cells, mixed acute and chronic infiltrate), perivillous fibrous proliferation (onion skin vessels), normoblastemia, necrotizing funisitis, acute chorioamnionitis, plasma cell deciduitis

· Umbilical cord
o Oedematous and may resemble a “barber’s pole” with spiral stripes of red and light blue discoloration alternating with streaks of chalky white

o May be significantly inflamed with an abscess-like foci of necrosis within Wharton’s jelly, centred around the umbilical vessels (necrotizing funisitis

Question 35

Is breastfeeding save with syph infection?

Answer 35

· Treponema pallidum is not transferred in breast milk · Recommend breastfeeding unless an infectious lesion (e.g. chancre) is present on the woman’s breast and/or axillae

Question 36

Ongoing neonatal monitoring

Answer 36

If syphilis requiring treatment in pregnancy recommend clinical and serological follow-up at birth three, six and 12 months

· Discuss with the QSSS and an expert practitioner if titres:
o Do not decrease four-fold within 12 months
o Increase four-fold
· If syphilis (any stage) diagnosed within three months postpartum, assess the baby for congenital syphilis

Question 37

Suspect congenital syphilis in babies born to women who: ??

Answer 37

· Had syphilis requiring treatment in pregnancy irrespective of adequacy of treatment

· Limited or no antenatal care

· Are diagnosed as having syphilis (any stage) within three months postpartum

Question 38

If congential syph is a possibility then:

Answer 38

If congenital syphilis is a possibility, do all of the following:

· Conduct a full clinical examination

· Collect syphilis serology

· Review placental histopathology and PCR

· Review maternal serology and adequacy of treatment during pregnancy

· Collaborate with QSSS and an expert practitioner about the ongoing plan of care

Question 39

presentation of congential syph?

Answer 39

· 60–90% asymptomatic at birth
· Signs and symptoms often subtle, non-specific and variable
· Usually appear by three months of age, most often by five weeks
Hepatomegaly
· Hepatomegaly almost always present with congenital syphilis—may be associated with splenomegaly (but not splenomegaly in isolation)
· May have abnormal liver function tests (LFT)
· Associated with jaundice and cholestasis
Rhinitis
· Usually during the first week of life and seldom after the third month
· White nasal discharge, may be bloody (secondary to mucosal erosion) or purulent if secondary bacterial infection · Nasal discharge contains spirochaetes, is contagious, and can transmit infection by direct contact
· Use direct detection testing (e.g. PCR) to confirm diagnosis

Rash
· Usually appears one to two weeks after the rhinitis
· Commonly presents with peeling of the hands and feet
· Maculopapular consisting of small, initially red or pink spots

· Progresses over one to three weeks, followed by desquamation and crusting becoming dusky red or copper-coloured

o Pigmentation may persist
· Use direct testing (e.g. PCR) to confirm diagnosis

Generalised lymphadenopathy
· Common manifestation
· Palpable epitrochlear lymphadenopathy is highly suggestive

Other signs
· Nonimmune fetal hydrops
· Soft tissue swelling of the fingers and/or hands62 (dactylitis)
· Failure to move extremity secondary to pain (pseudoparalysis of Parrot)
· Ophthalmologic manifestations (e.g. loss of eyebrows, chorioretinitis, uveitis, cataract, glaucoma, and chancre of the eyelid)
· Nephrotic syndrome
(immune complex mediated; responsive to penicillin)

· Gastrointestinal manifestations (e.g. rectal bleeding (from ileitis), necrotising enterocolitis, malabsorption)

Question 40

Serological testing for congenital syph

Answer 40

Mother and baby serology
· Relationship between maternal and baby’s titre can indicate likelihood of congenital syphilis
o A baby’s non-treponemal titre that is four-fold or more the maternal titre is diagnostic of congenital syphilis
o A baby’s non-treponemal titre that is less than four-fold the maternal titre may indicate congenital syphilis and requires additional confirmatory tests
§ IgM may assist clarification and interpretation
Serology
· Collect serology from baby
o Do not use umbilical cord blood due to risk of false positive
o Venepuncture preferable to heel prick collection
· Test mother and baby syphilis serology in parallel to aid diagnosis of congenital syphilis

· Request syphilis serology including IgM
o IgM antibodies do not normally cross the placenta therefore, a positive IgM is strongly indicative of infection in the symptomatic baby (but is not diagnostic in isolation)

o Negative IgM does not exclude congenital syphilis–liaise with an expert practitioner Dry swab and PCR · Dry swab and request PCR of suspicious mucocutaneous lesions or body fluids identified on clinical examination Placental histopathology

· Review placental histopathology and PCR (if available)

Additional investigations  
Consider  
· FBC,  
ELFT  
· Chest x-ray  
· Long bone radiographs  
· CSF  
· Neuroimaging  
· Ophthalmologic exam  
· Auditory brain stem response

Question 41

How to treat congential syph

Answer 41

Treatment for congenital syphilis

0–7 days of age

· Benzyl penicillin 50 mg/kg IV 12 hourly for 10 days

8–30 days of age

· Benzyl penicillin 50 mg/kg IV 8 hourly for 10 days

> 30 days of age · Benzyl penicillin 50 mg/kg IV 4–6 hourly for 10 days

Question 42

How to follow up congential syph

Answer 42

Follow-up

Communication

· Document need for follow-up
· Advise local services of follow-up needs Clinical assessment
· At each opportunity Serology
· At 3, 6 and 12 months of age
o If follow-up difficult, aim for 2 tests by 6 months of age (> 4 weeks apart)
· If serology persistently reactive at 12 months seek advice from expert practitioner

· If at birth CNS or CSF abnormal, repeat CSF at 6 months for VDRL, cell count and protein