Download syphilis - Sandyford

Sandyford Protocols
SYPHILIS
Significant changes in this guideline:

A confirmatory sample should be taken when an initial sample indicates a diagnosis
of syphilis. If clinical suspicion confirms this test result treatment should not be
delayed until the result of this second sample.
History Taking:
In the last few years major outbreaks of syphilis (mostly in men who have sex with men) have
been reported in London, Manchester, Brighton and Dublin as well as Glasgow and
Edinburgh. Ask about sex in scene venues (saunas, back rooms) and record geographical
location of sex partners.
Please document clearly where applicable:

Possible symptoms of primary or secondary syphilis

Previous treatment (when, where, what with, VDRL on discharge)

Obstetric history and blood donation history
Clinical and Laboratory Assessment:

The primary screen for syphilis in GGC is an automated EIA (Architect): Specialist
Virology Laboratory, Gartnavel for Glasgow sites and Inverclyde Royal for all Clyde
sites. A single specimen is all that is needed for HIV, syphilis and Hep B testing.
Positive screens at IRH are sent immediately to Gartnavel.

The serological screening test used routinely is a Treponemal EIA combined IgG/IgM
test. If this is found to be positive VDRL, TPPA, Inno-LIA blot and specific IgM will be
performed. IgM is positive from around second week, IgG from fourth week after
infection. (see testing algorithm)

If syphilis is suspected clinically, indicate this clearly on the request form, asking for
‘Full syphilis testing’ and the lab will do IgM, VDRL and TPPA as well as screening
EIA. However, do NOT request full serology on NaSH patient order as all syphilis
tests are reported and managed under the NaSH test “Syphilis EIA”. Positive results
are usually phoned back within 48 hours. Do NOT request full serological tests for no
good reason as we end up with likely false +ve IgMs etc.

A confirmatory sample should be taken at the time the patient presents for treatment
after initial sample is positive. Treatment should not be delayed waiting for this result
if clinical suspicion from the history or examination supports the diagnosis.

Arrange repeat serology a week later and ideally at 6 weeks and 3 months if initial
serology is inconclusive or clinical suspicion.

Always do dark ground testing on all suspicious lesions and take a Genital Ulcer PCR
(which will get a T pallidum PCR and HSV PCR test) (applies throughout all services
including Clyde)

In a Sandyford HUB patients with suspicious lesions should be sent to Sandyford
Central for dark ground microscopy if possible and they are willing to travel.

Full clinical examination, with particular emphasis on the skin, genitals, lymph nodes
and mucosal surfaces (anogenital and mouth) is essential in all patients found to
have positive syphilis serology. Cardiovascular and neurological examination is
required in secondary syphilis and apparent latent syphilis. Syphilis cannot be
considered latent until end-organ damage is excluded.
SYPHILIS CEG DEC 2015
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Sandyford Protocols

HIV testing should be recommended to all patients diagnosed with syphilis.
Testing Algorithm
1. Initial sample
Screening test
Reactive
VDRL+ TPPA+
VDRL – TPPA+
IgM testing
Non reactive
VDRL – TPPA-
IgM testing
IgM testing
Referred for
immunoblot
All samples will be authorised unless waiting for an immunoblot result when an
interim report marked with “further results to follow” will be authorised.
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2. Follow up sample
Screening EIA
Reactive
VDRL
IgM and TPPA only if requested
Follow up samples are tested in the screening test too as this ensures no samples are
missed in the laboratory and ensure that all positive samples are “flagged” to the
Sandyford (if GGC sample).
Surveillance:
A national surveillance scheme exists for all early infectious syphilis utilising laboratory data
and clinician-initiated reports. This is coordinated locally by Dr Andy Winter. Separate HPS
notification forms need completion – this is done by Sexual Health Advisers.
HIV Infection:
Limited case review data suggests higher risk of neurosyphilis in HIV+ if VDRL >=1:32.
In known HIV+ with new syphilis be alert for

increased risk of neurological involvement,

unusual neurological manifestations

rapid progression to gummatous syphilis.

False negative or low titre serological tests
HIV infected patients also commonly have neurological abnormalities which may be difficult to
differentiate from neurosyphilis.
If in doubt seek senior help and arrange admission to Brownlee for imaging and LP.
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Incubating Syphilis / Epidemiological Treatment
If patients report exposure to contacts with infectious syphilis, discuss option of immediate
treatment versus waiting with repeat serology at monthly intervals for three months. In
outbreak situations we believe epidemiologic treatment should be given especially if there is a
chance the patient will not return. However injections are painful
Benzathine penicillin 2.4MU IM ??stat (see appendix)
(if no penicillin allergy)
Or
Doxycycline 100mg BD po x 14 days
Note: there have been some reports of azithromycin resistance for syphilis – so it should not
be used! Epidemiologically treated patients still require serological follow-up.
Diagnosis Primary syphilis:
Dark ground microscopy of serous exudate from any visible ulcers (slide to be prepared in
a clinical room room adjacent to the laboratory to reduce time to microscope and reduce
transit
of
potentially
highly
infectious
material
around
the
clinic))
(NB: No value in intra-anal or oral lesions). Only take a dark ground if you know how!! Get
help if you don’t.
PCR testing is now routine on all HSV samples in Sandyford services
In a Sandyford Hub refer the patient to Sandyford Central for dark ground microscopy, the
patient should be fast tracked and the consultant or senior doctor on clinic notified to expect
the patient.
Serological tests
 May be negative in primary stage

ALWAYS request full range of serological tests if suspicious of primary syphilis and tell
the lab for each blood test. The lab can provide a 48 hr turn-round if notified.

Avoid use of antibiotics if possible at this stage if diagnosis remains uncertain and the
patient reports no exposure to syphilis as treatment may prevent any serological
response. If pyogenic component then use trimethoprim 400mg po bd for 7 days (or cotrimoxazole 960 mg bd for 7days if no sulphur allergy)

If a suspicious lesion is dark ground negative, bring the patient back for up to two more
dark grounds and repeat serology one week later.
Secondary Syphilis:
Dark-ground microscopy: from mucous patches or condylomata lata.
Serological tests: invariably all positive.
Other tests: Full blood count, liver and renal function tests
Rapid tests: We have a small supply of Abbott Determine TP fingerprick tests. These are
especially useful for confirming clinical suspicion of secondary syphilis. See separate leaflet
for how to use them. They are insufficiently sensitive to exclude syphilis completely and
should not replace formal serological testing.
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Early Latent syphilis:
Serological
tests:
positive
(on
two
separate
occasions)
and (i) known to have been negative within the last two years or (ii) positive specific IgM with
likelihood of infection in the last two years.
And:
Patient asymptomatic, with no clinical evidence of disease after thorough examination.
If in doubt the patient should be managed as if LATE infection but notified as a possible early
case, this is especially important with the move to a single dose regimen.
Management:
Treatment must be initiated as soon as a diagnosis is reasonably established to limit
infectivity. Please do not defer therapy because someone is uncertain about HIV testing or to
bring patients back for further confirmatory tests. If you are happy with the clinical picture and
the dark ground is positive or typical symptoms in an exposed individual then start treatment
immediately..
Penicillin non-allergic:
Benzathine penicillin G 2.4 MU IM?? single dose (see appendix)
Preparation Instructions for Benzathine penicillin G 2.4MU
1. Take one vial of Benzathine penicillin G 2.4MU aqueous suspension, shake, then
perforate the stopper with a needle
2. Aspirate 6ml-8ml (depending on form of benzathine being used) 1% lidocaine for injection into a
syringe and add to the vial.
3. Remove the syringe from the needle and leaving both needles in place shake the bottle to create
a homogenous suspension
4. Carefully aspirate the suspension
5. Inject
I/M,
half
into
the
upper
outer
quadrant
of
each
buttock
OR (if Penicillin allergic and not pregnant, or declines parenteral treatment)
Doxycycline 100 mg PO BD for 14 days
There is little good clinical evidence to support this regimen and parenteral penicillin is the
preferred treatment. Discuss desensitisation with consultant.
Complications of Treatment
(i)
Jarisch Herxheimer reaction occurs at approximately 8 hours.
Warn patients (document in notes), advise bed rest, paracetamol or aspirin.
(ii)
Procaine reaction (if procaine penicillin used as in neurosyphilis regime – see later
section)
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Partner Notification
All patients diagnosed with primary syphilis should see a sexual health adviser at diagnosis
and at each follow up visit, until partner notification and any local surveillance is documented
as complete.
Follow-up

Sexual Health Advisers will plan follow-up.

Assess clinically and serologically at the end of treatment. Repeat serology at 1, 2
and 3 months then three monthly for a year irrespective of results.

If VDRL was positive at presentation expect a four-fold drop in titre by six months. If
VDRL titre does not fall, or at any stage shows a >2-fold rise, discuss with senior
doctor.

There is a robust system of consultant review of all positive results and recall
and all positive results should be interpreted by a senior doctor annotating the
case record.

Discharge if serofast at 12 months. Ask permission to write to GP to confirm
treatment complete and/or give patient a written summary of treatment (there are
proforma letters).
Late Latent Syphilis
Diagnosis
Serological tests positive and not known to have been negative within the last two years.
Patient asymptomatic, with no evidence of disease.
Examination

All patients need careful clinical cardiovascular, abdominal, skin, fundoscopic and
neurological examination recorded in NaSH under the examination form
(‘Examination for syphilis at foot of form’)
Investigations

All patients should be offered full STI screen and HIV test

Patients with clinical evidence of aortic valve disease should be referred for an
echocardiogram (via Radiology) to chase pathway for cardiac ECHO If this suggests
syphilitic aortic disease, referral to a cardiologist is mandatory.

Lumbar puncture after imaging should be performed in patients with neurological or
ophthalmic signs or symptoms and considered in treatment failure.
Treatment
There much less urgency in treating late syphilis and it is better to plan treatment so that it
can be reliably completed than start treatment and find someone defaults.
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Benzathine penicillin G 2.4 MU IM at day 1 & 8 & 15 (see appendix)
*For administration, see instructions for primary syphilis*
Partner Notification

All patients to see sexual health adviser.
Follow-up

3 weeks - to check compliance and partner notification.

3 months - to repeat serology ± HIV test

If VDRL titre was raised prior to treatment, repeat at three monthly intervals until VDRL
negative or serologically stable on two occasions.

Ask permission to write to GP to confirm treatment complete or give patient a written
summary of treatment.
Maternal syphilis

Transplacental infection is commoner with early stage syphilis and high titre VDRL.

Refer women at greater than 26 weeks gestation to obstetric unit for monitoring at
initiation of treatment (risk of pre-term delivery) and fetal ultrasound.

In early syphilis (primary, secondary, early latent), national guidelines suggest it is safe to
use a single dose of benzathine up to 24 weeks gestation. However the implications of
failed treatment in pregnancy are so profound, with risk to the fetus and risk of the infant
requiring parenteral penicillin, it is better to give 2 doses - (local clinician preference Dr
Andy Winter, Dr Anthony Rea).

All infants require examination and paediatric assessment.

Discuss all maternal cases with a GUM consultant. Discuss penicillin allergic patients with
a GUM consultant.
Benzathine penicillin G 2.4 MU IM?? at day 1 & 8
*For administration, see instructions for primary syphilis*
If pregnant and penicillin allergic
Erythromycin 500mg QID for 21 days, but may not adequately treat foetus, therefore baby
will require treatment once delivered. Discuss desensitisation with consultant.
Neurosyphilis
Meningovascular: may be associated with early (secondary stage) or late syphilis.
Parenchymatous: GPI and/or tabes dorsalis.
CSF tests should include:
SYPHILIS CEG DEC 2015
Cell count
Total protein
Oligoclonal bands
CSF albumin and CSF IgG are ideally needed but not
obtainable locally to calculate the TPHA index
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CSF FTA has lower specificity for a diagnosis of neurosyphilis than VDRL/RPR, but may be
more sensitive. A negative FTA in CSF would usually exclude neurosyphilis.
Treatment for Neurosyphilis
Procaine penicillin 1.8 megaunits IM daily for 17 days (As TUBEX 1ml + TUBEX 2ml)
PLUS
Probenecid 500 mg PO QDS for 17 days
PLUS
Prednisolone 20 mg PO to be given as a single dose on the day prior to antibiotic therapy and
for the following three days.
Cardiovascular Syphilis
Asymptomatic: diagnosed on clinical, radiological and echocardiographic changes.
Symptomatic: usually from aortic valve disease, aneurysmal changes of the aorta or
coronary ostial occlusion.
Requires cardiological assessment. Discuss with senior doctor before referring.
Treatment For Cardiovascular Syphilis
As for neurosyphilis PLUS Prednisolone 20 mg to be given as a single dose on the day prior
to antibiotic therapy and for the following three days.
OR
Oral therapies as for late latent syphilis PLUS Prednisolone as above.
For ENT or optic atrophy complicating syphilis infection, include longer prednisolone course.
Start with 60 mg/day (divided doses). Consultant to assess. Refer ENT/Ophthalmology
opinion.
Partner notification and follow-up as for late latent syphilis but also will need to see relevant
specialist for life.
Appendix
This protocol is to be used for the reconstitution of Benzathine penicillin for the treatment
of syphilis with lidocaine 1%
Medicine: Benzathine penicillin as a 2.4 Mega unit dose presented as a powder solution for
injection.
Contraindications:
Allergy to penicillin or lidocaine.
Concomitant anticoagulant therapy
Bleeding diathesis (e.g. Haemophilia)
Patient declines IM therapy
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Administration
To reduce the pain experienced by patients receiving this injection, 1% lidocaine
(lignocaine) can be prescribed as the diluent. This may be outside the licence of
some brands of Benzathine but is supported practice within Sandyford Services.
Reconstitute the vial of Benzathine penicillin with 6-8ml of 1% Lidocaine
Hydrochloride BP solution (depending on type of benzathine being used –
Sandyford currently has three forms made by different companies) Split the
resultant solution into two equal volumes.
The solution should be administered by intramuscular injection at two different
sites (left and right upper outer quadrant of each buttock or ventro-gluteal site).
Use 19G (1.10) needle owing to recognised needle-clogging with a concentrated
formulation
References
Amir. J.,Ginat.S., et. al. (1998). Lidocaine as a diluent for administration of benzathine
penicillin G. The Pediatric Infectious Disease Journal. 17. 890-3.
Kingston. M., French. P. et. al. (2008). UK National Guidelines on the Management of
Syphilis 2008. Appendix 1. International Journal of STD & AIDS. 19. 729-740.
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