Background

Syphilis is caused by the bacterial spirochete Treponema pallidum. It is transmitted sexually or vertically (from mother to child).  Early syphilis is fully treatable with penicillin. Congenital syphilis can be significantly reduced with adequate maternal screening in early pregnancy and treatment [1], screening for syphilis is part of routine antenatal care in Australia.

Syphilis is a notifiable disease in Australia; rates of syphilis have increased in recent years. Congenital syphilis is uncommon in the Australian population [4]. Limited data suggest syphilis may be slightly more prevalent in recently arrived refugees than in the general population [5, 6], although this varies depending on country or origin [7]. Worldwide syphilis is most common in sub-Saharan Africa, south and southeast Asia, Latin America and the Caribbean.[8] 

Assessment

Sexually transmitted syphilis

• Primary or early infection - painless chancre (or ulcerative lesion) at the site of infection, this usually resolves within a few weeks.
• Secondary syphilis - Dissemination of the organism over the period of a few months results in systemic symptoms - maculopapular rash (covering palms and soles), fever, headache, malaise, anorexia and diffuse lymphadenopathy.
• Latent syphilis – secondary syphilis is generally followed by a ‘latent’ phase, where the patient has no symptoms, but infection is present (serology is positive). Latency can be divided into ‘early’ (<1 year from infection) and ‘late’ (>1 year from infection [2]). Without treatment, approximately 40% of individuals with latent syphilis will develop symptoms of late (or ‘tertiary’) syphilis,
• Late or tertiary syphilis – is characterised by neurological, cardiovascular or gummatous complications, these may occur 1-30 years after infection [2].

Vertically transmitted syphilis

During pregnancy there is a high risk of vertical transmission in early syphilis (~50% of infants are infected) and a lower risk in late syphilis (~40% in early latency and 10% in late latency) [2]. Congenital syphilis probably follows the same stages of infection as sexually transmitted infection, but manifests differently in infants, who lack adequate immune control. Congenital syphilis may:

• Be asymptomatic – in up to 50% of infants [2, 3].
• Cause stillbirth- in ~30% of infected mothers
• Present postnatally with symptoms of disseminated (secondary) syphilis, such as ‘snuffles’ (rhinitis), maculopapular rash, necrotising funisitis, lymphadenopathy, conjugated hyperbilirubinemia, hepatosplenomegaly and glomerulonephritis.
• Present as late congenital syphilis ( after 2 years of age) with scarring and gumma formation. This form occurs in ~40% of infants born to women with untreated syphilis. Symptomatic neurosyphilis occurs in 1-5% of these children, often characterized by sudden deafness (usually around 8-10 years or age) and/or interstitial keratitis or chorioretinitis.

Diagnosis of syphilis

• Non-treponemal tests are serological tests that detect lipoidal substances released from cells during syphilis infection.
  • Tests include the RPR (Rapid Plasma Reagin) and VDRL (Venereal Diseases Research Laboratory).
  • These tests are more sensitive but less specific than treponemal tests.
  • False positives are common (EBV,hepatitis, varicella, measles, lymphoma, TB, malaria, pregnancy, cord blood).
  • These tests usually correlate with disease activity and become negative after adequate treatment. Successful therapy is generally regarded as a 4-fold fall in RPR titre (e.g. from 1:32 to 1:8).
• Treponemal tests are serological tests that detect syphilis antigens.
  • These assays include TPPA (Treponema Pallidum Particle Agglutination), TPHA (Treponema Pallidum Haemagglutination), FTA (Fluorescent Treponemal Antibody absorption) and syphilis EIA (enzyme immunoassay).
  • These tests are generally more specific and less sensitive than non-treponemal tests.
  • These tests do not correlate with disease activity and usually remain positive for life.
• Darkfield microscopy can be used to visualise treponemes from a primary chancre or nasal secretions. Failure to identify treponemes does not exclude a syphilis diagnosis. Note – it is not possible to culture T Pallidum using standard media
• Syphilis PCR can be performed on swabs from a primary chancre, nasal secretions or CSF. It is not adequately sensitive for screening (e.g. on blood).
• CSF should be collected for VDRL, FTA-Abs or PCR testing where neurosyphilis is suspected.

In Australia, pregnant women are screened for syphilis (preferably in the first trimester) using a treponemal test. Women will then be offered treatment with penicillin (usually benzathine penicillin, according to the Australian Therapeutic Guidelines[9]) and their RPR titre will be monitored to ensure that is has fallen 4-fold prior to delivery.

Screening and management

Infants born to women with syphilis during pregnancy

Infants born to women with syphilis during pregnancy (regardless of adequacy of treatment) should have screening with:

• Full examination for signs of congenital syphilis
• Serology (from infant, not to be performed on cord blood) for:
• RPR titre (in parallel with maternal RPR)
• IgM capture EIA [10]
• Pathologic examination of the placenta with syphilis PCR or fluorescent antitreponemal antibody staining

Treponemal tests may be positive for up to 18 months due to transplacental transfer of IgG; therefore they are not a good indicator of infection in the infant.

Management and follow-up

Infants born to women who received adequate treatment* during pregnancy, who have a normal examination AND an RPR titre the same or less than 4-fold maternal RPR titre may not require treatment, but should be followed at 3,6 and 12 months with clinical examination and syphilis serology until the RPR is negative.*Adequate treatment = penicillin, more than 4 weeks prior to delivery with treatment confirmed by 4-fold fall in RPR titre)

All other infants should be considered potentially infected and should receive further investigations and treatment for congenital syphilis. A child is considered to have congenital syphilis[11] if either:

• They have physical, laboratory, or radiographic signs of congenital syphilis (confirmed/highly probable congenital syphilis) OR
• They were born to a mother with untreated, inadequately, or suboptimally treated syphilis (presumed congenital syphilis).

Additional investigations in infants with congenital syphilis

• Liver function tests (+/- abdominal U/S)
• Long bone X-rays (tibia, tubular bones of hands/feet, skull, clavicles: look for irregular epiphyseal lines, decalcification of subchondral bone, metaphyseal destruction of proximal tibia)
• CSF VDRL (Up to 40% of infants with symptomatic congenital syphilis will have a positive VDRL from CSF)
• Ophthalmological assessment

Management of infants with congenital syphilis

• Infants should be treated with Intravenous benzyl penicillin 50mg/kg bd for 10 days.
• Follow up at 1,2,4, 6,12 months and until RPR negative.
• Infants with evidence of neurosyphilis should have repeat CSF at 6-monthly intervals to ensure changes have resolved.
• Infants with persistently reactive RPR should be re-evaluated (including CSF) and treated for 10 days with IV benzyl penicillin [9].

Syphilis screening in people of refugee background

In the United States, syphilis testing is recommended for all refugees over 15 years AND refugees <15 years who are sexually active or have a history of sexual abuse or with a mother who tests positive for syphilis. It is a visa requirement that persons >15 years applying for either an offshore or onshore protection visa have syphilis testing and treatment if needed. For offshore entrants, this occurs prior to arrival in Australia. In Australia, syphilis screening is not routine for refugee children. In general:

• Consider STI risk factors (all ages)
• Syphilis (and STI) screen for people (adults, adolescents, children) with risk factors, or on request - usually syphilis EIA, but may be laboratory dependent 
  • STI screen = self-collected swab or first pass urine nucleic acid amplification (NAAT) test and consideration of throat and rectal swabs for Chlamydia and Gonorrhoea, and serology for HIV, syphilis and hepatitis B
    
    
• Children <15 years should have syphilis serology performed if:
• They are unaccompanied/separated minors
• There is a history of sexual abuse/sexual violence
• A parent has evidence of syphilis
• History or examination suggests signs or symptoms consistent with congenital syphilis (e.g. sensorineural hearing loss, chorioretinitis, CNS abnormalities)

Additional investigations in children with positive serology for syphilis

• Repeat the test to confirm the diagnosis (the laboratory will also perform specific treponemal tests on the sample as initial confirmation).
• Request maternal serology (often the distinction between congenital or horizontally acquired syphilis is difficult in older children)
• Consider possibility of sexual abuse/sexual violence, particularly if maternal treponemal tests are negative (these usually remain positive for life, even after treatment)
• Consider further investigation, depending on clinical circumstances:
• Syphilis PCR on nasal discharge, if early infection (e.g. infant)
• CSF if >1 month of age at diagnosis
• Consider testing for other sexually transmitted infections, such as HIV and hepatitis B
• Consider testing sibling’s serology if infection is likely congenital.

Syphilis is a notifiable disease (Group C condition)

Management and follow-up

• Older infants >1 month and children: Benzylpenicillin 50mg/kg bd IV 10 days [9] . Intravenous therapy is preferable. If this is not possible an alternative is: procaine penicillin 50mg/kg IM, daily for 10 days
• Benzathine penicillin (3 x weekly doses) may be an alternative in an older child, where the CSF examination and VDRL tests are negative. Seek specialist advice. Benzathine penicillin is painful, if possible it should be administered in the buttock with 2mL lignocaine 1% (or 4mL 0.5% lignocaine).
• Children who receive treatment should be followed with serology every 2-3 months until RPR is negative. If the initial CSF is abnormal, serial CSF should be collected every 6 months to confirm adequate treatment, until CSF parameters have normalised.

Resources

• Victoria Department of Health website information
• Better Health Channel patient information sheet
• CDC information

References

• References

_{Immigrant health resources. Author: Vanessa Clifford and Georgie Paxton, June 2013. Last review April 2017. Contact: georgia.paxton@rch.org.au}