Congenital syphilis

• A sexually transmitted bacterial infection that can cause serious congenital infection.
• Most congenitally infected infants will be asymptomatic at birth, with symptoms usually appearing over the coming months if untreated.
• Symptomatic infants can have a wide variety of manifestations.

• Congenital infection occurs when organisms in maternal blood infect the placenta.
• Organisms are more likely to be in maternal blood in early syphilis (primary/secondary), which is why the congenital infection risk is highest at these stages.
• With late maternal syphilis the risk is much lower, as organisms are rarely in the blood.
• A larger placenta is more likely to be infected than a smaller one, which is why the risk of congenital infection goes up in the later stages of pregnancy.

• Testing is recommended as part of the standard antenatal ‘booking bloods’ in NZ
• Higher risk women (e.g. STI diagnosed during pregnancy, new or multiple partners during pregnancy) should be rescreened at 28-32 weeks
• Testing is recommended in women at any gestation with symptoms of primary infection (e.g. ulcerative skin lesions) or secondary infection (e.g. skin rash and/or flu like symptoms)
• Testing is recommended in women with fetal death at >20 weeks or if abnormal USS findings
• Testing is recommended for all neonates where congenital syphilis is a possibility

Request Syphilis serology

• This is mostly to confirm/refute maternal infection, confirmation of congenital infection is usually done in the neonatal setting
• Can answer two questions:
  • Has mother ever had infection with syphilis (including if treated/cleared)?
    • EIA and TPPA
  • Does mother have current active infection?
    • RPR
• Syphilis EIA detects anti-treponemal antibodies (a ‘treponemal’ test). These develop shortly after primary infection and usually last lifelong i.e. indicate infection at some stage.
  • Excellent sensitivity – a negative result excludes syphilis unless very early infection/treatment, or rarelyin HIV/immune compromise
  • Good specificity – however, a second test is used to confirm a positive result, as false positives can occur.
    • TPPA (another ‘treponemal’ test) is used for this purpose
      • EIA pos &TPPA pos = treponemal infection at some stage. Note, other treponemal infections, e.g. Yaws, give the same result.
      • EIA pos &TPPA neg = false positive EIA (most common explanation) or very early infection.
    • RPR detects non-specific antibodies (a ‘non-treponemal’ test) caused by active infection.
      • This is added on automatically by the lab if EIA positive (even if TPPA negative).
      • Unlike EIA/TPPA, which remain positive regardless, the value of this test changes over time due to treatment or the immune response to infection.
        • Used to assess for inactive vs active infection and response to treatment.
      • Any pregnant woman with positive EIA & TPPA (regardless of RPR) should be discussed with a relevant specialist regarding the need for treatment

• Testing is complicated and should be under specialist guidance and combined with maternal history and infant physical examination.
• It is often not possible to confidently rule in or rule out the diagnosis perinatally, so the pre-test probability (i.e. maternal treatment and exposure history) often influences treatment decisions more than testing.
• Syphilis serology:
  • Infant RPR tested in parallel to maternal RPR
    • Should not be performed on cord blood samples (risk of maternal blood interference)
    • Infant RPR ≥4-fold higher than maternal RPR considered evidence of proven/highly probable congenital syphilis
      • RPR <4-fold higher is less definitive, doesn’t rule in or out
• Placental investigations:
  • Histopathology + PCR
    • Certain features can be highly specific so make congenital syphilis likely
    • Can confirm the diagnosis if combined with immunohistochemical stains or PCR demonstrating the organism.
    • Sensitivity is less certain, so a normal result doesn’t exclude the diagnosis.
• Syphilis PCR
  • Excellent specificity – a positive result confirms the diagnosisUncertain sensitivity – a negative result doesn’t exclude the diagnosis. Can be performed on nasal discharge, swab of infant rash
  • Not yet widely available
• CSF testing (cell count, protein, VDRL/FTA-Abs)
  • Typically indicated if any abnormal findings on examination or above tests

• Interval follow-up serology testing is performed, with frequency usually determined by initial results
  • This should be under specialist guidance
• Infant syphilis IgM
  • This is recommended in some guidelines, however lacks specificity, so in our experience rarely alters management and isn’t recommended.

Note that EIA/TPPA does not give useful information in the neonatal setting, as there is no way to differentiate between passively acquired maternal antibodies and the infant’s own antibodies.