Treatment

In pregnancy

Infectious syphilis in pregnancy requires an urgent response with treatment and follow up commenced as soon as possible and ideally within 24 hours.

• Seek urgent advice from an expert in sexual health or infectious diseases regarding the care of pregnant people who test positive and their partners.
• Fetal monitoring may be advised if more than 20 weeks gestation.
• Treat pregnant people with symptoms of syphilis or a new positive PoCT as soon as possible without waiting for confirmatory testing, particularly if there is a risk of loss to follow-up.
• For pregnant people with newly confirmed infectious syphilis, give intramuscular 2.4 million units (given as two 1,200,000 units injections) benzathine penicillin as soon as possible, ensuring that treatment is received at least 30 days before the estimated date of birth to reduce the likelihood of congenital syphilis.
• Prioritise contact tracing of partner/s and treat presumptively
• Monitor treatment and repeat testing eight weeks after treatment or at birth – whichever occurs first. Otherwise, repeat syphilis testing on any suspicion of reinfection or treatment failure.

HIV co-infection

Epidemiological evidence supports the fact that incident syphilis infection increases sexual acquisition of HIV, via breaches in mucosa and/or skin during early syphilis infection (1) and the associated impact of local recruitment of CD4+ immune cells to the area (2).

In general, the clinical manifestations of syphilis are similar in HIV-positive and -negative individuals (3). However, important differences exist, as outlined below.

Infectious syphilis

In the US Syphilis and HIV cohort study (4), HIV-infected individuals presenting with primary syphilis were more likely to have larger and more numerous chancres. In addition, secondary syphilis among HIV-infected individuals was more likely to present with concurrent chancres indicating an overlap between the primary and secondary stages. “Malignant” secondary syphilis, also known as “ulceronodular” syphilis, is a rare manifestation thought to be more common in HIV-infected individuals due to impaired cell-mediated immunity, which is characterised by disseminated papulopustular ulcers with a crusty base (5).

Neurosyphilis

Syphilis of the central nervous system (CNS) can occur at any stage of disease, with HIV infection being consistently demonstrated as a risk factor. Neurosyphilis is estimated to affect around 1-2% of syphilis/HIV co-infected individuals (6). Seek specialist advice for patients with suspected neurosyphilis.

Penicillin allergy

For people with penicillin hypersensitivity (allergies to penicillin), there are two alternative therapies for treatment:

1. Desensitisation to penicillin: only penicillin is effective in pregnancy, those allergic should be desensitised then treated with penicillin. Seek specialist advice.
2. Non-penicillin regimes: while there is less evidence than penicillin, doxycycline has been shown to be effective; seek specialist advice.

References

1. Lynn WA, Lightman S. Syphilis and HIV: a dangerous combination. Lancet Infect Dis. 2004;4(7):456-66.
2. Salazar JC, Cruz AR, Pope CD, Valderrama L, Trujillo R, Saravia NG, et al. Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis. J Infect Dis. 2007;195(6):879-87.
3. Australian STI Management Guidelines [Internet]. Sydney: ASHM; 2025 [cited 17 Apr 2026]. Available from: https://sti.guidelines.org.au/
4. Rompalo AM, Joesoef MR, O’Donnell JA, Augenbraun M, Brady W, Radolf JD, et al. Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study. Sex Transm Dis. 2001;28(3):158-65.
5. Tucker JD, Shah S, Jarell AD, Tsai KY, Zembowicz A, Kroshinsky D. Lues maligna in early HIV infection case report and review of the literature. Sex Transm Dis. 2009;36(8):512-4.
6. Tuddenham S, Ghanem KG. Neurosyphilis: knowledge gaps and controversies. Sex Transm Dis. 2018;45(3):147-51.