In 2020, the World Health Organization (WHO) reported that 7.1 million adults aged 15 to 49 were diagnosed with syphilis worldwide. Some population groups are disproportionately affected by syphilis, such as men who have sex with men (MSM). This could be attributed to various factors, including elevated levels of stigma and discrimination, as well as limited access to healthcare services.

Among the notified syphilis cases, the incidence rate of infectious syphilis decreased from 8.6 per 100,000 population in 2019 to 5.1 in 2020 in Singapore; and there were no cases of congenital syphilis in 2019 and two cases in 2020.

Pathogen(s)

Treponema pallidum.

Transmission

Syphilis is transmitted during oral, anal, or vaginal sex through direct contact with infectious lesions.

An infected mother can also pass syphilis during pregnancy through the placenta.

Incubation period: From 10 to 90 days, with an average of 21 days.

Infectious period: During the primary and secondary stages and possibly the first two years of the latent period. A person is no longer infectious five days after starting appropriate antibiotic treatment or until their symptoms resolve.

Clinical features

Many people with syphilis do not notice any symptoms.

Syphilis has several stages:

Primary syphilis: Usually occurs 2 to 6 weeks following infection. Characterised by a single or less often multiple, painless, indurated ulcer (chancre) at the site of inoculation. Regional lymph nodes are enlarged, feel rubbery and are painless.
Secondary syphilis: Usually occurs 2 to 6 months following primary syphilis. Characterised by variable mucocutaneous and systemic signs e.g. symmetrical non-itchy rashes, mucous membrane lesions, patchy alopecia, generalised lymphadenopathy.
Latent syphilis: Asymptomatic phase with no clinical signs of organ involvement. It is categorised into:
- Early latent syphilis (less than one year of infection)
- Late latent syphilis (more than one year of infection)
Tertiary Syphilis: Occurs 5 to 10 years after secondary syphilis and includes:
- Benign tertiary syphilis characterised by gumma formation
- Cardiovascular syphilis
- Neurosyphilis

Risk factors

Risk factors include:

Unprotected sex with an infected person
Having multiple sex partners
Inconsistent condom use if the relationship is not monogamous
Persons who exchange sex for money or drugs
History or current presence of other STIs

Diagnosis

T. pallidum cannot be cultured on routine laboratory culture media. Nucleic acid amplification testing (NAAT) for T. pallidum DNA is not commercially available.

Tests for diagnosis include:

Dark-Field Microscopy (DFM): Useful in early syphilis when antibodies are not yet detectable. The diagnosis of syphilis may be confirmed by demonstrating T. pallidum on wet mounts of secretions from the primary chancre, or moist lesions of secondary syphilis.
Serological tests:
- Non-Treponemal Tests (Rapid Plasma Reagin (RPR) test and the Venereal Disease Research Laboratory (VDRL) test) are monitored serially to assess the serological response to treatment. A positive RPR/VDRL test needs to be confirmed by a treponemal test.
- Treponemal Tests (Treponema Pallidum Haemagglutination Assay (TPHA), Treponema Pallidum Particle Agglutination (TPPA) test, the Line Immunoassay (LIA), the Fluorescent Treponemal Antibody Absorption (FTA-Abs) test, Rapid diagnostic tests (e.g. Abbott Determine Syphilis TP) and the treponemal EIA test) are specific and can be used as screening tests. Once positive, specific tests tend to remain positive even after the syphilis has been successfully treated. The titres of treponemal tests are not useful in monitoring treatment response.

Refer to DSC’s website for more information on laboratory tests.

Treatment and management

Parenteral penicillin G (aqueous crystalline, aqueous procaine, or benzathine) is the drug of choice for treating all stages of syphilis. If the patient is allergic to penicillin, tetracycline, doxycycline, azithromycin, and erythromycin are the alternatives. However, they do not have the established and well-evaluated high rate of success of penicillin.

Recommended regimens for primary, secondary, or early latent:

Benzathine Penicillin G 2.4 million units intramuscularly (IM) single dose; or
Aq. Procaine Penicillin G 600,000 units IM daily for 10 days.

Recommended regimens for late latent:

Benzathine penicillin G 2.4 million units IM weekly, 3 doses (7.2 million units total); or
Aq. Procaine penicillin G 600,000 units IM daily for 17 to 21 days.

Follow-up:

Quantitative nontreponemal tests should be repeated for a total period of 2 years, at 3, 6, 12, 18, and 24 months).

Following treatment of early syphilis, RPR/VDRL should demonstrate a four time (two dilutions) decrease in titre within six months. Failure to do so probably means treatment failure, and is an indication for retreatment with three injections of Benzathine penicillin. Some experts recommend cerebrospinal fluid (CSF) evaluation.

Clinical signs that persist or recur, or a rising RPR/VDRL titre of four times or more suggests either reinfection or relapse. In these situations, CSF examination is recommended before retreatment. Seroreversion in primary syphilis often occurs within 12 months. It may take a longer time for secondary and early latent syphilis but usually occurs within 24 months.

For latent syphilis non-treponemal tests should be repeated at six, 12, and 24 months. Serologic response to treatment associated with multiple factors, viz. syphilis stage, initial non-treponemal titres (less than 1:8 are less likely to decline four-fold), and age (titres in older patients might be less likely to decrease fourfold than younger patients). These persons should be examined for HIV infection and neurologic disease, clinical and serologic follow-up annually. If additional follow-up cannot be ensured or if an initially high titre (more than 1:32) does not decrease at least four-fold 24 months after treatment, retreatment with weekly injections of benzathine penicillin G 2.4 million units IM for three weeks is recommended. Because treatment failure might be the result of unrecognised CNS infection, CSF examination can be considered in such situations where follow-up is uncertain or initial high titres do not decrease after 24 months.

Following treatment of late syphilis, seroreversion occurs rarely as a stable, low titre, serological scar, is the result in most patients.

All patients treated for neurosyphilis should be followed up for life at six-month intervals. If CSF pleocytosis was present initially, CSF examinations should be repeated every six to 12 months until the cell count returns to normal. Serologic tests for HIV should be performed three months after the last risky exposure.

Refer to the Department of Sexually Transmitted Infections Control (DSC) website for other treatment options.

Precaution, prevention, and control

Annual or more frequent screening for syphilis symptoms and other STIs is recommended for:

Individuals with multiple sex partners, change in sex partner, or engaging in unprotected sex
All pregnant women in their first prenatal visit; and thereafter, if there is risk of infection from their regular partner
Individuals who are at risk depending on their risk behaviours

Prevention of syphilis:

Informing current or recent sexual partners if a syphilis diagnosis has been confirmed
Avoiding sexual intercourse until treatment is completed
Not having sex
Usingly condoms consistently and correctly when engaging in sexual activity
Limiting the number of sex partners
Getting tested for STIs regularly

Management of sexual contacts:

At risk partners are those who have been exposed within the following periods:

3 months, plus duration of symptoms for primary syphilis
6 months, plus duration of symptoms for secondary syphilis;
1 year for early latent syphilis

Epidemiologic treatment should be given to sexual contacts who were exposed three months prior to the diagnosis of primary, secondary, or early latent syphilis, if follow-up is uncertain. Sexual partners of late syphilis should be screened and evaluated for syphilis and treated on the basis of these findings.

Notification

Syphilis is a notifiable disease.

Who should notify:

Medical practitioners
Laboratories

When to notify:

On clinical suspicion or laboratory confirmation

How to notify:

Please refer to the Infectious Disease Notifications for more information.

Notification timeline:

Within 72 hours from time of diagnosis

Resources

Refer to resources for the communicable disease surveillance in Singapore.

Refer to DSC’s website for more information about syphilis.

References

Centers for Disease Control and Prevention. STI treatment guidelines: Syphilis. 2021.
Department of Sexually Transmitted Infections Control (DSC). STI management guidelines 7^th edition. 2021.
World Health Organization. Syphilis. 2023.