Syphilis: early signs and modern methods of diagnosis

What is syphilis and why does it remain a threat?

Syphilis is a chronic infectious disease caused by the bacterium Treponema pallidum and transmitted mainly through sexual contact. Despite the availability of effective treatment, syphilis remains a serious global problem: according to WHO data, more than 7.1 million new cases are recorded worldwide each year. In Ukraine the incidence of syphilis has risen by 23% over the past five years, with the greatest increase among young people aged 20–34. The particular danger lies in the infection's ability to run a symptomless course for months and even years while damaging the cardiovascular and nervous systems. Congenital syphilis — transmission from mother to child during pregnancy — remains a cause of stillbirth and severe birth defects. Risk factors include unprotected sex, a large number of sexual partners, HIV infection and injecting drug use. Early diagnosis and treatment cure the disease completely and prevent serious complications.

The stages of syphilis and their clinical features

Syphilis progresses in stages, and each stage has characteristic features. Four main stages are distinguished:

• Primary syphilis: 10–90 days after infection (on average 21 days), a chancre appears at the point where the treponeme entered — a painless ulcer with firm edges and a clean base. It is most often on the genitals, but it can occur on the lips, tongue, tonsils, in the anal area or on the fingers. The chancre is usually solitary, round, 1–2 cm across, and neither bleeds nor hurts. Without treatment it heals on its own within 3–6 weeks, which creates a false sense of recovery.
• Secondary syphilis: develops 6–12 weeks after infection and is characterised by a generalised rash — roseolar (pale pink macules), papular or pustular. Condylomata lata in the anogenital area and "moth-eaten" alopecia are typical signs. Patients report general malaise, a temperature of 37.5–38°C, sore throat and lymphadenopathy.
• Latent syphilis: the infection enters a symptomless phase that may last years. Early latent syphilis (up to 2 years) still carries a risk of secondary relapses and of infecting sexual partners. Late latent syphilis (more than 2 years) is usually not transmitted by sexual contact, but it can pass from mother to fetus. The diagnosis is made serologically alone.
• Tertiary syphilis: develops in 15–40% of untreated patients after 3–15 years. It affects the cardiovascular system (syphilitic aortitis, aortic aneurysm), the nervous system (neurosyphilis — meningitis, tabes dorsalis, general paresis) and the skin and bones (gummatous syphilis). Neurosyphilis can develop at any stage and may present with headache and disturbances of vision, coordination and cognition.

Modern methods of diagnosis

Diagnosis rests on a combination of clinical examination and laboratory tests. Dark-field microscopy — direct visualisation of Treponema pallidum in material from a chancre or a rash — allows the diagnosis to be made before serological markers appear. Non-treponemal tests (RPR, VDRL) are screening methods that detect antibodies to lipoidal antigens; they can be falsely positive in pregnancy, in autoimmune disease and in infections. Treponemal tests (FTA-ABS, TPHA, ELISA, immunoblot) are highly specific confirmatory methods that detect antibodies to the treponeme itself. Important: serological tests become positive only 1–4 weeks after the chancre appears (the serological window). PCR is a molecular method for detecting treponemal DNA and is particularly useful in neurosyphilis (testing cerebrospinal fluid). The full algorithm: ELISA screening → confirmation with TPHA/immunoblot → quantitative RPR to monitor treatment.

Treatment: current protocols

Benzathine benzylpenicillin has been the drug of choice for syphilis for more than 70 years, and no treponemal resistance to it has been recorded. Primary and secondary syphilis: a single injection of benzathine benzylpenicillin G 2.4 million units intramuscularly. Early latent syphilis: the same regimen. Late latent and tertiary syphilis (without neurosyphilis): three injections of 2.4 million units at intervals of 7 days. Neurosyphilis: aqueous benzylpenicillin 18–24 million units a day intravenously for 10–14 days. In penicillin allergy: doxycycline 100 mg twice a day for 14–28 days, or ceftriaxone 1–2 g intramuscularly for 10–14 days. Pregnant women with penicillin allergy undergo desensitisation. The Jarisch–Herxheimer reaction — fever, chills and muscle aches within 24 hours of the first injection — occurs in 50% of patients with early syphilis and is an expected reaction, not an allergic one. Serological follow-up (RPR) is carried out at 6, 12 and 24 months after treatment.

Prevention and screening

Using barrier contraception (condoms) reduces the risk of transmitting syphilis by 50–70%, but does not give complete protection, because a chancre may lie outside the area a condom covers. Limiting the number of sexual partners and avoiding anonymous sexual contact substantially reduces the risk. Screening is recommended: for all pregnant women at the first antenatal visit and again in the third trimester; for people with HIV — annually, or more often where the risk is high; for men who have sex with men — every 3–6 months; and after any other STI is diagnosed. Partner notification is essential: all sexual partners from the past 90 days (in primary syphilis) or 6 months (in secondary syphilis) should be tested and treated. Preventive treatment of contacts — benzathine benzylpenicillin 2.4 million units as a single dose — is given even where serological tests are negative, if contact occurred within the past 90 days.

When to seek help immediately

See a venereologist or dermatovenerologist immediately if you notice a painless ulcer (chancre) on the genitals, in the mouth or in the anal area — even if it does not trouble you and is starting to heal on its own. An urgent examination is needed if an unexplained symmetrical rash appears on the trunk, the palms or the soles that neither itches nor hurts. See a doctor if lymph nodes enlarge for no apparent reason, if hair is lost in patches ("syphilitic alopecia"), or if condylomata lata appear in the anogenital area. Testing is essential after unprotected sex with an infected person or someone whose status is unknown, when planning a pregnancy and during pregnancy, and if you are HIV-positive. Remember: syphilis in its early stages is completely curable with a single injection of an antibiotic, but untreated it can cause irreversible damage to the internal organs.