Syphilis

Syphilis is a sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum. It is characterised by a diverse range of clinical presentations and a natural history that progresses through four distinct stages: primary, secondary, latent, and tertiary. Because of its highly variable manifestations, syphilis has long been referred to as “the Great Imitator”, capable of mimicking many other medical conditions. The disease may also be transmitted vertically from mother to child during pregnancy or at delivery, resulting in congenital syphilis. Other diseases caused by related Treponema species include yaws, pinta, and endemic (non-venereal) syphilis, none of which are typically transmitted through sexual contact.
Syphilis remains a significant global health issue. Despite the introduction of effective antibiotic therapy in the mid-twentieth century, infection rates have risen again in many regions since the early 2000s, often associated with co-infection with HIV, changes in sexual behaviour, and reduced condom use. Diagnosis relies on serological tests, sometimes supplemented by dark-field microscopy to visualise the organism directly. Treatment is highly effective, with benzathine benzylpenicillin the preferred therapy for most stages.

Causes and Transmission

Syphilis is primarily transmitted through sexual contact—vaginal, anal, or oral—with infectious lesions. The bacterium enters through mucous membranes or tiny skin abrasions. Vertical transmission can occur during pregnancy or at birth, contributing to significant infant morbidity and mortality worldwide. The risk of transmission can be reduced through consistent use of latex or polyurethane condoms, although these do not provide complete protection if lesions lie outside the area covered.

Global Epidemiology

As of 2015, an estimated 45 million people worldwide were living with syphilis, with approximately six million new infections recorded annually. While mortality has fallen substantially since the widespread availability of penicillin, syphilis still contributes to over 100,000 deaths per year, often through congenital disease or complications of late infection. After dramatic declines in the mid-twentieth century, incidence began rising again around the turn of the millennium, driven by factors such as unsafe drug use, increased commercial sex work, and reductions in safer-sex practices.

Clinical Presentation

Syphilis may progress through several stages, each with characteristic features, though there is considerable variation between individuals. Some people remain asymptomatic, especially in latent phases.

Primary Stage

Primary syphilis typically develops around two to six weeks after exposure. The hallmark lesion is the chancre—a firm, painless, non-itchy ulcer with a clean base and well-defined borders. Although usually solitary, multiple chancres may occur, particularly in individuals co-infected with HIV. Lesions may appear at genital, anal, or oral sites depending on exposure. Regional lymphadenopathy is common, usually arising about a week after the chancre appears. Without treatment, the chancre resolves spontaneously within three to six weeks.

Secondary Stage

Secondary syphilis emerges four to ten weeks after the primary lesion and is notable for its systemic involvement. It commonly presents with:
• a symmetrical reddish–pink rash, often involving the trunk, limbs, palms, and soles• mucous membrane lesions, including wart-like condylomata lata• generalised lymphadenopathy
Other symptoms may include fever, sore throat, malaise, weight loss, headache, patchy hair loss, and ocular involvement such as uveitis or interstitial keratitis. Although these lesions are highly infectious, the symptoms typically resolve within several weeks. Approximately one-quarter of individuals may experience recurrent secondary episodes.
A substantial proportion of individuals with secondary syphilis do not recall having a primary chancre, suggesting unrecognised or atypical early infection.

Latent Stage

Latent syphilis is characterised by serological evidence of infection without clinical symptoms. It is subdivided into:
• early latent syphilis—occurring within two years of infection and potentially infectious if secondary symptoms recur• late latent syphilis—occurring after two years, usually non-infectious
The latent stage can persist for many years. Without treatment, approximately 15–40 per cent of individuals progress to tertiary disease.

Tertiary Stage

Tertiary syphilis may arise three to fifteen years after initial infection and encompasses three major forms:
• Gummatous syphilis—marked by soft, tumour-like inflammatory lesions (gummata) affecting the skin, bones, or liver• Cardiovascular syphilis—most commonly involving syphilitic aortitis, which may lead to aneurysm formation• Neurosyphilis—affecting the central nervous system either early or late in the infection
Neurosyphilis may be asymptomatic or present with a range of syndromes. Early forms include meningeal or meningovascular inflammation, which can cause stroke-like events, cranial nerve palsies, or spinal cord dysfunction. Late forms include:
• general paresis—characterised by cognitive decline, personality changes, delusions, psychosis, and seizures• tabes dorsalis—involving deterioration of the spinal cord’s dorsal columns, producing gait instability, sharp limb pains, impaired proprioception, and a positive Romberg sign
Both general paresis and tabes dorsalis may feature the Argyll Robertson pupil, which accommodates but does not react to light.
Tertiary syphilis is not considered infectious but can be severely debilitating.

Congenital Syphilis

Congenital syphilis occurs when T. pallidum is transmitted from an infected mother to her fetus. It can lead to miscarriage, stillbirth, severe neonatal disease, or long-term developmental complications. Routine antenatal screening is recommended to identify and treat syphilis early in pregnancy.

Diagnosis

Diagnosis relies primarily on serological tests. These include:
• non-treponemal tests (e.g., RPR, VDRL) used for screening and monitoring treatment response• treponemal tests (e.g., TPHA, FTA-ABS) used to confirm infection
Dark-field microscopy or direct detection methods can visualise the organism in primary or secondary lesions. In suspected neurosyphilis, cerebrospinal fluid examination is required.

Treatment and Management

Benzathine benzylpenicillin administered intramuscularly is the treatment of choice for most stages. For neurosyphilis, intravenous benzylpenicillin or ceftriaxone is recommended. For individuals with severe penicillin allergy, alternatives such as doxycycline or tetracycline may be used, though desensitisation is preferred in pregnancy.
During treatment some patients develop the Jarisch–Herxheimer reaction, a transient feverish response accompanied by headache and muscle aches.

Prevention

Preventive measures include consistent use of condoms, regular testing in sexually active individuals at risk, and antenatal screening. Public health strategies focus on education, contact tracing, and early treatment to reduce community transmission.