Syphilis

• Syphilis is a systemic infection caused by the spirochete Treponema pallidum. It enters through skin or mucous membranes, spreads in the bloodstream, and can involve almost any organ, sometimes years or decades later.
• It progresses through four stages: primary, secondary, latent and tertiary. Primary syphilis classically presents as a painless hard chancre; secondary syphilis as a generalised rash, often including the palms and soles, plus mucous patches and condylomata lata.
• Latent syphilis has no symptoms but serologic evidence of infection; early latent syphilis is infection acquired within the preceding year, late latent syphilis is older than 1 year. ^[1]
• Tertiary syphilis produces gummas, cardiovascular disease such as aortitis and aortic regurgitation, and neurosyphilis, including tabes dorsalis and general paresis. Neurosyphilis can occur at any stage.
• Diagnosis requires a nontreponemal test (VDRL or RPR) plus a treponemal test (TPPA, EIA, or similar). Penicillin G given parenterally is the preferred drug for all stages; benzathine penicillin G intramuscularly cures early disease in a single dose.

By the end of this page you should be able to:

1. Describe the organism, transmission and natural history of syphilis and name the four stages with their characteristic findings.
2. Recognise primary and secondary syphilis at the bedside and distinguish latent, early latent, late latent and tertiary disease.
3. Interpret nontreponemal and treponemal tests, the traditional and reverse sequence algorithms, and the indications for cerebrospinal fluid (CSF) examination.
4. Plan penicillin treatment by stage and by special situation (pregnancy, neurosyphilis, HIV coinfection, children), and manage the Jarisch-Herxheimer reaction and sex partners.
5. Recognise congenital syphilis and its late stigmata.
6. Explain how syphilis is approached when tests, drugs or specialist care are limited.

Infection passes through four stages. Primary and secondary syphilis, with mucocutaneous lesions, are the "early" stages and are infectious by skin-to-skin contact. Latent syphilis is serological evidence of infection without clinical signs; it is further split into early latent (acquired within the preceding year) and late latent (older than 1 year, or of unknown duration). Tertiary syphilis is symptomatic late disease: gummas, cardiovascular syphilis and late neurosyphilis. Neurosyphilis is central nervous system invasion by T. pallidum; it can occur at any stage, not only late disease. Ocular syphilis and otosyphilis are treated like neurosyphilis. ^[1]

Humans are the only host. T. pallidum is too delicate to survive outside the body, and an inoculum of about 500 to 1,000 organisms can establish infection. ^[10]

Syphilis remains a worldwide problem and its incidence is rising in many regions. In 2022 an estimated 8 million adults aged 18 to 49 years acquired syphilis; in the United States reported cases rose 61% between 2019 and 2023, with congenital syphilis cases rising 106%. ^[10] Syphilis is more common in the developing world, particularly among the poorest populations with the least access to health care. ^[10] Infection is far more prevalent in people with HIV, and anyone who tests positive for one should be tested for the other. ^[10]

Congenital syphilis is rising too: in the United States 1,870 cases were reported in 2019 by the CDC STI Treatment Guidelines (including 94 stillbirths and 34 infant deaths), a 477% increase from 2012; final CDC STI Surveillance lists 1,884 cases for 2019. ^[8] Up to 40% of fetuses exposed to syphilis in utero are stillborn or die of infection during infancy. ^[10]

T. pallidum enters through minute abrasions in skin or mucous membranes during vaginal, anal or oral sex with a person who has an infectious lesion. Primary transmission is sexual; congenital transmission occurs transplacentally during pregnancy. Congenital syphilis is also, rarely, acquired at birth from active genital lesions. ^[1][10]

Risk factors include men who have sex with men, multiple or anonymous partners, coinfection with HIV, condomless sex, sex work or drug use, and residence in areas with high prevalence. Coinfection rates with HIV are high, especially in men who have sex with men. ^[6][10]

T. pallidum is a long, thin spirochete that cannot be seen on standard light microscopy and cannot yet be cultured on routine media. It divides only once every 30 hours. After entry it multiplies locally, then disseminates through blood and lymph to lymph nodes and distant organs. Its outer membrane has few exposed proteins and no lipopolysaccharide, so the early immune response is muted, allowing widespread seeding before symptoms appear. ^[10]

The untreated infection follows its four stages. In primary disease a chancre forms at the inoculation site and heals spontaneously in 3 to 8 weeks. In secondary disease the organism is disseminated, producing rash, mucous lesions and generalised lymphadenopathy. In latent disease the host partly controls the organism but does not clear it. In tertiary disease, years later, chronic inflammation, obliterative endarteritis and granulomatous inflammation (gummas) damage the cardiovascular system, nervous system and other organs. ^[10]

Figure 1Chancres on the penile shaft due to a primary syphilitic infection caused by Treponema pallidum 6803 lores

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A clinical photograph showing chancres on the penile shaft caused by a primary syphilitic infection with Treponema pallidum.

After an incubation of about 3 to 4 weeks (shorter with a larger inoculum), a single, firm, painless, well-demarcated ulcer with a clean base and indurated margin appears at the site of inoculation: the chancre. It may be atypical, multiple or painful, especially in people coinfected with HIV. ^[1][10] Regional lymph nodes are enlarged, firm and non-tender. The lesion heals without scarring even without treatment, in 3 to 8 weeks. ^[10]

Figure 2Tab 67, Combycomata, female patient, Mracek 1898

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A historical colour plate labelled 'Combycomata, female perineum' showing wart-like lesions of the female perineum/vulva.

Figure 3Secondary Syphilis on palms CDC 6809 lores.rsh

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Close-up clinical photograph of keratotic lesions on the palms of a patient's hands due to a secondary syphilitic infection.

Figure 4Secondary syphilitic rash Treponema pallidum 6756 lores

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Clinical photograph of a patient's back covered by a secondary syphilitic rash of rough, red or reddish-brown papulosquamous lesions representing systemic spread of Treponema pallidum (CDC PHIL #6756).

Figure 5Secondary syphilis-palmar rash

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Rash on the palms of both hands due to secondary syphilis.

Two to 4 weeks after the chancre (or 6 to 8 weeks after infection), secondary syphilis reflects haematogenous dissemination. Manifestations include: ^[10]

• a generalised, non-itching, maculopapular rash that specifically involves the palms and soles, a distribution that is unusual for other rashes;
• mucous patches: painless, greyish, slightly eroded lesions on oral, genital or anal mucosa;
• condylomata lata: broad, flat, moist, wart-like papules at mucocutaneous junctions and in skin folds;
• generalised, non-tender lymphadenopathy;
• constitutional symptoms: fever, malaise, sore throat, weight loss;
• less often, alopecia in patches, anterior uveitis, periostitis, hepatitis, nephrotic syndrome or glomerulonephritis.

Condylomata lata and mucous patches are highly infectious. ^[10]

Latent syphilis is serological evidence of infection without clinical signs or symptoms of active disease. ^[1] It is classified by duration.

• Early latent syphilis: acquired within the preceding year. It is often diagnosed because of documented seroconversion, a fourfold rise in nontreponemal titre, symptoms of primary or secondary syphilis in the last year, a partner with early syphilis, or the only possible exposure within 12 months. ^[3]
• Late latent syphilis: longer than 1 year.
• Latent syphilis of unknown duration: used when neither early nor late can be established.

Latent infection is not sexually transmissible, but vertical transmission to a fetus can occur. ^[3]

Figure 6Bone and soft tissue erosion, tertiary syphilis

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A composite medical photograph plate showing the faces of female and male patients with bone and soft-tissue erosion and facial lesions characteristic of tertiary syphilis, plus the inside of a male patient's mouth and tonsils with lesions.

Tertiary syphilis appears months to decades after infection and occurs in untreated disease. It includes:

• gummas: granulomatous, destructive lesions of skin, bone, liver or other organs;
• cardiovascular syphilis: aortitis (classically the ascending aorta), aortic regurgitation, aortic aneurysm and coronary ostial stenosis;
• late neurosyphilis: tabes dorsalis and general paresis, described below.

About one third of untreated patients show tertiary manifestations. ^[10]

Neurosyphilis is invasion of the central nervous system by T. pallidum. Early manifestations (within months to a few years) include syphilitic meningitis, cranial nerve palsies, meningovascular syphilis and stroke. Late manifestations, 10 to 30 years or more after infection, include tabes dorsalis and general paresis (dementia, personality change, psychiatric states). General paresis is a chronic meningoencephalitis that usually appears many years (commonly 10 to 30 or more) after the original infection. Tabes dorsalis results from degeneration of the dorsal columns and roots: a wide-based, stamping or ataxic gait, lancinating or stabbing pains, loss of proprioception and vibration sense, Argyll Robertson pupils, a positive Romberg test, Charcot joints and visceral crises (episodic severe abdominal pain with nausea). Argyll Robertson pupils are small, irregular pupils that do not constrict to light but constrict on accommodation. Ocular syphilis (uveitis, interstitial keratitis, optic neuritis) and otosyphilis (tinnitus, vertigo, sensorineural deafness) can occur at any stage and are managed as neurosyphilis. ^{[5] [1]}

T. pallidum can also produce cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, and loss of vibration sense at any stage. ^[1]

Figure 7Hutchinson teeth congenital syphilis PHIL 2385.rsh

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Clinical photograph of Hutchinson's teeth from congenital syphilis, with narrow, notched ('screwdriver') upper central incisors.

Figure 8PHIL 2389 lores

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Clinical photograph of an infant with congenital syphilis showing rhagades, or cracks/fissures in the skin around the mouth, which the CDC caption states result from persistent infantile syphilitic rhinitis (snuffles).

Congenital syphilis results from transplacental transmission. Many affected infants are asymptomatic at birth. Early findings include non-immune hydrops, prematurity, hepatosplenomegaly (in 50 to 90% of those with clinical disease), jaundice, rhinitis ("snuffles") with a thick or bloody nasal discharge, a copper-coloured maculopapular rash with desquamation that is prominent on the palms and soles, condylomata lata, pseudoparalysis of an extremity, anaemia and thrombocytopenia. Later stigmata (after 2 years) include Hutchinson teeth (small, peg-shaped, notched upper central incisors), mulberry molars, saddle nose from destruction of cartilage, frontal bossing, saber shins, Clutton joints, interstitial keratitis, and sensorineural deafness (Hutchinson's triad is Hutchinson teeth, interstitial keratitis and eighth-nerve deafness). ^[9]

The differential depends on the presentation, but syphilis is commonly mistaken for other conditions. Primary chancre may be confused with herpes simplex, chancroid, lymphogranuloma venereum or traumatic ulcers; secondary rash with psoriasis, pityriasis rosea, drug eruptions or viral exanthems; mucous patches with leucoplakia. Tertiary gummas mimic malignancy or tuberculosis, and cardiovascular or neurosyphilis may masquerade as aortic stenosis or regurgitation, dementia, psychiatric illness or spinal cord disease. Because findings are protean, a low threshold for testing is essential in sexually active adults with unexplained mucocutaneous, cardiovascular, neurological or psychiatric disease. ^[10]

Figure 9Treponema pallidum cropped

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Dark field photomicrograph of Treponema pallidum bacteria from a control slide of Nichol's strain of T. pallidum obtained from a rabbit testicle, stained by fluorescent antibody technique at 54X magnification.

Dark field examination and molecular tests for detecting T. pallidum directly from lesion exudate or tissue are the definitive methods for diagnosing early and congenital syphilis. ^[1] Dark field requires fresh exudate and a trained microscopist. No T. pallidum direct-detection nucleic acid amplification tests are commercially cleared for routine use in many countries, although some laboratories offer validated polymerase chain reaction.

A presumptive diagnosis requires both a nontreponemal test (VDRL or RPR) and a treponemal test (TPPA, EIA, chemiluminescence assay or similar). ^[1] Using only one type of test is insufficient: it can produce false negatives in primary syphilis and false positives in people without syphilis or with previously treated disease. ^[1]

Nontreponemal tests (VDRL, RPR) are screening tests that may become reactive within the first weeks after infection. They are quantitative: the titre roughly reflects disease activity and is used to monitor treatment response. False positive nontreponemal results occur in HIV infection, autoimmune disease, recent vaccination, injecting drug use, pregnancy and older age. ^[1] VDRL and RPR are both valid, but their quantitative results are not interchangeable and RPR titres are usually slightly higher than VDRL titres. ^[1]

Treponemal tests are specific confirmatory tests that remain reactive for life in most treated infections; 15 to 25% of patients treated in the primary stage revert to nonreactivity after 2 to 3 years. ^[1] Treponemal antibody titres do not indicate disease activity or response to treatment and must not be used for follow-up. ^[1]

When serology and clinical findings do not match (for example, primary syphilis with a nonreactive test), presumptive treatment is recommended when risk factors exist, and further tests such as lesion biopsy with immunostaining or PCR may help. ^[1]

A reactive nontreponemal test is confirmed by a treponemal test. This is suitable for most settings.

Many laboratories now screen first with an automated treponemal EIA or chemiluminescence assay. If the treponemal screen is positive, a standard quantitative nontreponemal test is done reflexively. If the nontreponemal test is negative, a second treponemal test (preferably TPPA or one based on different antigens) is used to adjudicate. If the second treponemal test is positive, persons with previous treatment need no further management unless there is re-exposure; those without previous treatment should be treated. If it is negative and epidemiological risk is low, no further evaluation is needed. ^[1]

A fourfold change in nontreponemal titre (two dilutions, for example 1:16 to 1:4 or 1:8 to 1:32) is the minimum change regarded as clinically significant; tests should be performed with the same assay, preferably by the same laboratory. ^[1] After treatment titres usually decline and may become nonreactive over time, but some patients (serofast) retain low positive titres despite adequate treatment. Atypical results, unusually high, low or fluctuating, can occur regardless of HIV status. ^[1]

CSF examination is warranted for persons with clinical signs of neurosyphilis: cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, or loss of vibration sense. ^[1] All patients with ocular symptoms and reactive serology need a full ocular examination; CSF examination is needed only if cranial nerve dysfunction is present. Isolated auditory symptoms make a CSF examination likely unnecessary before treatment. ^[1]

Diagnosis of neurosyphilis depends on a combination of CSF cell count, protein, and reactive CSF-VDRL in a person with reactive serology and neurological signs or symptoms. CSF-VDRL is highly specific but insensitive; a reactive CSF-VDRL in the absence of blood contamination is diagnostic. If it is negative despite clinical signs, lymphocytic pleocytosis or raised protein, neurosyphilis should still be considered and CSF fluorescent treponemal antibody absorption (FTA-ABS) or TPPA may help. Neurosyphilis is highly unlikely with a negative CSF FTA-ABS, especially when neurological signs are nonspecific. ^[1] In HIV coinfection a CSF white cell count over 20 per cubic millimetre may be a more specific threshold. ^[1]

Syphilis is staged clinically and serologically. Active disease states are:

1. Primary syphilis: chancre with reactive or changing serology.
2. Secondary syphilis: characteristic rash, mucous patches or condylomata lata.
3. Early latent syphilis: asymptomatic, acquired within 12 months.
4. Late latent syphilis or latent of unknown duration: asymptomatic, older than 12 months.
5. Tertiary syphilis: gummas, cardiovascular or late neurosyphilis.

There is no single numeric score. Severity is judged by stage and organ involvement: the presence of neurosyphilis, ocular or otic disease, cardiovascular disease, pregnancy or HIV coinfection changes management, duration and urgency.

Penicillin G administered parenterally is the preferred drug for treating patients in all stages of syphilis. The preparation, dose and duration depend on stage and clinical manifestations. Combinations of benzathine penicillin, procaine penicillin and oral penicillins are not appropriate. Reports of practitioners prescribing combination benzathine-procaine penicillin (Bicillin C-R) instead of the recommended benzathine penicillin (Bicillin L-A) have led to treatment errors; the product name should be checked. ^[1]

Additional doses of benzathine penicillin in early syphilis do not improve efficacy, whether or not the patient has HIV infection. ^[2][6]

For non-pregnant adults with primary or secondary syphilis and penicillin allergy, doxycycline (100 mg orally twice daily for 14 days) or tetracycline (500 mg orally four times daily for 14 days) can be used. If follow-up is uncertain, desensitise and give penicillin. Ceftriaxone (1 g daily intramuscularly or intravenously for 10 days) can be considered but optimal dose and duration are not established. CDC no longer recommends azithromycin because of T. pallidum resistance and documented treatment failures; WHO permits a single 2 g oral dose of azithromycin only in special circumstances where local susceptibility is likely. ^[2]

Late latent syphilis or syphilis of unknown duration in a non-pregnant person with penicillin allergy should be treated with doxycycline (100 mg orally twice daily) or tetracycline (500 mg orally four times daily) for 28 days (CDC); WHO recommends the same doxycycline dose for 30 days. For neurosyphilis with penicillin allergy, ceftriaxone (1-2 g daily intramuscularly or intravenously for 10-14 days) may be used; where there is concern about cross-sensitivity, skin testing or desensitisation with specialist input is recommended. ^[3][5]

Parenteral penicillin G is the only therapy with documented efficacy for syphilis during pregnancy. Benzathine penicillin G is given according to the woman's syphilis stage; for early syphilis a second dose of 2.4 million units intramuscularly 1 week after the first may provide additional protection for the fetus. Pregnant women who are allergic to penicillin must be desensitised and treated with penicillin G. Tetracyclines are avoided, and erythromycin and azithromycin should not be used because they do not reliably cure fetal infection. Every pregnant woman with syphilis needs coordinated follow-up; a fourfold increase in titre after treatment for over 2 weeks suggests reinfection or treatment failure. In pregnancy CDC does not accept an interval of more than 9 days between benzathine doses and repeats the full course if that occurs; WHO advises that the interval between benzathine doses should not exceed 14 days. ^[7]

All women should be screened at the first prenatal visit, again at 28 weeks' gestation and at delivery if they live in communities with high syphilis rates or have risk of acquisition; newer ACOG guidance recommends 28-week and delivery screening for all pregnant women. No mother or newborn should leave hospital without maternal serologic status being documented at least once during pregnancy. ^[7]

Persons with HIV and syphilis should be treated the same as persons without HIV: single dose benzathine penicillin G 2.4 million units intramuscularly for early syphilis, and 7.2 million units in 3 weekly doses for late latent disease. ^[6] People with HIV and early syphilis may have a higher risk of neurologic complications and inadequate serologic response, and careful follow-up is essential. A thorough neurological, ocular and otic examination should be done; CSF examination is reserved for those with an abnormal neurological examination. Serologic follow-up for primary or secondary syphilis occurs at 3, 6, 9, 12 and 24 months; titres that do not fall fourfold within 24 months may prompt CSF examination and retreatment. HIV treatment (antiretroviral therapy) may improve outcomes in coinfected patients. Neurosyphilis in a person with HIV is treated as in a person without HIV, using parenteral aqueous penicillin G. ^{[6] [2]}

Treatment depends on the neonate's scenario. Confirmed or highly probable congenital syphilis is treated with aqueous crystalline penicillin G 100,000-150,000 units/kg/day intravenously (50,000 units/kg per dose every 12 hours for the first 7 days, then every 8 hours to complete 10 days), or procaine penicillin G 50,000 units/kg intramuscularly once daily for 10 days (CDC; WHO allows 10 to 15 days). Possible congenital syphilis allows a third option of a single dose of benzathine penicillin G (50,000 units/kg) after a normal evaluation and certain follow-up. Infected infants and children aged 1 month or older are treated with aqueous crystalline penicillin G 200,000-300,000 units/kg/day intravenously for 10 days. ^[8] All neonates with reactive nontreponemal tests need clinical and serological follow-up every 2 to 3 months until the test becomes nonreactive. ^[8]

The Jarisch-Herxheimer reaction is an acute febrile response with headache, myalgia and fever that can occur within the first 24 hours of any syphilis therapy. It is a reaction to treatment, not an allergy to penicillin, and occurs most often in early syphilis, presumably because bacterial loads are higher. Antipyretics may be used for symptoms but have not been proven to prevent the reaction. It can induce early labour or fetal distress in pregnant women and so must not delay therapy. ^[1]

Sexual transmission occurs only when mucocutaneous syphilitic lesions are present, which is uncommon after the first year. Sex partners of people diagnosed with primary, secondary or early latent syphilis within 90 days before diagnosis should be treated presumptively for early syphilis even with negative serology. Beyond 90 days, treat presumptively only if serology is not available and follow-up is uncertain; treat by stage if serology is positive, and no treatment is needed if serology is negative. ^[1]

Partners at risk who should be notified are those with sexual contact within 3 months plus duration of symptoms for primary syphilis, 6 months plus duration of symptoms for secondary syphilis, and 1 year for early latent syphilis. Longer-term partners of patients with late latent syphilis should be evaluated and treated according to the evaluation. In populations or areas with high syphilis rates, partners of patients with syphilis of unknown duration and high nontreponemal titres (over 1:32) are sometimes managed as if the index patient had early syphilis. ^[1]

For primary or secondary syphilis, clinical and serological evaluation occurs at 6 and 12 months; HIV testing at diagnosis and treatment, and HIV pre-exposure prophylaxis offered if HIV-negative. Serological follow-up after latent syphilis is at 6, 12 and 24 months. Titres should be compared with the pretreatment titre using the same test. Reinfection or treatment failure is suspected with a sustained fourfold increase in nontreponemal titre for more than 2 weeks, or new symptoms of primary or secondary syphilis. Failure of titres to fall fourfold within 12 months (primary/secondary) or 24 months (latent) may indicate treatment failure; 10 to 20% of patients with primary or secondary syphilis will not achieve a fourfold fall within 12 months. Management includes HIV re-evaluation, careful neurological examination and, when appropriate, CSF examination or retreatment with weekly benzathine penicillin 2.4 million units intramuscularly for 3 weeks. Serofast low titres often persist and do not require additional treatment in an asymptomatic person with a negative neurological examination. ^[2][3]

• Gummas with destruction of skin, mucosa and bone.
• Cardiovascular syphilis: aortitis, aortic regurgitation, aortic aneurysm, coronary ostial stenosis.
• Neurosyphilis: meningitis, cranial nerve palsies, stroke, tabes dorsalis, general paresis, optic and otic disease.
• Congenital syphilis: stillbirth, prematurity, neonatal death, multisystem disease and late stigmata.
• Reinfection and repeated episodes in high-risk populations.

Syphilis is curable at every stage with appropriate penicillin. Early treatment prevents tertiary and congenital complications. Untreated, about one third of patients develop tertiary manifestations many years later, and late cardiovascular and neurological damage may be irreversible. Serologic cure is monitored by nontreponemal titres; slow decline or serofast titres are common and do not equal failure. ^[10]

• Safer sex, consistent condom use (noting that lesions may be in uncovered areas), mutual monogamy and regular testing.
• Screening of sexually active people for syphilis varies by jurisdiction: California screens sexually active people aged 15 to 44 years at least once (and annually thereafter if at increased risk), while federal CDC and USPSTF guidance screen at increased risk. Where a risk-based screen is used, all sexually active people with risk factors should be tested, and all pregnant people at the first visit. ^[10]
• In pregnancy, screening at first visit, at 28 weeks and at delivery in high-prevalence settings or when risk persists. ^[7]
• Doxycycline post-exposure prophylaxis (200 mg doxycycline within 72 hours after sex) is recommended for some groups at high risk, such as men who have sex with men and transgender women with a prior sexually transmitted infection. ^[10]
• Contact tracing, reporting and community education reduce transmission.

Pregnancy: penicillin only, desensitise if allergic; treat according to stage; screen at 28 weeks and delivery when risk exists. Children: treat congenital infection as above and evaluate for acquired (sexual abuse) syphilis in older children. HIV: same regimens, closer serological follow-up, CSF reserved for abnormal neurology. Immunocompromised patients and those with advanced HIV need careful neurological evaluation and specialist input.

Syphilis and its consequences are concentrated where access to care is weakest. In such settings:

• Nontreponemal tests such as RPR are inexpensive, rapid and do not need complex equipment; where possible use treponemal tests to confirm, but do not let confirmation delay treatment in high-probability disease.
• Dark field microscopy is cheap but needs a trained microscopist and fresh exudate; if unavailable, rely on clinical assessment and serology.
• Benzathine penicillin G is inexpensive and the regimens above use it for almost all non-neurological stages; aqueous crystalline penicillin and procaine plus probenecid may be harder to obtain, so neurosyphilis should be referred where possible.
• Doxycycline and tetracycline are the alternative drugs for penicillin-allergic non-pregnant patients but are less well studied, so clinical monitoring is important.
• Pregnancy and congenital syphilis prevention depend on screening at the first visit, at 28 weeks and at delivery when possible, and on treating partners.
• Congenital syphilis interventions (aqueous penicillin G) may be compromised by shortages; public health stock alerts and consultation with paediatric specialists are required. Single-dose benzathine penicillin G may be used in selected neonatal scenarios.
• Basic infection control, partner notification and health education matter most where rooms are crowded and follow-up is difficult.

• Syphilis is a systemic infection with Treponema pallidum; early disease is painless (chancre) or produces a generalised rash including palms and soles plus mucous patches and condylomata lata.
• Latent syphilis is seropositive but asymptomatic and is split into early (under 1 year) and late or unknown duration.
• Tertiary syphilis includes gummas, cardiovascular aortitis and regurgitation, and late neurosyphilis (tabes dorsalis, general paresis); neurosyphilis can occur at any stage.
• Diagnosis requires a nontreponemal test (VDRL/RPR) and a treponemal test (TPPA/EIA), plus dark field microscopy when a lesion allows; CSF examination is reserved for neurological, ocular cranial nerve or typical disease.
• A fourfold change in nontreponemal titre is the smallest change that is clinically significant; treponemal titres do not monitor treatment.
• Penicillin G parenterally is the drug of choice; benzathine penicillin G 2.4 million units intramuscularly once for primary, secondary and early latent disease; 7.2 million units in 3 weekly doses for late latent and tertiary non-neurological disease; aqueous crystalline penicillin G intravenously for 10-14 days for neurosyphilis. ^[3]
• Penicillin is the only effective agent during pregnancy; desensitise if allergic.
• Doxycycline or tetracycline are alternatives for non-pregnant penicillin-allergic patients; azithromycin is not recommended.
• The Jarisch-Herxheimer reaction is an expected febrile post-treatment reaction, not penicillin allergy, and most often occurs in early disease.
• Manage sex partners by stage and timing of exposure, and notify and test according to exposure windows.
• HIV coinfection uses the same regimens with closer serological follow-up and reserved CSF testing.
• Congenital syphilis produces early multisystem disease and late stigmata such as Hutchinson teeth, saddle nose, snuffles and hepatosplenomegaly.
• Screening in pregnancy at first visit, at 28 weeks and at delivery in high-risk situations prevents congenital syphilis.

Syphilis sits alongside the other sexually transmitted infections and the other major infections covered on MedGrasp, including gonorrhoea and chlamydia, HIV infection, hepatitis, tuberculosis, meningitis, immunodeficiency, and pregnancy care. All of these topics are cross-referenced through the site's topic list; links are added as those pages are verified.