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Basil Donovan

and Phillip Read



Clinical investigation—discussion of the role of PCR in the diagnosis of early syphilitic lesions, and use of rapid Point-of-Care tests.

Updated on 28 Nov 2013. The previous version of this content can be found here.
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date: 29 April 2017

Syphilis results from infection with the spirochaete Treponema pallidum subsp. pallidum, for which humans are the only known natural host. In adults it is transmitted primarily by sexual contact. The organism gains entry into the body through small breaks in the skin or the intact mucosal surfaces of the genitals, mouth, or anus, and is able to invade and survive in a wide variety of tissues.

Since the availability of penicillin, syphilis has become primarily (>90%) a disease of less affluent countries or of minority subpopulations in more affluent countries with poor access to health care. It is also a disease of people with rapid rates of partner change, e.g. men who have sex with men (MSM) and commercial sex workers.

Clinical features

Syphilis can manifest in three stages: (1) primary syphilis, which occurs within a few weeks to months after infection; (2) secondary syphilis, which presents after a few months up to a year; and (3) tertiary syphilis, which presents years to decades after primary infection. These stages can overlap, and they are frequently asymptomatic.

Primary syphilis—this appears 9 to 90 days after the organism gains entry via direct inoculation through the thin skin or mucosa of the anogenital tract or mouth during sexual exposure. The resulting lesion is typically a painless ulcer or ‘chancre’, sometimes indurated, that appears at the site of inoculation and is associated with regional lymphadenopathy; chancres can be multiple and atypical.

Secondary syphilis—occurs 3 to 6 weeks after the appearance of the chancre, with manifestations including fever, malaise, mucocutaneous lesions (rash, condyloma lata, mucous patches), generalized lymphadenopathy, and (uncommonly) visceral disease. Invasion of the central nervous system is common, but usually asymptomatic.

Latent syphilis—the lesions of both primary and secondary syphilis may wax and wane, but they eventually resolve; there are no signs or symptoms of active syphilis, but serological tests are positive for T. pallidum.

Tertiary syphilis—affects around one-third of infected people following a variable period of latent infection, with manifestations including (1) neurosyphilis—can present as (a) aseptic meningitis, with variable features, e.g. focal neurological deficits, cranial nerve palsies, hydrocephalus or psychiatric symptoms; (b) meningovascular disease, with endarteritis leading to cerebral infarction; (c) general paresis, involving changes in the parenchyma of the central nervous system that lead to the gradual onset of cognitive impairment, depression, and personality changes, later progressing to dementia, delirium, seizures, and delusions; (d) tabes dorsalis, with initial symptoms and signs including lightening pains and parasthesias, visceral crises, abnormal deep tendon reflexes, incontinence, ataxia with a wide-based gait, and pupillary abnormalities. (2) Gummatous syphilis—destructive granulomatous lesions most commonly present on skin, mucosal surfaces or in bone. (3) Cardiovascular syphilis—most commonly asymptomatic aortitis, aortic incompetence, aortic aneurysm, and coronary ostial stenosis.

Congenital syphilis—most pregnant women with early syphilis will transmit the condition to the fetus via the placenta, with congenital syphilis often resulting in fetal loss, stillbirth, or neonatal or childhood disease.

Diagnosis and treatment

Diagnosis—the transient nature of the lesions and the spirochetaemia limit the role of direct detection of T. pallidum, hence diagnosis usually relies on serology, with tests being (1) nonspecific (or nontreponemal or reagin)—e.g. rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests; detect phospholipid cardiolipin as an antigen; generally sensitive in early infection but tend to decline over the next several years without treatment; able to quantify disease activity and hence used for follow-up after treatment. (2) specific (or treponemal)—e.g. T. pallidum haemagglutination assay (TPHA); use T. pallidum as the antigen; may become positive shortly before the nonspecific tests; typically remain reactive for life after successful treatment and therefore have no role in assessing stage of infection, ‘cure,’ or reinfection.

Treatment—parenteral penicillin G remains the preferred treatment for syphilis, with doxycycline providing an oral alternative. Successful treatment of early disease relies on demonstrating a fourfold decrease in reagin (RPR or VDRL) titres over the next 6 to 12 months. Sexual contacts of early syphilis should be treated presumptively, regardless of their test results, if the contact was within 90 days, usually with a single dose of benzathine penicillin G.


The chance of acquiring syphilis following one act of intercourse with an infected person is 1 to 2%, which should be reduced by the use of condoms. Early treatment of disease decreases the duration of infectivity and thereby minimizes transmission to others, hence those at high risk of syphilis should be encouraged to undergo regular syphilis screening (as well as testing for HIV and other sexually transmissible infections).

Prevention of congenital infection and serious outcomes such as stillbirth and neonatal death rely on routine antenatal screening early in the pregnancy, with prompt treatment of infected mothers. Women in high-incidence settings should be rescreened later in pregnancy.

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