Principles

Syphilis is caused by the intracellular gram‑negative spirochete bacterium Treponema pallidum (TP) subspecies pallidum. 

Syphilis is mainly transmitted sexually, but also can be transmitted from mother to fetus during pregnancy or birth. The global incidence of syphilis infection was 5.1 cases per 100000 men and 0.9 cases per 100000 women in 2005. In the USA, since 2005, syphilis has increased by 59 %, and some European countries have seen increases and large localized outbreaks. Each year, globally, an estimated 2 million pregnancies are affected. 

Congenital syphilis in the newborn is still common in the developing world, as many women do not receive prenatal care or the care does not include syphilis screening. Up to 80 % of syphilis infected pregnant women show adverse pregnancy outcomes resulting in an overall perinatal mortality rate of 40 %. Septicemia, abortion, or neonatal death can occur, and congenital syphilis is associated with significant morbidity. The World Health Organization recommends all women to be tested at their first prenatal visit and again in the third trimester. If they are positive, they recommend their partners also be tested. Syphilis infection facilitates HIV infection. 

In the early stage of infection, the clinical diagnosis of syphilis can be very difficult. Typically, the symptoms start with a painless ulcer at the site of entry to the body (primary syphilis) followed by a widespread rash as the bacteria disseminate (secondary syphilis). A lengthy latent (asymptomatic) period follows. Eventually, tertiary syphilis ensues, characterized by the development of granulomatous dermal lesions, neurosyphilis, and/or cardiovascular syphilis (which can be fatal). 

The immune response to T. pallidum is the main driver of lesion development. The antibody response is directed not only against antigens specific to T. pallidum (treponemal antibodies) but also against antigens that are not specific to T. pallidum (non‑treponemal antibodies), for example, antigens released during the cellular damage caused by the organism. 

_{Source: Roche cobas Elecsys Syphilis method sheet, V 4.0 2025-09}