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Syphilis is a sexually transmitted bacterial infection caused by the spirochete bacterium Treponema pallidum. It is passed from person to person through direct contact with a syphilis sore and causes a systemic infection with symptoms that vary depending on the stage of the disease.
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About 12 million people worldwide are infected with syphilis and > 90% of cases are in developing countries. Syphilis can spread through sexual contact or in pregnancy (mother to fetus), however, it can be effectively treated with antibiotics. Without treatment, an infection can lead to serious consequences including small tumors (called gummas), neurological problems (stroke, meningitis, deafness, dementia), cardiovascular disease, and an increased risk of HIV infection (2-5x). An infected baby can also develop serious problems such as cataracts, deafness, seizures, or death. It has been reported that untreated early syphilis in pregnant women results in perinatal death in up to 40% of cases. If acquired during the 4 years before pregnancy, it can lead to infection of the fetus in 80% of cases.
The signs and symptoms of syphilis vary depending on which of the four stages it presents (primary, secondary, latent, and tertiary). During the first (primary) stage of syphilis, a sore appears at the point of contact where syphilis was transmitted. The sore is usually painless, lasts 3-6 weeks, and heals without treatment. Secondary syphilis occurs approximately 4-10 weeks after the primary infection and usually starts with a rash on one or more areas of the body (and these rashes harbor bacteria and are infectious). Other symptoms may include fever, sore throat, malaise, weight loss, hair loss, and headache. The latent stage of syphilis begins when all of the symptoms disappear and a latent infected person can continue to have syphilis for years without any symptoms. Without treatment, a third of infected people develop tertiary syphilis, which usually occurs 3-30 years after the initial infection.
Diagnosis
Syphilis has several clinical manifestations, making it difficult to diagnose based on clinical symptoms alone. Also, T. pallidum cannot be isolated in culture so confirmation must be performed either by ELISA-based serological assays or by direct visual inspection using microscopy. Serological tests are more commonly used however all syphilis diagnostic assays are unable to distinguish between the stages of the disease.
Categories of Serological Testing for Syphilis
Treponemal tests which are aimed at detecting an antigen or an antibody to T. pallidum. Examples include EIA assays that detect IgG and/or IgM and IgA antibodies to T. pallidum.
Non-treponemal tests which look for indirect indications of the infection such as the presence of cardiolipins (a mitochondrial membrane lipid), which are released when a treponeme bacteria damages cells. Since these tests do not detect the bacteria directly, they usually require confirmation testing. The T. pallidum genome is 1.14 Mb and encodes a putative 1,041 proteins (Genome Sequencing Project). Different strains of T. pallidum (Tp) may express different repertoires of Tp proteins as demonstrated by various immunologic studies (Leader, B. et al. (2003) Infect. Immun. 71:6054-6057). In the past few years, several highly immunogenic lipoproteins have been identified as diagnostic targets for the various stages of a syphilis infection, including Tp17, Tp15, Tp44.5 (TmpA), Tp47, Tp41, Tp35 (TmpC) and Tp0453. Several commercial tests have been developed using a combination of recombinant syphilis antigens and have proven to be highly sensitive and specific for the diagnosis of an active or latent syphilis infection. Other recent developments include rapid formats that can be performed at the point of care, such as lateral flow assays and agglutination tests using latex particles.
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