Syphilis is a complex infectious disease caused by Treponema pallidum, a spirochete capable of infecting almost any organ or tissue in the body and causing protean clinical manifestations Transmission occurs most frequently during sexual contact (including oral sex), through minor skin or mucosal lesions; sites of inoculation are usually genital but may be extragenital. The risk of developing syphilis after unprotected sex with an individual with early syphilis is approximately 30–50%. The organism is extremely sensitive to heat and drying but can survive for days in fluids; therefore, it can be transmitted in blood from infected persons. Syphilis can be transferred via the placenta from mother to fetus after the tenth week of pregnancy (congenital syphilis).
The immunologic response to infection is complex, but it provides the basis for most clinical diagnoses. The infection induces the synthesis of a number of antibodies, some of which react specifically with pathogenic treponemes and some with components of normal tissues (see below). If the disease is untreated, in most cases these immune reactions fail to eradicate existing infection and may contribute to tissue destruction in the late stages. Patients treated early in the disease are fully susceptible to reinfection.
The natural history of acquired syphilis is generally divided into two major clinical stages: early (infectious) syphilis and late syphilis. The two stages are separated by a symptom-free latent phase during the first part of which (early latency) the infectious stage is liable to recur. Infectious syphilis includes the primary lesions (chancre and regional lymphadenopathy), the secondary lesions (commonly involving skin and mucous membranes, occasionally bone, central nervous system, or liver), relapsing lesions during early latency, and congenital lesions. The hallmark of these lesions is an abundance of spirochetes; tissue reaction is usually minimal. Late syphilis consists of so-called benign (gummatous) lesions involving skin, bones, and viscera; cardiovascular disease (principally aortitis); and a variety of central nervous system and ocular syndromes. These forms of syphilis are not contagious. The lesions contain few demonstrable spirochetes, but tissue reactivity (vasculitis, necrosis) is severe and suggestive of hypersensitivity phenomena.
As a result of intensive public health efforts during and after World War II, there was a reduction in the incidence of infectious syphilis. With the marked increase in all sexually transmitted diseases since the 1970s, there has been a rise in the number of reported cases of syphilis. In the early 1980s, the incidence of infectious syphilis increased, with a particularly high rate among homosexual men. In the mid-1980s, there was a slight decrease, primarily a result of changes in sexual practices in response to the acquired immunodeficiency syndrome (AIDS) epidemic. Between 1985 and 1990, there was again a dramatic increase in infectious syphilis, with 50,223 cases of primary and secondary syphilis reported in 1990. This increase was broad based, affecting both men and women in inner city, urban, and rural areas, particularly in the southern regions of the United States. Although adolescent and young adult blacks were primarily affected, increases were seen in other ethnic groups also, as well as adults over 60 years of age. Limited access to health care, decreases in health department clinical services, increased use of illicit drugs (especially “crack cocaine”), the exchange of sex for drugs or money to buy drugs, and the difficulty of contact tracing when multiple sexual partners are involved all contributed to the dramatic increase. Concomitantly with the increase in acquired syphilis, there has also been an increase in congenital syphilis, particularly in urban areas. In response to this increase in infectious syphilis in 1998, the United States Congress allocated funds for a syphilis elimination program. This included intensive syphilis control programs targeting high-risk populations (women of childbearing age, sexually active teens, drug users, inmates of penal institutions, persons with multiple sexual partners or those who have sex with prostitutes) emphasizing screening, early treatment, contact tracing, and condom use. The effort has been successful, as evidenced by a decrease in the number of primary and secondary cases reported in 2001 (6103 cases) compared with 1998 (7035 cases). However, for the first time since 1990, the number of cases increased between 2000 (5979) and 2001 and increased 

again between 2001 and 2002 (6862 cases). These increases occurred only among men (suggesting that the increase is likely in the group of men having sex with men), whereas the number of cases actually declined among women and non-Hispanic blacks. Most cases are still reported from the South, but urban outbreaks (New York City, San Francisco) are being reported with increasing frequency, primarily among men having sex with men. Despite the increase in primary and secondary syphilis in men who have sex with men, there has not been a concomitant increase in the number of human immunodeficiency virus (HIV) cases.

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