- •
Syphilis is common among men who have sex with men and is associated with HIV acquisition.
- •
Syphilis can cause a wide range of systemic manifestations.
- •
Penicillin G remains the treatment of choice for all stages of syphilis.
- •
Syphilis partner services and presumptive treatment of contacts based on exposure history is essential to prevent syphilis reinfection and control the spread of disease.
Syphilis in the Modern Era: An Update for Physicians
Section snippets
Key points
Etiology and pathogenesis
Syphilis is caused by infection with the spirochetal bacterium Treponema subspecies pallidum. T pallidum is a highly motile coiled organism with tapering ends and 6 to 14 spirals. Of uniform cylindrical shape, the bacteria measure approximately 6 to 15 μm in length and 0.25 μm in width. T pallidum is a slowly metabolizing organism with an average multiplication time of approximately 30 hours. Humans are the only host for the organism.1 Most cases of syphilis are transmitted by sexual contact
Epidemiology
Infectious syphilis reached a historic low in the United States in 2000, with only 9756 primary and secondary cases (2.1 per 100,000 persons) compared with approximately 100,000 cases (71 per 100,000 persons) in 1946.9 In response to declining syphilis incidence, the Centers for Disease Control and Prevention released “The National Plan to Eliminate Syphilis from the United States” in 1999.10 However, starting in 2001, rates of primary and secondary syphilis have continued to rise, with an
Historical perspective
Current understanding of the natural course of syphilis infection among untreated individuals is largely based on historical data from the preantibiotic era. The Oslo Study was a large prospective natural history study in which Boeck observed approximately 2000 patients with primary and secondary syphilis admitted to the Oslo Clinic from 1891 to 1910.32 From 1932 to 1972 in Macon County, Alabama, the US Public Health Service conducted the infamous Tuskegee Syphilis Study to observe untreated
Early Syphilis
Early syphilis, which includes the primary, secondary, and early latent stages of infection, is defined as syphilis of less than 1 year’s duration. That designation is based on the observation that infectivity declines after the first year.
Diagnosis
Treponema pallidum cannot be cultivated in artificial media, is too slender to be observed by light microscopy, and fails to take up traditional Gram stains. It can be visualized using darkfield microscopy, which uses refracted light on a darkened background to identify the spirochete in clinical specimens; however, this technique is not widely available in clinical practice. Although polymerase chain reaction has been used to amplify genetic elements of T pallidum in clinical specimens, there
Treatment
Penicillin G remains the treatment of choice for all stages of syphilis. The treatment regimen (route of administration and duration) depends on the stage of disease (Table 1). Early syphilis (ie, primary, secondary, or early latent) can be treated with a single injection of 2.4 million units of intramuscular penicillin G benzathine; patients coinfected with HIV do not require additional doses of penicillin.37, 45, 46, 47 A nontreponemal antibody test should be obtained on the day of treatment
Follow-up
Patients with early stage syphilis, particularly those with high titer secondary syphilis, should be counseled about the possibility that they may experience a Jarisch-Herxheimer reaction after treatment. This immune-mediated process occurs within 2 to 24 hours of receiving penicillin G and is characterized by the acute onset of fever, headache, and myalgias. Peripheral leukocytosis and transaminitis can also occur. It occurs in 50% to 75% of patients with primary and secondary syphilis, is
Pregnancy and congenital syphilis
Pregnant women with syphilis who are allergic to penicillin should be desensitized and treated with penicillin according to the guidelines listed previously.37 In pregnant women the Jarisch-Herxheimer reaction can precipitate uterine contractions, fetal distress, or premature labor; thus, pregnant women should be treated in a monitored setting.2, 64 Treatment of neonates with proved or probable congenital syphilis should be done in consultation with a pediatric infectious diseases specialist.
Public health response: management of sex partners
Providers can work together with local health departments to prevent the spread of syphilis. Presumptive and confirmed cases of syphilis should be reported within 1 working day of diagnosis. Staff in public health departments are then able to contact and notify sex partners, and provide testing and treatment as appropriate. Internet partner notification (ie, using email and chat room “handles” to notify partners) can augment syphilis case management and is an important tool in the modern
References (65)
- et al.
Infectious syphilis in high-income settings in the 21st century
Lancet Infect Dis
(2008) - et al.
Syphilis in China: results of a national surveillance programme
Lancet
(2007) - et al.
Congenital syphilis: a continuing but neglected problem
Semin Fetal Neonatal Med
(2007) - et al.
Primary syphilis: serological treatment response to doxycycline/tetracycline versus benzathine penicillin
Am J Med
(2008) - et al.
Safety and effectiveness of a preoperative allergy clinic in decreasing vancomycin use in patients with a history of penicillin allergy
Ann Allergy Asthma Immunol
(2006) - et al.
Efficacy of ceftriaxone and doxycycline in the treatment of early syphilis
Med Mal Infect
(2012) - et al.
Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis
Otolaryngol Head Neck Surg
(2007) - et al.
The Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis
Obstet Gynecol
(1998) - et al.
Pathogenic treponema: molecular and cellular biology
(2006) - et al.
Syphilis infection during pregnancy: fetal risks and clinical management
Infect Dis Obstet Gynecol
(2012)
Syphilis in pregnancy
Sex Transm Infect
Congenital syphilis presenting in infants after the newborn period
N Engl J Med
Transmission of syphilis by fresh blood components
Transfusion
Transfusion-transmitted syphilis in teaching hospital, Ghana
Emerg Infect Dis
Transfusion-associated infections: 50 years of relentless challenges and remarkable progress
Transfusion
Robbins pathologic basis of disease
Sexually transmitted disease surveillance 2011
The National Plan to Eliminate syphilis from the United States
Epidemiologic characteristics of an ongoing syphilis epidemic among men who have sex with men, San Francisco
Sex Transm Dis
Rising rates of syphilis in the era of syphilis elimination
Sex Transm Dis
Syphilis and HIV infection: an update
Clin Infect Dis
Risk factors for repeat syphilis in men who have sex with men, San Francisco
Sex Transm Dis
HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco, and Los Angeles, 2004 to 2005
J Acquir Immune Defic Syndr
A multilevel approach to understanding the resurgence and evolution of infectious syphilis in Western Europe
Euro Surveill
Trends in primary and secondary syphilis among men who have sex with men in the United States
Am J Public Health
Risk factors for early syphilis among gay and bisexual men seen in an STD clinic: San Francisco, 2002-2003
Sex Transm Dis
Epidemic syphilis among homosexually active men in Sydney
Med J Aust
Refocusing health promotion for syphilis prevention: results of a case-control study of men who have sex with men on England's south coast
Sex Transm Infect
Prevalence of treatment optimism-related risk behavior and associated factors among men who have sex with men in 11 states, 2000-2001
AIDS Behav
Homosexual men change to risky sex when perceiving less threat of HIV/AIDS since availability of highly active antiretroviral therapy: a longitudinal study
AIDS
Internet use and early syphilis infection among men who have sex with men—San Francisco, California, 1999-2003
MMWR Morb Mortal Wkly Rep
Decreases in AIDS mortality and increases in primary and secondary syphilis in men who have sex with men in the United States
J Acquir Immune Defic Syndr
Cited by (76)
Asian guidelines for syphilis
2022, Journal of Infection and ChemotherapySecondary syphilis with alopecia and ocular manifestation
2021, Journal of Microbiology, Immunology and InfectionOcular syphilis in an immunocompetent host
2020, IDCasesTrends in prevalence of HIV and syphilis in a central blood bank of Veracruz, Mexico
2019, Transfusion and Apheresis ScienceCitation Excerpt :However, there has been a re-emergence of syphilis in many nations during the last 20 years, especially among men who have sex with men. In particular, there has been an increase in the number of congenital syphilis cases in developing countries [6]. From 2003 to 2013, Mexico had a 1.8-fold increase of acquired syphilis cases (2.13 to 3.25 per 100,000) and an increase in congenital syphilis cases (2.7 to 10.4 new cases for each 100,000 alive-born babies registered in 1990 and 2008, respectively) [7,8].
Diagnosing acquired syphilis through oral lesions: the 12 year experience of an Oral Medicine Center
2020, Brazilian Journal of Otorhinolaryngology
Disclosures: J. Engelman has nothing to disclose. S.E. Cohen has received research support from the US National Institutes of Health. In the past year, S. Philip has received research support from Roche Diagnostics, SeraCare Inc, Abbott Diagnostics, and Cepheid Inc. J.D. Klausner has received educational and research support from Hologic Gen-Probe Inc, Cepheid Inc, Standard Diagnostics, Inc, and the US National Institutes of Health.