Friday, March 9, 2012


Author: Dr H. Hunter Handsfield Clinical Professor of Medicine University of Washington 2008-10-20
Treponema pallidum bacteria. Source CDC

Syphilis is one of the five originally recognized venereal diseases, with gonorrhea and the now rare sexually transmitted diseases (STDs) chancroid, lymphogranuloma venereum, and Donovanosis (granuloma inguinale).  The causative organism, which belongs to a class of bacteria called spirochetes, is Treponema pallidum, one of the few important disease-causing organisms that still has not been successfully grown in the laboratory, significantly affecting diagnosis and impeding research. 

Before the emergence of AIDS, syphilis was far and away the STD with the greatest contribution to death and disability.  Although syphilis continues to have serious health impacts in many areas of the globe, it is now uncommon in the United States, with fewer than 20,000 new infections annually, largely limited to small population segments at particularly high risk.
This article addresses syphilis in the United States.  The information on frequency, risk factors, and populations at risk apply generally to other industrialized countries; the descriptions of symptoms, complications, treatment, and prevention are applicable everywhere. 


It is difficult to overstate the significance of syphilis and its impact on human history and culture.  It was long believed that syphilis was introduced to Europe by crewmembers of Columbus’ expeditions who were infected in the Americas.  However, other syphilis-like infections caused by closely related spirochetes—including the modern diseases called yaws, pinta, “endemic syphilis,” and perhaps other now-extinct variations of the disease—probably evolved in most human populations, and the “Columbian” theory remains uncertain, despite the recent exploitation of modern methods to analyze the genetic relatedness of various strains of T. pallidum and other spirochetes.  Whatever its origins, the European syphilis epidemic of the late 15th and early 16th centuries, spreading northward from what is now Italy, clearly was new.  Controversy exists as to whether morbus gallicus (the French disease), the dominant name at the time, was more severe or death rates higher than experienced in later centuries.  Rapid spread in a previously unexposed population could enhance the frequency of severe outcomes, but it is equally plausible that early writers unwittingly (or perhaps intentionally) exaggerated their descriptions of a new condition attributed both to a foreign invader and divine retribution. 
The social and cultural echoes of syphilis reverberate today.  Syphilis was “the pox,” with innumerable references throughout the works of Shakespeare.  Later it became known as “the great pox” to contrast with “the small pox,” which had its own historical impact.  Many historical personages were infected, apparently including Henry VIII and Beethoven, in whom it is thought by some historians to explain the former’s megalomania and the latter’s deafness.  Nietzsche’s “Man and Superman” probably was influenced by the author’s syphilitic dementia, and that work is said to have influenced Hitler, himself believed to have been infected most of his life.  Ibsen’s play “Ghosts” is a story of syphilis, as is Leroux’s “The Phantom of the Opera,” although that aspect was not explicit in the Andrew Lloyd Webber version.  The Latin word for syphilis, lues, led to unsavory literary characters named Louie by Hemingway and other authors.  Spencer Churchill’s mental illness, abandonment of family, and early death were attributed to syphilis and may have influenced his son Winston’s incomparable drive to excel.  The mid-twentieth century Tuskegee study of untreated syphilis, in which the United States Public Health Service withheld treatment from poor African American men for three decades, even after penicillin became available, stands as a signal event both in modern race relations and international policies on research in human subjects.  


Unlike most STDs, of which many cases go undiagnosed and unreported, almost all diagnosed cases of syphilis are confirmed by laboratory testing, and almost all laboratories routinely report their positive syphilis test results to local or state health departments.  Therefore, the data are more complete than for most reportable conditions, so that official case rates are highly accurate.  Accurate statistics are lacking outside industrialized countries.  
How Trends are Measured.  Syphilis is categorized into stages, described in detail below.  Primary syphilis is usually apparent 2-6 weeks after exposure and the secondary stage usually occurs 2-4 months later.  Following the secondary stage, the infection becomes asymptomatic, or latent, further divided into early latent (under a year in duration) and late latent cases (a year or more since infection).  The true total of new infections each year is close to the sum of primary, secondary, and early latent cases.  For example, in 2006 there were 9,756 reported cases of primary and secondary syphilis and 9,186 cases of early latent infection, for a total of 18,942 cases.  However, it can be difficult to distinguish early latent and late latent syphilis.  Therefore, to maximize transmission, the total of primary plus secondary syphilis cases is generally used for year-to-year comparisons and to track rates over time. 
Rates of Primary and Secondary Syphilis.  This graph shows the reported rates of primary and secondary syphilis per 100,000 population since 1987, with separate lines for trends in men and women.  Two salient observations are apparent.  First, as shown in the solid line, the count rose to a peak of 20.3 cases per 100,000 in 1990, the highest rate since 1949; declined ten-fold to case rates of 2.1 in 2000 and 2001; then began to rise.  Although the slope of the line does not look alarming, the rate of 3.3 cases per 100,000 in 2006 represents a dramatic 57% rise since 2001.   
Second, for many years the rates in males and females converged on one another.  In 1987 the rate in men was double that in women, about 20 and 10 cases per 100,000, respectively.  By 1998, the case rates in men and women were ten-fold lower and nearly equal.  Since then the male and female case rates have diverged once again, so that in 2006 the rate was almost 6 times higher in men than in women.  These observations are explained by opposite trends in syphilis control among heterosexual men and women compared with men who have sex with men (MSM).  As the incidence of syphilis rose in the late 1980s, most cases occurred in heterosexuals, driven by high rates of substance abuse (especially use of crack cocaine) in inner city environments, in concert with drug-related commercial sex.  At the same time, cases in MSM began to decline rapidly because of behavioral changes in response to the emerging AIDS epidemic.  The divergent male and female case rates in the past several years reflects both rising rates in MSM, resulting from a let-down in safe sex practices in response to improved HIV treatment and survival, and continuing improvement in syphilis control in heterosexual men and women. 
Trends in Congenital Syphilis.  Congenital syphilis of newborns results from transmission of infection from mother to fetus, and the rates parallel those in women.  Three hundred forty-nine cases were reported in 2006, a rate of 8.5 per 100,000 live births.  Reported rates somewhat underestimate the actual disease burden, because some congenital infections result in miscarriage or premature stillbirth without diagnosis.  Nonetheless,  the rate declined from 651 per 100,000 births in 1941, a 76-fold difference, one of the great achievements of public health.  Today most cases of congenital syphilis occur in highly disadvantaged populations, in infants born to mothers who do not receive prenatal care, especially in immigrant Hispanic populations.  Many cases are directly attributable to policies that dissuade undocumented immigrants from accessing health care. 
Populations with Syphilis.  In 1999, the US Centers for Disease Control and Prevention (CDC) announced the national plan to eliminate syphilis transmission in the United States.  From the perspective of prevention experts viewing the trends in the 1990s, that goal seemed realistic.  The syphilis elimination plan brought considerable benefit in controlling heterosexually transmitted syphilis, including virtual elimination of the disease from some metropolitan areas.  Nevertheless, for the foreseeable future elimination is a forlorn hope.  Still, syphilis now is a highly focal disease, and relatively few sexually active persons are at significant risk.  About two-thirds of cases occur in MSM, and heterosexually transmitted cases are concentrated in a few particularly disadvantaged populations, such as poor minorities in inner cities and southeastern states, and immigrant populations in the Southwest.   
As for all STDs, race and ethnicity also are associated with syphilis, a reflection of socioeconomic status, access to health care, and differences in sex partner networks (but not to promiscuity, since the average number of sex partners does not vary significantly by race).  Compared with whites, in 2006 the rates of primary and secondary syphilis were six-fold higher in blacks, and twice as high in Native Americans and persons of Hispanic ancestry.  The lowest rate occurs in persons of Asian or Pacific Island ancestry. 
Syphilis is closely linked with human immunodeficiency virus (HIV) infection and AIDS, especially among MSM.  A minority of MSM remain highly sexually active and inconsistently follow safe sex guidelines, comprising the core population for both syphilis and new HIV infections in the United States and most industrialized countries.  For example, about 60% of people with primary or secondary syphilis in King County, Washington are HIV positive.  As shown in this figure, the estimated rate of early syphilis in MSM in King County rose from nil in 1997 to almost 2,000 cases per 100,000 HIV infected MSM in 2005 (i.e., almost 2% of HIV-infected MSM acquire syphilis each year), and to a rate of almost 200 in HIV negative MSM.  These rates are roughly 500-fold and 50-fold higher, respectively, than the overall rate of early syphilis in the United States, and are among the highest rate of syphilis ever documented in any population.  Although such analyses have not been done elsewhere, it is likely that the rates are similar in other cities, and probably one third to half of all new syphilis infections in the United States occur in HIV-infected persons.  (Figure from Kerani et al 2007; see Suggested Reading.)  

Aside from congenital transmission to unborn children, syphilis is transmitted primarily by sexual activity.  However, syphilis carries a greater potential than most STDs for nonsexual transmission.  In the pre-antibiotic era, there were relatively frequent reports of transmission by blood transfusion, wet nurses infected by babies with congenital syphilis, dentists and physicians who sustained infections of the fingers in the course of caring for infected patients, and presumably “innocent” transmission among children in orphanages.  (The last might now be questioned in light of modern knowledge of child sexual abuse).
As for all sexually transmitted organisms, the syphilis spirochete does not survive drying or other environmental stresses, so that transmission requires the direct exchange of infected secretions or apposition of moist, infected surfaces, conditions that in adults are almost entirely limited to sex.  Insertive penile-vaginal and penile-anal intercourse are the dominant practices that transmit syphilis, although oral-genital and oral-anal contact account for a substantial minority of cases.  Transmission by kissing is theoretically possible but rarely if ever documented.  Sexual transmission a year or more after infection is rare, except that congenital transmission can occur during all stages of syphilis. 


The manifestations of syphilis are very broad, with the potential to mimic many other medical conditions.  The disease has been characterized as “the great imitator”, a characteristic also reflected in repeated, oft-quoted statements by Sir William Osler, the father of modern medicine, which approximate “He who knows syphilis, knows medicine.”  The descriptions that follow are common and often classical, but atypical cases abound; comprehensive descriptions literally have filled entire textbooks. 

Primary Syphilis
The hallmark of primary syphilis is the chancre, an open sore at the site where T. pallidum is inoculated.  The chancre usually appears 2 weeks to 6 weeks after exposure, starting as a papule, i.e., a bump on the skin, that soon ulcerates. The most common sites are those most subject to sexual friction, because infection usually occurs where the spirochete is massaged into exposed tissues, perhaps aided by microscopic trauma.  Accordingly, chancres most commonly occur on the penis, especially on the glans (head); the labia or at the vaginal opening; the anus, especially in MSM; and sometimes the lips or tongue.
The typical chancre is a single lesion, painless or with only mild discomfort.  Swelling of the immediately adjacent tissues results in a firm, rubbery consistency that helps distinguish syphilis from herpes and other causes of genital ulcer disease.  The photographs shows two typical examples, except that dual lesions are uncommon.  However, atypical lesions are common and include multiple or painful lesions, occurrence at nongenital sites of exposure, and internal lesions (vagina, cervix, rectum) that the patient may not notice.  Nearby lymph nodes often are enlarged, especially in the groin or, for oral lesions, under the jaw or in the neck.  All these symptoms commonly are absent, because the chancre itself can be small, transient, or internal, and subtle lymph node enlargement may not be noticed.  Therefore, probably about one third of patients with primary syphilis are asymptomatic.  Systemic symptoms, such as fever, are absent.  Without treatment, the chancre heals and enlarged lymph nodes regress, typically over 2-6 weeks.  

Secondary Syphilis
During the primary stage, the spirochete enters the bloodstream and disseminates throughout the body, without symptoms, setting the stage for secondary syphilis.  The most common manifestation of secondary syphilis is a skin rash.  The classical appearance is termed “papulosquamous,” i.e. the dominant features are papules (slightly raised bumps and patches) that often are accompanied by flaking of superficial (squamous) layers of the skin.  Itching usually is absent.  Any part of the body may be affected, but the trunk and limbs are most commonly involved.  A classical feature is involvement of the palms and soles, which is infrequent in most other skin rashes; sometimes the occurrence of a rash on the palms or soles is the clinician’s first clue to secondary syphilis.  Patchy hair loss can occur when the scalp is affected.  In moist areas of the body, such as the genital area, near the anus, and in the mouth, the rash of syphilis can cause flat, painless lesions called mucous patches, ulcerating lesions, or warty lesions called condylomata acuminata.  Such moist lesions of secondary syphilis are teeming with spirochetes, and transmission of syphilis to sex partners probably is most frequent during the secondary stage.

Syphilitic rashes are highly variable and can mimic numerous other common skin conditions, including psoriasis, certain fungal infections such as lichen planus, allergic drug rashes, patchy loss of pigment (vitiligo), and numerous others.  Perhaps the single most frequent error in diagnosing syphilis is the failure of clinicians to request syphilis blood tests in patients with unexplained rash.   
Secondary syphilis is more than a rash, and any organ may be affected.  Lymph nodes may enlarge in several areas of the body.  Fever is common, although often it is mild and may go unnoticed by the patient.  The liver or spleen may enlarge.  The eyes can be affected, with inflammation of the iris, retina, and surrounding structures (uveitis), and kidney disease and arthritis sometimes occur.  Headache, hearing loss, and other manifestations of infection of the central nervous system also are common, as discussed below (Neurosyphilis).   
Like primary syphilis, the secondary stage resolves spontaneously, usually over 1-3 months, as the immune system brings the infection under partial control.  However, spirochetes survive inside the cells of most if not all organs.  Secondary syphilis sometimes recurs up to a year, and rarely up to four years, after the initial infection. 

Latent Syphilis
By definition, syphilis is latent when infection persists in the absence of outward manifestations and can be detected only by laboratory testing.  Early latent syphilis refers to infection up to one year in duration, whereas more prolonged asymptomatic infection is called late latent.  Many persons with early latent syphilis remain infectious through subtle, unrecognized lesions, such as mucous patches in the mouth, vagina, or rectum.  On careful examination, some asymptomatic persons with apparent early latent syphilis in fact have continuing mild manifestations of secondary syphilis.  Late latent syphilis can no longer be transmitted, except to fetus in pregnant women. 

Tertiary Syphilis
The tertiary stage of syphilis can appear any time after a year.  Most cases occur within 30 years, but the potential for reactivation continues for life.  The spirochetes that seed most organs during primary and secondary syphilis typically remain inactive, held in check by the immune system.  However, if immune control fails, latent organisms can reactivate.  Sometimes this occurs when cancer, AIDS, or other disease impairs immunity, but usually no obvious explanation is apparent.  The result is tertiary syphilis, characterized by localized tissue destruction.  
Three types of tertiary syphilis once were common.  Cardiovascular syphilis results from infection of the aorta, causing secondary damage to the heart.  Gummatous syphilis is characterized by the gumma, a tumor-like lesion so named from the Latin for its rubbery consistency.  Gummas usually involve the skin, bones, and joints, but any organ may be affected, with irreversible damage caused by tumor-like growth.  Third, tertiary neurosyphilis causes a number of central nervous system manifestations, including stroke, blindness, deafness, paralysis and, most important from a historical perspective, “general paresis of the insane,” once the dominant cause of dementia worldwide and the explanation for much of the social impact of syphilis for five centuries.  All forms of tertiary syphilis now are rare in industrialized countries, the result of improved diagnosis of latent infection and the development of effective treatment.  In addition, many persons undergo antibiotic therapy for various conditions, unknowingly being treated for undiagnosed latent syphilis.  

Commonly considered a manifestation of tertiary syphilis, neurological involvement actually is most frequent during the early stages, within a year of infection.  Tertiary neurosyphilis now is a medical curiosity in industrialized countries, while awareness of early neurosyphilis is on the rise.  The central nervous system is inoculated when spirochetes circulate in the blood, and T. pallidum often can be found in the cerebrospinal fluid of persons with primary or secondary syphilis but no apparent neurological problem.  In those with symptoms of early neurosyphilis, the main manifestations are headache, hearing loss, blindness, and stroke, potentially devastating complications in otherwise healthy young persons.  All of these appear to be more common in HIV infected persons, who comprise up to half of all persons with early syphilis in the United States.  Fortunately, routine treatment for primary, secondary, or early latent syphilis probably eradicates most infections of the central nervous system.  However, diagnosis of neurosyphilis requires spinal tap in order to test cerebrospinal fluid, engendering controversy about how aggressively asymptomatic neurosyphilis should be sought and whether more aggressive treatment lowers the risk of serious outcomes. 

Congenital Syphilis
Once common worldwide and now rare in industrialized countries, congenital syphilis continues to be a major cause of stillbirth and lifelong disability in developing countries.  In infected babies who survive to birth, the most severe form of congenital syphilis is a devastating systemic infection, in essence an aggressive form of secondary syphilis with multiple organ failure, often resulting in early death or neurological damage in survivors.  Survivors of milder infection suffer such complications as abnormal bone growth leading to facial and other deformities, dental malformation, hearing loss, and psychological disabilities.  Other congenital infections are entirely asymptomatic, detected only by laboratory testing


Syphilis can be suspected by the trained clinician based on symptoms and physical examination and further informed by the epidemiological context, such as the gender of sex partners or other indicators of higher risk.  However, laboratory diagnosis is essential in all cases.  

Identification of Treponema pallidum
Unlike the organisms that cause most STDs, the syphilis spirochete cannot be cultured and DNA detection tests are available only in a few research laboratories.  Even the simple technique of staining specimens to identify the organism microscopically is not practical to identify T. pallidum.  The organism can be visualized by specialized “dark field” microscopy, taking advantage of the characteristic shape and motility of the organism, [Figure] but this cumbersome technique requires immediate examination of scrapings of chancres or skin lesions while still moist, and is rarely available outside health department STD clinics.  These limitations have serious implications for diagnosis . 

Blood Tests
Except for primary and some cases of secondary syphilis, serology—testing of blood to detect antibody, the immune system’s reaction to syphilis—is the mainstay of diagnosis, and the only means of diagnosing latent infection and most cases of neurosyphilis or tertiary disease.   
The Wasserman test, developed near the turn of the twentieth century, was a critical advance in its day.  Essentially the same test persists today in the form of the “nontreponemal” blood tests.  The most common of these are the test developed by the Venereal Disease Research Laboratory, the forerunner of today’s CDC, and therefore known as the VDRL test; and the rapid plasma regain test, or RPR.  Both tests are highly sensitive, missing few if any active cases of syphilis, once enough time has passed (4-6 weeks) for the tests to become positive.  However, both the VDRL and RPR are nonspecific, meaning they are prone to give false positive results in persons without syphilis.   
Therefore, positive VDRL or RPR tests are always confirmed by testing the same blood specimen with a “treponemal” antibody test that measures antibody to T. pallidum itself.  For several decades, the dominant treponemal test was the fluorescent treponemal antibody-absorbed test, or FTA-ABS.  Like the VDRL, The FTA-ABS was developed at CDC and was made available worldwide at no cost.  The FTA-ABS remains in use in special circumstances, but the most widely used treponemal test now is the Treponema pallidum particle agglutination test, or TPPA. 
In the United States, most syphilis testing is initiated with RPR or VDRL, and positive results are confirmed by TPPA.  With rare exceptions, positive results on both tests is definitive evidence of syphilis.  The strength of the VDRL or RPR result is related to the duration and activity of infection, with maximum strength typically during secondary syphilis, the strength of the positive result declines after effective treatment.  Therefore, the RPR or VDRL result gives clues about the likelihood of primary, secondary, or other stages of infection, and the decline after penicillin therapy helps measure the effectiveness of treatment.  Serological tests also are done on cerebrospinal fluid to diagnose neurosyphilis.   
A recent advance in syphilis serology is the development of automated treponemal antibody tests that can be done more rapidly and more cheaply than RPR or VDRL, including fast, simple tests done on a drop of blood obtained by finger prick that can be performed with minimal equipment in resource-poor settings.  Taking advantage of these technologies, initial testing increasingly is done in the opposite sequence than in the past, i.e. a rapid treponemal test followed by RPR or VDRL on positive specimens. 
Although laboratory testing is crucial, accurate diagnosis of syphilis often is highly dependent on the clinical judgment of well trained and experienced clinicians.  With all test methods, it often takes 4-6 weeks after infection the tests to become positive.  Therefore, some recently exposed patients are infected yet have negative results.  In patients with chancres indicating newly acquired primary syphilis, up to 40% have negative blood tests.  Finally, both false negative and false positive test results occur in other clinical settings.  Laboratory confirmation of neurosyphilis frequently is especially difficult.    


Syphilis is nearly unique among human diseases, by virtue of the fact that penicillin remains the drug of choice and is still the most reliable form of treatment more than six decades after the drug came into use.  In addition, T. pallidum is one of a very few pathogenic bacteria that have not developed significant resistance to antibiotics, with the single exception of recent evolution of some strains resistant to the drug class called macrolides (erythromycin, azithromycin, and related drugs).  Penicillin remains the drug of choice for all stages of syphilis, even in patients who previously experienced allergic reactions to the drug.  When strong reasons preclude penicillin therapy, the tetracycline class of drugs, such as doxycycline (Vibramycin® and generic brands) and the cephalosporins, such as ceftriaxone (Rocephin®), can be used.  Many other antibiotic classes are entirely inactive against syphilis and have no role in treatment, including the sulfonamides (“sulfa” drugs), aminoglycosides like streptomycin and related drugs, and the fluoroquinolones, such as ciprofloxacin (Cipro®). 
The table below lists the main treatment regimens recommended by CDC  For early syphilis, a single intramuscular injection of benzathine penicillin, a “repository” version of the drug that is absorbed into the bloodstream from the injection site over 1-2 weeks, immediately aborts infectivity and usually is curative.  Three doses of benzathine penicillin at weekly intervals are recommended for syphilis more than a year in duration.  High dose intravenous penicillin is used for symptomatic neurosyphilis and congenital syphilis.
                                                    Treatment of Syphilis 
                Primary, Secondary, and Early Latent Syphilis
                             Benzathine penicillin G, 2.4 million units by intramuscular injection
                Late Latent Syphilis and Tertiary Syphilis (Except Neurosyphilis)
                             Benzathine penicillin G, 2.4 million units by intramuscular injection, 3 doses at weekly                                      intervals 
                             Aqueous penicillin G, 18-24 million units intravenously per day, in divided doses or by                                      continuous infusion, for 10-14 days 
                             Procaine penicillin G, 2.4 million units by intramuscular injection once daily, PLUS                                          probenecid, 500 milligrams 4 times daily, for 10-14 days
Treatment generally is given before diagnostic confirmation in order to immediately prevent disease progression and complications and to prevent transmission by those who might continue to place their sex partners at risk.  The sex partners of persons with infectious syphilis are treated regardless of whether or not they are found to be infected, in order to abort incubating infection.  Similarly, babies born to infected mothers are treated without waiting for evidence that they actually are infected. 
Documenting that treatment is effective can be a challenge.  In most successfully treated patients, the RPR or VDRL becomes negative, or at least the strength of the positive test result declines dramatically.  But sometimes the test result changes little, leaving the outcome in doubt.  In a few cases, overt treatment failure occurs, especially when drugs other than penicillin are used, and rarely after penicillin treatment itself.  Treatment failure usually is manifested only by return of the blood test to positive, or strengthening of a weakly positive result, so that persons treated for syphilis often require prolonged follow-up, sometimes for several years, for repeat blood tests. 


Prevention and control of STD can be viewed from the perspective of the individual at risk, who prefers to avoid infection or, if already infected, wants to prevent complications; and from the perspective of health care providers and prevention agencies, such as health departments.  These perspectives overlap with one another.  For example, health care providers are advised to routinely test patients at risk for gonorrhea, but sexually active persons can request testing when the provider does not take the initiative.  Similarly, providers should promote condom use, but only persons at risk can choose to use them.  Prevention of all STDs, including HIV, is comprehensively addressed in the Knol on safe sex. [link] 
In the distant past, a common syphilis prevention strategy was quarantine, and often incarceration, of infected persons or those considered to be at risk, such as prostitutes and “loose women.”  (It was almost always women who were subjected to such strategies, or native populations in colonial lands, despite the obvious truth that most syphilis and other STDs were imported by the colonizers.)  If not incarcerated, infected persons were ostracized (“The Phantom of the Opera”).  “Moral prophylaxis” included public shaming of infected persons, laws that attempted to enforce abstinence or sexual fidelity, religious sermonizing, and intermittently draconian approaches to preventing prostitution and, paradoxically, suppression of knowledge about and access to condoms.  Such methods invariably failed and pragmatism eventually reigned; most of these strategies were attempted fitfully, followed by return to the status quo. 
Screening populations with syphilis blood tests has been a mainstay of syphilis prevention for a century.  Because current tests are inexpensive, blood screening often is cost effective even in persons at relatively low risk, and testing to detect asymptomatic infection is routine in persons obtaining care for other STDs, in MSM seeking routine health care, and in other populations at high risk (e.g., jail and prison inmates).  Additionally, routine testing is done in most pregnant women as a strategy to prevent congenital syphilis.   
Other key prevention strategies emphasize populations at particular risk, and include promotion of condom use and other aspects of safe sex, symptom awareness, treatment of infected persons, and notification and treatment of exposed partners.  However, all prevention strategies are challenged by the current epidemiology of the disease.  The syphilis epidemic in the United States and most industrialized countries has “contracted” around particularly high risk populations that typically are socioeconomically disadvantaged, subject to prejudice, or have especially high frequencies of anonymous partnerships, such as some MSM, commercial sex workers and their partners, and undocumented immigrants.  Continued syphilis is largely determined by behavioral patterns that include substance abuse, high rates of psychological morbidity, anonymous partnerships, resistance to condom use, and often reduced access to health care.  Selective mass treatment, i.e., distribution of antibiotics to entire groups of persons at risk, has been tried and found ineffective.  Collectively, these difficulties explain the futile hope, described above, for syphilis elimination.


1.    Sparling PF, et al.  Clinical Manifestations of Syphilis.  Chapter 37 in Holmes KK, et al (ed).  Sexually Transmitted Diseases, 4th edition. New York, McGraw-Hill, 2008:661-84.  The main chapter in the premier STD textbook. 
2.    Handsfield HH. Syphilis. Chapter 4 in Handsfield HH, Color Atlas and Synopsis of Sexually Transmitted Diseases, 2nd edition. New York, McGraw-Hill, 2001:33-54. An extensively illustrated review, intended for health professionals but easily understood by all readers. 
3.    CDC.  Sexually Transmitted Disease Surveillance, 2006.  Atlanta, GA, November 2007.  Annually updated statistics on reported STD in the United States.
4.    CDC.  Sexually Transmitted Diseases Treatment Guidelines, 2006.  Morbidity and Mortality Weekly Report 2006;55:RR-11.  CDC's treatment recommendations, including summaries of key information about all STDs.
5.    Kerani RP, et al. Rising rates of syphilis in the era of syphilis elimination.  Sexually Transmitted Diseases 2007;34:162-5.  Analysis of disease trends, with emphasis on resurgent syphilis and other STDs in men who have sex with men.  
6.    Marra CM.  Déjà vu all over again:  when to perform a lumbar puncture in HIV infected patients with syphilis.  Sexually Transmitted Diseases 2007;34:145-6.  An editorial that reviews current controversies on the importance of early recognition and diagnosis of neurosyphilis in the presence of HIV infection.