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PubMed2005

History of syphilis.

Evidence-based research now allows clear separation of syphilis from other diseases in its class of treponematoses. Examination of skeletons from populations with clinically diagnosed bejel and yaws revealed bone alterations distinctive to those diseases, clearly separating them from alterations due to syphilis, transcending the limitations of current DNA and immunologic technologies. These insights allowed confident identification of the New World origin of syphilis. Absence of skeletal evidence of any treponemal disease in continental Europe before the time of Columbus excludes it as site of origin of syphilis. Treponemal disease appears to have originated in East Africa with late transmission to England, perhaps as a complication of the slave trade. The original treponemal disease apparently spread from Africa through Asia, entering North America. Approximately 8 millennia later, it mutated to syphilis. Presence of skeletal evidence of syphilis at the site in the Dominican Republic where Columbus landed suggests the route by which it was transmitted to the Old World.

Bone Diseases↗

PubMed2006

Doxycycline compared with benzathine penicillin for the treatment of early syphilis.

BACKGROUND: Doxycycline is the preferred recommended second-line agent for the treatment of syphilis, although efficacy data from controlled trials are lacking. We compared the serological responses of patients with early syphilis treated with doxycycline with the responses of patients treated with benzathine penicillin G (BPG). METHODS: All patients who received a diagnosis of early syphilis attending 2 public sexually transmitted disease clinics in Baltimore, Maryland, who were treated with doxycycline (100 mg orally, twice daily for 14 days) between October 1993 and June 2000 were eligible. Patients treated with BPG (a single dose of 2.4 million units intramuscularly) were selected as the control group. Inclusion criteria included a clinician-recorded diagnosis of primary, secondary, or early latent syphilis with reactive serological test results at the time of diagnosis and at least 1 follow-up serological test titer. Serological failure was defined as lack of a 4-fold drop in rapid plasma reagin titer 270-400 days after treatment, or a 4-fold increase in titer 30-400 days after therapy. RESULTS: During the study period, 1558 patients were treated for early syphilis, and 87 received doxycycline. Of those treated with doxycycline, 34 met the inclusion criteria. Seventy-three patients from a randomly selected group of 200 age-matched individuals treated with BPG met the inclusion criteria. There were 4 patients with serological failure in the BPG group (5.5%; 95% confidence interval [CI], 1.6%-13.8%) and 0 patients with serological failure in the doxycycline group (0%; 95% CI, 0%-10.3%; P=.2). The median times to successful serological responses for patients in the doxycycline and BPG groups were 106 days (95% CI, 75-149 days) and 137 days (95% CI, 111-172 days), respectively (P=.6). CONCLUSION: Doxycycline appears to be an effective agent for the treatment of early syphilis.

Adolescent↗

PubMedDate not supplied

Treatment of syphilis: current recommendations, alternatives, and continuing problems.

Benzathine penicillin continues to be the cornerstone of recommended therapy for syphilis. Recent increases in the syphilis rates in the United States and concerns about the adequacy of currently recommended therapy for syphilis in patients with concomitant human immunodeficiency virus infection have stimulated reappraisal of alternatives to currently recommended therapy. Desirable features of antimicrobial agents for syphilotherapy include long serum half-life, good penetration into the central nervous system, and ease of administration. Benzathine penicillin provides prolonged treponemicidal levels of penicillin G in serum but does not reliably produce adequate levels of penicillin in the central nervous system. Tetracycline requires multiple daily dosing, has relatively frequent adverse effects, and has unproven efficacy for central nervous system involvement. Erythromycin, which may be less active than tetracycline for syphilis therapy, has similar shortcomings. Recent evaluations of ceftriaxone for early syphilis therapy are promising; however, the optimal dose and duration of therapy are unknown. No currently recommended therapy for syphilis is clearly optimal for reliable, cost-effective therapy. Careful reappraisal of currently available syphilotherapy and alternatives is needed.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Doppler systolic-diastolic ratios in pregnancies complicated by syphilis.

Maternal infection with syphilis can result in focal areas of vasculitis and, similarly, placental villitis and obliterative arteritis. We hypothesized that Doppler systolic-diastolic ratios (S/Ds) in pregnancies complicated by maternal syphilis infection might reflect an increased resistance to placental perfusion. Doppler velocity waveform analysis was used to study the uterine and umbilical arteries in third-trimester pregnancies complicated by maternal syphilis infection. A control group of similarly studied normal pregnancies was used for comparison. Statistically significant increases were found in the mean S/Ds of both the uterine and umbilical arteries in the syphilis group compared with the normal group, indicating an increased resistance to perfusion of the placenta in pregnancies complicated by syphilis. This difference was even greater in association with the identification of spirochetes in the amniotic fluid by dark-field microscopy, indicating that the S/D results are related to the presence of intrauterine infection. Serial S/Ds in a small subgroup of patients correlated with the clinical courses, including an apparent acute vascular-resistance change associated with treatment, probably due to the Jarisch-Herxheimer reaction. Because of these post-treatment vascular events, the pre-treatment S/D alone may have a limited clinical predictive value for treatment efficacy in congenital syphilis.

Amniotic Fluid↗

PubMedDate not supplied

Early congenital syphilis: clinico-radiologic features in 202 patients.

Venereal syphilis is highly prevalent among women of child-bearing age in Zambia. It is estimated to contribute 25-30% of the perinatal mortality rate of 50 per 1,000 births at the University Teaching Hospital in Lusaka. Because of multisystem involvement, early congenital syphilis, the offshoot of maternal syphilis, has varied criteria for its diagnosis. Therefore, in an attempt to draw guidelines for an easier and more reliable diagnosis, the authors analyzed the clinico-radiologic features of congenital syphilis in 202 patients. Although all infants were under the age of six months, there were several significant differences in the manifestations of the disease among neonates and the postneonates. The younger infants had a higher incidence of jaundice and mortality, whereas joint swellings, skin rash, snuffles, anemia, and periosteal reaction visible in x-rays of long bones were typical findings among the older group. The radiologic changes were seen in greater than 95% of patients in both groups. About 84% of mothers had attended prenatal clinics, but less than 20% of the women had been tested for syphilis. Since early congenital syphilis is common in many parts of the world and since all serologic tests have limitations, awareness of appropriate diagnostic criteria is recommended for all medical personnel.

Age Factors↗

PubMedDate not supplied

HIV and syphilis seroprevalence among clients with sexually transmitted diseases attending a walk-in clinic at Cook County Hospital.

BACKGROUND AND OBJECTIVES: To determine the HIV and syphilis seroprevalence in a patients with suspected sexually transmitted diseases at an urban walk-in clinic. METHODS: Between January and November 1991, 515 patients with suspected sexually transmitted diseases were simultaneously tested for syphilis and HIV antibodies. RESULTS: The cohort studied was young (85% were < 40 years), 81% were black, 11% Hispanic, and 71% reported heterosexual contact as the primary HIV risk factor. HIV seroprevalence was 8% (41/515), (95% confidence interval [95% CI], 5.66%, 10.34%). Syphilis seroprevalence rate was 21.4% (110/515), (95% CI 17.86%, 24.94%). Syphilis seroprevalence in those who were HIV positive was 31.7% (13/41), (95% CI 17.46%, 45.94%) as compared to 5.9% (28/574), (95% CI 3.78%, 8.02%) in those who were HIV negative. CONCLUSION: The HIV seroprevalence among patients with sexually transmitted diseases who are screened for syphilis was disturbingly high. Patients who were seropositive for HIV had a significantly higher rate of syphilis than those who were HIV negative.

Adult↗

PubMedDate not supplied

Providers of syphilis care in the southern United States.

BACKGROUND AND OBJECTIVES: The nadir in syphilis incidence in the 1950s provided evidence that current control methods could eliminate the transmission of syphilis. Planning such an effort will require information on the current state of the public and private infrastructure for the control of sexually transmitted disease (STD). GOAL OF THIS STUDY: To evaluate the accessibility, acceptability, and quality of delivery of clinical and preventive outreach services for syphilis control in the southern United States. STUDY DESIGN: A telephone-and-questionnaire survey of the 7 largest southern city, 10 state, and 9 nonsouthern comparison state STD control programs. RESULTS: The gender-race composition of public-sector STD providers is very different from their clients. Median ratio of STD clinicians per 1994 infectious syphilis patient was 0.08 (0.01-0.25) in southern states and 0.50(0.07-1.00) in comparison states. The proportion of clients treated within one day of care-seeking in southern states was 58% to 100%; regions with inadequate access were common. A median of 45% to 50% of patients with presumptive congenital syphilis underwent recommended diagnostic procedures. CONCLUSIONS: Serious deficiencies exist in the accessibility of STD care in the south that make the elimination of syphilis transmission difficult using current clinic-based diagnosis and treatment. A more community-based program of case finding and presumptive treatment may be indicated.

Female↗

PubMedDate not supplied

Serologic screening for syphilis. Rationale, cost, and realpolitik.

Serologic testing for syphilis is a cornerstone of syphilis control efforts, but our objectives for doing it and the costs involved are not always recognized. Tests applied to individuals with symptoms or signs may be viewed as diagnostic tests, and tests applied to individuals with no clinical indications for testing may be viewed as screening tests. Infected individuals whom we detect through screening efforts are important, mostly from an individual and economic standpoint, because treatment will prevent the late complications of syphilis and thus avoid high medical costs. Because they are uncommonly infectious for others, however, they are relatively unimportant from a public health intervention standpoint. The prevalence of infection above which we should screen is based mostly on economic grounds, but is undetermined. We intuitively recognize such a threshold, however, when we use epidemiologic markers to restrict our efforts to groups in whom we think the yield is worth the effort (i.e., targeted [focused] screening). In deciding whether to institute or increase screening efforts for syphilis, we must consider not only the dollar costs of these efforts, but also the opportunity costs (i.e., what programs we will forgo so that we can devote our resources to the increased efforts). Similarly, because syphilis is not the only priority with which governments, health departments, and sexually transmitted disease programs must contend, any broader plan to significantly enhance syphilis control must acknowledge this reality and show the benefit, economic and otherwise, of its adoption.

Cost-Benefit Analysis↗

PubMed2003

Characteristics of individuals with male-to-male and heterosexually acquired infectious syphilis during an outbreak in Calgary, Alberta, Canada.

BACKGROUND: Eliminating syphilis is important not only to prevent the sequelae of infection but also to control the spread of HIV. Current prevention and control efforts in Canada have been ineffective in eliminating this disease. GOAL: The goal of the study was to determine the characteristics of individuals with infectious syphilis due to male-to-male and heterosexual contact, diagnosed during an outbreak in Calgary, Alberta, Canada. STUDY DESIGN: This was a prospective study of individuals with infectious syphilis diagnosed at the STD clinic in Calgary between January 2000 and April 2002. RESULTS: The outbreak reported here (September 2000 to April 2002) involves 32 cases of infectious syphilis, corresponding to rates of 0.9/100,000 population during 2000 and 1.8/100,000 population during 2001. Between September 2000 and June 2001, the cases diagnosed were among men who have sex with men (MSM); between May 2001 and April 2002, they were due to locally acquired infections among heterosexuals, including one case of congenital syphilis. Compared to the heterosexuals, MSM tended to be older, be coinfected with HIV, and report excessive alcohol use (versus injection drug use) and had infectious syphilis diagnosed earlier. MSM used the Internet and bars or bathhouses to initiate sexual contact, whereas heterosexually acquired infections were largely among sex workers and their clients. Contact tracing was more successful among the heterosexuals than among MSM. The public health staff at the STD clinic initiated a series of multifaceted interventions in response to the outbreak. These interventions were moderately successful, as measured by the increased numbers of individuals seeking counseling and testing services at the clinic. CONCLUSION: The results highlight key differences in the risk factor-specific characteristics of the outbreak that should be taken into account when designing prevention and control strategies.

Adult↗

PubMed2004

A case-control study of syphilis among men who have sex with men in New York City: association With HIV infection.

OBJECTIVE: The objective of this study was to determine factors associated with syphilis among men who report sex with other men in New York City. DESIGN, SETTING AND STUDY SUBJECTS: We conducted a case-control study among 88 men who reported sex with men in the previous year, 18 to 55 years old and diagnosed with primary or secondary syphilis during 2001; and 176 control subjects frequently matched by age and type of health provider. RESULTS: HIV prevalence among syphilis cases was 48% compared with 15% among control subjects (P <0.001). Variables associated with syphilis in a multivariate model were HIV infection (odds ratio [OR], 7.3; 95% confidence interval [CI], 3.5-15.4), income >$30,000 per year (OR, 2.7; CI, 1.4-5.2), and barebacking (OR, 2.6; CI, 1.4-4.8). The median time since HIV diagnosis for HIV-positive was 6 years for cases and 7 years for control subjects (P = 0.70). Among HIV-infected participants, syphilis cases were more likely than control subjects to report being on antiretroviral therapy (69% vs. 44%, P = 0.05) and to report having undetectable viral load (58% vs. 24%, P = 0.02). CONCLUSION: HIV infection was strongly associated with syphilis in this study. High-risk behavior reported by both cases and control subjects indicates the potential for increased HIV transmission.

Adolescent↗

PubMed2005

Online syphilis testing--confidential and convenient.

OBJECTIVE: In response to the current syphilis epidemic among men who have sex with men, the San Francisco Department of Public Health sought to increase syphilis testing by offering testing in nonclinical settings. GOAL: The goal of this study was to collaborate with a community-based organization, Internet Sexuality Information Services, Inc. (ISIS), to design an innovative, confidential, online testing service for syphilis. STUDY: The service, called STDTest.org, was launched in June 2003. The web site allows people to print out a laboratory requisition slip, have their blood drawn, and receive their test results online. RESULTS: During the first year, 218 tests were performed and 13 persons had reactive serologies. Six patients were diagnosed with a new syphilis infection and treated. CONCLUSIONS: Online syphilis testing offers a free and convenient alternative to getting tested at the San Francisco municipal sexually transmitted disease clinic and an additional means for detecting syphilis cases.

Confidentiality↗

PubMed2006

Syphilis management in St. Petersburg, Russia: 1995-2001.

OBJECTIVES: The objectives of this study were to describe the recent syphilis epidemic in St. Petersburg, Russia; and to document the syphilis management practices in Russia to help inform the best way forward for a system in transition. DESIGN: This study was a retrospective cohort study of syphilis diagnosed and followed in St. Petersburg, 1995-2001. RESULTS: A total of 1,024 persons were identified with syphilis. Persons treated for secondary syphilis with 400,000 IU aqueous penicillin intramuscularly every 3 hours for 28 days or 2.4 micro benzathine penicillin intramuscularly weekly for 2 weeks responded most rapidly. Persons treated with 1.5 micro bicillin-5 intramuscularly at diagnosis and then two times per week for 3 weeks or 2.4 micro bicillin-1 intramuscularly weekly for 3 weeks displayed sluggish responses (P<0.0001). Regimens for treating later stages revealed similar responses (P=0.21). Benzathine penicillin at a dosage of 2.4 micro intramuscularly weekly for 3 weeks was not a used regimen. CONCLUSION: Benzathine penicillin at a dosage of 2.4 mu intramuscularly weekly for 1 to 2 weeks is in moderate use but its use should increase; 2.4 mu benzathine penicillin intramuscularly weekly for 3 weeks should be introduced as the standard of care for late syphilis. The efficacy of the locally manufactured bicillin-1 and bicillin-5 is in question.

Adult↗

PubMed2006

China's syphilis epidemic: a systematic review of seroprevalence studies.

OBJECTIVE: The objective of this study was to investigate syphilis prevalence among low- and high-risk groups in China. GOAL: The goal of this study was to explore the magnitude of China's syphilis epidemic. STUDY DESIGN: A systematic literature review of syphilis seroprevalence studies in China was performed searching PubMed and the Chinese Periodicals Database (CPD). RESULTS: Five and 169 studies were retrieved from PubMed and the CPD, respectively. From 2000 to 2005, select low-risk groups had the following median syphilis prevalence: antenatal women (0.45%), premarital individuals (0.66%), and food and service employees (0.3%). Select high-risk groups had the following median prevalence: incarcerated female sex workers (12.49%), drug users (6.81%), and men who have sex with men (14.56%). In the last decade, prevalence has increased in all groups with the steepest rises seen among high-risk groups. CONCLUSIONS: Syphilis infection is increasing among low- and high-risk groups in China, suggesting unsafe sexual behavior that may accelerate HIV transmission and challenge current syphilis prevention and control efforts.

China↗

PubMed2007

The resurgence of syphilis among men who have sex with men.

PURPOSE OF REVIEW: To identify recent progress and emerging problems in addressing syphilis among men who have sex with men. RECENT FINDINGS: A resurgence of syphilis has occurred among men who have sex with men in many developed countries. Infection has been associated with HIV coinfection, multiple partners, and recreational drug use. Unlike HIV, oral sex appears to be a common route of syphilis transmission. Many prevention approaches have shown, at best, modest success. Variable clinical presentation and potentially inconclusive lab tests make diagnosis confusing. SUMMARY: As the infection remains relatively rare, clinicians treating men who have sex with men should maintain a high index of suspicion for syphilis lesions, and should screen their sexually active patients for latent disease. Debates about syphilis control and treatment continue. The clinical manifestations, serologic responses, efficacy of treatment, and complications of syphilis have always been complicated. HIV coinfection adds to the confusion.

HIV Infections↗

PubMed2004

The histopathology of syphilis of the oral mucosa.

BACKGROUND: Reported cases of syphilis in the United States, Europe and elsewhere are increasing in number. Clinical manifestations are protean, and oral biopsies may be taken where the diagnosis is unsuspected, but data on the histopathology of oral mucosal syphilis are sparse. METHODS: The histopathology of five oral lesions in patients with serologically proven syphilis was reviewed. RESULTS: There were two cases of primary syphilis, one secondary and two tertiary. Epithelial hyperplasia was present in three cases, and was pseudocarcinomatous in one case of primary syphilis, and psoriasiform in the secondary lesion, where heaped-up epithelium surrounded a defined crater covered by flatter epithelium. Plasma cell (primary and secondary disease) and granulomatous (tertiary) infiltrates were prominent. Other features observed were endarteritis (5/5), plasma cell neuritis (3/5) and spirochetes (4/5). CONCLUSIONS: Although no single microscopic feature is specific, a diagnosis of syphilis should be considered where there is unusual epithelial hyperplasia, granulomatous or plasma cell-predominant chronic inflammation, endarteritis and neuritis.

Adult↗

PubMed1995

Secondary syphilis: a clinicopathologic study.

BACKGROUND: With the resurgence of syphilis in the HIV era, a greater awareness of the clinicopathologic features of the disease is desirable. This report describes and correlates the clinical and histopathologic features of secondary syphilis seen at a teaching hospital in Delhi, India. METHODS: Forty biopsies of mucocutaneous lesions from 31 consecutive patients with secondary syphilis, seen between September 1987 and January 1991, were studied and the histopathologic findings correlated with the clinical findings. RESULTS: A spectrum of histopathologic changes ranging from a minimal infiltrate to granulomatous inflammation throughout the dermis was seen. The pattern of inflammation correlated well with the type of skin lesion, with macules showing the least and nodules the most prominent changes. The predominant cell type in the infiltrate was the mononuclear cell/lymphocyte. Plasma cells were seen infrequently except in condylomata lata. Endothelial proliferation, the "classical" feature of the histopathology of syphilis was noted infrequently. CONCLUSIONS: The histologic manifestations of secondary syphilis appear to be as varied as the clinical ones. This calls for close interaction between the clinician and the pathologist to correlate the clinical, serologic, and histologic findings to establish the diagnosis of syphilis.

Adolescent↗

PubMed2001

Western immunoblotting with five Treponema pallidum recombinant antigens for serologic diagnosis of syphilis.

Five immunodominant Treponema pallidum recombinant polypeptides (rTpN47, rTmpA, rTpN37, rTpN17, and rTpN15) were blotted onto strips, and 450 sera (200 from blood donors, 200 from syphilis patients, and 50 potentially cross-reactive) were tested to evaluate the diagnostic performance of recombinant Western blotting (recWB) in comparison with in-house whole-cell lysate antigen-based immunoblotting (wclWB) and T. pallidum hemagglutination (MHA-TP) for the laboratory diagnosis of syphilis. None of the serum specimens from blood donors or from potential cross-reactors gave a positive result when evaluated by recWB, wclWB, or MHA-TP. The evaluation of the immunoglobulin G immune response by recWB in sera from patients with different stages of syphilis showed that rTmpA was the most frequently identified antigen (95%), whereas only 41% of the specimens were reactive to rTpN37. The remaining recombinant polypeptides were recognized as follows: rTpN47, 92.5%; rTpN17, 89.5%; and rTpN15, 67.5%. The agreement between recWB and MHA-TP was 95.0% (100% with sera from patients with latent and late disease), and the concordance between wclWB and MHA-TP was 92.0%. The overall concordance between recWB and wclWB was 97.5% (100% with sera from patients with secondary and late syphilis and 94.6 and 98.6% with sera from patients with primary and latent syphilis, respectively). The overall sensitivity of recWB was 98.8% and the specificity was 97.1% with MHA-TP as the reference method. These values for sensitivity and specificity were slightly superior to those calculated for wclWB (sensitivity, 97.1%, and specificity, 96.1%). With wclWB as the standard test, the sensitivity and specificity of recWB were 98.9 and 99.3%, respectively. These findings suggest that the five recombinant polypeptides used in this study could be used as substitutes for the whole-cell lysate T. pallidum antigens and that this newly developed recWB test is a good, easy-to-use confirmatory method for the detection of syphilis antibodies in serum.

Antigens, Bacterial↗

PubMed2001

Syphilis fast latex agglutination test, a rapid confirmatory test.

Using 255 serum samples with various reactivities, we evaluated the Syphilis Fast latex agglutination test (Syphilis Fast) against the Treponema pallidum particle agglutination test (TP-PA) for confirming a diagnosis of syphilis. We found 98.8% agreement between the Syphilis Fast and the TP-PA. The Syphilis Fast, however, had a couple of advantages over the TP-PA: the test takes only 8 min to perform and produces results that are easy to read. It appears to be a good confirmatory test for syphilis, especially for point-of-care clinics such as prenatal or sexually transmitted disease clinics.

Agglutination Tests↗