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PubMed1998

Syphilis management and treatment.

Syphilis poses a serious health problem in many developing countries and in some areas of North America and Europe, especially Eastern Europe. This article initially addresses the state of the art regarding the interaction between syphilis and HIV infection and its consequences for management and treatment. Further attention is given to laboratory diagnosis of syphilis and false-positive and false-negative serologic reactions. The diagnosis and management of neurosyphilis, ocular, cardiovascular, and congenital syphilis are addressed, as well as management of syphilis patients allergic to penicillin and the Jarisch-Herxheimer reaction. Finally, the role of partner(s) and contact tracing is discussed.

Contact Tracing↗

PubMed1987

Syphilis. Updated approach to an old disease.

Syphilis, a sexually transmitted disease caused by Treponema pallidum, is widespread but most common in large cities. The various stages include primary, secondary, latent, tertiary (late), and congenital syphilis and neurosyphilis. Definitive diagnosis is made by finding spirochetes on a darkfield examination of material from a chancre or moist mucosal lesion. Serologic tests for syphilis in common use in the United States include the VDRL and the FTA-ABS. Penicillin is the drug of choice for all stages of syphilis, with tetracycline or erythromycin indicated in certain patients. Accurate and prompt reporting of syphilis cases is an important factor in disease control.

Female↗

PubMedDate not supplied

Treatment of syphilis, 1989.

With the introduction of penicillin after World War II, the incidence of syphilis in the United States decreased. Because of penicillin's great success, clinical trials stopped after an initial period of intensive investigation. Syphilis is a difficult disease to study; the natural history may span decades in an individual, and diagnosis and outcome are usually defined serologically, not clinically or bacteriologically. Although the recommended penicillin regimens changed, clinical trials were not repeated. Furthermore, because the early studies occurred before modern clinical-trial methodology was developed, interpretation of the results is difficult. As a result, while current regimens for syphilis therapy are effective, they may or may not be optimal. With the accumulation of reports of treatment failures and the recent appearance of human immunodeficiency virus, current regimens for the treatment of syphilis are being questioned. As background for a meeting at which treatment guidelines were reviewed, the available literature on syphilis therapy is summarized herein.

Animals↗

PubMed1976

[Latent syphilis].

The wide use of penicillin and of other treponemacide antibiotics levels often to the treatment of patients with early-syphilis without knowing it. So the typical appearance of syphilis may be masked and the development of the classic serologic changes may be disturbed. From 1963 to 1974 569 cases of early-syphilis were treated as inpatients of the University clinic of Innsbruck, Department of Dermatology, 15% had proved and 20% had probable antibiotic therapy before syphilis was diagnosed. The influence on the course of disease due to treatment before noting the diagnosis is discussed by the means of own observations and reports in the literature. An attempt is made to explain the striking increase of symptomless early-syphilis.

Adult↗

PubMed1998

Contribution of long-bone radiographs to the management of congenital syphilis in the newborn infant.

OBJECTIVE: To determine the contribution of long-bone radiographs to the diagnosis and management of newborn infants at risk for congenital syphilis. DESIGN: Historical cohort. SETTING: Three large hospitals in Houston, Tex. PATIENTS: Eight hundred fifty-three live born infants who were evaluated for the presence of congenital syphilis. INTERVENTION: Long-bone radiographs done as part of the diagnostic evaluation for the presence of congenital syphilis. MAIN OUTCOME MEASURE: Changes in diagnostic classification or management decisions that were based on radiographic findings in the long bones. RESULTS: For 450 infants, radiographic results did not affect management because clinical or historical factors were present that dictated treatment: 26 infants had clinical symptoms of congenital syphilis (65% [17] had abnormalities on radiographs); and 424 infants were born to mothers who were untreated or reinfected (5.9% [25] had abnormalities on radiographs). All of these infants required a full course of therapy regardless of radiologic findings. Born to mothers with possibly inadequate therapy (according to 1993 Centers for Disease Control and Prevention guidelines), 237 asymptomatic newborn infants were candidates for a single injection of penicillin G benzathine if the results of their evaluations were normal; of these, 2 (0.8%) had abnormal radiographic findings. Of the 166 infants born to adequately treated mothers with appropriately falling serologic titer levels, 1 (0.6%) had abnormal radiographic findings (P=.99 between groups). The results of the long-bone radiographs did not alter management for any of the 853 infants who were evaluated for congenital syphilis. CONCLUSIONS: Long-bone radiographic findings, often abnormal in symptomatic infants, do not differentiate between active infection and past infection. The use of long-bone radiographs should be reconsidered in the routine evaluation of infants for congenital syphilis.

Bone and Bones↗

PubMed1992

IgM antibody to Treponema pallidum in cerebrospinal fluid of infants with congenital syphilis.

OBJECTIVES: To characterize the neonatal IgG and IgM response to specific Treponema pallidum antigens in the cerebrospinal fluid (CSF) of infants with congenital syphilis. DESIGN: Cross-sectional survey. SETTING: Newborn nursery and neonatal intensive care unit of a county hospital in Dallas, Tex. PARTICIPANTS: Twenty-one infants born to mothers with reactive serologic tests for syphilis were enrolled. Group 1 consisted of six infants with clinical and laboratory evidence of congenital syphilis; group 2, six asymptomatic infants born to mothers with untreated syphilis; and group 3, nine asymptomatic infants whose mothers were treated for syphilis before delivery. SELECTION PROCEDURES: Random sample. MEASUREMENTS AND RESULTS: Immunoblotting was used to examine the IgM and IgG reactivities of neonatal serum and CSF against T pallidum antigens. Among serum samples of all group 1 infants, a specific IgM response to T pallidum antigens with apparent molecular masses of 47, 45, and 17 kd was observed. Cerebrospinal fluid IgM reactivity to a 47-kd antigen of T pallidum was seen in four group 1 infants. Serum samples from two group 2 and three group 3 infants demonstrated IgM reactivity against the 47-kd antigen and, in some cases, against the 45-kd antigen of T pallidum. None of 15 group 2 and 3 infants had a positive CSF IgM immunoblot result. The IgG reactivity in CSF was similar in the three groups and was directed against T pallidum antigens with apparent molecular masses of 72, 59, 47, 45, 42, 37, 34, 17, and 15 kd. CONCLUSIONS: A specific IgM response to T pallidum antigens, particularly the 47-kd antigen, was detected in the CSF of some infants with clinical and laboratory evidence of congenital syphilis. The potential usefulness of this test for the diagnosis of congenital neurosyphilis merits further study.

Adult↗

PubMed2006

Histological identification of syphilis in pre-Columbian England.

Microscopic analyses served to complement the macroscopic identification of venereal syphilis in two of four pre-Columbian skeletons from the site Hull Magistrates Court in England. Diagnosis was based on parameters presented by Schultz ([1994] Origin of Syphilis in Europe, Toulon: Centre Archaeologique du Var, p. 63-67; [2001] Yrbk. Phys. Anthropol. 44:106-147; [2003] Identification of Pathological Conditions in Human Remains, New York: Academic Press, p. 73-109), which characterized venereal syphilis at a histological level. Observation of the microarchitecture of these samples allowed a more comprehensive approach to identification of the disease (processes). In most samples, Polsters and Grenzstreifen (or remnants of such structures) could be identified, suggesting the presence of a chronic, inflammatory disease such as venereal syphilis. Sinous lacunae were also observed in all histological samples, pointing to lytic activity (osteitis). The combination of both proliferative and destructive processes is pathognomonic for syphilis, and histological analyses provided a more accurate diagnosis of this infectious disease in these four individuals. As a result, the histological evidence suggests that venereal syphilis was present in England prior to 1492. This secondary form of evidence supports the macroscopic identification of the disease, and shows the power of a multimethodological approach to paleopathological diagnoses.

Bone and Bones↗

PubMed2006

The pathogenesis of syphilis: the Great Mimicker, revisited.

Syphilis is a chronic sexually transmitted infection caused by Treponema pallidum subspecies pallidum. Its protean clinical presentations earned it the name of the 'Great Mimicker'. Understanding of disease pathogenesis and how host-pathogen interactions influence the course of disease have been compromised by the facts that the organism cannot be grown in vitro and, as an exclusively human pathogen, inferences made from animal models are of limited applicability. Many questions remain about how T. pallidum biology contributes to distinctive features of syphilis, such as its ability to persist in the presence of a brisk host response or its propensity for neuro-invasion and congenital transmission. In 1998, the genome of T. pallidum was sequenced. The organism has a relatively small genome, suggesting that it utilizes host biosynthesis to fulfil some of its metabolic needs. While biological functions are suggested for only about 55% of T. pallidum's 1041 open reading frames, even these relatively early studies offer important insights into syphilis pathogenesis. A family of repeat genes, the Tp genes, encode proteins homologous to the major sheath proteins of T. denticola. Antibodies to the TprK variable regions are protective in a rabbit model. With successive passage, increasing diversity is observed in the TprK V region genes. Antigenic variation through gene conversion has been hypothesized to be one mechanism of escaping immune surveillance, allowing for prolonged infection and persistence in the presence of a robust host response. Human and animal studies suggest that a Th1 response is elicited in primary syphilis. Progression to the secondary stage is accompanied by a shift to a Th2 response, allowing for incomplete clearance of the pathogen. In pregnancy, intense inflammatory responses and prostaglandins induced by fetal infection may be responsible for fetal death or pre-term delivery and severe growth retardation or other manifestations of congenital syphilis. Understanding of the molecular targets of these immune responses may facilitate the development of vaccines for syphilis.

Antibodies, Bacterial↗

PubMed1988

Ig class and IgG subclass responses to Treponema pallidum in patients with syphilis.

The Ig class and IgG subclasses of anti-Treponema pallidum antibodies in human serum were quantified using solid-phase enzyme-linked immunosorbent assays. Development of these assays with monoclonal antibodies, each specific for a human immunoglobulin class or IgG subclass, provided quantitative data concerning the major antibody specificities. In patients with primary syphilis, anti-T. pallidum activity was limited almost exclusively to IgG1 and IgM. Coordinate, restricted expression of IgG1 and IgG3 responses in T. pallidum-specific assays was observed with sera from patients with active secondary syphilis. IgG1 and IgG3 accounted for roughly 53 and 43% of the total anti-treponemal IgG antibody activity, respectively. While IgM antibody levels were elevated in the patients with secondary syphilis, IgG2 and IgG4 levels, if present at all, represented less than 10 and 2% of the total IgG activity, respectively. Ig in sera from patients who had been treated adequately for secondary syphilis were restricted almost entirely to IgG3 and IgG1. Considering the low level of IgG3 in serum, disproportionately high percentages of antitreponemal antibodies were found in this subclass during and after treatment for secondary syphilis. The restricted, coexpression of the IgG1 and IgG3 isotypes may reflect the close genetic linkage of the gamma 1 and gamma 3 genes and possibly the impact of immunoregulatory mechanisms in response to the induction and expression of autoantibodies which arise during the course of secondary syphilis.

Adolescent↗

PubMed1995

Syphilis control in pregnancy: decentralization of screening facilities to primary care level, a demonstration project in Nairobi, Kenya.

A decentralized syphilis control program in pregnant women was implemented in nine Nairobi City Council antenatal clinics between July 1992 and August 1993, whereby pregnant women were screened for syphilis, treated before leaving the clinic if RPR seroreactive, and counselled on the importance of partner treatment and sexual abstinence during treatment in order to protect their unborn babies from getting congenital syphilis. A total of 13,131 pregnant women were screened for syphilis (RPR test), 87.3% of seroreactive women were treated on site and 50% of partners returned to the clinic and were treated. The prevalence of RPR reactivity was 6.5%. Based on other data the program could theoretically have prevented 413 cases of congenital syphilis at a cost of approximately 50 USD per prevented case. This demonstration project shows that decentralized prevention of congenital syphilis in antenatal clinics by nurses is feasible and inexpensive and should receive priority in resource allocation in reproductive health and child survival programs.

Female↗

PubMed1994

Prevalence, incidence, and correlates of syphilis seroreactivity in multiethnic San Francisco neighborhoods.

To examine the extent of infection with syphilis in an inner-city community, we determined the prevalence, incidence, and correlates of syphilis seroreactivity in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. One thousand seven hundred seventy single men and women aged 20 to 44 were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Syphilitic infection was determined by testing specimens with the microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP). Of blood samples available from 1262 participants from the initial survey, 32 (2.5%) were MHA-TP reactive. After adjustment for age, a reactive syphilis serology was significantly predicted (P < 0.05) by African American race, homosexual activity (men), and less education. In homosexually active men, lifetime number of male sex partners and the presence of antibody to the human immunodeficiency virus (HIV) significantly predicted syphilis seroreactivity (P < 0.01). One year later, of 841 specimens available for testing, an additional 13 (1.5%) had become MHA-TP reactive. Eleven (85%) of the new cases were in heterosexual men and women. Although San Francisco citywide incidence data indicate that syphilis may be decreasing for the city as a whole, incidence data on a community level suggests that syphilitic infection is increasing in high-risk heterosexual communities. Thus, syphilis prevention programs should rely on serologic testing at the community level to plan effective intervention strategies.

Adult↗

PubMed1992

Substance abuse and syphilis in urban adolescents: a new risk factor for an old disease.

The incidence of syphilis is increasing. To identify the epidemiologic characteristics of adolescents with syphilis in an urban adolescent clinic, we performed a retrospective review and case-control study of 59 patients with syphilis and 111 sex-matched controls seen at our institution between 1985 and 1988. Only 24% of cases occurred in males, in contrast with 61% in a 1977-1981 study. Almost one-half (46%) of cases occurred in asymptomatic individuals, and only 24% were diagnosed at the initial visit. Patients with syphilis were more likely to have a history of substance abuse (odds ratio, 4.94; 95% confidence interval, 1.83, 13.3). This study suggests that the epidemiology of syphilis in adolescents may be changing. The high percentage of asymptomatic syphilis cases underscores the need for a high index of suspicion, particularly in sexually active adolescents who abuse drugs.

Adolescent↗

PubMed2005

The continuing scourge of congenital syphilis in 21st century: a case report.

Although the rate of congenital syphilis is declining in developed countries, a significant increase has been observed in the underdeveloped countries. Unfortunately, little concern is raised about the increasing numbers of babies born with congenital syphilis. The procedure to prevent congenital syphilis through antenatal screening and treatment is well established. But implementation of effective programs has proved very difficult especially in resource--poor settings. Congenital syphilis, if not treated promptly and adequately, may result in significant physical and emotional squeal in children. A case of complicated late congenital syphilis is reported in order to emphasize that syphilis is still present nowadays, and re-emerging many countries even some of the industrialized ones. Most of the cases can not be prevented by routine antenatal screening. Thus it is essential to develop strategies to prevent sexually transmitted disease from being a hidden and neglected problem.

Abnormalities, Multiple↗

PubMed2006

Syphilis: reemergence of an old adversary.

OBJECTIVE: To describe the clinical findings in 4 patients with ocular syphilis and to provide a review of the recent rise in syphilis cases in the United States, along with a brief description of current diagnosis and treatment guidelines. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four consecutive patients who presented to our facility during a 6-month interval in 2005 with ocular syphilis. METHODS: Review of clinical, laboratory, photographic, and angiographic records of patients with neurosyphilis who underwent intravenous penicillin G treatment. MAIN OUTCOME MEASURES: Resolution of signs and symptoms of ocular syphilis, including changes in visual acuity. RESULTS: Four patients (3 male: mean age, 46 [range, 39-60 years]; 1 female: age 46 years) demonstrated cerebrospinal fluid findings consistent with neurosyphilis, as evidenced by increased leukocyte counts (>5 white blood cells/mm3), and positive Venereal Disease Research Laboratory or serum fluorescent treponemal antibody absorbed tests. All 4 patients presented with a variety of clinical findings that led to a delay in diagnosis and treatment. Two patients presented with discrete placoid lesions consistent with acute syphilitic posterior placoid chorioretinitis, a manifestation typically observed among the immunocompromised. CONCLUSIONS: Despite a decade of steady decline, syphilis has reemerged in the United States with outbreaks throughout the country in the past few years. Ocular findings, including posterior placoid chorioretinitis, are important diagnostic features in the early treatment of tertiary syphilis and neurosyphilis. Ophthalmologists have the opportunity to play a key role in the early diagnosis and management of this potentially fatal disease.

Adult↗

PubMed1997

The resurgence of congenital syphilis: a cocaine-related problem.

The relationship of maternal illicit drug use to congenital syphilis was studied in a population of newborn infants (N = 1012) who were screened for intrauterine exposure to illicit drugs by meconium analysis and whose mothers were screened for syphilis by the rapid plasmin reagin fluorescent treponemal antibody, absorbed (RPR/FTA-ABS) test. The result of the meconium drug screening was positive in 449 (44.3%) infants: 401 (39.6%) screening results were positive for cocaine, 71 (7%) positive for opiate, and 31 (3.1%) positive for cannabinoid. The maternal RPR/FTA-ABS result was positive in 72 (7.1%) women, and congenital syphilis was diagnosed in 46 (4.5%) infants on the basis of Centers for Disease Control and Prevention definitions. The incidence of positive RPR/FTA-ABS result (10.5% vs 4.4%) and congenital syphilis (7% vs 2.5%) was significantly higher (p < 0.01) among infants with positive results compared with those with negative drug screening results. Similarly, the incidence of positive RPR/FTA-ABS (11% vs 4.6%) and congenital syphilis (8% vs 2.3%) was significantly (p < 0.01) higher among infants with cocaine-positive results compared with those with cocaine-negative results. We conclude that maternal illicit drug use, specifically cocaine, is significantly related to the resurgence of congenital syphilis among newborn infants.

Adult↗

PubMed1996

Diagnosis of congenital syphilis from placental examination: comparison of histopathology, Steiner stain, and polymerase chain reaction for Treponema pallidum DNA.

Congenital syphilis is often a presumptive diagnosis (based on serologies), because confirmation requires identification of Treponema pallidum in fetal/neonatal tissues or in the placenta. Placental histological features associated with congenital syphilis include the triad of enlarged hypercellular villi, proliferative fetal vascular changes, and acute or chronic villitis. The authors blindly evaluated 49 formalin-fixed, paraffin-embedded placentas (38 with positive maternal syphilis serologies; 11 with negative serologies) and compared results of histology, Steiner stain, and polymerase chain reaction (PCR) for T pallidum DNA. Histology was categorized as positive (triad present), suspicious (two thirds of triad present), or negative. Treponemal DNA was detected by amplifying a 189 base pair region of the 47 kd treponemal membrane antigen with 44 cycles of PCR; products were detected by Southern blot. Placentas from the 11 seronegative mothers were all negative by histology, Steiner stain, and PCR. Among the 38 placentas from serologically positive mothers, 4 had positive histology (2 of 4 positive Steiner, 4 of 4 positive PCR); 6 had suggestive histology (0 of 6 positive Steiner; 1 of 6 positive PCR); and, 28 had negative histology (0 of 28 positive Steiner; 1 of 28 positive PCR). PCR identification of treponemal DNA was significantly associated with the triad (P = .0003), proliferative fetal vascular changes (P = .0003), acute villitis (P = .003), chronic villitis (P = .004), and spirochetes on Steiner stain (P = .01). These results (1) confirm a strong association between placental histopathologic features and congenital syphilis; (2) indicate that when such features are present, PCR of placental tissue may confirm the diagnosis of congenital syphilis; and (3) suggest that even when such features are absent, PCR of placental tissue may identify additional cases of histologically unsuspected congenital syphilis.

Base Sequence↗

PubMed1999

The social ecology of syphilis.

Factors affecting the transmission of syphilis can be categorized into those acting at the level of individuals (e.g., number of sex partners) and others at the level of the sociophysical environment (e.g., availability of treatment services for curable infections). In a prior study, we identified several sociophysical factors correlated with the ten-year mean syphilis rate in a regression analysis of United States counties. In the present study we used qualitative methods to investigate additional aspects of some factors in the regression, as well as to identify entirely new factors. Twelve counties with populations less than 100,000 and ten-year mean syphilis rates that were greater or less than expected by the regression model were selected for a three to five day visit. The case study protocol included observations, unstructured interviews with care providers and county residents, and a standardized questionnaire completed by state and local sexually transmitted disease control personnel pertaining to characteristics and practices of the local health department. Comparisons of the field notes and questionnaires revealed patterns of factors of the sociophysical environment that potentially affect county syphilis rates. These included access to the health department STD clinic, race relations, employment opportunities for minorities, interagency coordination, STD outreach activities, the social acceptability of discussing STDs, and intercommunity dynamics. In addition we noted the disproportionate influence of particular individuals on these factors. Some of the factors identified are readily quantifiable and could enhance the predictive power of multivariable models of county syphilis rates. The hypotheses generated by this study may also lead to a better measurement and understanding of potentially important environmental determinants of community syphilis rates, and the development of new or enhanced prevention strategies.

Black or African American↗

PubMed2002

Syphilis 2001--a palaeopathological reappraisal.

The origin and subsequent spread of the treponematoses, especially that of venereal syphilis, has been the subject of considerable scientific attention. Various theories were put forth and palaeopathological specimens were used for their validation in recent times. One influential contribution was the paper by Baker & Armelagos in 1988. Numerous new findings and results on both sides of the Atlantic call for a new evaluation of the available osseous material. A review of the recent literature leads to the suggestion of a worldwide distribution of non-venereal treponemal disease since the emergence of Homo and to a first epidemic outbreak of venereal syphilis in Europe of the late 15th and the early 16th century, which was a time of change and enormous sexual liberty. Old World specimens with pathological alterations attributed to venereal syphilis and dated to precolumbian times seem to invalidate the Columbian theory and call for a more differentiated analysis of the phenomenon of syphilis than a theory based on a single factor can provide. With the help of molecular methods which now allow a positive identification of Treponema pallidum pallidum, causative agent of venereal syphilis, in palaeopathological material, it seems possible to elucidate the matter of origin and spread of syphilis further and to evaluate previous diagnoses of treponemal disease.

Anthropology, Physical↗