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Phase-specific network differences associated with the syphilis epidemic in Baltimore city, 1996-2000.

OBJECTIVES: The objective of this study was to determine whether the syphilis epidemic in Baltimore City during the mid-1990s was associated with changes in sexual networks. METHODS: Data on index cases of syphilis and their partners were collected from 1996 to 2000 and entered into CDC STD*MIS software. Unique pairs of dyads were used to create networks using SAS Interactive Matrix Language. PAJEK and UCINET were used to analyze the largest component from all years (1996-2000), during the epidemic (1997-1998), and after the epidemic (1999-2000). RESULTS: Between 1996 and 2000, there were 3343 components containing 18,709 nodes. The 2 largest components were comprised of 1103 nodes and 125 nodes, respectively. From the period during the epidemic to after the epidemic, the average distance among reachable pairs, network centralization, number of n-cliques (n = 2, size = 3), and number of k-plexes (k = 2, n = 3) declined, whereas the block densities increased. CONCLUSIONS: Important differences exist between the sexual networks during and after the syphilis epidemic.

Baltimore↗

Effectiveness of syphilis treatment using azithromycin and/or benzathine penicillin in Rakai, Uganda.

OBJECTIVE: The goal of this study was to assess azithromycin and/or benzathine penicillin for treatment of syphilis. METHODS: In a population-based study, participants with serologic syphilis (TRUST with TPHA confirmation) were offered 2.4 MU benzathine penicillin intramuscularly. Intervention arm participants received 1 g presumptive oral azithromycin. We assessed cure rates with penicillin or azithromycin given alone and in combination. Cure assessed after 10 months was defined as seroreversion or a 4-fold decrease in titer. The rate ratio (RR) of cure and 95% confidence intervals (95% CIs) were estimated by log binomial regression. RESULTS: Among 952 cases with syphilis, 18% received penicillin alone, 17% azithromycin only, and 65% dual treatment. The overall cure rate was 61%. Cure rates were lower in males compared with females (RR, 0.89; 95% CI, 0.80-0.99) and in subjects with initial titers > or =1:4 compared with < or =1:2 (RR, 0.77; 95% CI, 0.69-0.86). There was no significant differences in cure rates among HIV-positive and HIV-negative persons. With initial titers < or =1:2, there were no differences in cure rates by treatment regimen. However, with initial titers > or =1:4, significantly higher cure rates were observed with azithromycin alone (adjusted RR, 1.38; 95% CI, 0.97-1.96), and with dual treatment of azithromycin and benzathine penicillin (RR, 1.38; 95% CI, 1.03-1.87) compared with penicillin alone. CONCLUSION: Azithromycin alone or in combination with penicillin achieved higher cure rates than penicillin alone in cases with a high initial TRUST titer. In low-titer infections, the 3 drug combinations were equally effective. HIV status did not affect cure rates.

Adolescent↗

The re-emergence of syphilis in the United Kingdom: the new epidemic phases.

OBJECTIVE: The objective of this study was to characterize the resurgence of infectious syphilis in the United Kingdom between 1997 and 2003. STUDY: The authors conducted a retrospective analysis of routine surveillance data from genitourinary medicine clinics and data collected through enhanced surveillance. RESULTS: Between 1997 and 2002, diagnoses of primary, secondary, and early latent syphilis made at genitourinary medicine clinics increased by 213% in heterosexual males, 1412% in men who have sex with men (MSM), and 22% in females. These increases have been driven by a series of outbreaks, the largest of which were seen in Manchester (528) and London (1222) up to the end of October 2003. All the outbreaks have been geographically localized and the majority of cases occurred in MSM. A high percentage of concurrent HIV infection was reported, and oral sex was often reported as a route of transmission. CONCLUSIONS: Syphilis has re-emerged in response to behavior change, probably driven by changes in the HIV epidemic. The future course of the epidemic is difficult to predict and control remains elusive.

Adolescent↗

A study evaluating ceftriaxone as a treatment agent for primary and secondary syphilis in pregnancy.

OBJECTIVES: To evaluate the efficacy of ceftriaxone in pregnant women who were diagnosed with early syphilis. STUDY: Eleven women with a history of penicillin allergy, positive skin test, but prior history of safe usage of cephalosporins were included. Ceftriaxone (250 mg) was given intramuscularly once daily for 7 and 10 days to patients with primary and secondary syphilis, respectively. A second course of therapy was provided at 28 weeks' gestation. The rapid plasma reagin test (RPR) was measured before and after therapy. The blood of neonates was also tested at delivery and during the follow-up period. RESULTS: The serum RPR titers of 11 mothers decreased fourfold, 3 months after treatment. Ten patients developed negative RPR results. The serum RPR was negative at delivery or 6 months after delivery in all neonates. CONCLUSIONS: Ceftriaxone may be considered as an alternative for treatment of early syphilis in pregnancy.

Adult↗

HIV and syphilis: when to perform a lumbar puncture.

OBJECTIVES: The objectives of this study were to determine predictive factors for neurosyphilis in HIV-infected patients with syphilis and optimize the use of lumbar puncture. STUDY DESIGN: The authors reviewed 112 cases of HIV-infected patients with syphilis who underwent a lumbar puncture. Diagnosis of neurosyphilis was based on a cerebrospinal fluid white blood cells count > or =20/microL, and/or a reactive cerebrospinal fluid-Venereal Disease Research Laboratory, and/or a positive intrathecal T. pallidum antibody (ITPA) index. RESULTS: Twenty-six of 112 had neurosyphilis. Neurologic manifestations and serum rapid plasma reagin (RPR) were associated with neurosyphilis (P = 0.036, P = 0.018, respectively). In multivariate analysis, log(2)RPR was still associated with neurosyphilis (P = 0.005). In patients without neurologic manifestations, the risk of neurosyphilis increases gradually with log(2)RPR. A serum RPR of 1/32 seems to be the best cutoff point to decide the performance or not of a lumbar puncture (sensitivity 100%, specificity 40%). CONCLUSION: In HIV-infected patients with syphilis, lumbar puncture could be restricted to those with neurologic manifestations or a serum RPR > or =1/32.

Adult↗

Early syphilis among men in Connecticut: epidemiologic and spatial patterns.

OBJECTIVE: The objective of this study was to describe the epidemiology of early syphilis among men in Connecticut, a moderate-prevalence region, in 2004. STUDY DESIGN: The authors conducted a cross-sectional analysis of health department data. RESULTS: Fifty-five cases were reported from 25 different towns. A majority of cases (82%) were reported among men who have sex with men, and 22% reported coinfection with HIV. Spatial analysis indicated moderate clustering of cases. Approximately half of 197 reported sex partners were not from Connecticut, including 28% from New York City and 20% from other states/countries. The median distance between partners was 48 km (30 miles). Twenty-three percent of syphilis cases had both local and nonlocal partners. CONCLUSIONS: The current epidemiology of early syphilis in Connecticut is consistent with national trends. However, the dispersal of cases throughout the state and the high proportion of reported sex partners residing outside of Connecticut suggest that this state is not a core area of endemic transmission.

Adult↗

Secondary syphilis: a histologic and immunohistochemical evaluation.

The usual method for detecting spirochetes in tissue sections is the silver stain; however, they are often difficult to detect due to marked background staining commonly seen with this technique. In certain clinical settings, such as neurosyphilis, congenital syphilis, and immunosuppressive conditions including human immunodeficiency virus (HIV) infection, a better method of detecting spirochetes in tissue sections is needed. We compare immunohistochemistry (IHC) with a monoclonal antibody to Treponema pallidum to silver staining in 19 biopsies from 17 patients with serologic evidence of secondary syphilis. IHC demonstrated a sensitivity of 71%, which was superior to the 41% sensitivity of the silver stain (p = 0.084). Furthermore, specificity was improved with IHC, as background artifacts were markedly reduced. Dermal spirochetes were visualized in all 12 positive cases, while epidermal organisms were seen in only eight cases. This finding lies contrary to accepted teaching that organisms are most commonly seen at the dermal epidermal junction. Of interest, perineural plasmacellular infiltrates were frequently seen in our cases (74%). Spirochetes were not seen in any of 14 control cases with similar histopathologic patterns. Although serologic studies remain the gold standard, IHC is more sensitive and specific than silver stain for detecting T. pallidum in biopsies of secondary syphilis.

Adult↗

Clinical expression of secondary syphilis in a patient with HIV infection.

There are increasing reports of unusual clinical features and atypical courses of syphilis in patients with acquired immunodeficiency syndrome. Recently, we had the opportunity to study an HIV-positive female patient with strong manifestations of secondary syphilis. The case is discussed together with the implications of secondary syphilis in her concomitant ocular affliction. Moreover, we comment on the clinico-therapeutic controversies brought about by the association of infection with Treponema pallidum and HIV.

Adult↗

Distinguishing beta 2-glycoprotein I dependent (systemic lupus erythematosus type) and independent (syphilis type) anticardiolipin antibody with Tween 20.

We investigated whether or not the use of Tween 20 could help to distinguish beta 2-glycoprotein I (GPI) independent anticardiolipin antibody (aCL) (syphilis-type aCL) from GPI-dependent aCL (SLE-type aCL) in a GPI-dependent/independent aCL ELISA. aCL was positive in all 16 SLE patients and all 15 syphilis patients, who were positive for aCL in the standard ELISA, in the GPI-independent ELISA with Tween 20. GPI-dependent aCL was detected in 12/16 SLE patients by the GPI-dependent ELISA with Tween 20. aCL was not detected in any of the syphilis patients by GPI-dependent ELISAs. On the basis of these results, we recommend that Tween 20 should be used in ELISAs to distinguish GPI-dependent aCL from GPI-independent aCL.

Adult↗

Immune studies in infants with congenital syphilis.

Seventeen neonates with congenital syphilis were studied to determine the immune response of the fetus following intra-uterine infection with Treponema pallidum. The results were compared with those from healthy controls matched for gestational age, birth weight and sex. B cells, IgM, and circulating immune complexes were significantly elevated in the infected newborns. There were no differences in lymphocyte transformation to phytohaemagglutinin (PHA) and in the CD3, CD4, and CD8 lymphocytes between infants with congenital syphilis and controls. Newborns with congenital syphilis have a heightened humoral response but no quantitative abnormality in cell-mediated immunity. Speculation on the role of the circulating immune complexes is presented.

Antigen-Antibody Complex↗

The H3 anti-phospholipid idiotype is found in patients with systemic lupus erythematosus (SLE) but not in patients with syphilis.

The human H3 idiotype, defined by a mouse monoclonal antibody S2.9, is commonly found in patients with SLE where it is correlated with the amount of anti-cardiolipin antibodies. No correlation between the amount of anti-cardiolipin antibody and the H3 idiotype is found in patients with syphilis. Using the S2.9 antibody, serum from each of 10 patients with SLE and eight patients with syphilis was separated into H3-bearing and H3-negative fractions. Comparison of the partition of anti-cardiolipin antibody in these two groups of patients revealed that much of the anti-cardiolipin antibody (44-91%) was found in the H3+ fraction in patients with SLE; in patients with syphilis, virtually none of the anti-cardiolipin antibody was H3+. In patients with SLE, the H3+ fraction contained both IgG and IgM and antibodies of both kappa and lambda light chains. The H3+ fraction was polyspecific and frequently reacted with dsDNA.

Antibody Specificity↗

Age at first episode of venereal syphilis in an aboriginal population: an application of survival analysis.

OBJECTIVE: To identify the age at which screening for syphilis could be ceased in Kimberley Aboriginal people who had remained seronegative and whether this age was the same for people with and without a past history of gonorrhea. DESIGN: Retrospective cohort study. SETTING: The Kimberley region in the far north of Western Australia. PARTICIPANTS: Kimberley Aboriginal residents. MAIN OUTCOME MEASURE: Age at seroconversion. RESULTS: Survival analysis showed that seroconversion due to venereal syphilis occurred largely during the years between the late teens and early 20s. The probability of seroconverting by a given age was related to the time at which the subject's last gonorrhea infection occurred. CONCLUSIONS: As a result of this study, annual periodic screening for syphilis is now offered to Kimberley Aboriginal people only between the ages of 15 and 25 years, allowing for the redistribution of resources to other activities that have greater potential to decrease the incidence of all STDs.

Adolescent↗

Antenatal screening for hepatitis B infection and syphilis in the UK.

OBJECTIVES: To assess antenatal hepatitis B and syphilis screening policies in the UK. DESIGN: Postal questionnaire survey. SETTING: One hundred and ninety-two obstetric units and 116 Public Health directorates. MAIN OUTCOME MEASURES: Antenatal screening policy and line of responsibility for ensuring vaccine uptake in hepatitis B virus exposed children. RESULTS: Replies were received from 140 (73%) obstetric centres and 99 (85%) Public Health directors. Forty per cent of obstetric centres now offer hepatitis B virus tests to all pregnant women, and nearly one-quarter (24.1%) of all births in the UK in 1996 occurred in centres with a universal testing policy. The prevalence of chronic hepatitis B virus ranged from 0.3 to 17.5 per 1000 deliveries. Universal antenatal screening for serological evidence of syphilis was the norm, but five obstetric centres respondents and three Public Health directors were considering its discontinuation. In the nine London centres, syphilis prevalence was 2.06 per 1000 pregnant women, compared with 0.24 per 1000 elsewhere. Responses from Public Health directors indicated the nonspecific nature of the antenatal care contract. Responsibility for hepatitis B virus vaccination of the newly born infant rests with the hospital paediatrician, with transfer of responsibility to the community usually occurring through a discharge letter. Only two areas had a monitoring system to ensure full hepatitis B virus vaccination coverage of exposed infants. CONCLUSIONS: If antenatal screening policies are to be equitable there is a need for a clear national policy, and systems need to be established to monitor local policy and practice.

Female↗

Routine serological screening for syphilis during pregnancy--disposable anachronism or fundamental necessity?

Between 1984 and 1988 inclusive 34 patients with syphilis during pregnancy were identified in this unit by routine serological screening. There were 2 stillbirths in this group of patients giving a perinatal mortality rate of 59 per 1,000 total births. Analysis of the patients' history and physical examination findings did not reveal any predictive factors for sexually transmitted diseases in most cases. Despite the dramatic fall in the prevalence of syphilis both during pregnancy and the general population in Hong Kong, routine serological screening for syphilis during pregnancy must continue.

Female↗

Syphilis. An old disease, a contemporary perinatal problem.

The incidence of syphilis in the United States has almost doubled in the past 5 years, with some cities posting an increase of more than 500% during this period. As a result, greater numbers of neonates infected with congenital syphilis are treated in nurseries across the country. The incidence, pathogenesis, diagnosis, and treatment of syphilis are described, and the nursing implications associated with caring for those at risk of contracting the disease are presented.

Humans↗

Syphilis in an HIV infected patient misdiagnosed as leprosy.

A 42-year-old man with uveitis and a widespread cutaneous eruption, histopathologically characterized by dermal granulomatous infiltrates with perineurial invasion, was incorrectly diagnosed and treated as having borderline leprosy. Further studies demonstrated secondary syphilis and human immunodeficiency virus (HIV) infection. Standard penicillin therapy resolved his cutaneous and ocular lesions. Reports on clinical and pathological findings of active syphilis in HIV infected patients are scarce but this case and isolated previous case reports suggest that granulomatous infiltrates might be a common feature in secondary syphilis with short evolution in HIV infected patients.

Adult↗

Studies on the Treponema pallidum immobilizing activity in normal human serum. 5. On the protective role against syphilis.

It was shown that T. pallidum immobilized in vitro by normal serum had lost its infectivity in rabbits. This finding suggested that the immobilizing activity of normal serum might play a role in the natural resistance of man against infections with T. pallidum. However, the results of serological studies of acquired early syphilis in man and of experimental syphilis in cynomolgus monkeys did not present evidence that the immobilizing activity of normal serum protected against syphilis infection.

Animals↗

Biological basis for syphilis.

Syphilis is a chronic sexually transmitted disease caused by Treponema pallidum subsp. pallidum. Clinical manifestations separate the disease into stages; late stages of disease are now uncommon compared to the preantibiotic era. T. pallidum has an unusually small genome and lacks genes that encode many metabolic functions and classical virulence factors. The organism is extremely sensitive to environmental conditions and has not been continuously cultivated in vitro. Nonetheless, T. pallidum is highly infectious and survives for decades in the untreated host. Early syphilis lesions result from the host's immune response to the treponemes. Bacterial clearance and resolution of early lesions results from a delayed hypersensitivity response, although some organisms escape to cause persistent infection. One factor contributing to T. pallidum's chronicity is the paucity of integral outer membrane proteins, rendering intact organisms virtually invisible to the immune system. Antigenic variation of TprK, a putative surface-exposed protein, is likely to contribute to immune evasion. T. pallidum remains exquisitely sensitive to penicillin, but macrolide resistance has recently been identified in a number of geographic regions. The development of a syphilis vaccine, thus far elusive, would have a significant positive impact on global health.

Amino Acid Sequence↗