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Cerebrospinal fluid tau protein is increased in neurosyphilis: a discrimination from syphilis without nervous system involvement?

OBJECTIVE: The objective of this study was to investigate the levels of tau protein in neurosyphilis. STUDY DESIGN: Total tau protein in the cerebrospinal fluid of 12 patients with neurosyphilis, 17 with syphilis without nervous system involvement, 14 controls, and 14 patients with Alzheimer disease of comparable age were analyzed. Double-sandwich enzyme-linked immunosorbent assay was used for measurements. RESULTS: Increased levels of cerebrospinal fluid total tau were observed in neurosyphilis (median [25th-75th percentile]: 349 pg/mL [312-429]) and in Alzheimer disease (543 [441-1017]) as compared with the controls (189 [106-220]) and syphilis without nervous system involvement (190 [160-223]). Using a cutoff level of 300 pg/mL, increased tau discriminated cases of neurosyphilis from syphilis without nervous system involvement with a sensitivity and specificity of 83% and 94%, respectively. CONCLUSIONS: These results indicate that increased total tau may be useful in the discrimination of neurosyphilis from syphilis without nervous system involvement.

Adult↗

Factors and the sociosexual network associated with a syphilis outbreak in rural North Carolina.

OBJECTIVE: An investigation was conducted to determine factors associated with a syphilis outbreak in a rural North Carolina county. STUDY DESIGN: A retrospective chart review was performed on 61 primary (PS), secondary (SS), and early latent (ELS) syphilis case patients reported in Columbus County between January 2001 and February 2002. Sociosexual network analysis was conducted using electronic contact tracing information. RESULTS: We identified 20 PS, 25 SS, and 16 ELS case patients who were predominantly black. Seventy-two percent had reported >or=1 sexual partner with early syphilis, 51% used crack cocaine and/or had sex with a crack-using partner, and 31% exchanged sex for drugs or money. The sexual network exhibited predominantly linear connections between case patients and sexual partners. Adding social connections to the network further demonstrated dense cyclic interactions characteristic of core groups. CONCLUSIONS: The syphilis outbreak in this rural community was associated with crack cocaine and exchange of sex for drugs in a densely interconnected sociosexual network.

Adolescent↗

Contact-tracing outcomes among male syphilis patients in Fulton County, Georgia, 2003.

OBJECTIVES: Contact tracing may be less effective in populations with casual sex partners such as male syphilis patients who report sex with men; this opinion is widely held, but few quantitative comparisons are available. GOAL: The goal of this study was to compare contact-tracing outcomes among male syphilis patients reporting sex with men (MSM) or with women only (MSWO). STUDY DESIGN: The authors conducted a record review of cases of early syphilis among MSM and MSWO comparing contact-tracing outcomes. RESULTS: Interviews of MSM case-patients resulted in higher mean numbers of contacts named and located per case than interviews of MSWO. Mean numbers of contacts of MSM and MSWO diagnosed with syphilis per case were not significantly different. The mean number of unlocatable sex partners per case was slightly higher for MSM than MSWO. CONCLUSION: This study comparing contact tracing by the same trained health department personnel demonstrated that outcomes of contact tracing were similar for MSM and MSWO.

Adolescent↗

Relapsing syphilis.

Although penicillin still remains highly effective for syphilis, concerns have been raised that current regimens may be inadequate for the treatment of early syphilis. We report the failure of benzathine penicillin in the treatment of secondary syphilis. Extensive tracing of sexual contact history failed to identify sources of possible reinfection; therefore, we believe that this case represents a treatment failure and an ensuing relapse of secondary syphilis.

Adult↗

Prevalence of HIV, hepatitis C and syphilis among injecting drug users in Russia: a multi-city study.

OBJECTIVES: To estimate the prevalence of HIV, hepatitis C virus (HCV) and syphilis in injecting drug users (IDUs) in Russia. METHODS: Unlinked anonymous cross-sectional survey of 1473 IDUs recruited from non-treatment settings in Moscow, Volgograd and Barnaul (Siberia), with oral fluid sample collection for HIV, HCV antibody (anti-HIV, anti-HCV) and syphilis testing. RESULTS: Prevalence of antibody to HIV was 14% in Moscow, 3% in Volgograd and 9% in Barnaul. HCV prevalence was 67% in Moscow, 70% in Volgograd and 54% in Barnaul. Prevalence of positive syphilis serology was 8% in Moscow, 20% in Volgograd and 6% in Barnaul. Half of those HIV positive and a third of those HCV positive were unaware of their positive status. Common risk factors associated with HIV and HCV infection across the cities included both direct and indirect sharing of injecting equipment and injection of home-produced drugs. Among environmental risk factors, we found increased odds of anti-HIV associated with being in prison in Moscow, and some association between official registration as a drug user and anti-HIV and anti-HCV. No associations were found between sexual risk behaviours and anti-HIV in any city. CONCLUSIONS: HIV prevalence among IDUs was markedly higher than city routine surveillance data suggests and at potentially critical levels in terms of HIV prevention in two cities. HCV prevalence was high in all cities. Syphilis prevalence highlights the potential for sexual risk and sexual HIV transmission. Despite large-scale testing programmes, knowledge of positive status was poor. The scaling-up of harm reduction for IDUs in Russia, including sexual risk reduction, is an urgent priority.

Adolescent↗

Treatment of maternal syphilis in rural South Africa: effect of multiple doses of benzathine penicillin on pregnancy loss.

OBJECTIVES: Despite few data, the treatment of syphilis in pregnant women using a single dose of benzathine penicillin is the standard of care in many resource-poor settings. We examined the effect of various doses of benzathine penicillin on pregnancy loss among women with a positive Rapid Plasma Reagin (RPR) test result in a rural South African district. METHODS: All pregnant women making their first antenatal care visit during pregnancy were screened for syphilis using the RPR test. Those testing positive were counselled to receive three weekly doses of benzathine penicillin, and received a partner notification card. Pregnancy outcomes were determined from facility records or home visits where necessary. RESULTS: Of 8917 women screened, 1043 (12%) had reactive syphilis serology; of those with titre data available, 30% had titres of 1:8 or greater. While 41% (n = 430) of women received all three doses as counselled, 30% (n = 312) received only one dose, and 20% (n = 207) did not return to the clinic to receive treatment. Among the 947 women with pregnancy outcome data available, there were 17 miscarriages and 48 perinatal deaths observed. There was a strong trend towards reduced risk of pregnancy loss among women receiving multiple doses of penicillin (adjusted OR for perinatal mortality for each additional dose received, 0.63; 95% CI, 0.48-0.84). CONCLUSIONS: While this association requires further investigation, these results suggest that there may be substantial benefit to providing multiple doses of benzathine penicillin to treat maternal syphilis in this setting.

Abortion, Spontaneous↗

Routine antenatal screening for syphilis in Lothian: a study of the results 1988 to 1994.

A retrospective study was carried out of the cases of positive syphilis serology detected by routine antenatal screening within Edinburgh (and surrounding district) over the six years 1988 to 1994. The study demonstrated a low incidence of syphilis with only 15 pregnancies in 58,445 screened. In eight cases serology and history were suggestive of late latent syphilis and in the remainder of previous infection which had been treated. All women were delivered of liveborn infants at term without stigmata of congenital syphilis. Lack of identifiable risk factors in women with positive serology suggests that routine rather than selective screening should continue.

Adult↗

Early diffuse alopecia in a neonate with congenital syphilis.

Neonatal alopecia has been described in many circumstances but never as a part of the constellation of signs in congenital syphilis. Common clinical features of early congenital syphilis include hepatosplenomegaly, skeletal deformities, hematologic disturbances, and mucocutaneous features such as rhinitis and maculopapular rash. Syphilitic alopecia has previously been described only in conjunction with secondary syphilis. In this article, we describe the first occurrence of alopecia in a neonate with congenital syphilis.

Adult↗

Transmission of syphilis by solid organ transplantation.

Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.

Adult↗

Laboratory diagnosis of congenital syphilis by immunoglobulin M (IgM) and IgA immunoblotting.

We screened cord blood or serum samples from 101 infants at risk for congenital syphilis and serum samples from their mothers for immunoglobulin G (IgG), IgM, and IgA antibodies to Treponema pallidum by western blotting (immunoblotting). Clinical evaluation showed that six infants had signs and/or symptoms consistent with congenital syphilis. The sera from five of these infants were IgM blot positive, and four were IgA blot positive. Four asymptomatic infants had serologic evidence of congenital syphilis. The sera from three of these infants were IgM blot positive, and two were IgA blot positive. However, the IgM reactivity of the serum from one asymptomatic infant, which was also IgA positive, was abolished by protein G treatment. An IgM capture enzyme-linked immunosorbent assay corroborated the presence of IgM antibodies in six of seven IgM blot-reactive sera. Overall, for detection of symptomatic congenital syphilis, a sensitivity of 83% for IgM blotting and 67% for IgA blotting was obtained. The significance of positive IgM or IgA Western blots for asymptomatic infants requires further study to confirm infection in these infants.

Blotting, Western↗

Defibrination of blood plasma for use in serological tests for syphilis.

Syphilitic plasma can be salvaged from discarded blood donations and converted to serum by defibrination. Sixty-nine units of plasma were treated with a stock solution of 100 U of thrombin per ml in 1 M calcium chloride and then with a 10% (wt/vol) solution of kaolin. Fibrinogen concentrations detected in initial plasma samples ranged from 94 to 4970 mg/liter (mean, 2532 mg/liter) for samples that were reactive by the rapid plasma reagin circle card test (RPR) and from 314 to 2742 mg/liter (mean 1528 mg/liter) for samples that were not reactive by the RPR. The treated samples showed no measurable fibrinogen remaining after the defibrination process. In the nontreponemal RPR for syphilis, 86% of the treated plasma samples retained the same endpoint titer as that of the initial plasma sample. When the Treponema pallidum passive-particle-agglutination test was used, 98% retained the same reactivity. In the Captia Syphilis-G enzyme immunoassay, 89% of the treated samples demonstrated no change in reactivity index, and in the fluorescent treponemal antibody absorption test, 96% showed no reduction in fluorescence. Human sera containing antibodies to syphilis are used at the Centers for Disease Control and Prevention for the preparation of reference controls or as samples for proficiency testing. Finding reactive sera is becoming more difficult due to the general decline of syphilis cases in the United States. The decreasing availability of these sera can be alleviated by salvaging plasma and converting it to serum.

Blood Specimen Collection↗

Immunoglobulin G subclasses of fluorescent anti-Treponema pallidum antibodies: evidence for sequential development of specific anti-T. pallidum immunoglobulin G responses in patients with early syphilis.

The development of immunoglobulin G (IgG) subclass-specific anti-Treponema pallidum antibodies during the course of syphilis in humans was studied with sera from 50 untreated male patients. The patients were divided into five diagnosis groups. In the fluorescent treponemal antibody test, which delineates the presence of cross-reacting antibodies, as well as specific antitreponema antibodies, IgG1, IgG2, and IgG3 subclass antibodies were already present during the seronegative primary stage. Specific antibodies, which were detected by the fluorescent treponemal antibody absorption test, were first present during the serotype-variable primary stage. These antibodies were almost exclusively of the IgG1 and IgG3 subclasses. In later stages, antibodies of other subclasses were detectable. Titration of IgG1 antitreponema antibodies in three electrophoretically different IgG fractions revealed an asymmetric distribution in these fractions during primary syphilis. The antibodies were largely confined to the most basic fraction during primary syphilis. A sudden change in the distribution was noted between the end of the primary stage and the secondary stage; an even distribution of IgG1 antitreponema antibodies existed in the late latent stage. These findings confirm and extend previous results from our laboratory. The development of antibodies detected by both tests is discussed in terms of a sequential stimulation of the immune system due to the presence of an extracellular layer covering the treponemas or, alternatively, in terms of a suppression of the immune response during early syphilis.

Adult↗

A new attempt to distinguish serologically the subspecies of Treponema pallidum causing syphilis and yaws.

In an effort to serologically differentiate syphilis from yaws, 69 monoclonal antibody species raised against Treponema pallidum subsp. pallidum were tested by immunoblotting for their reactivity with Treponema pallidum subsp. pertenue. All monoclonal antibodies reacted with antigens with the same molecular weight of both subspecies. Furthermore, no differences in reactivity between sera from yaws patients and from syphilis patients were found by Western blot (immunoblot) analysis of cell lysates of T. pallidum subsp. pallidum and T. pallidum subsp. pertenue. We tried to exploit the only known molecular difference between the subspecies. The subunits of the 190-kilodalton multimeric proteins TpF1 and TyF1 of T. pallidum subsp. pallidum and T. pallidum subsp. pertenue, respectively, have previously been shown to differ in one amino acid residue at position 40. In this study, no difference was found in immunoreactivity of TpF1 or TyF1 with either syphilis sera or yaws sera. Synthetic peptides based on the sequence of TpF1 and of TyF1 were used in an enzyme-linked immunosorbent assay with syphilis sera and yaws sera. Again, no difference in reactivity between the T. pallidum subsp. pallidum- and T. pallidum subsp. pertenue-derived peptides was observed.

Amino Acid Sequence↗

Validation of the INNO-LIA syphilis kit as a confirmatory assay for Treponema pallidum antibodies.

The commercially available diagnostic tests for syphilis are mostly based on the use of extracted antigens of Treponema pallidum. Pronounced cross-reactivities with other spirochete antigens are often reported. The aim of this study was to validate a novel multiparametric assay (the assay performed with the kit) INNO-LIA Syphilis for the confirmation of syphilis antibodies in a set of 840 documented human serum samples. All serum samples were previously tested at the French World Health Organization reference center for venereal diseases (Institute Alfred Fournier, Paris, France), with a consensus result provided for each sample. The study was conducted in two phases, with each phase involving a validation set (500 well-documented serum samples) and an exploratory set (340 serum samples) of serum samples, respectively. By measuring the sensitivity and specificity, we compared the result of the new assay with the consensus result on the basis of the results of a variable number of classical serological methods and clinical information when available. A sensitivity of 99.6% (95% confidence internal [CI], 98.5 to 99.9%) and a specificity of 99.5% (95% CI, 98.1 to 99.9%) were found for the new line immunoassay. Six of seven samples with indeterminate results by classical serology tested positive with the INNO-LIA Syphilis kit. This single multiparametric assay provides reliable confirmatory diagnostic information that must currently be obtained by the performance and interpretation of results of a combination of serological assays.

Antibodies, Bacterial↗

Comparative evaluation of nine different enzyme-linked immunosorbent assays for determination of antibodies against Treponema pallidum in patients with primary syphilis.

Nine different enzyme-linked immunosorbent assays (ELISAs) with a sonicate or recombinant proteins of Treponema pallidum as antigen have been evaluated comparatively by testing 52 highly selected sera from patients with primary syphilis, all negative in the microhemagglutination test for T. pallidum (MHA-TP). Eight tests exhibited greater sensitivity (48.5 to 76.9%) than the commonly used Venereal Disease Research Laboratory test (44.2%). Higher sensitivity could be related to (i) the volume and dilution of the serum, (ii) the design of the assay (capture and competitive tests showed higher sensitivity than sandwich-based assays), and (iii) the ability to detected specific immunoglobulin M antibodies. The specificity of the ICE Syphilis and the Enzygnost Syphilis tests was 99.5 and 99.8%, respectively, as determined by routine testing of 2, 053 unselected sera in comparison with the MHA-TP test. ELISAs tested offered high sensitivity in patients with primary syphilis; however, recommendations to use these tests as screening assays do need further data on specificity and reactivity in late stages of the disease.

Antibodies, Bacterial↗

Serodiagnosis of syphilis: antibodies to recombinant Tp0453, Tp92, and Gpd proteins are sensitive and specific indicators of infection by Treponema pallidum.

Syphilis serodiagnosis relies on a combination of nonspecific screening tests (antilipoidal antibodies) and Treponema pallidum-specific tests (anti-T. pallidum antibodies). We studied a group of six recombinant T. pallidum antigens for their sensitivities and specificities with sera from individuals with syphilis (n = 43), relapsing fever (n = 8), Lyme disease (n = 8), and leptospirosis (n = 9) and from uninfected individuals (n = 15). Three recombinant proteins, Tp0155, Tp0483, and Tp0751, demonstrated sensitivity values that ranged from 28 to 42%. In contrast, three other recombinant proteins exhibited the following sensitivity and specificity values: Tp0453, 100% sensitivity and 100% specificity; Tp92 (Tp0326), 98% sensitivity and 97% specificity; and Gpd (Tp0257), 91% sensitivity and 93% specificity. Tp0453, Tp92, and Gpd also were recognized by sera from individuals with early primary syphilis that were nonreactive with the antilipoidal Venereal Disease Research Laboratory test. The reactivities of syphilis patient sera with Tp0453, Tp92, and Gpd were proportional to the titers of these sera with the treponemal test MHA-TP (microhemagglutination assay for T. pallidum). Thus, the recombinant T. pallidum antigens Tp0453, Tp92, and Gpd show promise as diagnostic antigens in the enzyme-linked immunosorbent assay-based assay.

Antigens, Bacterial↗

The biological false positive reaction to serological tests for syphilis.

Acute and chronic biological false positive reactions to serological tests for syphilis are discussed. Three cases are presented, one showing an acute and one a chronic reaction, and one in which it was not possible to determine if the reaction was acute or chronic. Once a biological false positive reaction is found, serum from the patient should be tested at intervals for at least six months to determine if the reaction is acute or chronic. If a chronic reaction is found the patient should then be investigated to find the underlying cause. Problem sera from 753 patients are reviewed. Biological false positive reactions were shown by 47 sera and 257 sera gave results indicating they came from patients infected with syphilis. The reactive sera were divided into four groups: sera from blood donors, antenatal patients, cases of recent vaccination, and a miscellaneous group. It was found that in the first three groups the number of sera from patients showing biological false positive reactions was equalled or exceeded by the number showing syphilitic reactions. Biological false positive reactions in sera from cases of lepromatous leprosy and in sera from the inhabitants of the Okapa region of New Guinea are also discussed. It is concluded that sera which give reactive results to reagin detection tests for syphilis and come from patients known to have conditions which cause acute or chronic biological false positive reactions should never be dismissed as such. Experience has shown that a number of these sera will give reactive Treponema pallidum immobilization test results, that is, they come from patients who have or have had syphilis.

Adult↗

Chronic biological false-positive reactions to serological tests for syphilis in blood donors.

Problem sera from 375 blood donors were investigated for biological false-positive reactions to serological tests for syphilis. Problem sera are those sera in which submitting laboratories have found a reactive result to a screening test for syphilis. On each serum a cardiolipin Wassermann reaction, a Venereal Disease Research Laboratory test, a Reiter protein-complement fixation test, a Treponema pallidum immobilization test, and a fluorescent treponemal antibody absorption test were performed. Of the sera 49.9% were found to be non-reactive in all five tests, 28.8% gave results indicating a diagnosis of syphilis, and 21.3% showed biological false-positive reactions. There were 80 sera from blood donors which gave biological false-positive reactions. A further specimen of serum from 67 of these donors was tested after an interval of a minimum of six months. Sixty-six of the sera showed chronic biological false-positive reactions. Some donors were only found reactive for the first time after they had given very many donations of blood. It is concluded that sudden blood loss, as in blood donation, appears to stimulate the production of excess reagin in certain individuals, causing a chronic biological false positive reaction to serological tests for syphilis. This may only appear after several blood donations have been made.

Blood Donors↗