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Evaluation of the Bio-Rad syphilis IgG test performed on the CODA system for serologic diagnosis of syphilis.

The performance of the Bio-Rad Syphilis IgG EIA test as a "screen for syphilis" [testing first by EIA and then by the rapid plasma reagin (RPR) assay if the EIA was positive or equivocal] and as a confirmatory test was evaluated by comparing results to those obtained by CAPTIA Syphilis-G. Discrepancies were resolved by repeating both EIAs and/or the SeroDia TP-PA (a particle agglutination assay that replaced the microhemagglutination Treponema pallidum test). Both EIAs were totally automated, the Bio-Rad test using the AutoPrep instrument for pipetting and the CODA system to perform all of the steps required to complete the EIA and interpret results, and the CAPTIA test using the LabOTech(R) to accomplish both functions. Of 449 unselected sera submitted to "screen for syphilis," both EIAs agreed for 432 (96.2%) specimens: 395 negative, 36 positive, and one equivocal. Fifty-four specimens were positive or equivocal by one or both EIAs; 41 of these were RPR reactive. Three of these 41 were incorrectly called negative by Bio-Rad (sensitivity 92.7%), and there was 1 false-negative result by CAPTIA (sensitivity, 97.6%) (P, not significant). To further evaluate the Bio-Rad assay as a confirmatory test, 144 known RPR-reactive specimens were tested by both EIAs. Results agreed for 134 (93.1%): 123 positive, 11 negative. After resolving discrepancies, there were 3 false-negative and no false-positive results by Bio-Rad (sensitivity 97.8%, specificity 100%), and with CAPTIA there were no false-negative results and 1 false-positive (sensitivity 100%, specificity 91.7%) (P, not significant). The sensitivity of the Bio-Rad assay could be improved, without altering specificity, by lowering the cut-off value for equivocal results. In summary, the Bio-Rad Syphilis IgG EIA performed using the AutoPrep instrument and CODA system is a reliable, efficient method of syphilis testing.

Evaluation Studies as Topic↗

Networks of persons with syphilis and at risk for syphilis in Louisiana: evidence of core transmitters.

BACKGROUND AND OBJECTIVES: Differences in sociodemographic attributes and healthcare access may explain differences in regional sexually transmitted disease rates but don't fully explain why syphilis persists disproportionately in certain populations. GOAL OF THIS STUDY: To understand the behavioral epidemiology of syphilis, we conducted a social network analysis of persons with syphilis and their contacts and developed and applied a definition of core transmitters. STUDY DESIGN: We interviewed 10 index persons with primary or secondary untreated syphilis and 80 of their named sexual and social contacts. RESULTS: Fourteen (16%) of 90 interviewed persons met the definition of core transmitters, 9 of whom had past or current syphilis. The other interviewed persons had only moderately risky behaviors. Seventy-eight (42%) of the network sexual contacts were connected directly or indirectly to a core transmitter. CONCLUSION: This analysis suggests that syphilis transmission is maintained by a community with a small percentage of high-risk persons centrally placed amidst a larger group with moderately risky behavior.

Adult↗

The syphilis reactor grid: help or hindrance for syphilis surveillance?

BACKGROUND: Health departments use reactor grids (sex, age, and serologic test for syphilis [STS] titer criteria) to determine which persons to evaluate for untreated syphilis. GOAL: The goal of the study was to assess reactor grid performance in Chicago and reactor grid use nationally in 1999 to 2000. STUDY DESIGN: We reviewed Chicago health department records to identify characteristics of persons with a reactive STS excluded from evaluation by reactor grid criteria and syphilis cases not meeting evaluation criteria. We surveyed health departments regarding reactor grid use. RESULTS: Of persons with a reactive STS, 46% did not meet criteria for health department evaluation, including 62% of men, 29% of women, and 21% with titers > or =1:8. The reactor grid would have excluded 17% of primary syphilis cases. Overall, 82% of health departments use reactor grids. CONCLUSIONS: Reactor grids are widely used and may exclude persons with infectious syphilis from health department evaluation, especially men. The impact of reactor grid use on syphilis control and surveillance in the United States should be evaluated.

Adolescent↗

Evaluation of INNO-LIA syphilis assay as a confirmatory test for syphilis.

We evaluated the sensitivity and specificity of a new confirmatory test for treponemal antibodies, INNO-LIA Syphilis (Innogenetics NV, Ghent, Belgium), on a large number of sera from a clinical laboratory. This multiparameter line immunoassay (LIA) uses recombinant and synthetic polypeptide antigens derived from Treponema pallidum proteins. In a single-blinded cross-sectional retrospective study, 289 seronegative sera, 219 seropositive sera, and 23 sera with an indeterminate serological status for syphilis were analyzed. All sera were tested by the T. pallidum hemagglutination assay (TPHA), the immunoglobulin (IgG)-fluorescent T. pallidum absorption assay (IgG-FTA-ABS), and the Venereal Disease Research Laboratory (VDRL) test. In addition, some seropositive samples were analyzed by the 19S-IgM-FTA-ABS test, an enzyme immunoassay (IgM-EIA), and the MarDx immunoblotting assay. Based on a consensus diagnosis derived from conventional serology, all of the sera were classified as positive, negative, or indeterminate, and the results were compared with the findings of the INNO-LIA Syphilis assay. The sensitivity and specificity of the LIA were 100% (219 of 219) and 99.3% (286 of 288), respectively. Compared to TPHA and IgG-FTA-ABS, the new test gave a significantly higher number (P = 0.021 and P < 0.0001, respectively) of correct results than either of the other two tests. The multiparameter INNO-LIA Syphilis assay is a useful confirmatory test for syphilis because it increases the reliability of syphilis diagnosis with respect to current conventional techniques.

Antibodies, Bacterial↗

Serological diagnosis of syphilis. PHLS Syphilis Serology Working Group.

The availability of an increasing number of enzyme immunoassays (EIAs) for detecting syphilis antibodies makes it appropriate to review approaches to syphilis serology and to assess the role of syphilis EIAs in routine diagnostic microbiology laboratories. This paper summarises the principles and practice of syphilis serology and provides recommendations on the use of laboratory tests for syphilis in UK diagnostic microbiology laboratories. The main recommendations are summarised in a testing algorithm. Treponemal EIAs are an appropriate alternative to the use of combined Venereal Disease Research Laboratories/rapid plasma reagin and Treponema pallidum haemagglutination assay (TPHA) tests for screening for syphilis. If a treponemal EIA is used for screening an alternative treponemal test, such as TPHA, should be used for confirmatory testing. The fluorescent treponemal antibody-absorbed test is probably best reserved for specimens giving discrepant results. Such specimens may be referred to the PHLS laboratories that provide confirmatory treponemal testing for reference testing and to facilitate collection of surveillance data on what remains an important public health problem.

Algorithms↗

Treatment of syphilis in pregnancy and prevention of congenital syphilis.

Studies about the management of syphilis during pregnancy were reviewed. They lacked uniformity in diagnostic criteria and study design. Currently recommended doses of benzathine penicillin G are effective in preventing congenital syphilis in most settings, although studies are needed regarding increased dosing regimens. Azithromycin and ceftriaxone offer potential alternatives for penicillin-allergic women, but insufficient data on efficacy limit their use in pregnancy. Ultrasonography provides a noninvasive means to examine pregnant women for signs of fetal syphilis, and abnormal findings indicate a risk for obstetric complications and fetal treatment failure. Ultrasonography should precede antepartum treatment during the latter half of pregnancy to gauge severity of fetal infection. However, optimal management of the affected fetus has not been established; collaborative management with a specialist is recommended. Antepartum screening remains a critical component of congenital syphilis prevention, even in the era of syphilis elimination.

Female↗

Analysis of the operational costs of using rapid syphilis tests for the detection of maternal syphilis in Bolivia and Mozambique.

OBJECTIVE: The objective of this study was to compare the costs of antenatal syphilis screening with the rapid plasma reagin (RPR) test and the immunochromatographic strip (ICS) test in low-resource settings. GOAL: The goal of this study was to assess the costs of introducing rapid syphilis tests to reduce maternal and congenital syphilis. STUDY DESIGN: Cost data were collected from participating study hospitals and antenatal clinics during 4 field visits to the 2 countries in 2003 and 2004. Health utilization outcome data on the number of women screened and treated routinely during the demonstration projects were used with unit cost data to estimate the incremental costs and average cost per woman screened and treated for maternal syphilis. RESULTS: In Mozambique, the average cost per woman screened was U.S. $0.91 and U.S. $1.05 for the RPR and ICS tests, respectively. In Bolivia, the average cost of screening was U.S. $1.48 and U.S. $1.91 using the RPR and ICS test, respectively. In health centers without laboratories, the cost per woman screened using the ICS test ranged from U.S. $1.02 in Mozambique to U.S. $2.84 in Bolivia. CONCLUSIONS: It is feasible to introduce rapid syphilis testing in settings without laboratory services at a small incremental cost per woman screened. In settings with laboratories, the cost of ICS is similar to that of RPR.

Ambulatory Care Facilities↗

Evaluation of the serodia Treponema pallidum particle agglutination, the Murex Syphilis ICE and the Enzywell TP tests for serodiagnosis of syphilis.

We evaluated the Treponema pallidum haemagglutination assay (TPHA), a treponemal test, with three other treponemal tests, the Serodia T. pallidum particle agglutination assay, the Murex Syphilis ICE IgG + IgM enzyme immunoassay (EIA) and the Enzywell TP IgG + M EIA (a new rapid EIA) for use in conjunction with the rapid plasma reagin test (RPR), a non-treponemal test, for serodiagnosis of syphilis. In all, 124 serum samples were found reactive with RPR and/or TPHA after testing by the routine laboratory protocol. Twenty-three (18.5%) of them were positive only by RPR test and were evaluated as biologically false-positive, 16 were positive only by the TPHA and 84 by both the RPR and TPHA tests; one sample was non-specific (heterophile reaction) in the TPHA. Agreements of the TPHA with the Serodia TPPA, the Murex Syphilis ICE and the Enzywell TP tests were 96.7%, 100% and 99.1%, respectively. We conclude that each one of the tests, the Serodia TPPA, the Murex Syphilis ICE and the Enzywell TP, is an appropriate substitute for screening for serodiagnosis of syphilis.

Antibodies, Bacterial↗

The decentralization of syphilis screening for improved care in Jamaican public clinics. Collaborative Working Group on Decentralized Syphilis Screening.

OBJECTIVES: This study examined the decentralization of syphilis screening for improved care in Jamaican public clinics. METHODS: One of every five serum samples tested at the six peripheral sites was frozen and retested at the central laboratory in Kingston. Patient files and laboratory logbooks were compared over a 3-month period. RESULTS: Between May 1993 and December 1994, 15.5% of 32913 patients with sexually transmitted diseases and 8.3% of 8914 women seeking prenatal care were found syphilis seroreactive. Of 2001 samples evaluated, 1933 (96.6%) had been correctly reported at the peripheral sites. Of 129 syphilis seroreactors detected at the peripheral sites, 88 (68%) were treated the same day and 21 (16%) more within 3 days after testing. CONCLUSIONS: Syphilis seroreactors were accurately detected and quickly treated at the peripheral sites. If these efforts can be sustained, Jamaican syphilis rates should decrease.

Ambulatory Care Facilities↗

Is syphilis resurgent in New Zealand in the 21st century? A case series of infectious syphilis presenting to the Auckland Sexual Health Service.

Bacterial sexually transmitted infections such as chlamydia and gonorrhoea have been on the rise in recent years in New Zealand. Infectious syphilis has however remained rare over the last few decades, except in New Zealanders who have had sex overseas or in recent immigrants. However, in the previous 2 and a half years (1/2002-9/2004), the number of people presenting to Auckland Sexual Health Service with infectious syphilis has more than doubled. The main people at risk for acquiring infectious syphilis appear to be either men who have sex with men, or heterosexuals who have recently had sex overseas. More information is urgently required about the epidemiology of syphilis in New Zealand. One expedient way to determine whether we have an emerging epidemic would be to make syphilis a notifiable condition.

Adult↗

A randomized trial of enhanced therapy for early syphilis in patients with and without human immunodeficiency virus infection. The Syphilis and HIV Study Group.

BACKGROUND: Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus (HIV) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis. METHODS: In a multicenter, randomized, double-blind trial, we assessed two treatments for early syphilis: 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid. The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up. RESULTS: From 1991 through 1994, 541 patients were enrolled, including 101 patients (19 percent) who had HIV infection but differed little from the uninfected patients in their clinical presentations. The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status. Serologically defined treatment failures were more common among the HIV-infected patients. The single clinically defined treatment failure was in an HIV-infected patient. Rates of serologically defined treatment failure did not differ according to treatment group (18 percent at six months with usual therapy; 17 percent with enhanced therapy). T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients (24 percent) and after therapy in 7 of 35 patients tested. None had clinically evident neurosyphilis, and the rate of detection of T. pallidum did not differ according to HIV status. CONCLUSIONS: After treatment for primary or secondary syphilis, the HIV-infected patients responded less well serologically than the patients without HIV infection, but clinically defined failure was uncommon in both groups. Enhanced treatment with amoxicillin and probenecid did not improve the outcomes. Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested, such a finding did not predict treatment failure. The current recommendations for treating early syphilis appear adequate for most patients, whether or not they have HIV infection.

Adult↗

Evaluation of the DCL Syphilis-G enzyme immunoassay test kit for the serologic diagnosis of syphilis.

Sera have been submitted to the authors' laboratory for syphilis testing at a dramatically increased rate since the start of the human immunodeficiency virus type 1 epidemic. Thus they were interested in evaluating a new enzyme immunoassay, the DCL Syphilis-G test kit (DCL-G, Diagnostic Chemicals Ltd., Oxford, CT) for detection of immunoglobulin G antibodies to Treponema pallidum. The enzyme immunoassay format, with its potential for automation, is ideally suited for large volume batch testing. Five hundred eighty-five sera collected primarily from pediatric patients were subjected to rapid plasma reagin and DCL-G testing. The patients ranged in age from 1 day to 45 years (mean, 14.4 years). Sera yielding positive or equivocal results in duplicate by either method were tested further for T. pallidum immunoglobulin G and M antibodies by the fluorescent treponemal antibody absorbed test and the DCL Syphilis-M test kit. The sensitivity and specificity of DCL-G, considering the combined rapid plasma reagin and fluorescent treponemal antibody absorbed results as the reference, were 100% and 99.8%, respectively. It was concluded that the DCL-G assay was a simple, efficient, and accurate method for obtaining confirmed serologic evidence of past or present syphilis.

Adolescent↗

Comparison of CAPTIA syphilis G enzyme immunoassay with rapid plasma reagin test for detection of syphilis.

The CAPTIA Syphilis G enzyme-linked immunosorbent assay compared favorably with the rapid plasma reagin test when used to screen for syphilis in a low-risk population. The sensitivity and specificity of the CAPTIA Syphilis G test were 100 and 97.8%, respectively, for 646 routine specimens and 100 and 99.2%, respectively, for 265 specimens from obstetrics patients. Overall, for 911 specimens, the CAPTIA Syphilis G test showed a sensitivity of 100%, a specificity of 98.2%, and positive and negative predictive values of 78.9 and 100%, respectively. For the same population, the rapid plasma reagin test showed a sensitivity and a specificity of 96.4 and 97.5%, respectively, and positive and negative predictive values of 72 and 99.8%, respectively.

Antibodies, Bacterial↗

UK National Audit of Early Syphilis Management. Clinics audit: screening for and management of early syphilis.

Data were provided by 131 clinics, and 56% of cases were managed in clinics in the London regions in 2003. Three clinics (2%) do not routinely screen new patients for syphilis, and 28 clinics (21%) do not routinely screen 'rebook' patients who have had a new partner. More than 80% of clinics routinely conduct cardiovascular and neurological examinations, although chest radiography is only performed by 50% of clinics and lumbar puncture by 13%. Only 19 (14%) clinics indicated not routinely using the recommended procaine penicillin G (PPG) regimen or one- or two-dose benzathine penicillin G (BPG) regimens for early syphilis, with 57% providing two doses of BPG 2.4 g, 40% providing PPG 750 mg for 10 days, and 15% providing one dose of BPG 2.4 g. Only seven clinics (5%) indicated that they provided treatment for early syphilis with PPG that is inferior to that recommended in the national guidelines. Only 18 clinics specified using the recommended dose and duration (or in excess of this) of PPG for neurosyphilis for cases with HIV infection. Provision for management of severe penicillin reaction is good, although few patients are desensitized. All clinics report that contact tracing for early syphilis is provided, and is mainly the responsibility of health advisers. Compared with auditing outcomes, audit of management policies overestimated performance in contact tracing and provision of dark ground microscopy.

Anti-Bacterial Agents↗

Syphilis testing in association with gonorrhea/chlamydia testing during a syphilis outbreak.

We used an electronic medical records system retrospectively to evaluate how frequently, in a public hospital and its clinics, combined gonorrhea/chlamydia tests were accompanied by a syphilis test before and during a syphilis outbreak. Among 70,330 gonorrhea/chlamydia tests (1996-2000), the proportion with a syphilis test increased from 13% (preoutbreak) to 50% (intervention period) for men and from 6% to 13% for nonpregnant women. The increased syphilis testing coincided with a multifaceted public health intervention.

Adult↗

Syphilis among parturients at an inner city hospital: association with cocaine use and implications for congenital syphilis rates.

The frequency of positive cord blood rapid plasma reagin (RPR) tests among newborns at an inner city hospital and associations with maternal cocaine use, prenatal care, and adequacy of syphilis therapy were retrospectively assessed. The incidence of positive cord blood RPRs increased from 1.1% of all live births in 1985 to 3.4% in 1988. In 1987, 98 babies were born with positive cord blood RPRs; 86 of their charts were available for review. Four infants had false positive RPRs, and one patient delivered twins, leaving 81 mothers who could be evaluated. Almost 37% of these patients had had no prenatal care. More than 55% had inadequate or not therapy for syphilis. Of these, only 17.4% had prenatal care. Slightly more than 40% of patients acknowledged using drugs during pregnancy, 87.9% of whom used cocaine. Among the patients who used drugs, 75.8% received no prenatal care, in contrast to 10.4% of mothers who did not use drugs (p less than 0.001). It appears that drug use, particularly use of cocaine, is associated with low levels of utilization of prenatal services and inadequate therapy for syphilis. This may lead to increased risk of congenital syphilis in newborns.

Cocaine↗

Mathematical modeling of epidemic syphilis transmission. Implications for syphilis control programs.

BACKGROUND AND OBJECTIVES: The past 10 years' wave of syphilis epidemics has challenged syphilis control programs. Although apparently connected to drugs-for-sex trading of crack cocaine, the genesis and resolution of these epidemics is poorly understood. GOALS OF THE STUDY: The goals of this study were to develop a mathematical model of epidemic syphilis transmission based on empiric data, to stimulate and ascertain behavioral and sociologic features necessary to produce epidemic transmission, and to explore mechanisms leading to resolution of epidemic transmission. STUDY DESIGN: The study used multi-compartment iterative computer simulation using empirically derived input data. RESULTS: Epidemic transmission resulted from adding a small core group of individuals with very high levels of partner exchange (300-400 partners per year) to a population with levels of partner exchange seen in the general population. Epidemic resolution could result from immunity or subtle changes in the size or partner exchange rate of the core group. CONCLUSION: There is a need for sexually transmitted disease control programs to reevaluate their approach to prevention and control of epidemic syphilis in light of data on transmission dynamics.

Adolescent↗

Use of the Treponema pallidum-specific captia syphilis IgG assay in conjunction with the rapid plasma reagin to test for syphilis.

The Captia Syphilis IgG enzyme immunoassay (EIA) was evaluated for use in conjunction with the rapid plasma reagin test (RPR) as a method to test for syphilis. A total of 1,288 serum specimens were tested by the routine laboratory protocol of the RPR followed by microhemagluttination assay for Treponema pallidum (MHA-TP) testing of RPR-reactive sera as well as the EIA-RPR protocol in which the automated EIA followed by a manual RPR test for EIA-positive specimens is used. When using the routine protocol, 131 specimens were initially reactive by the RPR, and 113 of these were reactive by MHA-TP. When using the EIA-RPR protocol, 170 specimens were initially positive by EIA, and of these, 112 were RPR reactive, indicating active disease. When compared to the routine protocol, the EIA-RPR protocol had sensitivity, specificity, and positive and negative predictive values of 96.5, 99.7, 97.3, and 99.7%, respectively. After resolution of discrepancies by additional testing, the adjusted sensitivity, specificity, and positive and negative predictive values were 100, 99.8, 98.3, and 100%, respectively. This evaluation demonstrates that when used in conjunction with the RPR, the Captia Syphilis EIA is a reliable method by which to test for syphilis.

Antibodies, Bacterial↗