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Performance of rapid syphilis tests in venous and fingerstick whole blood specimens.

OBJECTIVE: Rapid syphilis screening could facilitate case-identification during U.S. outbreaks. GOAL: The goal of this study was to determine the performance of 3 rapid syphilis tests in whole blood specimens in the laboratory and in patients at a sexually transmitted disease (STD) clinic. STUDY: We tested whole blood samples from STD clinic patients with 3 rapid tests and compared results with the serum treponemal pallidum particle agglutination (TP-PA) test. We evaluated the best performing of the 3 rapid tests on fingerstick specimens from STD clinic patients. RESULTS: The Abbott Determine TP (n = 127) had the highest sensitivity (88%; 95% confidence interval [CI], 81-96%) and lowest rate of indeterminate tests (0.8%), followed by Guardian Biosciences One Step (n = 116) (sensitivity 72%; 95% CI, 60-84%; indeterminate 6.5%), and Phoenix Biotech Trep-Strip IV (n = 71) (sensitivity 70%; 95% CI, 54-85%; indeterminate 30.3%). All 3 tests were 100% specific. The Abbott Determine TP showed excellent performance on fingerstick specimens (n = 99), exhibiting 100% sensitivity (95% CI, 93-100%), 100% specificity, and 2.9% indeterminate. CONCLUSIONS: The Abbott Determine TP test was an easy and accurate test that could facilitate rapid detection of syphilis in at-risk patients.

Adult↗

Depressed CD4/CD8 ratio in TPHA-negative patients with syphilis.

The Treponema pallidum hemagglutination assay (TPHA) is a widely used method for screening syphilis. We report our experience with six elderly (age 72.4 +/- 8.3 years) patients with syphilis, whose TPHA was negative. Their cardiolipin (RPR) and absorbed fluorescence treponemal tests (FTA-ABS) were positive. TPHA-negative patients with syphilis were compared with TPHA-positive syphilitics by immunological analysis. We found that both the numbers and the percentage of CD4 cells in TPHA-negative syphilitics were significantly lower than those in TPHA-positive syphilitics (722 +/- 142 vs. 1,064 +/- 141/mm3, P less than 0.01: 35.1 +/- 6.9 vs. 48.4 +/- 6.4%, P less than 0.01) and that the ratio of CD4 to CD8 was also lower in TPHA-negative syphilitics compared with TPHA-positive syphilitics (1.08 +/- 0.46 vs. 2.24 +/- 1.07, P less than 0.05). These data suggest that the TPHA is insufficient for excluding elderly syphilitics because of immunological impairment seen in aged patients.

Adult↗

Extensive annular verrucous late secondary syphilis.

We report an illustrative case of an apparently healthy 38-year-old man with a past history of alopecia universalis who developed extensive, slightly pruritic, infiltrated annular verrucous lesions of the scalp, perioral, lumbar, perianal and genital areas over a 6-month period. The combination of an unusual clinical presentation, positive syphilis serology and rapid response to penicillin therapy was consistent with a diagnosis of extensive annular and verrucous late secondary syphilis. We present this case to illustrate a rare and potentially misleading clinical feature of late secondary syphilis, a disease considered to be of the past but still present in today's practice.

Adult↗

Bullous secondary syphilis.

An earlier standard syphilology textbook states that 'If vesicles are an essential part of an eruption in an adult, the lesions are not due to secondary syphilis'. However, vesicular and bullous eruptions do occur in congenital syphilis and rare reports of both vesicular and pustular eruptions in adults with secondary syphilis have been published. We describe a patient with a bullous-pemphigoid-like eruption and a positive VDRL in whom treatment with a course of procaine penicillin resulted in rapid permanent resolution of the eruption.

Adult↗

An unusual presentation of secondary syphilis in the Northern Territory.

OBJECTIVE: To present a case which demonstrates the unusual clinical features of secondary syphilis that may be encountered in tropical Australia. CLINICAL FEATURES: A syphilitic aetiology was initially missed in a Caucasian female presenting with a rare form of syphilis, "lues maligna", characterised by nodulo-ulcerative skin lesions, fever, meningism and a relapsing course. CONCLUSION: Secondary syphilis is usually manifest in the Northern Territory by a characteristic palmo-plantar psoriasiform eruption with variable involvement of skin in other body areas. The disease is most commonly seen in the young adult Aboriginal population. However, atypical presentations can occur and vigilance must be maintained for a syphilitic aetiology in unusual skin lesions. The disease may produce significant individual morbidity and may be transmitted non-venereally to close contacts in the secondary stage. Genital lesions facilitate the transmission of HIV, making early diagnosis and treatment even more important.

Adult↗

Interstitial keratitis in untreated latent (late) syphilis.

Untreated latent syphilis with interstitial keratitis is not uncommon in the older age group who may present with refractive problems. It is important to investigate these patients with a full range of serological tests for syphilis to determine whether they have been treated adequately in the past. If there is evidence of untreated latent syphilis, examination of the cerebrospinal fluid is important to exclude asymptomatic neurosyphilis for which intensive systemic therapy in hospital is indicated. If there is no evidence of central nervous system involvement a course of penicillin is still indicated, but may be given on an outpatient basis. This is illustrated by the histories of six patients who presented to The Royal Victorian Eye and Ear Hospital between 1962 and 1979.

Adult↗

Syphilis presenting as scleritis in an HIV-positive man undergoing immune reconstitution.

A 45-year-old HIV-positive man receiving highly active antiretroviral therapy (HAART) presented with 6 weeks of right-sided headache and right eye pain. He had been diagnosed seropositive 2 years previously and screened negative for syphilis at that time. Examination demonstrated focal anterior scleritis with underlying retinitis and a mild vitritis. He was found to have positive syphilis serology and further investigations were consistent with neurosyphilis. Parenteral penicillin was commenced with prompt clinical response. This initial presentation of syphilis as acute scleritis emphasizes the need for thorough work-up of immunocompromised patients with inflammatory ocular disease.

Antiretroviral Therapy, Highly Active↗

Serological screening for syphilis during pregnancy in a multiethnic Asian population.

Out of 14,841 women who were serologically examined for syphilis at the antenatal booking clinic, University Hospital, Kuala Lumpur in Malaysia, 1.78% were VDRL positive and 1.05% TPHA positive with significant differences between the Malays, Indians and Chinese. These rates are higher than published series and were attributed to childhood yaws infection among the Malays. As differentiation between yaws and syphilitic infection in the clinic is difficult, all TPHA-reactive women were treated as for syphilis. Congenital syphilis was not diagnosed in those women who had been effectively treated before delivery.

China↗

Laboratory diagnosis and interpretation of tests for syphilis.

The lack of a method for demonstrating the presence of Treponema pallidum by growth necessitates the use of alternative methods. Traditionally, these methods are divided into direct detection methods (animal inoculation, dark-field microscopy, etc.) and serologic tests for the presence of patient antibody against T. pallidum. Serologic methods are further divided into two classes. One class, the nontreponemal tests, detects antibodies to lipoidal antigens present in either the host or T. pallidum; examples are the Venereal Disease Research Laboratory and rapid plasma reagin and tests. Reactivity in these tests generally indicates host tissue damage that may not be specific for syphilis. Because these tests are easy and inexpensive to perform, they are commonly used for screening, and with proper clinical signs they are suggestive of syphilis. The other class of test, the treponemal tests, uses specific treponemal antigens. Confirmation of infection requires a reactive treponemal test. Examples of the treponemal tests are the microhemagglutination assay for antibodies to T. pallidum and the fluorescent treponemal antibody absorption test. These tests are more expensive and complicated to perform than the nontreponemal tests. On the horizon are a number of direct antigen, enzyme-linked immunosorbent assay, and PCR techniques. Several of these techniques have shown promise in clinical trials for the diagnosis of congenital syphilis and neurosyphilis that are presently difficult to diagnose.

Bacteriological Techniques↗

Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.

Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis.

Albumins↗

Evaluation of a Treponema pallidum western immunoblot assay as a confirmatory test for syphilis.

Tests for the detection of antibodies to Treponema pallidum are recommended for the confirmation of reactive nontreponemal test results and the accurate diagnosis of syphilis. The present-day use of Western blot (immunoblot) technology for the diagnosis of retroviruses prompted the development and evaluation of a Western blot assay with whole-cell T. pallidum as the antigen. The assay detected antibodies in syphilitic serum or plasma from dilutions of specimens incubated overnight with test strips. A test was considered positive when at least three of four major antigens having molecular masses of 15.5, 17, 44.5, and 47 kDa were detected. The Western blot assay had 93.8% sensitivity and 100% specificity for clinically defined samples. The Western blot assay was compared with double-staining fluorescent treponemal antibody absorption [FTA-ABS (DS)], which had a sensitivity and a specificity of 91.7 and 92.0%, respectively. Dilution series studies of syphilis-positive specimens indicated that the Western blot assay has an endpoint of reactivity at least 3 to 4 serial dilutions greater than that for FTA-ABS (DS). Overall, the greater than 95% agreement between the Western blot assay and FTA-ABS (DS) for clinically defined specimens indicates that the sensitivity of the Western blot assay is equal to or greater than that of FTA-ABS (DS). The Western blot assay demonstrated no false-positive or equivocal reactivities for nonsyphilitic specimens, including normal specimens (both plasma and serum), biological false-positives, and specimens with elevated gamma globulin or antinuclear antibody. We conclude that the high sensitivity and specificity of the T. pallidum Western blot assay, together with its simplicity and objectivity, make it a good confirmatory test for syphilis.

Animals↗

Umbilical cord sclerosis as an indicator of congenital syphilis.

In two cases of congenital syphilis examination of the umbilical cord showed a distinctive picture of perivascular sclerosis and inflammation. Large numbers of spirochaetes were shown in the sclerotic zone in both cases. No organisms were demonstrable in the placental disc and there were no morphological changes suggestive of syphilis. It is concluded that the finding of sclerosing funisitis, together with the clinical circumstances, should raise the possibility of congenital syphilis.

Adolescent↗

Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests for syphilis.

OBJECTIVES: To evaluate prospectively four rapid, point-of-care serological tests for syphilis in prenatal or high risk populations in four countries. METHODS: Tests were performed on consecutive clinic attenders, using whole blood in the clinic, and whole blood and serum in the laboratory. The sensitivity and specificity of each test was evaluated, using a standard treponemal test (Treponema pallidum haemagglutination assay (TPHA) or fluorescent treponemal antibody, absorbed (FTA-ABS) as gold standard. Non-treponemal tests (rapid plasma reagin (RPR) or venereal diseases research laboratory (VDRL) tests) were also performed on all subjects at three sites. RESULTS: The specificity of each rapid test was >95% at each site. Sensitivities varied from 64-100% and, in most cases, were lower when whole blood was used rather than serum. CONCLUSIONS: Rapid serological tests for syphilis are an acceptable alternative to conventional laboratory tests. Since they do not require equipment or electricity, they could increase coverage of syphilis screening, and enable treatment to be given at the first clinic visit.

Adolescent↗

Quantitative evaluation of the FTA-ABS-IgM and VDRL test in treated and untreated syphilis.

Observations made on fluorescent treponemal antibody absorption (FTA-ABS) immunoglobulin M (IgM) titres in patients with untreated early syphilis showed non-reactive or weakly reactive results in patients with primary (one of five cases) and secondary (two of 16 cases) lesions. In patients with primary (19.5%) and secondary (15%) syphilis sera remained reactive with increased titres for more than one year after treatment. The respective figures in the results of the Venereal Disease Research Laboratory (VDRL) test were zero in primary and 20% in secondary syphilis. The non-reactive FTA-ABS IgM results may possibly be explained by competitive inhibition of IgM by immunoglobulin G (IgG). The persistence of reactivity in a comparable percentage has been observed by other investigators (Grin et al., 1974; Wilkinson and Rodin, 1976). The current results therefore suggest that FTA-ABS IgM titres are less reliable for assessing the effect of treatment than the course of the VDRL titres. The phenomenon of a decrease in FTA-ABS IgM titres soon after treatment with a later rise before final non-reactivity is a matter for further investigation.

Adult↗

A patient with primary syphilis of the hand.

The case history of a man with primary syphilis of the right hand is described. This type of luetic condition nowadays is rare. The incidence of genital, anorectal, and extragenital primary syphilis in both men and women and in sailors presenting at the Venereological Outpatient Clinic of the Department of Dermatology of the University Hospital Rotterdam-Dijkzigt during a period of seven years was studied. In sailors and women only genital primary lesions were found, whereas in male civilians 6.3% of cases of primary syphilis had anorectal lesions. The primary lesions in this study were different from those reported in earlier literature.

Adult↗

Fluctuations in natural killer cell activity in early syphilis.

The natural killer cell activity was studied in 25 patients with primary, secondary, or latent syphilis before and after treatment. In primary syphilis natural killer cell activity was increased, especially in patients lacking circulating lipoidal antibodies. In patients who had become seroreactive in the lipoidal tests it was depressed in those with secondary and latent syphilis. The natural killer cell activity thus becomes activated by the syphilitic infection but is significantly reduced during progression of the disease. The importance of the natural killer cell activity in controlling syphilitic infection is questionable.

Adolescent↗

Evaluation of an enzyme immunoassay for IgM antibodies to Treponema pallidum in syphilis in man.

An enzyme immunoassay (EIA) for the detection of immunoglobulin M (IgM) antibodies to Treponema pallidum was investigated for specificity and sensitivity. Using the results in serum from 1192 patients with successfully treated syphilis, the assay was calculated to be about 97% specific. As in any other IgM enzyme linked immunosorbent assay (ELISA), rheumatoid factor played an important part in causing false positive results. Pre-absorption of serum with aggregated IgG was therefore necessary to perform the test. Evaluation of the results in serum from 385 patients with untreated primary, secondary, and latent syphilis as well as patients with untreated reinfections showed that the sensitivity of the assay depended on the stage of infection and varied between 98% and 93%. IgM antibody titres were about ten times higher in the EIA than in the indirect immunofluorescence assay using the IgM fractions of serum. From the results it may be concluded that the EIA is an appropriate technique not only for rapid and sensitive measurement of IgM antibodies in most patients with untreated syphilis but also for selecting treponemal IgM non-reactive patients.

Antibody Specificity↗

Syphilis in women of reproductive age in Mogadishu, Somalia: serological survey.

In Mogadishu, Somalia 223 women of childbearing age, including prostitutes, were tested for serum markers for syphilis by the Venereal Disease Research Laboratory (VDRL) test and the Treponema pallidum haemagglutination assay (TPHA). Sera reactive in either of these tests were tested for IgM antibodies by solid phase haemadsorption assay (SPHA). Three per cent of sera from 67 pregnant women and none of those from 71 educated women gave positive results that were confirmed with the TPHA. In contrast, 58% of sera from 85 prostitutes were confirmed as being positive, 26% of which were SPHA positive, which indicated active syphilis. The proportion of TPHA positive sera increased with age among the prostitutes. As venereal syphilis is highly prevalent in prostitutes in Mogadishu, a strategy of intervention based on screening followed by treatment seems to be indispensable.

Adolescent↗