Serological tests for syphilis in Saudi Arabia.

A total of 6684 sera were initially screened for syphilis by the Venereal Disease Research Laboratory (VDRL) test and the Treponema pallidum haemagglutination assay (TPHA). Reactive sera from either or both these tests were tested for confirmation by the fluorescent treponemal antibody-absorbed (FTA-ABS) test. VDRL biological false positive reactors were detected in 0.5% of the total sera examined, with 0.4% and 0.8%, respectively, obtained in pregnant women and blood donors. Eight sera (0.1%) were found to be positive in the TPHA test alone. An overall positivity of 2.7% for syphilis was detected, with a 0.85% positivity in antenatal patients. Infection with T pallidum seemed to be more common in men than in women (1.6:1) and predominated in the age group 20-39 years. Serological testing of sera from 26 mother and infant pairs allowed one case of congenital syphilis to be detected by FTA-ABS (IgM) and identified VDRL biological false positivity in seven infants.     

Specificity of the FTA-ABS and TPHA tests during pregnancy.

In order to determine whether pregnancy influences the specificity of the fluorescent treponemal antibody absorption (FTA-ABS) and Treponema palidum haemagglutination assay (TPHA) tests, these tests, together with the quantitative fluorescent treponemal antibody (FTA) and Venereal Disease Research Laboratory (VDRL) tests, were carried out simultaneously on 2000 pregnant women who attended for compulsory prenatal screening. In only one patient (0.05% of the total investigated) was a positive result to the TPHA test obtained, the specificity of which it was impossibile to confirm. The FTA-ABS test gave a weakly reactive result of the borderline type but this was found to be non-specific in only four (0.2%) patients. The results of our investigations showed that the specificity of the FTA-ABS and the TPHA tests performed on pregnant women did not differ from the specificity of these tests when carried out on other population groups.     

Specificity of the FTA-ABS and TPHA tests during pregnancy.

In order to determine whether pregnancy influences the specificity of the fluorescent treponemal antibody absorption (FTA-ABS) and Treponema palidum haemagglutination assay (TPHA) tests, these tests, together with the quantitative fluorescent treponemal antibody (FTA) and Venereal Disease Research Laboratory (VDRL) tests, were carried out simultaneously on 2000 pregnant women who attended for compulsory prenatal screening. In only one patient (0.05% of the total investigated) was a positive result to the TPHA test obtained, the specificity of which it was impossibile to confirm. The FTA-ABS test gave a weakly reactive result of the borderline type but this was found to be non-specific in only four (0.2%) patients. The results of our investigations showed that the specificity of the FTA-ABS and the TPHA tests performed on pregnant women did not differ from the specificity of these tests when carried out on other population groups.     

Enzyme linked immunosorbent assays with Treponema pallidum or axial filament of T phagedenis biotype Reiter as antigen: evaluation as screening tests for syphilis.

Enzyme linked immunosorbent assays with an ultrasonicate of Treponema pallidum (TP-ELISA) or axial filament of Treponema phagedenis biotype Reiter (AF-ELISA) were developed to detect treponemal antibody. TP-ELISA and AF-ELISA were compared with the T pallidum haemagglutination assay (TPHA), the fluorescent treponemal antibody-absorbed (FTA-ABS) test, and the Venereal Disease Research Laboratory (VDRL) test for sensitivity and specificity of serodiagnosis of syphilis. A total of 1423 serum samples, 253 from patients with various stages of syphilis, 500 from patients attending a sexually transmitted disease (STD) clinic, and 670 from people without syphilis, were investigated. At all stages of syphilis the sensitivity of the TP-ELISA, the AF-ELISA, the TPHA, and the FTA-ABS test did not differ significantly, except that the AF-ELISA was less sensitive than the TPHA (p less than 0.05) for treated syphilis. In primary syphilis, neurosyphilis, and treated syphilis the TP-ELISA and AF-ELISA were significantly more sensitive than the VDRL test (p less than 0.05). The specificity of all tests was comparable (p greater than 0.05). The TP-ELISA and AF-ELISA appear to be good alternatives to the TPHA as screening tests for syphilis. Because of the easy availability of a well defined antigen the AF-ELISA seems to be better suited for large scale testing.     

Screening for treponemal infection by a new enzyme immunoassay.

A new enzyme immunoassay (EIA, Captia Syphilis-G) for detecting IgG antibodies against Treponema pallidum was evaluated as a screening test for syphilis. When serum samples were tested at a dilution of 1 in 20 (EIA20), the overall agreement between the IgG EIA and serological status based on the T pallidum haemagglutination assay (TPHA) and the fluorescent treponemal antibody absorption (FTA-ABS) test was 99.2% (1310/1321). The sensitivity of the EIA20 was 98.4% (60/61) and the specificity 99.3% (1251/1260). Discrimination between patients with and without treponemal infection was good: the mean EIA20 absorbance ratios (patient/mean low titre positive control results) were 0.49 for antibody negative patients, 3.30 for patients with positive Venereal Diseases Research Laboratory (VDRL) test and TPHA results, and 1.77 for patients with negative VDRL but positive TPHA results. The cut off point for excluding treponemal infection was taken as 0.9. Specimens with ratios of more than 0.9 should be confirmed by the FTA-ABS test and evaluated for specific IgM antibodies to treponemes. When serum samples were tested at a 1 in 50 dilution (EIA50) the sensitivity was lower (80.3%) but the specificity was absolute. The reduction in sensitivity correlated with low absorbance ratios in the patients who were VDRL negative and TPHA positive. The screening performance of the IgG EIA20 is thus comparable with that provided by a combination of the VDRL test and TPHA. The potential for automation makes the EIA an attractive alternative, particularly in larger centres. Alternatively, the test can be performed at a 1 in 50 dilution (EIA50), at which level it is ideally suited for confirming the treponemal status of antibodies in serum samples preselected by positive cardiolipin antigen screening test results.     

Biological false positive serological tests for syphilis in the Jamaican population.

A total of 19,067 sera were screened for biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test. Sera which were reactive in the VDRL test were confirmed by the fluorescent treponemal antibody absorption (FTA-ABS) test. BFP reactions were detected in 0.59% of the general population, 0.72% of pregnant women and 11.8% of patients with systemic lupus erythematosus (SLE). The rate of BFP reactors among pregnant women did not differ significantly from the general population. The female to male ratio of BFP in the general population was 2:1 whilst that in the group of patients with SLE was 8:1. The overall seroprevalence of syphilis was 2.2%.     

TPHA test. Experience at the Clinic of Dermatology, University of Milan.

The results of serological investigations with the treponemal haemagglutination (TPHA) test are reported in a large number of luetic and non-luetic patients. From these the following conclusions can be drawn: (1) The sensitivity of the TPHA test is decreased if the test is carried out with micromethods; however, in our opinion, the same degree of sensitivity can be obtained either with the macromethod at dilution 1/80-1/60 or with micromethods at 1/20-1/40. (2) The sensitivity of this test is high, being similar to that of the fluorescent treponemal antibody absorption (FTA-ABS) test in primary and secondary syphilis and even higher than that of the FTA-ABS test in treated subjects. (3) The specificity of the reaction is high, as demonstrated by examining sera in patients with a negative history and clinical examination together with negative results to Treponema pallidum immobilisation (TPI) and FTA-ABS tests, and by studying biological false positive sera. (4) For the serological screening, it may be sufficient to perform the TPHA test with the 1/20-1/40 micromethod together with the Venereal Disease Research Laboratory (VDRL) test. In patients with suspected syphilis, it is advisable to perform the TPHA test by the macromethod, in combination with the FTA-ABS test.     

Seroreversion of the serological tests for syphilis in the newborns born to treated syphilitic mothers.

BACKGROUND--IgG antibodies from mothers adequately treated for syphilis can cross the placenta and appear in the sera of healthy newborns without infection. In such infants, a false diagnosis of congenital syphilis is often made. We have designed a retrospective survey to determine the time of seroreversion of the serological tests for syphilis (STS) in uninfected newborns born to mothers who were adequately treated for syphilis. MATERIALS AND METHODS--Fifty two seropositive, untreated newborns born to 51 mothers treated for syphilis were studied. The newborns were followed at 1, 3, 6, 9, and 12 months of age until seroreversion was detected. The VDRL test was followed until 12 months in 12 of the 22 newborns who were positive at birth, the TPHA in 21 of the 46 newborns, and the FTA-ABS test in 22 of the 48 newborns. RESULTS--In the first serological tests done within 1 month after birth, the VDRL was positive in 22 newborns (42%), the TPHA in 46 (88%), and FTA-ABS in 48 (92%). The VDRL seroreverted within 6 months after birth in 84%, and within 1 year in 100%. The TPHA test seroreverted in 95% within 1 year after birth. The FTA-ABS test seroreverted in 100% within 1 year after birth. CONCLUSIONS--In most seropositive, untreated newborns born to treated mothers the VDRL became negative within 6 months after birth and the TPHA and FTA-ABS within 1 year. This result is consistent with current Centers for Disease Control (CDC) guidelines. However, although the CDC guidelines are adequate in general, we think that some revision is desirable concerning the IgM test and combination of the test results in order to rule out congenital syphilis in seropositive, nonsymptomatic newborns born to the treated mothers.     

Comparison of cardiolipin and treponemal tests in the serodiagnosis of yaws.

Results of the Veneral Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), Treponema pallidum haemagglutination (TPHA), T. pallidum immobilisation (TPI), and fluorescent treponemal antibody absorption (FTA-ABS) tests on sera of 661 children from a region where yaws is hypoendemic are compared. For 107 (16.2%) out of 661 sera the FTA-ABS test was the only one showing reactivity; in these instances the test was weakly reactive (intensity of fluorescence scored as +) and the children had no history and no signs or symptoms of treponemal disease. A solitary, weakly reactive FTA-ABS test result seems to have no clinical significance in these cases. The FTA-ABS test can be used as a confirmatory test for yaws instead of the TPI test, if only the results of sera showing an intensity of fluorescence scored as ++ or more are considered to be positive. There appeared to be no significant differences in the results of the VDRL, RPR, and TPHA tests as screening tests for yaws when the TPI or FTA-ABS tests were used as reference tests.     

TPHA test. Experience at the Clinic of Dermatology, University of Milan.

The results of serological investigations with the treponemal haemagglutination (TPHA) test are reported in a large number of luetic and non-luetic patients. From these the following conclusions can be drawn: (1) The sensitivity of the TPHA test is decreased if the test is carried out with micromethods; however, in our opinion, the same degree of sensitivity can be obtained either with the macromethod at dilution 1/80-1/60 or with micromethods at 1/20-1/40. (2) The sensitivity of this test is high, being similar to that of the fluorescent treponemal antibody absorption (FTA-ABS) test in primary and secondary syphilis and even higher than that of the FTA-ABS test in treated subjects. (3) The specificity of the reaction is high, as demonstrated by examining sera in patients with a negative history and clinical examination together with negative results to Treponema pallidum immobilisation (TPI) and FTA-ABS tests, and by studying biological false positive sera. (4) For the serological screening, it may be sufficient to perform the TPHA test with the 1/20-1/40 micromethod together with the Venereal Disease Research Laboratory (VDRL) test. In patients with suspected syphilis, it is advisable to perform the TPHA test by the macromethod, in combination with the FTA-ABS test.     

Comparison of cardiolipin and treponemal tests in the serodiagnosis of yaws.

Results of the Veneral Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), Treponema pallidum haemagglutination (TPHA), T. pallidum immobilisation (TPI), and fluorescent treponemal antibody absorption (FTA-ABS) tests on sera of 661 children from a region where yaws is hypoendemic are compared. For 107 (16.2%) out of 661 sera the FTA-ABS test was the only one showing reactivity; in these instances the test was weakly reactive (intensity of fluorescence scored as +) and the children had no history and no signs or symptoms of treponemal disease. A solitary, weakly reactive FTA-ABS test result seems to have no clinical significance in these cases. The FTA-ABS test can be used as a confirmatory test for yaws instead of the TPI test, if only the results of sera showing an intensity of fluorescence scored as ++ or more are considered to be positive. There appeared to be no significant differences in the results of the VDRL, RPR, and TPHA tests as screening tests for yaws when the TPI or FTA-ABS tests were used as reference tests.     

Clinical value of the Treponema pallidum haemagglutination test.

In 1,129 patients attending the Department for Sexually Transmitted Diseases, the serum was examined by three screening tests (VDRL slide, RPCF, and TPHA) and twelve cases of syphilis (1 per cent. of patients attenting the clinic) were discovered. Six of these patients were considered to have latent syphilis (5 acquired, 1 congenital) and were detected only by the TPHA; all six cases were confirmed by the FTA-ABS, The TPHA failed to detect three of the remaining six cases (2 primary and 1 very early, the latter in a contact of a patient with primary syphilis). All six cases were, however, detected by the VDRL. In seven cases, the TPHA was positive in the absence of other evidence of present or previous syphilis. In these cases the FTA-ABS was also negative. The clinical application of the TPHA test in the detection of syphilis is discussed.     

Prevalence of syphilis infection in Mozambican women with second trimester miscarriage and women attending antenatal care in second trimester.

OBJECTIVES--To elucidate whether recent syphilis infection is significantly more prevalent among women with mid-trimester miscarriage than among antenatal care attenders in midtrimester pregnancy. DESIGN--Two categories of pregnant women were compared regarding serological signs of syphilis. Rapid Plasma Reagin (RPR) analyses were done in Mozambique and Veneral Disease Research Laboratory (VDRL) tests in Sweden. In case of RPR and/or VDRL positivity, Treponema pallidum haemagglutination (TPHA) and Captia Syphilis-M were performed. SETTING--A suburban antenatal care clinic and the emergency ward at the Department of Obstetrics and Gynecology at the Central Hospital in Maputo, Mozambique, were studied June-August 1991. SUBJECTS--Randomly selected women seeking antenatal care in midtrimester pregnancy (N = 202) were compared with 114 women consecutively entering with clinical signs of midtrimester miscarriage. RESULTS--Among antenatal care attenders, 37/202 (18.3%), and among women with midtrimester miscarriage, 37/114 (32.5%), had syphilis confirmed with the Treponema pallidum haemagglutination test (p < 0.01). Significant titres of IgM antibodies tended to be more prevalent among women with miscarriage (7.0%) than among women attending antenatal care (4.5%), though the difference only approached statistical significance. CONCLUSION--The findings suggest a potential association between syphilis seropositivity and midtrimester miscarriage. Present findings justify more extensive studies to establish whether or not recent syphilis infection is a risk factor for midtrimester miscarriage.     

A new look at the serology of treponemal disease.

The serology of treponemal disease has become simpler and more rational in recent years, mainly as a result of the widespread adoption of specific antibody tests and the use of monospecific fluorescent antibody procedures which give information about the immunoglobulin class of antibodies. A set of tests which has proved particularly useful in routine diagnosis is the following: quantitative TPHA test, quantitative VDRL test, and monospecific (IgG and IgM) FTA-ABS tests. This combination is especially valuable in the assessment of new patients with positive results to serological tests and in the management of patients with treated syphilis.     

Influence of genital herpes on results of fluorescent treponemal antibody absorption test.

Both the fluorescent treponemal antibody absorption (FTS-ABS) test and Venereal Disease Laboratory (VDRL) test for syphilis were performed routinely on 113 men with histories of genital ulcerations. The difference in negative VDRL and borderline FTS-ABS results between patients with and without herpes simplex virus in their genital ulcers and no evidence of previous or untreated syphilis was not statistically significant. Furthermore, use of the FTA-ABS test as a confirmatory rather than a screening test eliminates false-positive, borderline, or reactive results in patients with non-syphilitic ulcers.     

Influence of genital herpes on results of fluorescent treponemal antibody absorption test.

Both the fluorescent treponemal antibody absorption (FTS-ABS) test and Venereal Disease Laboratory (VDRL) test for syphilis were performed routinely on 113 men with histories of genital ulcerations. The difference in negative VDRL and borderline FTS-ABS results between patients with and without herpes simplex virus in their genital ulcers and no evidence of previous or untreated syphilis was not statistically significant. Furthermore, use of the FTA-ABS test as a confirmatory rather than a screening test eliminates false-positive, borderline, or reactive results in patients with non-syphilitic ulcers.     

Specificity of the Treponema pallidum haemagglutination test. Analysis of results.

The automated haemagglutination assay using Treponema pallidum antigen (AMHA-TP) and the Venereal Disease Research Laboratory (VDRL) test were used to examine 330 163 sera. Reactive results were checked by the fluorescent treponemal antibody-absorption (FTA-ABS) test. When isolated reactivity or non-reactivity in the AMHA-TP test was investigated an estimated margin of error of 0.7% probably wrongly non-reactive and 0.008% presumably false non-reactive results were found. These figures were confirmed by randomised FTA-ABS tests on 504 sera with repeat AMHA-TP tests. The latter is therefore still the most reliable and practicable method for mass screening for syphilis.     

A prospective study of the influence of HIV status on the seroreversion of serological tests for syphilis.

The evolution of serological tests for syphilis (STSs) after therapy in HIV+ patients is a major point of controversy, with possible seroreactivation and illicit seroreversion in these patients. The aim of our study was to evaluate the long-term outcome of STSs in a cohort of HIV+ male homosexuals with a history of treated syphilis as compared with HIV- controls. PATIENTS AND METHODS: Sixty-nine HIV+ male homosexuals with a documented history of treated syphilis and positive baseline treponemal tests were prospectively studied between 1986 and 1993. A medical examination, HIV staging, CD4+ cell count, VDRL, FTA-Abs tests and TPHA were performed every 6 months. Controls consisted of 49 HIV- patients with similar inclusion criteria over the same period. Comparisons between subgroups were based on chi(2) and Kruskal-Wallis tests. Analysis of negativation of the STS used the failure data methods (Kaplan-Meier, log-rank and Cox's model). RESULTS: Patients had a mean age of 38 years, a baseline CD4+ cell count of 578/mm(3), elapsed time since last syphilis of 7.5 years and a median follow-up of 4.3 years. Controls had a mean age of 42 years, elapsed time since last syphilis of 5.3 years and a median follow-up of 4.7 years. Time to seroreversion was shorter in HIV+ patients for TPHA (p = 0.009, log-rank test) and FTA-Abs test (p = 0.001, log-rank test), even after adjustment for stage of syphilis, age and time since the last episode of syphilis. The decrease in VDRL titres was not different between the 2 groups (p = 0.053, log-rank test). Seroreversion of the TPHA, FTA-Abs test and VDRL test was not significantly related to stage of syphilis, time elapsed since the last episode of syphilis, age or history of STDs in both groups. Seroreversion of the TPHA and VDRL test was not related to baseline CD4+ cell count. However, seroreversion of the FTA-Abs test was related to a low baseline CD4+ cell count (p = 0. 003). In HIV+ patients, a significant decrease in titres was noticed for TPHA, FTA-Abs test and VDRL test over time, but this time effect remained only for TPHA titres after adjustment for the CD4+ cell count. CONCLUSION: TPHA may serorevert in HIV+ patients. Thus, a non-reactive TPHA does not exclude a past syphilis infection in such patients. Evolution of the VDRL test after therapy is regular in HIV+ patients. The VDRL test remains adequate for controlling the efficacy of treatment in these patients.     

Non-specific positive test results to syphilis in dermatological diseases.

Sera from 3028 patients attending a dermatological clinic were examined by the fluorescent treponemal antibody (FTA) test, the fluorescent antibody-absorbed (FTA-ABS) test, the Venereal Disease Research Laboratory (VDRL) test, and Kolmer's test. Eleven cases of late syphilis were found. Sera from 63 (2.08%) of the remaining 3017 patients showed non-specific results; these were found more frequently in patients with pyodermas, neoplasms, acne, mycoses, crural ulceration, and psoriasis than in those with other diseases. No non-specific results were observed in patients with bullous skin diseases and only a few in patients with viral skin diseases and chronic lupus erythematosus. The test producing the most non-specific results was the FTA test, followed by the FTA-ABS test, the VDRL test, and Kolmer's test.     

Observations on syphilis in Addis Ababa. 2. Prevalence and natural history.

Sera from various groups were tested for syphilis by cardiolipin, fluorescent treponemal antibody-absorbed (FTA-ABS), and treponemal haemagglutination (TPHA) tests. The proportion of positive results, 12.7%, obtained from an unselected urban population suggested that the prevalence of the disease had declined since 1953. The probable explanation is the widespread use of penicillin. Late manifestations of syphilis are much rarer in Ethiopia than would be predicted from the high incidence at the infectious stage and, if present, they affect the cardiovascular system. These findings confirm old observations. Llymphocytes from Ethiopians with early syphilis did not proliferate when cultured with Treponema pallidum in vitro, in contrast with cells from patients with cardiovascular syphilis. These findings differed from observations made previously on patients in England with early syphilis.