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.     

Rheumatoid factor in congenital syphilis.

The rheumatoid factor (RF) latex test was evaluated as a test for congenital syphilis. High risk newborns of mothers with untreated or inadequately treated syphilis were studied. The asymptomatic infants were followed up for between 3 and 4 months (or longer if the VDRL test was positive). The overall performance of the RF latex test was better than that of the other tests studied, even though the sensitivity was 46.7%. The specificity and positive predictive value of the test were 100% whilst the negative predictive value was 86.4%. The test was negative in all 84 controls studied. Although a negative RF latex test cannot be used to exclude congenital syphilis in an asymptomatic infant, a positive test in the presence of maternal syphilis should lead one to strongly suspect congenital syphilis.     

梅毒螺旋体IgM抗体蛋白印迹试验诊断新生儿胎传梅毒的探讨

目的探讨梅毒螺旋体IgM抗体蛋白印迹试验(Treponema pallidum IgM Western blot，TP-IgM-WB)在新生儿胎传梅毒早期诊断中的价值。方法对8例胎传梅毒新生儿(其母亲均为梅毒)进行TRUST、TPPA，FTA-ABS-19S-IgM和TP-IgM-WB 4种梅毒血清学检查，并结合临床对结果进行比较。结果8例中3例出现胎传梅毒的典型临床表现，包括典型皮肤损害，梅毒新生儿肺炎，伴发心、脑、肝、肾多脏器衰竭；另外5例无胎传梅毒的临床表现。梅毒血清学试验结果：所有8例TP-IgM-WB均为阳性；除1例外，7例FTA-ABS-19S-IgM试验为阳性；3例有症状的胎传梅毒及3例胎传潜伏梅毒中4种梅毒血清学试验均为阳性；1例TRUST和TPPA均阴性，但FTA-ABS-19S-IgM和TP-IgM-WB均阳性；1例FTA-ABS-19S-IgM阴性，但TRUST滴度是母亲的4倍，TPPA和TP-IgM-WB均阳性。结论梅毒螺旋体IgM抗体蛋白印迹试验可作为一种确诊试验应用于新生儿胎传梅毒，尤其是胎传潜伏梅毒的早期诊断。     

An IgM capture enzyme linked immunosorbent assay to detect IgM antibodies to treponemes in patients with syphilis.

A new IgM capture enzyme linked immunosorbent assay (ELISA) was compared with the 19S(IgM) fluorescent treponemal antibody absorption (19S(IgM)FTA-ABS) test for detecting IgM antibodies to treponemes. Serum samples from 180 people, 109 with various stages of untreated syphilis, 45 with treated syphilis, and 26 non-infected, were investigated. In all diagnostic groups of syphilis the reactivity of the IgM capture ELISA was similar to that of the 19S(IgM)FTA-ABS test except in untreated neurosyphilis, for which the IgM capture ELISA was significantly less sensitive. The IgM capture ELISA was very sensitive in congenital (100%, 5/5) and primary (82%, 18/22) syphilis, but less sensitive in secondary (60%, 12/20), latent (53%, 16/30), neurosyphilis (34%, 11/32), and treated (11%, 5/45) syphilis. False positive IgM capture ELISA results were not found in five people who gave false positive Venereal Disease Research Laboratory (VDRL) reactions or in 21 neonates born to mothers adequately treated for syphilis before or during pregnancy. This indicated that the IgM capture ELISA was very specific. The course of antitreponemal IgM reactivity after treatment of early infectious syphilis was followed up in six patients. The quantity of IgM antibody declined in nearly all patients after treatment, but still remained detectable in five patients up to six months after treatment. In contrast, non-treponemal antibodies measured by the VDRL test disappeared in four out of six patients within five months from starting treatment. In conclusion, the IgM capture ELISA may be useful for easy and sensitive detection of IgM antibodies to treponemes in patients with congenital and primary syphilis. A positive test result in these cases indicates that patients should receive treatment if they have not been treated recently. The test is not, however, recommended to replace the VDRL test to monitor patients treated for syphilis.     

Congenital syphilis in The Netherlands: cause and parental characteristics.

During 1982-5 the 19S (IgM) fluorescent treponemal antibody absorption (19S (IgM) FTA-ABS) test gave positive results in 19 children. The parental histories were analysed. As five of the children were adopted, 14 pregnancies were evaluated. Mothers of foreign origin and extramarital pregnancies were found to be over-represented. Of 13 women who attended for pregnancy checkup, three were not serologically screened for syphilis. In four the infection had developed late in the course of pregnancy. In at least four treatment had not been given or had been inadequate or too late. At least two had positive 19S (IgM) FTA-ABS test results that did not indicate congenital syphilis. The possibility of false positive 19S (IgM) FTA-ABS test results is pointed out. As the male sexual partners of four of the 14 mothers had presented elsewhere with early syphilis at the time of their partner's pregnancy, adequate contact tracing appears to be important to prevent congenital syphilis in future.     

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.     

IgM抗体诊断早期先天梅毒

我们用梅毒特异性19（s)IgM-TPPA抗体检测方法，对5例常规梅毒血清学方法RPR和TPPA两个试验均阳性的新生儿（其母亲已在怀孕时被确诊为不同病期梅毒）进行了检测。患儿中有3例19（s)IgM-TPPA阳性，另2例阴性。最终确诊3例新生儿为先天梅毒。特异性IgM检测应该作为新生儿和早期无症状先天梅毒确诊的实验诊断方法。加强婚前、孕前及早孕期的梅毒筛查和治疗，对控制先天梅毒的发生有重要意义。     

Essential mixed cryoglobulinaemia with false-positive serological tests for syphilis.

Analysis of serum from a patient with cutaneous leukocytoclastic vasculitis showed a mixed cryoglobulin with a monoclonal IgM kappa-antiglobulin component (6.5 mg/ml), strong rheumatoid factor activity (latex titre 1/5000), and positive serological tests for syphilis (fluorescent treponemal antibody-absorbed and Treponema pallidum haemagglutination assay). After removal of antiglobulin activity by immunoabsorption with heat-aggregated gammaglobulin all serological test results for treponemal infection became negative. Serological tests for syphilis and rheumatoid factor on the supernatant from whole serum (minus cryoglobulin) remained positive though at a lower titre (latex 1/1250). Cryoglobulin isolated from whole serum retained rheumatoid and TPHA reactivity but was negative in the FTA-ABS test. The IgM and IgG cryoglobulin components purified by gel filtration on Sepharose showed no antitreponemal reactivity even when tested individually. Reducing the concentration of cryoglobulin to 1.5 mg/ml by plasma exchange converted the test results for syphilis to doubtful-positive or negative. These results indicated that high concentrations of antiglobulin activity may be associated with falsely positive specific antitreponemal test results and that this phenomenon depends on the concentration of cryoglobulin in the test sample.     

Asymptomatic Neurosyphilis

Lumbar puncture was performed in 18 patients with latent syphilis to rule out asymptomatic neurosyphilis. In seven patients the CSF findings were abnormal. The parameters used in CSF were cell count, total protein, immunoglobulins (IgG, IgA, IgM), IgG index, and serologic tests for syphilis (VDRL, Kolmer, RPCF and FTA-ABS, including monospecific IgG and IgM conjugates). In three patients, the CSF findings 7-10 months after treatment are also given. Penicillin levels in serum and CSF were determined in two patients after aqueous procaine penicillin G im with and without oral probenecid. The effect of blood contamination on the differentiation between normal and abnormal CSF may not be significant.     

19S-IgM-TPPA试验诊断先天梅毒评价

目的:评价血清19S-IgM-梅毒螺旋体明胶颗粒凝集试验(19S-IgM-TPPA)诊断早期先天梅毒的应用价值,以指导临床实践。方法:以2003年3月-2006年2月期间符合纳入标准的156例婴儿为研究对象,对他们进行血清19S-IgM-TPPA试验,并随访至明确诊断。以回顾诊断为标准。结果:156例婴儿中,141例婴儿完成随访,其中123例排除先天梅毒,18例婴儿被确诊为早期先天梅毒(有症状14例,无症状4例)。19S-IgM-TPPA试验阳性结果16例,假阳性2例,假阴性4例,敏感性77.78%(有症状78.57%,无症状75%),特异性98.37%,诊断指数176.15%;阳性预测值87.5%,阴性预测值96.8%,调整预测值无改变;阳性似然比47.83,阴性似然比0.226。结论:19S-IgM-TP-PA诊断先天梅毒敏感性较好,特异性很高,对有症状早期先天梅毒,在常规标准血清试验确定前即可证实感染的存在,用于先天梅毒的诊断是良好的预测工具,在已经有TPPA的实验室中,19S-IgM-TP-PA不失为一种诊断先天梅毒的可供选择的方法。     

Microcapsule agglutination test for Treponema pallidum antibodies. A new serodiagnostic test for syphilis.

For the serodiagnosis of syphilis a quantitative passive agglutination (MCA-TP) test for antibodies to Treponema pallidum was performed with chemically stable microcapsules with no antigenic activity instead of with conventional sheep erythrocytes. The microcapsules were easily sensitised with the antigen of sonicated Treponema pallidum by treatment with glutaraldehyde. Compared with the Treponema pallidum haemagglutination test (TPHA) the MCA-TP test was superior for detecting cases of primary syphilis. Furthermore, the decrease in antibody titre during treatment was more evident in this test than in the FTA-ABS or the TPHA tests. The MCA-TP test performed on IgM and IgG gel-filtered fractions of sera from patients with syphilis proved that the sensitised microcapsule antigen reacted sharply with the IgM antibodies specific to syphilis.     

Study of FTA-CFS test using monospecific anti-immunoglobulin conjugates IgG, IgM, and IgA

The fluorescent treponemal antibody test for cerebrospinal fluid (FTA-CSF) using monospecific conjugates anti-IgG, IgM, and IgA was used to determine the presence of anti-treponemal antibodies in the spinal fluid of 335 patients with primary, secondary, and latent syphilis and symptomatic and asymptomatic neurosyphilis and of patients with certain neurological disorders. Of these, 230 (68·65%) patients had non-reactive results to this test. Of the remaining 105 patients, 78, 63, and 10 had reactive results with anti-IgG, IgM, and IgA conjugates respectively. Of the 129 cases of known syphilis, 11 were diagnosed as primary, 32 as secondary, and 50 as latent, and 36 patients had neurosyphilis. None of the specimens from the patients with primary syphilis gave reactive results to the test. Specimens from 21 (65·62%) of the 32 patients with secondary syphilis, 30 (60%) of the 50 patients with latent syphilis, and all (97·22%), except one, of the 36 patients with neurosyphilis gave reactive results to one at least of the IgG, IgM, or IgA FTA-CSF tests. Among the specimens from patients with secondary syphilis twice as many gave reactive results with anti-IgG conjugate than with anti-IgM conjugate. However, with specimens from patients with latent syphilis and neurosyphilis this ratio was diminished to 1·5:1. The Kolmer complement-fixation test, although superior in sensitivity and specificity to the Venereal Disease Research Laboratory (VDRL) test, in patients with secondary and latent syphilis and neurosyphilis, was greatly inferior to the FTA-CSF test. Data indicate that anti-treponemal antibodies can be detected in the spinal fluid even in patients with no neurological symptoms in cases of secondary syphilis and that the FTA-CSF test can be a valuable tool in the early detection of an immunological response to treponemal infection in the spinal fluid.     

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.     

Congenital syphilis and fluorescent treponemal antibody test reactivity after the age of 1 year.

BACKGROUND: Many believe that a persistently reactive fluorescent treponemal antibody absorption (FTA-ABS) is manifested with congenital syphilis after the age of 1 year, that it is useful in the retrospective diagnosis of children with congenital syphilis, and that it can be used to confirm other treponemal tests. GOAL: To determine whether a reactive FTA-ABS after the age of 12 months is indicative of congenital syphilis. STUDY DESIGN: Prospective outpatient follow-up evaluation until at least the age of 12 months was conducted for 194 babies born to mothers with reactive syphilis serology at delivery, and for two additional children with congenital syphilis diagnosed when they were younger than 1 year (total, 196 children). RESULTS: In the study group, 54 children had reactive FTA-ABS (reactors) until the age of at least 12 months or more, and 142 children had nonreactive FTA-ABS (nonreactors) at the age of 12 months or more. Of the 54 reactors, 17 (31%) had evidence of congenital syphilis at birth, whereas evidence of congenital syphilis was seen in 14 of the 142 (10%) nonreactors (P = 0.0002). At 15 months, nonreactive FTA-ABS developed in six reactors, and eventually in 15 of 44 reactors (34%) tested. CONCLUSIONS: A reactive FTA-ABS may be seen at 12 months in children with and without evidence of congenital syphilis at birth. Not all children with congenital syphilis will manifest reactive FTA-ABS at 12 months, and FTA-ABS reactivity wanes with time.     

Treponema pallidum specific IgM haemagglutination test for serodiagnosis of syphilis

The Treponema pallidum specific IgM haemagglutination (TP-IgM-HA) test uses erythrocytes sensitised with antiserum to human IgM to separate IgM from IgG in serum. Specific antitreponemal IgM captured in this way is detected by adding a second reagent comprising erythrocytes sensitised with T pallidum antigen. Eighty two serum samples from 82 patients with untreated syphilis, 521 samples from 73 patients with treated syphilis, and 1872 samples from people who did not have syphilis were examined by the 19S(IgM)-TPHA (T pallidum haemagglutination), IgM-FTA-ABS (fluorescent treponemal antibody absorbed), TP-IgM-ELISA (enzyme linked immunosorbent assay), and TP-IgM-HA tests for the presence of 19S(IgM) antibodies specific to treponemes. The sensitivity of the TP-IgM-HA test was 97.6% and the specificity was 99.7%. We also traced IgM specific to treponemes in untreated patients with primary syphilis by four different tests. The TP-IgM-HA test results clearly reflected the effect of the treatment.     

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.     

Treponema pallidum specific IgM haemagglutination test for serodiagnosis of syphilis.

The Treponema pallidum specific IgM haemagglutination (TP-IgM-HA) test uses erythrocytes sensitised with antiserum to human IgM to separate IgM from IgG in serum. Specific antitreponemal IgM captured in this way is detected by adding a second reagent comprising erythrocytes sensitised with T pallidum antigen. Eighty two serum samples from 82 patients with untreated syphilis, 521 samples from 73 patients with treated syphilis, and 1872 samples from people who did not have syphilis were examined by the 19S(IgM)-TPHA (T pallidum haemagglutination), IgM-FTA-ABS (fluorescent treponemal antibody absorbed), TP-IgM-ELISA (enzyme linked immunosorbent assay), and TP-IgM-HA tests for the presence of 19S(IgM) antibodies specific to treponemes. The sensitivity of the TP-IgM-HA test was 97.6% and the specificity was 99.7%. We also traced IgM specific to treponemes in untreated patients with primary syphilis by four different tests. The TP-IgM-HA test results clearly reflected the effect of the treatment.     

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.     

19SIgM-TPPA对新生儿先天潜伏梅毒诊断的意义

目的探讨特异性19SIgM-TPPA抗体检测方法在诊断新生儿先天潜伏梅毒中的价值,同时观察妊娠梅毒患者垂直传播发生情况,并探讨其意义。方法应用特异性19SIgM-TPPA抗体检测方法对177例孕妇梅毒所生的新生儿进行检测。结果177例受检新生儿中,TRUST阳性112例(63.3%),TPPA阳性156例(88.13%),19SIgM阳性27例(15.25%)。早期先天梅毒患儿TRUST≥母亲TRUST2个滴度以上9例、>母亲TRUST2个滴度以内7例、<母亲TRUST滴度5例;因母亲血清标本缺或血清量不足,无法作比较的6例。27例先天梅毒有临床表现的6例,无临床表现21例。结论特异性19SIgM-TPPA抗体检测方法可作为先天梅毒特别是无症状新生儿先天梅毒诊断的试验。产前梅毒筛查和治疗对预防梅毒垂直传播有重要意义。     

潜在血源传播患者梅毒血清学TRUST/TPPA与IgM抗体联合检测

目的为潜在血源传播患者筛选梅毒血清学传染病指标。方法采用回顾性研究,对2006年6月1日～2009年12月31日本院23720例潜在血源传播患者与门诊患者的TRUST/TPPA联合检测结果进行分析比较;分析不同年度潜在血源传播患者TRUST-/TPPA+的百分率变化;对其中118份TRUST-/TPPA+的潜在血源传播患者血清标本同时采用TPPA法和FTA-ABS法进行Tp-IgM抗体检测。结果潜在血源传播患者和门诊患者的梅毒抗体阳性率分别为8.62%和26.69%,二者差异有显著性;在梅毒抗体阳性标本中,TRUST-/TPPA+占有相当的比例,二者分别为3.12%和7.50%;潜在血源传播患者中TRUST-/TPPA+的百分率呈逐年上升趋势;118份TRUST-/TPPA+的潜在血源传播患者血清,经TPPA法和FTA-ABS法检出TP-IgM抗体阳性分别为13例和10例。结论潜在血源传播患者的梅毒传染性指标的监测应至少包含特异性抗体试验,如TPPA;TP-IgM检测有助于判断其传染性。