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Enzyme-linked immunosorbent assay for detection of antibodies to the venereal disease research laboratory (VDRL) antigen in syphilis.

An enzyme-linked immunosorbent assay (ELISA) for detection of immunoglobulin G (IgG) and IgM to cardiolipin, lecithin, and cholesterol (VDRL [Venereal Disease Research Laboratory] ELISA) is described. The specificity of the VDRL ELISA for IgG and IgM was 99.6 and 99.5%, respectively, with sera from 1,008 persons without syphilis. For a group of patients with false-positive results in traditional nontreponemal tests and for patients with autoimmune diseases, the VDRL ELISA for IgG had a higher specificity than the VDRL ELISA for IgM. The sensitivity for IgG and IgM with 118 sera from patients with untreated syphilis was 96.6 and 94.9%, respectively, which was equivalent to the sensitivities of the traditional nontreponemal tests. The performance of the VDRL ELISA was compared with that of an ELISA that uses cardiolipin as the antigen (cardiolipin ELISA). The VDRL ELISA was significantly more sensitive (P less than or equal to 0.01) than the cardiolipin ELISA with 25 sera from syphilis patients but was less sensitive (P less than or equal to 0.01) with 53 sera from patients with autoimmune diseases. The antibody reactivity in the VDRL ELISA could not be absorbed out by lecithin and cholesterol, and the sera from patients with syphilis did not react in an ELISA that uses cholesterol and lecithin as the antigen. This indicates that cholesterol and lecithin, although not antigenic by themselves, may change the structural form of the epitope on cardiolipin so that it becomes more recognizable for antibodies in syphilis and less recognizable for antibodies in autoimmune diseases. The results of the VDRL ELISA were expressed in percentages of the absorbance value of a positive control. The VDRL ELISA gave, without titration of sera, quantitative results that correlated with the quantitative results of the traditional nontreponemal tests obtained by titration. The VDRL ELISA will be well suited for large-scale testing for syphilis and may replace other nontreponemal tests.

Antibodies, Bacterial↗

Impact of on-site testing for maternal syphilis on treatment delays, treatment rates, and perinatal mortality in rural South Africa: a randomised controlled trial.

BACKGROUND: Syphilis remains a significant cause of preventable perinatal death in developing countries, with many women remaining untested and thus untreated. Syphilis testing in the clinic (on-site testing) may be a useful strategy to overcome this. We studied the impact of on-site syphilis testing on treatment delays and rates, and perinatal mortality. METHODS: We conducted a cluster randomised controlled trial among seven pairs of primary healthcare clinics in rural South Africa, comparing on-site testing complemented by laboratory confirmation versus laboratory testing alone. Intervention clinics used the on-site test conducted by primary care nurses, with results and treatment available within an hour. Control clinics sent blood samples to the provincial laboratory, with results returned 2 weeks later. RESULTS: Of 7134 women seeking antenatal care with available test results, 793 (11.1%) tested positive for syphilis. Women at intervention clinics completed treatment 16 days sooner on average (95% confidence interval: 11 to 21), though there was no significant difference in the proportion receiving adequate treatment at intervention (64%) and control (69%) clinics. There was also no significant difference in the proportion experiencing perinatal loss (3.3% v 5.1%; adjusted risk difference: -0.9%; 95% CI -4.4 to 2.7). CONCLUSIONS: Despite reducing treatment delays, the addition of on-site syphilis testing to existing laboratory testing services did not lead to higher treatment rates or reduce perinatal mortality. However on-site testing for syphilis may remain an important option for improving antenatal care in settings where laboratory facilities are not available.

Adult↗

Is increased surveillance for asymptomatic syphilis in an HIV outpatient department worthwhile?

OBJECTIVES: Syphilis outbreaks have recently been reported in the United Kingdom, some of which have included cohorts of HIV positive individuals. As a result we commenced 3 monthly screening of syphilis serology (STS) for HIV positive patients having routine follow up blood tests. We assessed if there was an increased number of individuals being screened and also whether the screening programme was diagnosing early cases of syphilis. METHODS: Data from a 1 year period following introduction of screening (May 2001) were analysed and compared with data from the same period last year. The case notes of patients with a positive VDRL were reviewed to establish, firstly, whether these represented new diagnoses and, secondly, whether patients were asymptomatic at the time of screening. RESULTS: 2670 patients had at least one CD4 count measured in the period (surrogate for patients having routine bloods). Of these, 2266 patients had STS performed (85%). 38 patients had a positive VDRL. Of these, 20 were confirmed as having early syphilis which was asymptomatic at the time of screening. Six asymptomatic cases were also confirmed with newly positive TPPAs and a negative VDRL. These 26 asymptomatic cases represent 29% of all cases of early syphilis diagnosed in our department and 50% of cases in the HIV positive cohort. CONCLUSION: With intensive surveillance significant numbers of cases of asymptomatic early syphilis are being identified in a group of HIV individuals under routine follow up, at an earlier stage than would otherwise have been the case. This presents an opportunity to intervene not only to prevent clinical illness but also to institute infection control measures.

AIDS-Related Opportunistic Infections↗

[Syphilis positivity in puerperal women: still a challenge in Brazil].

OBJECTIVE: To investigate the factors associated with positive syphilis serology results in puerperal women who were receiving care at 24 health centers accredited by Brazil's National Program on Sexually Transmitted Diseases and AIDS. METHODS: This cross-sectional study included a probabilistic random sample of 3047 puerperal women. The eligibility criterion was being admitted for delivery or curettage in the selected centers. After an interview to collect demographic and clinical information, a blood sample was taken and then examined with the Venereal Disease Research Laboratory (VDRL) slide test. With positive VDRL results, the fluorescent treponemal antibody-absorption test (FTA-Abs) was used for confirmation. The event considered for analysis was positivity on the VDRL test, with confirmation by the FTA-Abs. For the statistical analysis, odds ratios and 95% confidence intervals were calculated. The model fit was assessed using the Hosmer-Lemeshow test. RESULTS: The prevalence of syphilis among the women studied was 1.7%. Multivariate analysis showed that increased risk for positive VDRL and FTA-Abs results was associated with the following characteristics: family income below one minimum wage, age < 17 years at first sexual intercourse, age < or = 14 years at first pregnancy, history of syphilis or of other sexually transmitted diseases prior to the current pregnancy, treatment for syphilis during the current pregnancy, partner having been tested for syphilis, having a positive HIV test result or having no HIV test result on record, previous preterm delivery, and stillbirth as an outcome of pregnancy. Only 43% of the women had had six or more prenatal visits, and only 3% had had one VDRL test during the first trimester of pregnancy and another VDRL test during the third trimester, as is recommended by Brazil's national Ministry of Health. CONCLUSIONS: This study shows that the problem of congenital syphilis is far from being solved in Brazil. It is necessary to provide adolescents with family planning services as well as guidance on sexual issues, to improve prenatal follow-up, and to research the history of sexually transmitted diseases in both the pregnant woman and her sexual partner.

Adolescent↗

ELISA inhibition test using monoclonal antibody specific for Treponema pallidum as the serologic test for syphilis.

Monoclonal antibodies (Mabs) specific for Treponema pallidum were produced using hybridoma technology. In this study an ELISA inhibition test based on competitive inhibition by antibodies from human test sera of the binding of the enzyme-labelled Mabs to T. pallidum was performed. Inhibition of the seroreactivity of Mabs was decreased according to the dilution of rabbit antiserum to T. pallidum. Seropositivity was found in 100% of secondary and early latent syphilis patients, 75% of primary syphilis patients, and 80% of late latent syphilis patients. The mean percentage inhibition was significantly higher in each syphilis group than in the controls, and statistically significant differences were shown between all the syphilis groups. VDRL and TPHA titers were correlated with the percentage inhibitions. Therefore the ELISA inhibition test using Mab specific for T. pallidum might well be a suitable tool as a new serologic test for syphilis.

Analysis of Variance↗

Congenital syphilis in an immunocompromised neonate: case report.

Syphilis is a notifiable and preventable disease, congenital syphilis more so. Consequently, attention has been recently focused on prenatal diagnosis of foetal syphilis by the use of ultrasonography apart from the conventional serologic screening. Congenital syphilis has not been reported from the Kingdom of Lesotho. We report the case of a 3.0 kg male neonate with florid joint and bone lesions of congenital syphilis associated with HIV infection seen at the Queen Elizabeth II Hospital, Maseru, Kingdom of Lesotho. Co-existing HIV infection influences the clinical manifestation of syphilis, the progression of neurosyphilis and the response to standard therapy. The baby had the recommended standard treatment with good response and he was followed-up for a period of twelve months with serologic screening and radiographic evaluation.

AIDS Serodiagnosis↗

Antenatal screening for syphilis at a tertiary care hospital in Riyadh.

BACKGROUND: Routine serologic screening for syphilis is recommended for all pregnant women in Saudi Arabia. This study examined the results of routine antenatal syphilis screening at a tertiary care hospital in Riyadh. PATIENTS AND METHODS: The results of rapid plasma reagin (RPR) tests were compiled for in 3270 pregnant women tested between October 2002 and March 2003 at King Khalid University Hospital. Any RPR reactivity observed in neat or diluted serum was considered positive and confirmed by a Treponema pallidum hemagglutination (TPHA) test. RESULTS: Syphilis screening constituted 87% of RPR tests requested for all reasons during the study period. The majority of women (73%) were screened between 15 to 22 weeks of gestation. Of the 3270 women tested only one was found to have syphilis, a prevalence rate of 0.03%. CONCLUSION: The prevalence of syphilis is extremely low in the antenatal care population at King Khalid University Hospital in Riyadh. This calls for a nation-wide survey to assess the need for continuation of antenatal syphilis screening with regards to its potential benefits and cost effectiveness in the Kingdom of Saudi Arabia.

Adolescent↗

Routine screening of hospital blood samples for syphilis. A pilot study in Mount Isa, Queensland.

During a seven-month study, 4005 blood samples taken for haematological investigations at the Mount Isa Base Hospital, Queensland, were routinely screened for syphilis. Two hundred and twenty-nine of these yielded serological evidence of syphilis. One hundred and eighty-eight persons were either aware of, or had recorded evidence of, previous infection. Serological evidence of hitherto unsuspected syphilis was found in 24 persons. Seventeen persons with serological evidence of syphilis, but without a recorded history of the disease, could not be contacted. The relatively high prevalence (1%) of undetected syphilis in this population sample led to the continuation of routine screening at Mount Isa Base Hospital. Hospitals which serve towns with similar demographic profiles may find routine screening for syphilis of all blood samples, taken for unrelated investigations, a useful procedure.

Adolescent↗

Effect of human immunodeficiency virus (HIV) infection on the course of syphilis and on the response to treatment.

PURPOSE: To evaluate evidence that concurrent infection with human immunodeficiency virus (HIV) alters both the natural history of syphilis (by increasing the frequency of early neurosyphilis) and the response to penicillin. DATA IDENTIFICATION: Review of major works on syphilis in the English language and files maintained since 1971, supplemented by a systematic search using Index Medicus and MEDLARS. DATA EXTRACTION: The works mentioned above were critically reviewed for information on early neurosyphilis and, where relevant, HIV infection. RESULTS OF DATA ANALYSIS: The central nervous system is regularly involved in early syphilis. Standard recommended doses of benzathine penicillin provide cerebrospinal fluid levels that are probably at the borderline of efficacy, and cure relies on treatment and an adequate host immune response. Early neurosyphilis, appearing within 2 years of onset of infection with Treponema pallidum, was uncommon in the prepenicillin era and usually occurred after inadequate therapy. This complication was exceedingly rare in the first three decades of penicillin use. In contrast, in the past decade, 40 patients with HIV infection have been reported to have asymptomatic neurosyphilis, or syphilitic meningitis, cranial nerve abnormalities (predominantly in cranial nerves II and VIII), or cerebrovascular accidents, singly or together. In 40% of cases, HIV infection was first diagnosed when neurologic symptoms appeared. Of the 38 patients for whom information was available, 18 had the acquired immunodeficiency syndrome (AIDS), 7 had AIDS-related complex, and 13 had antibody to HIV. Sixteen had previously been treated for syphilis, of whom 5 (31%) had received benzathine penicillin within the previous 6 months. Preliminary data also suggest that skin lesions and VDRL (Venereal Disease Research Laboratory) antibody in HIV-infected patients with secondary syphilis respond more slowly to conventional penicillin therapy. CONCLUSION: Intensive therapy and follow-up observation is indicated for early syphilis in HIV-infected subjects. Novel approaches to treatment deserve systematic evaluation.

HIV Infections↗

Gestational and congenital syphilis in Hualien.

From September 1987 to April 1991, 19 pregnant women (0.97%) with syphilis were detected out of 1,955 pregnant women who received prenatal serologic screening at the Buddhist Tz'u-Chi General Hospital. The ages ranged from 17 to 34 years (average, 26). Three cases had recurrent gestational syphilis. The time of diagnosis was: the third trimester, 11 cases; the second trimester, six cases; and the first trimester, two cases. The reasons for late (third trimester) diagnosis were: delay of prenatal care, four cases; failure to screen syphilis in the pregnancy, four cases; and negative first test and late infection, three cases. Late diagnosis and treatment often resulted in poor fetal outcome: syphilitic stillbirth, two cases; probable and possible congenital syphilis, seven cases; and normal infant, two cases. Patients (delivered, five; undelivered, two; abortion, one) who had been diagnosed before the third trimester had a better fetal outcome: possible congenital syphilis, one case; and normal infant, four cases. The perinatal mortality and morbidity were significantly higher in the late diagnosis group (9/11) than in the early diagnosis group (1/5). Pregnant women should be screened in early pregnancy by a serologic test for syphilis. In areas of high prevalence, or in patients at high risk, screening should be repeated in the third trimester and again at delivery.

Adolescent↗

Detection of Treponema pallidum DNA in cutaneous lesions of secondary syphilis and characterization of the inflammatory infiltrate.

OBJECTIVE: To investigate the possible mechanism of the cutaneous lesion formation in secondary syphilis and role of cellular immunity in the pathogenesis of syphilis. METHODS: Treponema pallidum DNA was detected in 24 formalin-fixed, paraffin-embedded skin specimens from lesions of secondary syphilis by nested PCR. The inflammatory infiltrate in the cutaneous lesions of secondary syphilis was investigated using immunohistochemical technique. RESULTS: The TP-specific DNA was found in 10 of 24 (45.8%) lesions of secondary syphilis. However, no Treponema pallidum were found in all 24 tissue section samples when silver staining was performed. CD45RO (+) Tcells were found in all syphilis lesions with strong staining. CD68 (+) cells were found in 68.2% of the skin specimens. Meanwhile, a few CD20 (+) cells and CD57 (+) cells were seen in the infiltrates. CONCLUSION: The cutaneous lesions might be formed by invasion of TP to skin rather than an allergic reaction. The predominant T cells and macrophages infiltrating in secondary syphilitic lesions indicate that cellular immunity might play a critical role in host reaction against TP infection.

DNA, Bacterial↗

Diagnostic tools for preventing and managing maternal and congenital syphilis: an overview.

Syphilis is a major cause of adverse outcomes in pregnancy in developing countries. Fetal death and morbidity due to congenital syphilis are preventable if infected mothers are identified and treated appropriately by the middle of the second trimester. Most pregnant women with syphilis are asymptomatic and can only be identified through serological screening. Non-treponemal tests, such as the rapid plasma reagin (RPR) test, are sensitive, simple to perform, and inexpensive. However, they have often not been available at primary health-care settings because they required cold storage for reagents and electricity to operate a rotator. Additionally, as many as 28% of positive RPR results in pregnant women are biological false positives. Confirmatory assays are usually available only in reference laboratories. Technological advances have resulted in improved serodiagnostic tools for syphilis. New enzyme immunoassays are available for surveillance and for large-scale screening programmes. Decentralized antenatal screening with on-site confirmation is now possible since new RPR reagents that are stable at room temperature have become commercially available, as have solar-powered rotators and simple, rapid point-of-care treponemal tests that use whole blood and do not require electricity or equipment. These will be valuable tools for preventing or eliminating congenital syphilis. The development of a non-invasive rapid treponemal test that distinguishes between active and past infections remains a high priority in areas where syphilis is endemic.

Female↗

[Serological diagnosis of syphilis in Cuban HIV/AIDS patients].

The non-treponemic fast detection test of plasmatic reagines (RPR) and the treponemic hemagglutination test of Treponema pallidum were used in the detection of infection due to T. pallidum in 60 males presenting HIV/AIDS infection with clinicoepidemiological diagnosis of syphilis. It was confirmed that 30% presented recently acquired symptomatic or latent syphilis and that 10% had markers of past treated infection or of late acquired latent syphilis, whereas in the other 60% no serological reactivity was detected. A seroprevalence study of reaginic antibodies was conducted by RPR in 59 HIV/AIDS females, using 67 women negative to this virus as controls. All of them had no symptoms compatible with the syphilitic infection. It was concluded that 20.3% and 11.9%, respectively, presented reactivity, which established a probable diagnosis of syphilis or a seroresistance to a previouos syphilis. These results showed a close association between syphilis and HIV/AIDS and that both diseases may coexist in a same patient.

Acquired Immunodeficiency Syndrome↗

Acquired ocular syphilis: diagnosis and treatment.

We present our findings in 14 patients with a serologically verified diagnosis of ocular syphilis. Although most patients had iridocyclitis, other ocular findings included episcleritis, scleritis, vitritis, retinitis, papillitis, panuveitis, cystoid macular edema, and retinal detachment. Most patients had only ocular manifestations of syphilis with no other definitive symptoms. Without the use of specific treponemal serologic tests, the diagnosis of ocular syphilis would have been missed in at least 20% of patients. Furthermore, 80% of patients were negative for antibody to syphilis in the cerebrospinal fluid, and therefore, this test should not be used to determine treatment for ocular syphilis. Currently, the most effective therapy for ocular syphilis is the same as that for neurosyphilis (i.e., high-dose intravenous penicillin G 12 to 24 million units/day for ten to 14 days). Human immunodeficiency virus-positive patients should receive a full 14 days of high-dose intravenous penicillin G plus intramuscular benzathine penicillin 2.4 million units weekly for three weeks because their immune defenses are likely to be impaired.

Adult↗

Syphilis screening in primary care.

BACKGROUND: Reported cases of early syphilis have increased dramatically since 1987. Screening high-risk patients has been advocated as an intervention strategy to control the syphilis epidemic. METHODS: This study determined the prevalence of previously unrecognized positive syphilis serologies among patients at an urgent care center. Two hundred sixty-five patients treated empirically for gonorrhea were screened. RESULTS: Two patients had positive serology; both were previously treated for syphilis and had no evidence of recurrent infection. The yield from screening the study population was 0. CONCLUSIONS: Serologic diagnosis of syphilis is not reliable or cost effective in groups with a very low prevalence of disease. Routine screening for syphilis in asymptomatic high-risk patients may not be indicated in all primary care settings.

Adolescent↗

[The characteristics of the current course and the outcome of pregnancy in syphilis].

The authors have analyzed 184 case histories of pregnant women hospitalized at a department for obstetrics and gynecology of hospital No. 52 (134 women) and at the female department for sexually transmitted diseases of the City Center for Skin and Sexually Transmitted Diseases (50 women) in the town of Tashkent in 1980-1988. This analysis has revealed the predominance of latent forms of syphilis in pregnant women; therefore consultation centers for females play the principal role in the detection of syphilis in pregnant women by timely serologic screenings for syphilis. Health-educating activities are inadequate, therefore many women consult a doctor only in the second or even third trimester of pregnancy, and some do not consult a doctor at all. A considerable reduction in the rate of late spontaneous abortions and stillbirths vs. the 'preantibiotic period' of syphilis treatment indicates a relatively benign course of syphilis as far as its fetal effect is concerned. Specific therapy of pregnant syphilis patients with benzylpenicillin procaine salt combined with theonikal essentially reduced the incidence rate of uterine inertia. To prevent intrauterine fetal hypoxia and correct the course of labor sygethin should be administered.

Adult↗

Secondary syphilis: uncommon manifestations of a common disease.

Reports of cases of primary and secondary syphilis are increasing in the United States, particularly in urban areas and among homosexual men. While primary syphilis poses little diagnostic difficulty, many physicians are unfamiliar with the multisystem nature of secondary lues. Patients who have secondary syphilis commonly present with systemic signs, skin rash, mucous membrane lesions and generalized adenopathy. Less commonly, secondary syphilis may occur as acute meningitis, sensorineural hearing loss, iritis, anterior uveitis, optic neuritis, Bell's palsy, gastropathy, proctitis, hepatitis, pulmonary infiltration, nephrotic syndrome, glomerulonephritis, periostitis, tenosynovitis and polyarthritis. The diagnosis of secondary syphilis is easily confirmed. Its various manifestations are readily treated with penicillin and, if treated early, are entirely reversible. Two recent cases of secondary syphilis, one presenting as nephrotic syndrome and one as chorioretinitis and ptosis, illustrate the usual and unusual features of this common infection.

Adult↗

Current status of the treatment of syphilis.

Penicillin remains the treatment of choice for syphilis, with sustained low blood levels curing virtually all patients having early syphilis and halting disease progression in most patients with symptomatic syphilis. Tetracycline, erythromycin or cephalothin yields similar cure rates for patients with early syphilis who are allergic to penicillin. The efficacy of non-penicillin regimens for the treatment of late syphilis is uncertain. Results of Venereal Disease Research Laboratory (VDRL) or other reagin tests should become negative or remain at very low titer following adequate therapy, although results of Treponema pallidum immobilization (TPI) and fluorescent treponemal antibody-absorbed (FTA-ABS) tests often remain positive.

Cephalexin↗