Indian J Sex Transm Dis Indian J Sex Transm Dis
Official Publication of the Indian Association for the Study of Sexually Transmitted Diseases
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Year : 2015  |  Volume : 36  |  Issue : 2  |  Page : 211-213

Abstracts from global literature: Current trends in clinical features and diagnosis of syphilis

Department of Dermatology, Baroda Medical College, Vadodara, Gujarat, India

Date of Web Publication12-Oct-2015

Correspondence Address:
Maulik A Shinojia
Department of Dermatology, Baroda Medical College, Vadodara, Gujarat
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Source of Support: None, Conflict of Interest: None

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How to cite this article:
Shinojia MA, Patel D, Marfatia YS. Abstracts from global literature: Current trends in clinical features and diagnosis of syphilis. Indian J Sex Transm Dis 2015;36:211-3

How to cite this URL:
Shinojia MA, Patel D, Marfatia YS. Abstracts from global literature: Current trends in clinical features and diagnosis of syphilis. Indian J Sex Transm Dis [serial online] 2015 [cited 2023 Nov 28];36:211-3. Available from:

Sensitivity, specificity and likelihood ratios of polymerase chain reaction in the diagnosis of syphilis: A systematic review and meta-analysis

Gayet-Ageron A, Lautenschlager S, Ninet B, et al. Sex Transm Infect doi:10.1136/sextrans-2012-050622.

Objective: To systematically review and estimate pooled sensitivity and specificity of the polymerase chain reaction (PCR) technique compared to recommended reference tests in the diagnosis of suspected syphilis at various stages and in various biological materials. Design: Systematic review and meta-analysis. Review Methods: We included studies that used both reference tests to diagnose syphilis plus PCR and we presented pooled estimates of PCR sensitivity, specificity, and positive and negative likelihood ratios (LR) per syphilis stages and biological materials. Results: Of 1160 identified abstracts, 69 were selected and 46 studies used adequate reference tests to diagnose syphilis. Sensitivity was highest in the swabs from primary genital or anal chancres (78.4%; 95% confidence interval: 68.2-86.0) and in blood from neonates with congenital syphilis (83.0%; 55.0-95.2). Most pooled specificities were ∼95%, except those in blood. A positive PCR is highly informative with a positive LR around 20 in ulcers or skin lesions. In the blood, the positive LR was <10. Conclusions: The pooled values of LR showed that Treponema pallidum PCR was more efficient to confirm than to exclude syphilis diagnosis in lesions. PCR is a useful diagnostic tool in ulcers, especially when serology is still negative and in medical settings with a high prevalence of syphilis.

Analysis of three algorithms for syphilis serodiagnosis and implications for clinical management

Tong ML, Lin LR, Liu LL, et al. Clin Infect Dis 2014;58:1116-24. doi: 10.1093/cid/ciu087.

Background: Algorithms for the diagnosis of syphilis continue to be a source of great controversy, and numerous test interpretations have perplexed many clinicians. Methods: We conducted a cross-sectional study of 24,124 subjects to analyze three syphilis testing algorithms: Traditional algorithm, reverse algorithm, and the European Centre for Disease Prevention and Control (ECDC) algorithm. Every serum sample was simultaneously evaluated using the rapid plasma reagin, Treponema pallidum particle agglutination, and chemiluminescence immunoassay tests. With the results of clinical diagnoses of syphilis as a gold standard, we evaluated the diagnostic accuracy of the three syphilis testing algorithms. The kappa coefficient was used to compare the concordance between the reverse algorithm and the ECDC algorithm. Results: Overall, 2749 patients in our cohort were diagnosed with syphilis. The traditional algorithm had the highest negative likelihood ratio (0.24), a missed diagnosis rate of 24.2%, and only 75.81% sensitivity. However, both the reverse and ECDC algorithms had higher diagnostic efficacy than the traditional algorithm. Their sensitivity, specificity, and accuracy were 99.38-99.85%, 99.98-100.00%, and 99.93-99.96%, respectively. Moreover, the overall percent agreement and kappa value between the reverse and the ECDC algorithms were 99.9% and 0.996, respectively. Conclusions: Our research supported use of the ECDC algorithm, in which syphilis screening begins with a treponemal immunoassay that is followed by a second, different treponemal assay as a confirmatory test in high-prevalence populations. In addition, our results indicated that nontreponemal assay is unnecessary for syphilis diagnosis but can be recommended for determining serological activity and the effect of syphilis treatment.

Incidence and risk factors for the prozone phenomenon in serologic testing for syphilis in a large cohort

Liu LL, Lin LR, Tong ML, et al. Clin Infect Dis 2014;59:384-9. doi: 10.1093/cid/ciu325.

Background: The prozone phenomenon is known to be associated with high antibody titers; other associations, such as host factors, have not been elucidated. Methods: A retrospective analysis was conducted to evaluate the incidence of the prozone phenomenon of the syphilis rapid plasma reagin (RPR) test among 46,856 clinical samples, between June 2010 and June 2013. Logistic regression was used to analyze the risk factors of the prozone phenomenon. Results: Our results showed that the incidence of the prozone phenomenon was low (0.83%) and could occur during any clinical phase, particularly during primary and secondary syphilis. Pregnancy and neurosyphilis were associated with the prozone phenomenon; sex, age, and whether the patient had been treated were not. The results also revealed that the prozone phenomenon not only occurred in patients with a high titer but also could occur in patients with a moderate/low titer. In fact, almost 31% of the patients with the prozone phenomenon had titers ≤1:16. Conclusions: The prozone phenomenon in the RPR test was associated with the phase of syphilis, pregnancy, and neurosyphilis as well as a range of RPR titers between 1:8 and 1:512. This latter finding is in contrast to previous reports that the prozone phenomenon is associated with very high RPR titers.

Recent trends in the serologic diagnosis of syphilis

Morshed MG, Singh AE. Recent Trends in the Serologic Diagnosis of Syphilis. Clinical and Vaccine Immunology 2015;22:137-47.

Complexities in the diagnosis of syphilis continue to challenge clinicians. While direct tests (e.g., microscopy or polymerase chain reaction) are helpful in early syphilis, the mainstay of diagnosis remains serologic tests. The traditional algorithm using a nontreponemal test (NTT) followed by a treponemal test (TT) remains the standard in many parts of the world. More recently, the ability to automate the TT has led to the increasingly widespread use of reverse algorithms using treponemal enzyme immunoassays (EIAs). Rapid, point-of-care TTs are in widespread use in developing countries because of low cost, ease of use, and reasonable performance. However, none of the current diagnostic algorithms are able to distinguish current from previously treated infections. In addition, the reversal of traditional syphilis algorithms has led to uncertainty in the clinical management of patients. The interpretation of syphilis tests is further complicated by the lack of a reliable gold standard for syphilis diagnostics, and the newer tests can result in false-positive reactions similar to those seen with older tests. Little progress has been made in the area of serologic diagnostics for congenital syphilis, which requires assessment of maternal treatment and serologic response as well as clinical and laboratory investigation of the neonate for appropriate management. The diagnosis of neurosyphilis continues to require the collection of cerebrospinal fluid for a combination of NTT and TT, and while newer treponemal EIAs look promising, more studies are needed to confirm their utility. This article reviews current tests and discusses current controversies in syphilis diagnosis, with a focus on serologic tests.

Which algorithm should be used to screen for syphilis?

Binnicker MJ. Current Opinion in Infectious Diseases 2012;25:79-85.

Purpose of Review: A growing number of laboratories have implemented a reverse screening algorithm for syphilis testing, which has created confusion among many healthcare providers. This review focuses on recent data addressing the clinical and economical impact of reverse screening and discusses the advantages and limitations of the traditional and contemporary algorithms. Recent Findings: Screening for syphilis using a treponemal assay detects a higher number of patients with reactive results compared to traditional screening by rapid plasma reagin (RPR). Furthermore, a significant percentage of patients who are reactive by a treponemal screening assay are nonreactive by RPR. These discordant results may occur in patients with past, treated or untreated syphilis; early syphilis; or no syphilis. Recent reports suggest that the reverse screening algorithm may result in increased patient follow-ups, overtreatment, and potentially higher cost. However, other data suggest that reverse screening facilitates the detection of latent and early syphilis, while offering an objective and automated screening approach. Summary: The Centers for Disease Control and Prevention currently recommends syphilis screening with a nontreponemal test. However, as laboratories continue to implement the reverse screening algorithm, it is important that samples with discordant screen-reactive, RPR-nonreactive results be tested by a second treponemal assay to assist in the interpretation of results.

Comparison of an automated rapid plasma reagin test with the conventional rapid plasma reagin card test in syphilis testing

Lee JH, Lim CS, Lee MG, Kim HS, BMJ Open 2014;4:e005664.

Objective: We compared the automated nontreponemalreagin (rapid plasma reagin [RPR]) test with the conventional RPR card test for usefulness in clinical applications. Setting: A comparative study of laboratory methods using clinical specimens in a single institute. Participants: A total of 112 serum samples including 59 Treponema pallidum particle agglutination (TPPA)-positive and 53 TPPA-negative specimens were evaluated. Outcome Measures: HiSens Auto RPR LTIA (HBI, Anyang, Korea) was compared with Macro-Vue RPR Card Tests (Becton Dickinson BD Microbiology Systems, Sparks, Maryland, USA). Treponemal-specific tests were performed by Serodia TPPA assay (Fujirebio, Tokyo, Japan). The percentage agreement, κ value and overall sensitivity and specificity of the two RPR tests were compared. Seroconversion rates after treatment were also compared for each RPR test. Results: The percentage agreement between the two RPR tests was 78.6% (κ: 0.565; 95% confidence interval [CI]: 0.422-0.709). Sensitivity and specificity of the automated RPR test relative to the TPPA test was 52.5% (95% CI: 39.1-65.7%) and 94.3% (95% CI: 84.3-98.8%), respectively, while the same values for the conventional RPR card test were 86.4% (95% CI: 75-93.9%) and 94.3% (95% CI: 84.3-98.8%), respectively. The conventional RPR card test showed overall higher positivity than the automated RPR test, whereas the automated RPR test showed higher seroconversion (43.5%, 10/23) than the conventional RPR card test (4.3%, 1/23) in treated patients. Conclusions: The automated RPR test showed overall lower sensitivity than the conventional RPR test based on the treponemal test, but higher seroconversion after treatment. The automated RPR test could be used to monitor treatment response, especially in the reverse screening algorithm in syphilis testing.

Syphilis presenting as isolated cervical lymphadenopathy: Two related cases

 vanCrevel R, Grefte JM, van Doorninck D, Sturm P, Journal of Infection 2009;58:76-8.

Two young adult brothers, with no apparent risk for sexually transmitted infections (STI), presented with unilateral cervical lymphadenitis. Syphilis was diagnosed by fine-needle aspiration cytology in one case, and subsequent serology and revision of a resected lymph node in the second case. Clinicians should have a high index of suspicion and a low diagnostic threshold in patients with unexplained lymphadenopathy, even in the absence of a history of primary syphilis, or obvious risk for STI.

The great pretender: Early syphilis mimicking acute sclerosing cholangitis

Wallace HE, Harrison L, Monteiro E, et al. Frontline Gastroenterol 2015;6:178-81. doi:10.1136/flgastro-2015-100577.

A 36-year-old man with known HIV infection presented to an outpatient genitourinary service with jaundice, rash and sore throat. Investigations revealed marked biochemical abnormalities, including alkaline phosphatase and alanine transaminase >10 times the upper limit of normal. Liver ultrasound was normal, but stricturing and beading of the intrahepatic biliary tree was seen on magnetic resonance cholangiopancreatography (MRCP), similar to changes associated with sclerosing cholangitis. Serological syphilis antibodies were detected with a positive immunoglobulin M and rapid plasma reagin of 1:128, in keeping with early infection. Liver biopsy showed large bile duct obstruction with portal oedema, bilirubinostasis and neutrophil polymorph infiltration around proliferating ductules; specific stains for spirochaetes were negative. Symptoms and biochemical markers improved rapidly after treatment for secondary syphilis with oral steroids and intramuscular benzathine penicillin. A repeat MRCP 18 months postsyphilis treatment showed resolution. This case illustrates syphilis presenting as acute sclerosing


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