The mainstay of diagnosis for Treponema pallidum infections is based on nontreponemal and treponemal serologic tests. Many new diagnostic methods for syphilis have been developed, using specific treponemal antigens and novel formats, including rapid point-of-care tests, enzyme immunoassays, and chemiluminescence assays. Although most of these newer tests are not yet cleared for use in the United States by the Food and Drug Administration, their performance and ease of automation have promoted their application for syphilis screening. Both sensitive and specific, new screening tests detect antitreponemal IgM and IgG antibodies by use of wild-type or recombinant T. pallidum antigens. However, these tests cannot distinguish between recent and remote or treated versus untreated infections. In addition, the screening tests require confirmation with nontreponemal tests. This use of treponemal tests for screening and nontreponemal serologic tests as confirmatory tests is a reversal of long-held practice. Clinicians need to understand the science behind these tests to use them properly in syphilis management.

Novel Treponema pallidum Serologic Tests: A Paradigm Shift in Syphilis Screening for the 21st Century

Background: Globally syphilis is an important yet preventable cause of stillbirth, neonatal mortality and morbidity. Objectives: This review sought to estimate the effect of detection and treatment of active syphilis in pregnancy with at least 2.4MU benzathine penicillin (or equivalent) on syphilis-related stillbirths and neonatal mortality. Methods: We conducted a systematic literature review of multiple databases to identify relevant studies. Data were abstracted into standardised tables and the quality of evidence was assessed using adapted GRADE criteria. Where appropriate, meta-analyses were undertaken. Results: Moderate quality evidence (3 studies) supports a reduction in the incidence of clinical congenital syphilis of 97% (95% c.i 93 – 98%) with detection and treatment of women with active syphilis in pregnancy with at least 2.4MU penicillin. The results of meta-analyses suggest that treatment with penicillin is associated with an 82% reduction in stillbirth (95% c.i. 67 – 90%) (8 studies), a 64% reduction in preterm delivery (95% c.i. 53 – 73%) (7 studies) and an 80% reduction in neonatal deaths (95% c.i. 68 – 87%) (5 studies). Although these effect estimates were large and remarkably consistent across studies, few of the studies adjusted for potential confounding factors and thus the overall quality of the evidence was considered low. However, given these large observed effects and a clear biological mechanism for effectiveness the GRADE recommendation is strong. Conclusion: Detection and appropriate, timely penicillin treatment is a highly effective intervention to reduce adverse syphilis-related pregnancy outcomes. More research is required to identify the most cost-effective strategies for achieving maximum coverage of screening for all pregnant women, and access to treatment if required.

/pdf/lives-saved-tool-supplement-detection-and-treatment-of-cqweu2972w.pdf

Lives Saved Tool supplement detection and treatment of syphilis in pregnancy to reduce syphilis related stillbirths and neonatal mortality

Summary Background About 2·1 million pregnant women have active syphilis every year. Without screening and treatment, 69% of these women will have an adverse outcome of pregnancy. The objectives of this study were to review the literature systematically to determine the effectiveness of screening interventions to prevent congenital syphilis and other adverse pregnancy outcomes. Methods We searched four electronic databases and selected studies to examine evidence for effectiveness of interventions on three outcomes: increased uptake of syphilis testing, increased treatment rates, and reduction in adverse pregnancy outcomes. We used fixed effects meta-analysis to estimate pooled relative risks if no or little evidence of heterogeneity between trials existed. Findings Ten studies met the inclusion criteria, including two randomised trials. Only two studies aimed to encourage women to seek care earlier in pregnancy. Nine studies included decentralisation of screening and treatment. The effects of the interventions on uptake of testing for antenatal syphilis and receiving at least one dose of penicillin were variable and could not be combined statistically. Study interventions were associated with a reduction in perinatal death (pooled risk ratio [RR] from three studies 0·46, 95% CI 0·26–0·82) and stillbirth (pooled RR from three studies 0·42, 95% CI 0·19–0·93). The incidence of congenital syphilis was reduced in all four studies that measured this outcome with heterogeneous results. Interpretation Interventions to improve the coverage and effect of screening programmes for antenatal syphilis could reduce the syphilis-attributable incidence of stillbirth and perinatal death by 50%. The resources required to roll out antenatal screening programmes would be a worthwhile investment for reduction of adverse pregnancy outcomes and improvement of neonatal and child survival. Funding None.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(11)70104-9.pdf

Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis.

Background
Rapid and point-of-care (POC) tests for syphilis are an invaluable screening tool, yet inadequate evaluation of their diagnostic accuracy against best reference standards limits their widespread global uptake. To fill this gap, a systematic review and meta-analysis was conducted to evaluate the sensitivity and specificity of rapid and POC tests in blood and serum samples against Treponema pallidum (TP) specific reference standards.

http://www.med.mcgill.ca/epidemiology/Joseph/publications/Methodological/jafari2013.pdf

Are Treponema pallidum specific rapid and point-of-care tests for syphilis accurate enough for screening in resource limited settings? Evidence from a meta-analysis.

We describe a point-of-care immunochromatographic test for the simultaneous detection of both nontreponemal and treponemal antibodies in the sera of patients with syphilis that acts as both a screening and a confirmatory test. A total of 1,601 banked serum samples were examined by the dual test, and the results were compared to those obtained using a quantitative rapid plasma reagin (RPR) test and the Treponema pallidum passive particle agglutination (TP-PA) assay. Compared to the RPR test, the reactive concordance of the dual test nontreponemal line was 98.4% when the RPR titers of sera were ≥1:2 and the nonreactive concordance was 98.6%. Compared to the TP-PA assay, the reactive and nonreactive concordances of the treponemal line were 96.5% and 95.5%, respectively. These results indicate that the dual test could be used for the serological diagnosis of syphilis in primary health care clinics or resource-poor settings and therefore improve rates of treatment where patients may fail to return for their laboratory results.

Novel Point-of-Care Test for Simultaneous Detection of Nontreponemal and Treponemal Antibodies in Patients with Syphilis

EP02.03-020 Patient Outcomes Following Salvage Lung Cancer Surgery Post Definitive Chemotherapy or Radiation

Objectives:Congenital syphilis is a significant cause of adverse pregnancy outcomes. In South Africa, rural clinics perform antenatal screening offsite, but unreliable transport and poor client follow up impede effective treatment. We compared 3 syphilis screening strategies at rural clinics: onsite

On-site rapid antenatal syphilis screening with an immunochromatographic strip improves case detection and treatment in rural South African clinics.

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EP02.03-020 Patient Outcomes Following Salvage Lung Cancer Surgery Post Definitive Chemotherapy or Radiation

On-site rapid antenatal syphilis screening with an immunochromatographic strip improves case detection and treatment in rural South African clinics.