CDC Laboratory Recommendations for Syphilis Testing, United States, 2024.

This report provides new CDC recommendations for tests that can support a diagnosis of syphilis, including serologic testing and methods for the identification of the causative agent Treponema pallidum. These comprehensive recommendations are the first published by CDC on laboratory testing for syphilis, which has traditionally been based on serologic algorithms to detect a humoral immune response to T. pallidum. These tests can be divided into nontreponemal and treponemal tests depending on whether they detect antibodies that are broadly reactive to lipoidal antigens shared by both host and T. pallidum or antibodies specific to T. pallidum, respectively. Both types of tests must be used in conjunction to help distinguish between an untreated infection or a past infection that has been successfully treated. Newer serologic tests allow for laboratory automation but must be used in an algorithm, which also can involve older manual serologic tests. Direct detection of T. pallidum continues to evolve from microscopic examination of material from lesions for visualization of T. pallidum to molecular detection of the organism. Limited point-of-care tests for syphilis are available in the United States; increased availability of point-of-care tests that are sensitive and specific could facilitate expansion of screening programs and reduce the time from test result to treatment. These recommendations are intended for use by clinical laboratory directors, laboratory staff, clinicians, and disease control personnel who must choose among the multiple available testing methods, establish standard operating procedures for collecting and processing specimens, interpret test results for laboratory reporting, and counsel and treat patients. Future revisions to these recommendations will be based on new research or technologic advancements for syphilis clinical laboratory science.

Congenital Syphilis: a Review of Global Epidemiology.

In 2007, the World Health Organization (WHO) launched a global health initiative for the elimination of mother-to-child transmission (MTCT) of syphilis. This condition is highly preventable through antenatal identification of syphilis infection and treatment with penicillin during pregnancy. This review summarizes the global status of MTCT of syphilis and concludes that this condition remains a significant issue worldwide. There are large variations in case rates by region, with the highest numbers of cases in the African and Eastern Mediterranean regions, where there are also the least data available. There are also pockets of high-incidence areas within the other regions. Although the general trend is of decreasing rates over time, there are concerning indications of consistently increasing congenital syphilis cases in some areas, particularly in areas which have previously had very low case numbers. A concerted effort will be required to achieve the 2007 WHO goal of worldwide elimination of MTCT of syphilis in the near future.

Prevalence and Predictors of Oral Treponema pallidum Detection by Quantitative Polymerase Chain Reaction in Early Syphilis.

BACKGROUND: Treponema pallidum prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by quantitative polymerase chain reaction (qPCR). Factors associated with oral shedding were also examined. METHODS: Pretreatment oral and lesion swabs were collected from adults with early syphilis in a US multicenter syphilis treatment trial. Oral swabs were collected in the presence and absence of oral lesions. Following DNA extraction, qPCR and whole-genome sequencing (WGS) were performed to assess burden and strain variability. RESULTS: All 32 participants were male, mean age was 35 years, and 90.6% with human immunodeficiency virus (HIV). T. pallidum oral PCR positivity varied by stage: 16.7% primary, 44.4% secondary, and 62.5% in early latent syphilis. Median oral T. pallidum burden was highest in secondary syphilis at 63.2 copies/µL. Lesion PCR positivity was similar in primary (40.0%) and secondary syphilis (38.5%). Age 18-29 years was significantly associated with oral shedding (vs age 40+ years) in adjusted models. WGS identified 2 distinct strains. CONCLUSIONS: T. pallidum DNA was directly detected at oral and lesion sites in a significant proportion of men with early syphilis. Younger age was associated with oral shedding. Ease of oral specimen collection and increased PCR availability suggest opportunities to improve syphilis diagnostic testing. Clinical Trials Registration. NCT03637660.

Relapsed Mpox Keratitis, St. Louis, Missouri, USA.

We describe a case of a 46-year-old man in Missouri, USA, with newly diagnosed advanced HIV and PCR-confirmed mpox keratitis. The keratitis initially resolved after intravenous tecovirimat and penicillin for suspected ocular syphilis coinfection. Despite a confirmatory negative PCR, he developed relapsed, ipsilateral PCR-positive keratitis and severe ocular mpox requiring corneal transplant.

Syphilis.

Syphilis is a sexually and vertically transmitted bacterial infection caused by the bacterium Treponema pallidum. Its prevalence is high in low-income and middle-income countries, and its incidence has increased in high-income countries in the last few decades among men who have sex with men. Syphilis is a major cause of adverse pregnancy outcomes in low-income and middle-income countries. Clinical features include a primary chancre at the point of inoculation, followed weeks later by the rash of secondary syphilis, a latent period, and in some cases, involvement of the eyes, CNS, and cardiovascular systems. It is diagnosed serologically. A single intramuscular dose of long-acting benzathine penicillin is recommended for people who have had syphilis for less than 1 year and longer courses for people with late latent syphilis. Control strategies include screening and treatment of all pregnant women, and targeted interventions for groups at high risk. Vaccine development, research on antibiotic prophylaxis, and digital messaging as prevention strategies are ongoing.

Improved efficiency using sequential automated immunoassays for syphilis screening in blood donors.

Using sequential immunoassays for the screening of blood donors is well described for viral serology testing but not for the screening of syphilis. In this study, we report the evaluation results and 2-year sequential testing data using two highly sensitive automated serology assays, the Alinity s Syphilis chemiluminescent immunoassay for screening, with all repeatedly reactive samples then tested on the Elecsys Syphilis electrochemiluminescence immunoassay. We screened 1,767,782 blood donor samples between 7 July 2021 and 6 July 2023 and found the Alinity false-positive rate to be low at 0.08% (1,456/1,767,782). The common false-positive rate between the two assays was also low (3.83%, 58/1,514). Concordantly reactive samples were further tested using a Treponema pallidum particle agglutination test, a rapid plasma reagin test, and a fluorescent treponemal antibody absorption test. There were 262/1,376 concordantly reactive Alinity and Elecsys blood donor samples with reactivity on one or more of the confirmatory tests. A total of 26/1,376 donors had a current syphilis infection, 152/1,376 reported a past history of syphilis and had been treated, and 84/1,376 did not report a past history of syphilis. We suggest that future studies could explore the use of sequential immunoassays to aid in the serodiagnosis for syphilis. IMPORTANCE: The serodiagnosis for syphilis usually follows two methodologies-a "traditional" algorithm using a non-treponemal test followed by confirmation using a treponemal test, or a "reverse" algorithm using a treponemal test followed by a non-treponemal test. There are limited reports in the literature of using a modified reverse algorithm (treponemal test followed by a second treponemal test), and to the best of knowledge, there are currently no published articles using two highly sensitive automated immunoassays to aid the serodiagnosis of syphilis. In addition, the Treponema pallidum particle agglutination (TPPA) assay is commonly used as a confirmatory test for the diagnosis of syphilis. With the withdrawal of the TPPA assay from Australia and presumably from the global market also, alternative testing algorithms are now required. This study provides proof of concept for using sequential immunoassays in the diagnosis of syphilis.

Anti-Neuron-Derived Neurotrophic Factor Antibodies in Secondary Membranous Nephropathy Caused by Syphilis: A Case Report.

We present the case of a 61-year-old man who developed nephrotic syndrome as a result of syphilis-associated secondary membranous nephropathy (MN). The patient showed nephrotic syndrome remission following antibiotic treatment for syphilis alone. Pathologically, the target antigen of immune complexes accumulated on glomerular basement membranes (GBM) in secondary MN caused by syphilis has been reported to be neuron-derived neurotrophic factor (NDNF). His renal histopathology was consistent with secondary MN caused by syphilis, with a full-house pattern on immunofluorescence microscopy, in addition to NDNF deposits that colocalized with IgG deposits granularly on the GBM. However, to date, there is no serological evidence for the involvement of NDNF in the GBM. In the present study, we found that anti-NDNF autoantibodies in the acute-phase serum disappeared in the convalescent-phase serum of a patient who recovered from syphilis and nephrotic syndrome after antibiotic therapy alone. This result supports the hypothesis that treatment of syphilis with antibiotics suppresses NDNF's antigenicity. In summary, we found new serological evidence emphasizing that NDNF is an etiological antigen in secondary MN caused by syphilis.

High-speed centrifugation rather than Lipoclear reagent can be used for removing the interference of lipemia on serological tests of infectious diseases: AIDS, hepatitis B, hepatitis C, and syphilis by chemiluminescent microparticle immunoassay.

The aim of this study was to investigate the interference of lipemia on measurement of HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, anti-HCV, HIV Ag/Ab, and anti-TP in serum by chemiluminescent microparticle immunoassay (CMIA) and compare lipemia removing performance between high-speed centrifugation and Lipoclear reagent. Mixed native serum samples (NSs) and hyperlipemia serum samples (HLS) were prepared for the investigated parameters. The levels of these parameters in NS and HLS were determined by CMIA on an Abbott ARCHITECT i2000SR immunoassay analyzer. HBsAg, anti-HBs, and anti-TP were affected with relative bias >12.5% (acceptable limit) when the level of triacylglycerol (TG) was higher than 27.12 mmol/L in HLS. Clinically unacceptable bias were observed for HBeAg and anti-HBe in HLS with TG higher than 40.52 mmol/L. However, anti-HCV and HIV Ag/Ab were not interfered in severe lipemia with TG < 52.03 mmol/L. In addition, the Lipoclear reagent did not reduce the interference of lipemia with relative bias from -62.50% to -18.02%. The high-speed centrifugation under the optimized condition of 12 000g for 10 min successfully removed the interference of lipemia with relative bias from -5.93% to 0% for HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. To conclude, high-speed centrifugation can be used for removing the interference of lipemia to measure HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc, and anti-TP. Accordingly, a standardized sample preanalytical preparation of the patients and other screening participants as well as a specimen examination procedure for removing lipemia interference on the serological tests was recommended.

Seroconversion in syphilis screening without positive confirmatory tests points at early infection.

INTRODUCTION: The chemiluminescence immunoassay (CLIA) is a widely used screening test for syphilis. A CLIA seroconversion in the absence of a positive line immunoassay (LIA) or rapid plasma reagin (RPR) could indicate either an early incubating syphilis or a false positive result. We aimed to evaluate the diagnostic value of such seroconversions. METHODS: We retrospectively analysed data of clients visiting the Centre for Sexual Health Amsterdam between July 2013 and August 2021 with a positive CLIA and a negative RPR and negative or indeterminate LIA (at time To), and a preceding visit (T-1) with a negative CLIA <6 months of To ('unconfirmed CLIA seroconversion'). If available, data of follow-up visits (T1) <2 months of To were also included. A syphilis diagnosis was confirmed if darkfield microscopy or PCR for Treponema pallidum was positive at T0 or T1, or if RPR and/or LIA were positive at T1. RESULTS: We included data of 107 clients with unconfirmed CLIA seroconversion. The value of CLIA seroconversion could not be established in 13 (12.1%) clients. In the remaining 94 clients, the unconfirmed CLIA seroconversion was confirmed as early syphilis in 72 (76.6%) clients and probable syphilis in 6 (6.4%) clients. In 16 (17.0%) clients, the unconfirmed CLIA seroconversion was regarded as a false positive reaction of whom 4 (5.3%) clients had a seroreversion of the CLIA at T1. CONCLUSION: The majority of unconfirmed CLIA seroconversions represented early syphilis infections. Therefore, additional T. pallidum PCR, a follow-up consultation or early treatment is recommended.

Can laboratory HIV and infectious syphilis data inform future pre-exposure prophylaxis use in women in Ontario, Canada?

OBJECTIVES: Infectious syphilis has been proposed as an indication for HIV pre-exposure prophylaxis (PrEP) in women. We explored how many women experienced HIV seroconversion after being diagnosed with syphilis in Ontario between 20 April 2010 and 31 December 2021. METHODS: Through deterministic linkage of laboratory data at the Public Health Ontario laboratory, which conducts the vast majority of syphilis and HIV testing in Ontario, we quantified the number of females with positive syphilis diagnoses who subsequently exhibited HIV seroconversion between April 2010 and December 2021. New HIV cases were identified by diagnostic serology or HIV viral load test result of ≥20 copies/mL at least 60 days after the positive syphilis test. We report aggregate numbers of women with new laboratory evidence of HIV infection after their first positive syphilis test. RESULTS: Among 7957 women with positive syphilis tests during the study period, 6554 (82.4%) had linkable HIV serology tests and 133 (1.7%) ever tested HIV positive. With further linkage to viral load data, the number of women who ever had laboratory evidence of HIV infection increased to 184 (2.3%). However, when restricting to women whose first positive HIV test or HIV viral load occurred after their first positive syphilis test, this number decreased to 34 (0.4%). The median (IQR) time between the positive syphilis test and the first laboratory evidence of HIV was 551 (IQR=226-1159) days. CONCLUSION: Although it is clinically appropriate to recommend HIV PrEP to women with syphilis, Ontario surveillance data suggest that the population-level impact of this strategy on the HIV epidemic in Ontario would have been modest during this 11-year period. Future studies should explore additional ways of prioritising women for PrEP.

Painful proctitis associated with anorectal mpox, syphilis, HSV, LGV, gonorrhoea and Mycoplasma genitalium in a person living with virologically suppressed HIV and vaccinated against mpox.

A gay man with well-controlled HIV and vaccinated against mpox presented with severe proctitis. Testing revealed anorectal mpox, herpes simplex virus, lymphogranuloma venereum, Neisseria gonorrhoeae and Mycoplasma genitalium Serology was indicative of infectious syphilis. This case highlights the need to consider a wide range of concurrent sexually transmitted infections in patients with proctitis, including those vaccinated against mpox.

Sexually transmitted infections diagnosed in individuals presenting for forensic and medical care following sexual assault.

BACKGROUND: People who report sexual assault express concerns regarding contracting sexually transmitted infection (STI); however, published literature regarding the risk of STI transmission in this context is sparse. METHOD: We audited STI and blood-borne virus (BBV) testing at a forensic and medical sexual assault care service in the Australian Capital Territory between 2004 and 2022. Eligibility for testing among 1928 presentations was defined based on risk (eg, reported penetration). Testing at presentation included chlamydia and gonorrhoea 1850, syphilis and BBV 1472, and after 2-6 weeks, 890 out of 1928 (46.2%) and after 3 months 881 out of 1928 (45.7%), respectively. RESULTS: At presentation, 100 out of 1928 (5.2%) individuals were diagnosed with chlamydia, of those, 95 out of 1799 (5.3%) were female, and 5 out of 121 (4.1%) were male. Gonorrhoea was diagnosed in 7 out of 1920 (0.4%), 5 out of 95 female and 2 out of 5 male. Hepatitis B, which was all pre-existing, was diagnosed in 5 out of 1799 (0.3%). Overall, chlamydia prophylaxis was given to 203 out of 1928 (10.5%) and HIV post-exposure prophylaxis to 141 out of 1928 (7.3%).At 2-6 weeks of follow-up, 10 out of 890 (1.1%) individuals were diagnosed with chlamydia, with no gonorrhoea diagnosed. There were no cases of syphilis, hepatitis B or HIV diagnosed at 3-month serology testing in 881 individuals. Chlamydia detection at follow-up was more common in the group aged 15-29 years. Of those provided with chlamydia prophylaxis, 203 out of 1928, only 16 out of 203 (7.9%) were diagnosed with chlamydia. CONCLUSIONS: The offer of STI testing is almost universally accepted by individuals presenting for post-sexual assault care. There were no identifiable factors to justify the routine use of chlamydia prophylaxis. STI testing provided an opportunity for screening and should remain part of the clinical care of people who report sexual assault.

Sexual network characteristics and partnership types among men who have sex with men diagnosed with syphilis, gonorrhoea and/or chlamydia in Lima, Peru.

OBJECTIVES: Sexual networks are known to structure sexually transmitted infection (STI) transmission among men who have sex with men (MSM). We sought to estimate the risks of STI diagnosis for various partnership types within these networks. METHODS: Our cross-sectional survey analysed data from 1376 MSM screened for a partner management intervention in Lima, Peru. Participants were tested for HIV, syphilis, gonorrhoea (NG) and chlamydia (CT) and completed surveys on their demographics, sexual identity/role, HIV status, partnership types and sexual network from the prior 90 days. χ2 and Wilcoxon rank-sum tests compared participants without an STI to those diagnosed with (1) syphilis, (2) NG and/or CT (NG/CT) and (3) syphilis and NG/CT coinfection (coinfection). RESULTS: 40.8% (n=561/1376) of participants were diagnosed with an STI (syphilis: 14.9%, NG/CT: 16.4%, coinfection: 9.5%). 47.9% of all participants were living with HIV and 8.9% were newly diagnosed. A greater proportion of participants with syphilis and coinfection were living with HIV (73.5%, p<0.001; 71.0%, p<0.001) compared with those with NG/CT (47.8%) or no STI (37.8%). Participants with syphilis more often reported sex-on-premises venues (SOPVs) as the location of their last sexual encounter (51.7%, p=0.038) while those with NG/CT tended to meet their last sexual partner online (72.8%, p=0.031). Respondents with coinfection were the only STI group more likely to report transactional sex than participants without an STI (31.3%, p=0.039). CONCLUSIONS: Sexual networks and partnership types of Peruvian MSM are associated with differential risks for STIs. Participants diagnosed with syphilis tended to meet single-encounter casual partners at SOPV, while MSM with NG/CT were younger and often contacted casual partners online. Coinfection had higher frequency of transactional sex. These findings suggest the potential importance of public health interventions through combined syphilis/HIV screening at SOPV, syphilis screening at routine clinic appointments for MSM living with HIV and directed advertisements and/or access to NG/CT testing through online platforms.

Syphilis Screening Among Young Black Men Who Have Sex With Women in New Orleans, LA.

BACKGROUND: Current US syphilis screening focuses on men who have sex with men (MSM), because of the increased risk of infection in their sexual networks, and on pregnant people, because of complications associated with congenital syphilis. However, screening for men who have sex with women (MSW) who are at increased risk of syphilis is also recommended. Factors associated with syphilis testing and positivity were assessed among young, Black MSW. METHODS: Data from the Check It study-a seek, test, and treat study for chlamydia in New Orleans, LA, among Black MSW aged 15 to 26 years-were used. Survey data were used to elicit self-reported syphilis testing, self-reported testing results, and sociodemographic and behavioral factors associated with these 2 outcomes. RESULTS: Per the Centers for Disease Control and Prevention, all men in the study were recommended for syphilis screening because of their age, race, and geographic location. Of the 1458 men included, 272 (18.7%) reported ever having been syphilis tested, 267 men reported their results, and 23 (8.6%) reported testing positive. In logistic regression, older age (odds ratio [OR], 1.21 per year older; P < 0.001), prior Chlamydia trachomatis , Neisseria gonorrhoeae , and/or HIV testing (OR, 50.32; P < 0.001), and younger age at sexual debut (0.90 per year older, P = 0.005) were significantly associated with prior syphilis testing. In addition, testing positive for C. trachomatis and/or N. gonorrhoeae during the study was significantly associated with a history of syphilis positivity (OR, 3.08; P = 0.031). CONCLUSIONS: Although syphilis testing was associated with factors that might increase the risk of acquisition, only 19% of individuals meeting Centers for Disease Control and Prevention testing recommendations had ever been screened.

The Tenacious Treponema: A Retrospective Examination of Syphilis Treatment Disparities in Washington, DC.

BACKGROUND: Since 2000, there have been rising rates of syphilis infections nationally with higher incidence among minorities and persons living with human immunodeficiency virus (HIV) (PLWH). The purpose of this study was to determine syphilis treatment adequacy and factors associated with treatment delay. METHODS: This was a retrospective academic-public health collaboration with the District of Columbia Department of Public Health reviewing surveillance data of all primary, secondary, and early latent syphilis cases diagnosed between January 1, 2015, and December 31, 2019. Data were analyzed using multivariable logistic regression to identify factors associated with delayed treatment >14 days from diagnosis. RESULTS: Among 1852 individuals diagnosed with early syphilis, 93% (1730/1852) were male; 48% (893/1852) were coinfected with HIV; 43% (n = 796/1852) were African American/Black, 27% (n = 492/1852) were White, and race/ethnicity was unknown for 17% (n = 318/1852) of cases. Among 679 PLWH for whom viral load (VL) was known, 41% (278/679) had a VL < 20 copies/mL, and 18% (123/679) had VL >10,000 copies/mL. Treatment adequacy overall was 96.5%. Median time to syphilis treatment was 6 days (interquartile range = 4-7). Factors associated with delay of treatment included refused/unknown race (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.00-3.79), and HIV VL > 10,000 copies/mL (aOR, 1.97; 95% CI, 1.08-3.58). CONCLUSIONS: The factors we identified associated with delayed treatment may reflect systemic factors contributing to the increased rates of infection among key populations. This highlights the importance of targeted public health efforts with the goal of reducing transmission of both HIV and syphilis.

Estimating the Proportion of People Living With HIV Who May Benefit From the Reverse Algorithm for the Diagnosis of Incident Syphilis.

ABSTRACT: Among 8455 people engaged in HIV care in 4 US cities, 4925 (58%) had treponemal testing at care entry. Of the 4925 tested, 3795 (77%) had a nonreactive result and might benefit from the reverse algorithm for a future incident syphilis diagnosis. Furthermore, low-barrier treponemal testing as a first step in the reverse algorithm may increase syphilis screening and decrease time to treatment.

Evaluation of Automated Processing of Electronically Reported Serological Tests for Syphilis Using Current and Historical Syphilis Results Compared With Traditional Reactor Grid Processing in Florida.

BACKGROUND: Syphilis in Florida increased 49% from 2016 to 2020. Moreover, many serological tests for syphilis (STS) do not indicate current infection. Traditionally, syphilis surveillance systems used reactor grids, a method for prioritizing STS for investigation based on age, nontreponemal titer, and/or sex. In 2022, Florida's sexually transmitted disease surveillance system implemented an automated method for processing electronically reported STS (eSTS), expanding upon the reactor grid, using an individual's current STS (treponemal and nontreponemal), treatment history, and historical STS results aiming for more efficiently processing eSTS. We compared the new method of processing eSTS results against the reactor grid and determined potential value in time/cost savings of this change. METHODS: All eSTSs (n = 4144) from January 2, 2023 to January 8, 2023, were compared by how the logic-based method processed test results versus how the reactor grid processed test results. Each method was compared using measurements of accuracy (e.g., sensitivity/specificity). Time and cost savings in eSTS processing were estimated. RESULTS: Using the surveillance case definition as reference, the accuracy of the logic-based method for processing eSTS was nearly double (82.3% vs. 43.6%), had greater specificity (79.0% vs. 33.0%), and increased positive predictive value (47.5% vs. 22.0%) when compared with the reactor grid method. Sensitivity (99.5% vs. 98.6%) and negative predictive value (99.9% vs. 99.2%) remained similar. The logic-based method is estimated to save 7783 hours annually (~$185,000). CONCLUSIONS: Processing eSTS based on current and historical STS results is significantly more accurate than using a reactor grid. Moreover, these improvements save time and resources that can be better allocated to other program prevention activities.

Access to Benzathine Penicillin G Treatment for Persons With Syphilis, Maricopa County, Arizona, 2021.

BACKGROUND: As the incidence of syphilis continues to increase, examining benzathine penicillin G (BPG) treatment data provides valuable insight for public health strategies. This study analyzed the trends of where BPG is administered relative to the initial clinical site of syphilis diagnosis. Our findings are timely in the context of recent national BPG shortages. METHODS: The analysis included persons diagnosed with any syphilis stage in Maricopa County, Arizona, from January 1, 2021, to December 31, 2021. The Arizona surveillance database (PRISM) was the source of demographic, testing, and treatment data. RESULTS: Of a total of 4028 persons with syphilis, 3038 (75.4%) received at least 1 injection of BPG. Among persons who received an initial BPG injection, only 1719 (56.6%) were diagnosed and treated at the same clinical site type. The Maricopa County Sexually Transmitted Disease Clinic administered BPG to 48.8% (n = 1483) of persons with syphilis who received an initial injection. CONCLUSIONS: Our findings analyze trends in BPG administration that are likely due to treatment referral practices and medication cost. Administration of BPG is not guaranteed at the clinical site of diagnosis, highlighting concerns regarding access to BPG. A burden is placed on patients who are required to leave their diagnosing provider to seek syphilis treatment at other health facilities that administer BPG.

A Novel Treponema pallidum Subspecies pallidum Strain Associated With a Painful Oral Lesion Is a Member of a Potentially Emerging Nichols-Related Subgroup.

BACKGROUND: Early syphilitic lesions are typically painless; however, several recent case studies have included patients with tender lesions and no evidence of concurrent infections. Here we present the manifestations and serological and molecular findings of a patient from New York State with a painful tongue lesion. METHODS: The diagnosis of syphilis was based on a combination of physical examination, serologic, pathologic, and immunohistochemical findings. DNA obtained from a formalin-fixed, paraffin-embedded biopsy was used to characterize the infecting pathogen using polymerase chain reaction, multilocus sequence typing, and whole-genome sequencing methods. RESULTS: Polymerase chain reaction and multilocus sequence typing of the biopsy specimen confirmed infection with T. pallidum subspecies pallidum ( T. pallidum ) of the Nichols cluster. Whole-genome sequencing analysis of this strain (herein called NYMC01) showed that it contained 17 unique single nucleotide variations and 4 more complex genetic differences; this novel genotype matched only 2 specimens, both from a patient in Seattle, Washington. The presence of this rare genotype in 2 geographically distinct locations suggests the potential emergence and spread of a new subgroup of the Nichols cluster. CONCLUSIONS: To our knowledge, this is the first genomic sequence obtained from a T. pallidum strain linked to a painful lesion, and the third description of whole-genome sequencing of T. pallidum from formalin-fixed, paraffin-embedded tissue. Analysis of additional specimens may reveal that the NYMC01-related genotype represents an emerging T. pallidum subgroup and may also aid in determining whether the painful clinical presentation of primary syphilis is related to specific T. pallidum genotypes.

The Congenital Syphilis Prevention Cascade: Reimagining a Missed Prevention Opportunities Framework for Effective Intervention.

ABSTRACT: Congenital syphilis (CS) rates have risen in the United States since 2013. Prevention of CS requires testing and treatment of pregnant and pregnancy-capable persons at high risk for syphilis. We developed a CS Prevention Cascade to assess how effectively testing and treatment interventions reached pregnant persons with a CS outcome.