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Syphilis, ‘the great imitator’, caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

This study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH). This observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated. There was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010–2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018). The recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population. [ABSTRACT FROM AUTHOR]

Sexually transmitted infections (STIs) are more commonly seen in patients with human immunodeficiency virus (PWH). Routine sexual history taking and appropriate multisite screening practices support prompt identification and treatment of patients, which in turn reduces morbidity and spread of STIs including HIV. Nucleic acid amplification testing has high accuracy for diagnosing many of the major STIs. Diagnosis of syphilis remains complex, requiring 2 stage serologic testing, along with provider awareness of the myriad symptoms that can be attributable to this disease. Prevention through mechanisms such as vaccines and postexposure prophylaxis hold promise to reduce the burden of STIs in PWH., Competing Interests: Disclosure Dr J. Tuan: no conflicts; Dr W. Trebelcock: no conflicts; Dr D. Dunne’s spouse holds stock in Pfizer, Inc., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To analyze the frequent multimodal imaging features in posterior syphilitic uveitis., Purpose: Syphilis infection has re-emerged as a global health problem. Multimodal imaging approach has been proposed for diagnosis and follow-up; there are not previous reports dedicated to the anatomic and visual outcomes in patients diagnosed with ocular syphilis and concomitant HIV infection., Methods: All demographic information was recovered; a complete ophthalmological examination and multimodal imaging evaluation (retinal fluorescein angiography (FA), autofluorescence (AF), optical coherence tomography (OCT)) were performed on initial visit and 1 month after antibiotic therapy., Results:    18 eyes of 9 patients were included. The most frequent features observed were: Hyperfluorescence on optic disk on FA, Hyperautofluorescence punctate pattern on AF, Vitritis on SD-OCT. After treatment, there was a functional and anatomical improvement., Conclusion: Ocular syphilis represents a diagnostic challenge. Multimodal imaging approach allows identification of structural changes, follow-up and early detection of complications.

Purpose: The goal of this study is to describe the clinical and laboratory outcomes of patients with syphilitic uveitis treated with 2 g intravenous Ceftriaxone daily on an outpatient treatment basis for 14 days, in the setting of the COVID pandemic and lack of hospitalization availability., Methods: This study included a review of the clinical records from patients from January 2020 to December 2021 and who were then followed for 6 months at the Research Laboratory of Infectious Diseases in Ophthalmology of the National Institute of Infectious Diseases Evandro Chagas (INI) FIOCRUZ, Rio de Janeiro, Brazil., Conclusion: This study showed that almost all of the 15 patients were well treated for ocular syphilis with Ceftriaxone without any signs of therapeutic failure with documented clinical improvement and satisfactory decreasing VDRL titers.

Purpose: Uveitis is the most common ocular manifestation of syphilis. However, an association between syphilitic uveitis and rhegmatogenous retinal detachment (RRD) is not widely recognized. We report a consecutive series of six new cases of syphilitic uveitis complicated by RRD and describe the typical characteristics, clinical course, and surgical management of such cases., Methods: Consecutive case series and comprehensive review of the literature., Results: We identified a total of 19 cases (23 eyes) with syphilitic uveitis subsequently complicated by RRD, including six new cases (seven eyes) reported here and 13 cases (16 eyes) previously reported in the literature. Fifteen patients (79%) were positive for human immunodeficiency virus (HIV) and not on combination antiretroviral therapy. Most retinal detachments developed within two months of uveitis presentation; retinal breaks were often found in areas of previous retinitis. Sixteen eyes (70%) were complicated by early proliferative vitreoretinopathy. Twenty-one eyes underwent surgical repair, of which six (26%) suffered re-detachment. Surgical management commonly involved pars-plana vitrectomy and silicone oil tamponade, with or without scleral buckling. Visual outcomes were generally poor: only six eyes (26%) attained visual acuity of 20/40 or better and 11 eyes (48%) remained 20/200 or worse., Conclusions: Patients with syphilitic uveitis, as with viral retinitis, should be monitored closely for the development of retinal tears and RRD. A combination of pars plana vitrectomy with silicone oil tamponade and/or scleral buckle placement is a prudent surgical approach to most cases of syphilitic RRD, although visual prognosis remains guarded.

Introduction: Serological tests of non-treponemal and treponemal types are the most frequently used for syphilis diagnosis. Nontreponemal tests are used to monitor disease activity. Toluidine red unheated serum test (TRUST), as one of nontreponemal tests, is generally applicable to hospitals at different levels. However, accurate judgment of TRUST results is inseparable from an experienced and accurate operator. To reduce current shortcomings of manual TRUST method, we attempted to convert the manual TRUST test into automatic TRUST test, that is, to determine the degree of aggregation of toluidine red particles by detecting the absorbance value of serum after reaction with toluidine red particles., Methods: 50 μL of serum sample and 80 μL toluidine red particles were added to 96-well plate. Then, the 96-well plate was placed on a microplate reader at medium grade for 8 min to mix. Then, plasma reagin reacted with toluidine red particles and promoted the aggregation of toluidine red particles to form a large clot, which eventually caused a decrease in the absorbance at 540 nm., Results: The results showed that the specificity of the automatic TRUST test was 100%, the sensitivity was 87%. And this method showed 93.5% correlation with manual TRUST test. The developed method is simple and involves less subjectivity in reading results, opening new avenues for syphilis diagnostic testing., Conclusion: Turbidimetric immunoassay can avoid the shortcomings of subjective interpretation, time-consuming and manual operation of manual TRUST method, and is more suitable for large-scale screening in health examination., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Syphilis is an ancient sexually transmitted infection that plagues communities across the United States and the world. Cutaneous syphilis has a wide variety of manifestations and presentations, and is notoriously difficult to identify clinically as a result. In this report, we describe the case of a 30-year-old patient with condyloma lata on the umbilicus, an extremely rare site for the presentation of these lesions. With the recent surge in syphilis infections nationwide, including congenital infections, this case underscores the urgent necessity for heightened syphilis awareness and suspicion among clinicians., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Intérêts concurrents:: Andrea Chittle a travaillé à cet article alors qu’elle occupait un emploi rémunéré à l’Agence de la santé publique du Canada. Joseph Cox signale avoir reçu des subventions des sociétés ViiV Healthcare et Gilead Canada ou avoir conclu des contrats avec celles-ci, en plus d’avoir perçu des honoraires de consultation ou autres ainsi qu’une aide pour sa participation à des réunions de ViiV Healthcare. Raymond Tsang procède à des évaluations des tests de détection de la syphilis aux points de service, en laboratoire et sur le terrain. Aucun autre intérêt concurrent n’a été déclaré.

Objective: To investigate the prior testing for HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) among transgender women and travestis (TGW) in five Brazilian cities and identify factors associated with each of these previous tests., Methods: This is a cross-sectional study with the recruitment of TGW through respondent-driven sampling (TransOdara Study). The investigated outcome variable was prior testing for HIV, syphilis, HBV, and HCV in the last 12 months. The association between sociodemographic and behavioral factors with the outcome was analyzed using a binomial logistic regression with mixed effects. Adjusted odds ratios (aOR) and 95% confidence intervals (CI95%) were estimated., Results: The proportions of individuals with prior testing in the past year were as follows: 56.3% for HIV, 58.0% for syphilis, 42.1% for HBV, and 44.7% for HCV. Negative associations with prior testing were observed for individuals aged 35 years or older, whereas positive associations were found for those with high school education, those who experienced verbal or psychological violence in the last 12 months, and those who had commercial or casual partners in the last 6 months., Conclusion: There was low frequency of testing in the 12 months preceding the study for HIV, syphilis, HBV, and HCV compared to the guidelines established by the Ministry of Health. Expanding access to and engagement with healthcare and prevention services for TGW is an essential strategy in reducing the transmission chain of HIV and other sexually transmitted infections (STIs).

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., Competing Interests: The authors declare no conflict of interest.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis., Competing Interests: The authors declare no conflict of interest.

Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background In Australia, syphilis notifications increased 2.5-fold during 2013-2022 and 83 congenital syphilis cases were reported. Timely diagnosis and management are crucial. We developed a tool to promote syphilis testing into our existing 'Future Health Today' (FHT) software and explored its acceptability in general practice. Methods Our tool (FHT-syphilis) scans electronic medical record data to identify and prompt testing for pregnant women, and, people recently tested for sexually transmissible infection (STI) or HIV, but not syphilis. It links to relevant guidelines and patient resources. We implemented FHT-syphilis in 52 general practices using FHT for other conditions and interviewed practice clinicians (n =9) to explore it's acceptability. Data were analysed deductively guided by the Theoretical Framework of Acceptability. Results Interviewees considered syphilis an important infection to focus on and broadly viewed FHT-syphilis as acceptable for identifying patients and giving clinicians authority to discuss syphilis testing. Time constraints and unrelated reasons for a patient's visit were barriers to initiating syphilis testing discussions. Australian STI guidelines were considered appropriate to link to. Some interviewees considered prompts should be based on sexual behaviour, however this is not well captured in the electonic medical record. Two interviewees were alerted to updated Australian STI guidelines via their interaction with FHT-syphilis and expanded their syphilis testing practices. Expertise to initiate discussions about syphilis and risk was deemed important. Conclusions A digital tool for prompting syphilis testing was acceptable to clinicians already using FHT. Linkage to STI guidelines alerted some end-users to updated guidelines, informing STI testing practices.

Background: A new chemiluminescence assay, the Anti-TP-Ⅱ assay, is going to be commercially available in clinical laboratories in China and other countries. This study examined the performance of the new assay for the detection of TP infection and compared it with that of the Anti-TP assay by using large amounts of clinical samples., Methods: The precision, accuracy, anti-interference ability, and the clinical sensitivity and specificity of the Anti-TP-Ⅱ assay were evaluated. In addition, compared with those of the Anti-TP assay, the false positive and false negative rates of the Anti-TP-Ⅱ assay were evaluated for 2,436 clinical routine samples and 711 preselected Anti-TP assay reactive samples. Discrepancy of the samples was investigated with the recomLinec Treponema IgM/IgG kit or the Elecsys syphilis assay., Results: The precision, accuracy, and anti-interference ability of the Anti-TP-Ⅱ assay met the national standard of China, and there was an overall agreement of 96.75% (Kappa = 0.91) between the two assays. The sensitivity and specificity of the Anti-TP-Ⅱ assay were 100% (95% CI: 94.13% to 100%) and 99.92% (95% CI: 99.70% to 99.99%), respectively. Compared with the Anti-TP assay, the Anti-TP-Ⅱ assay significantly reduced the number of borderline samples and the false positive rate., Conclusions: Considering its excellent performance, the Anti-TP-Ⅱ assay is a good screening test for high-throughput laboratories and can replace the previous generation of reagents, the Anti-TP assay, with a superior specificity.

BackgroundSyphilis in blood donors (BD) has increased in many countries.AimWe aimed to describe trends in syphilis seroposivity in BD in France, to identify risk factors and assess if a non-treponemic test (NTT) could define BD having recovered from syphilis for more than 1 year.MethodsThe analysis covered the period 2007 to 2022 and 45,875,939 donations. Of the 474 BD syphilis-positive in 2022, 429 underwent additional investigations with an NTT. History of syphilis was obtained at the post-donation interview or based on serology results for repeat donors.ResultsUntil 2021, positivity rates remained stable (mean: 1.18/10,000 donations, range: 1.01-1.38). An increased rate was observed in 2022 (1.74/10,000; p = 0.02). Over the whole study period, prevalence was 2.2 times higher in male than in female BD (4.1 times higher in 2022). The proportion of males with an identified risk factor who have sex with men increased from 16.7% in 2007 to 64.9% in 2022. Based on NTT, 79 (18%) of the donors who were seropositive in 2022 were classified as having been infected in the previous year. History of syphilis was available for 30 of them. All had an infection within the previous 3 years. Among seven donors with a syphilis < 12 months before testing, one had an NTT titre ≥ 8, three a titre between 1 and 4, three were negative.ConclusionSyphilis seropositivity increased considerably in BDs in 2022, mostly in males, notably MSM. Available data did not allow appropriate evaluation of the NTT to distinguish recent from past infection.

Background and Objectives: The detection of treponemal antibodies, which are used to make a diagnosis of syphilis, is important both for diagnostic purposes and as a mandatory blood donor test in most countries. We evaluated the feasibility of using Kode Technology to make syphilis peptide red cell kodecytes for use in column agglutination serologic platforms., Materials and Methods: Candidate Kode Technology function-spacer-lipid (FSL) constructs were made for the Treponema pallidum lipoprotein (TmpA) of T. pallidum, using the peptide and FSL selection algorithms, and then used to make kodecytes. Developmental kodecytes were evaluated against a large range of syphilis antibody reactive and non-reactive samples in column agglutination platforms and compared against established methodologies. Overall, 150 reactive and 2072 non-reactive Syphicheck assay (a modified T. pallidum particle agglutination) blood donor samples were used to evaluate the agreement rate of the developed kodecyte assay., Results: From three FSL-peptide candidate constructs, one was found to be the most suitable for diagnostics. Of 150 Syphicheck assay reactive samples, 146 were TmpA-kodecyte reactive (97.3% agreement), compared with 58.0% with the rapid plasmin reagin (RPR) assay for the same samples. Against the 2072 expected syphilis non-reactive samples the agreement rate for TmpA-kodecytes was 98.8%., Conclusion: TmpA-kodecytes are viable for use as cost-effective serologic reagent red cells for the detection of treponemal antibodies to diagnose syphilis with a high level of specificity in blood centres. This kodecyte methodology also potentially allows for introduction of the reverse-algorithm testing into low-volume laboratories, by utilizing existing transfusion laboratory infrastructure., (© 2024 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

This article reviews key concepts in the epidemiology, clinical features, diagnosis and management of ocular syphilis. It is not a systematic review or meta-analysis, but highlights the critical clinical features and investigations in patients with ocular syphilis. It reviews the overlap and interplay between ocular and neuro syphilis and provides practical guidance to diagnose and manage patients with ocular syphilis., (© 2024. The Author(s).)

Syphilitic hepatitis is a very rare presentation of syphilis infection, characterized by inflammation of the liver due to the invasion of hepatic tissue by the bacterium Treponema pallidum. This review article provides an in-depth analysis of the existing body of information pertaining to syphilitic hepatitis. The article primarily concentrates on key aspects such as the epidemiology, clinical manifestations, diagnostic methods, and therapeutic approaches associated with this condition. Despite its rarity, awareness of syphilitic hepatitis is vital for accurate diagnosis and appropriate intervention. The clinical presentations frequently exhibit similarities with many liver illnesses, hence presenting difficulties in making an accurate diagnosis. Common symptoms include fatigue, stomach pain, and jaundice. Diagnostic procedures encompass the use of serological assays, including rapid plasma reagin (RPR) and fluorescent treponemal antibody absorption (FTA-ABS), in conjunction with imaging modalities to evaluate hepatic engagement. The primary therapeutic approach is the prompt initiation of antibiotic therapy, with a particular emphasis on penicillin, to eradicate the causative bacterial infection and facilitate the restoration of liver function. Failure to swiftly manage this condition may result in substantial morbidity. In summary, syphilitic hepatitis is a very uncommon but medically relevant manifestation of syphilis infection. The significance of increased clinical suspicion, precise diagnostic techniques, and prompt antibiotic administration is emphasized in this review since these are crucial in reducing the potentially severe outcomes associated with this illness., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary Gastric syphilis is rare and presents in 1% of patients with syphilis. The most common presenting symptom is abdominal pain and fullness (92%), followed by nausea/vomiting (71%), weight loss (60%), and gastric bleeding (35%). Multisystem involvement may be seen, as with our patients who presented with a rash and chancre, but in up to two-thirds of patients, there may be no concurrent extraintestinal manifestation of syphilis. The endoscopic appearance typically consists of multiple annular ulcerations and erosions, sometimes with a purple/brown hue at the ulcer margin, as well as nodular mucosa, thickened gastric folds, and nondistensibility of the stomach. This presentation leaves the clinician with a broad differential diagnosis, including lymphoma, infiltrative tumors, Crohn’s disease, and tuberculosis, to name a few. Histologic examination can demonstrate a chronic gastritis with dense plasmacytic and lymphocytic infiltrate, proliferative endarteritis or endophlebitis, and perivascular cuffing. A high index of suspicion for T pallidum is needed to appropriately diagnose gastric syphilis with serologic testing and to detect spirochetes on gastric biopsy specimens with immunostaining, silver staining, dark field microscopy, or polymerase chain reaction. Treatment is prescribed based on the clinical stage of syphilis and results in full resolution of symptoms. The nonspecific clinical and endoscopic presentation of gastric syphilis indeed makes it “the great imitator” of other gastric diseases. Therefore, as highlighted in these cases, gastric syphilis should be suspected in high-risk patients who present with abdominal symptoms and unusual endoscopic findings. Early diagnosis can lead to prompt treatment and a significant decrease in syphilis-associated morbidity. Deepika Satish, MD, Assistant Professor of Medicine, Baylor College of Medicine, Houston, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Home-based sampling could create accessible testing opportunities for men who have sex with men (MSM) who use pre-exposure prophylaxis (PrEP). Blood collection is required for the most reliable laboratory results for HIV and syphilis testing. An innovative blood collection method (Tasso+) creates a vacuum and semi-automatically collects larger volumes of blood from the upper arm. This study aimed to assess acceptability and feasibility of this device among PrEP-using MSM and the performance of blood collection., Methods: Between August 2022 and January 2023, 47 MSM were recruited during their routine PrEP consultations at a Dutch Centre for Sexual Health. Participants tested the method directly after consultation, and an online questionnaire determined acceptability and feasibility. Blood and residual serum volumes were measured after sampling and after HIV and syphilis testing., Results: Of the participants, 87% had a positive attitude toward use of the device, and 77% would use it again for self-sampling at home. Participants rated the use of the blood collection device as easy (96%). On average, 536 μL whole blood (244 μL serum) was collected. All samples were tested for HIV and syphilis, and most samples had sufficient blood for routine HIV (91%) and syphilis testing (89%). Most samples (85%) had 220 μL residual blood, sufficient for further testing (e.g., confirmation)., Conclusions: Blood self-sampling with a method that creates a vacuum from the upper arm is highly acceptable by users and performs well in blood collection for multiple tests. This method has promising potential for use in home-based sexual health care for PrEP-using MSM., Competing Interests: Conflict of Interest and Sources of Funding: None declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: Human immunodeficiency virus (HIV) and syphilis disproportionately impact communities with low access to primary care, who often utilize urgent care centers (UCCs) for sexual health care. UCC visits represent an opportunity for identification and treatment of syphilis and linkage to HIV testing and prevention services. We describe a universal, opt-out syphilis screening program pilot at an Atlanta UCC., Methods: A chart review was performed on patients 18 years and older who were offered opt-out syphilis screening and had a rapid plasma reagin (RPR) test collected from September 1, 2021 to December 31, 2021. Demographic data, syphilis stage and treatment, and HIV testing and serostatus were abstracted from the electronic health record. Patients with reactive RPRs were contacted by a study physician for syphilis staging and treatment, counseling, and referral for HIV preexposure prophylaxis (PrEP) or treatment., Results: From September 1, 2021 to December 31, 2021, 5794 patients were triaged and 1381 underwent RPR screening (23.8%). Eighty (5.8%) had reactive RPRs, and 42 (52.5%) had active syphilis. Of those with active syphilis, 39 (92.9%) received any treatment, and 35 (83.3%) completed treatment. Patients with late syphilis were less likely to complete syphilis treatment (adjusted odds ratio, 0.03; P = 0.009; 95% confidence interval, 0.002-0.42). Among 955 offered PrEP, 41 (4.3%) expressed interest in PrEP, and 7 (0.7%) completed PrEP clinic intake. Univariate analysis did not identify any factors associated with interest in PrEP., Conclusions: In a UCC setting, routine, opt-out syphilis testing resulted in increased syphilis identification and treatment. It also provided an opportunity for PrEP counseling and referral, although few patients completed PrEP clinic intake., Competing Interests: Conflict of Interest and Sources of Funding: The authors report no financial or nonfinancial conflicts of interest. Some of the material in this manuscript has been previously presented as an abstract at the Infectious Disease Week (ID Week) 2023 conference. This work was supported by internal departmental funding., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Competing Interests: Disclosure Supported by 2023 Weifang Traditional Chinese Medicine Research Project Approval (project number: WFZYY2023-4-002) and Affiliated Hospital of Weifang Medical University Seed Fund Project in 2021(project number: 2021wyfyzzjj07). All authors disclosed no financial relationships. Commentary Gastric syphilis is rare and presents in 1% of patients with syphilis. The most common presenting symptom is abdominal pain and fullness (92%), followed by nausea/vomiting (71%), weight loss (60%), and gastric bleeding (35%). Multisystem involvement may be seen, as with our patients who presented with a rash and chancre, but in up to two-thirds of patients, there may be no concurrent extraintestinal manifestation of syphilis. The endoscopic appearance typically consists of multiple annular ulcerations and erosions, sometimes with a purple/brown hue at the ulcer margin, as well as nodular mucosa, thickened gastric folds, and nondistensibility of the stomach. This presentation leaves the clinician with a broad differential diagnosis, including lymphoma, infiltrative tumors, Crohn’s disease, and tuberculosis, to name a few. Histologic examination can demonstrate a chronic gastritis with dense plasmacytic and lymphocytic infiltrate, proliferative endarteritis or endophlebitis, and perivascular cuffing. A high index of suspicion for T. pallidum is needed to appropriately diagnose gastric syphilis with serologic testing and to detect spirochetes on gastric biopsy specimens with immunostaining, silver staining, dark field microscopy, or polymerase chain reaction. Treatment is prescribed based on the clinical stage of syphilis and results in full resolution of symptoms. The nonspecific clinical and endoscopic presentation of gastric syphilis indeed makes it “the great imitator” of other gastric diseases. Therefore, as highlighted in these cases, gastric syphilis should be suspected in high-risk patients who present with abdominal symptoms and unusual endoscopic findings. Early diagnosis can lead to prompt treatment and a significant decrease in syphilis-associated morbidity. Deepika Satish, MD, Assistant Professor of Medicine, Baylor College of Medicine, Houston, Texas, USA Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Competing Interests: Conflicts of interest None disclosed.

Ocular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders., (© 2024. The Author(s).)

Syphilis is becoming an increasingly concerning sexually transmitted infection in the primary care setting with a precipitous rise in cases in the USA over the past decade according to the CDC surveillance data. This rise in cases is particularly relevant in military medicine as the greatest increase in cases is among adults in their 20s. Nodular syphilis is a rare presentation of the secondary stage of syphilis, and contrary to the well-known maculopapular rash seen with syphilis infection, little is known about effective treatment of nodular manifestations of the disease. We present a case of a 54-year-old HIV-positive man with nodular secondary syphilis effectively treated with an empiric 2-week course of oral doxycycline. Initial differential diagnosis included erythema nodosum, arthropod vector disease, skin infection, and erythema elevatum diutinum. Biopsy demonstrated granulomatous dermatitis, and serology revealed positive Treponema pallidum antibodies with a rapid plasma reagin of 1:256, confirming the diagnosis of secondary syphilis with granulomatous dermatitis. This case indicates that clinicians should consider this unusual cutaneous presentation of secondary syphilis when evaluating patients with nodular skin lesions, especially in high-risk individuals., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

This is a case report of 51-year-old male patient with various symptoms including skin rashes, sensory disturbances, and non-cicatricial hair loss. Despite previous tests, the cause remained elusive until a dermatological examination revealed signs of syphilis. The patient's history, including his sexual relationships, became key in confirming the diagnosis, leading to treatment for neurosyphilis. With a rising incidence of syphilis in Denmark, this case highlights the importance of considering syphilis as a potential diagnosis across medical specialities because of the diverse and challenging clinical manifestations., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Nearly half of all sexually transmitted infections occur in adolescents and young adults. Among them, syphilis infections are on the rise in the United States. Sexually active adolescents, especially those who do not use condoms consistently or are men who have sex with men, are at particular risk for syphilis infection. With the rise in acquired syphilis infections, the incidence of congenital syphilis has also increased. Syphilis can have a variety of presentations based on infectious stage and central nervous system involvement. Careful physical examination and history can elicit the diagnosis. Screening with a nontreponemal test followed by treponemal testing can confirm the diagnosis, and staging is determined clinically. Testing for all sexually transmitted infections should be pursued because coinfections are common. Penicillin is the first-line treatment for syphilis, and duration of therapy depends on the presence of neurologic symptoms; all infants with possible congenital syphilis should receive treatment. Posttreatment monitoring is essential to confirm successful eradication of syphilis. All sexually active, at-risk patients, including pregnant persons, should be screened for syphilis, and those diagnosed as having syphilis should be counseled on disclosure to partners. Although not often found in a pediatric population, with the increasing incidence of syphilis infections in the United States, pediatric providers should have a low threshold for syphilis screening in adolescents and a high index of suspicion for congenital syphilis in infants., (© American Academy of Pediatrics, 2024. All rights reserved.)

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.

A recent resurgence in the incidence of syphilis has sparked a new interest in this old disease. Syphilitic uveitis remains a challenging disease, among the variable syphilis infections, due to the diagnostic complexity and the wide clinical manifestations. Here, we provide recommendations regarding clinical manifestations, diagnosis, and treatment for patients with syphilitic uveitis in Taiwan based on an expert meeting and consensus from experienced uveitis specialists., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Syphilis remains a public health concern in Brazil, and the data on the characterization and resistance of Treponema pallidum in Brazil is limited. The present study aimed to detect Treponema DNA in the lesions and blood samples obtained from individuals diagnosed with syphilis. The Brazilian isolates were submitted to the Enhanced Centers for Disease Control and Prevention (ECDC) scheme and also analyzed for resistance gene. Treponemal DNA from 18 lesions and 18 blood specimens were submitted for amplification using Polymerase Chain Reaction (PCR) and Polymerase Chain Reaction in Real Time (RT-PCR). Eight samples from lesions and eight from blood were positive in the RT-PCR analysis. Eight lesions and three blood samples were positive using PCR. Two samples exhibited azithromycin resistance. The Brazilian isolate types 14d/g, 14 d/c, 15d/c, and 15d/e were identified using the ECDC scheme. The three subtypes 14d/c, 15d/c, and 15d/e have been identified in Brazil for the first time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We studied the detection of Treponema pallidum (TP)-IgM antibodies in the serum of 69 patients treated for syphilis. The persistence of TP-IgM antibodies in serum for more than 3 years was the only clue to suspect an active infection and, therefore, to investigate a central nervous system involvement., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Infectious diseases including syphilis, HIV, and hepatitis B are major contributors to maternal and neonatal morbidity and mortality worldwide, especially in low- and middle-income countries (LMICs). The World Health Organization has prioritized elimination of vertical transmission of these three diseases., Objectives: To rapidly assess the impact of interventions designed to improve antenatal screening rates for syphilis, HIV, and hepatitis B in LMICs and to identify areas for future implementation research., Search Strategy: A comprehensive search was conducted across PubMed, Embase, and EconLit, targeting articles published between January 1, 2013, and June 27, 2023., Selection Criteria: We included quantitative interventional studies in English, involving pregnant adults (15 years or older) from LMICs. Exclusions were studies based in high-income countries, qualitative studies, or those investigating accuracy of diagnostic methods., Data Collection and Analysis: From an initial 5549 potential studies, 27 were finalized for review after various screening stages. Data extraction covered aspects such as study design, intervention details, and outcomes. Findings were qualitatively synthesized within a systems thinking framework., Main Results: The interventions assessed varied in terms of geographic locations, health care system levels, and modalities. The review highlighted the effectiveness of interventions such as community health interventions, service quality improvements, and financial incentives., Conclusions: The study underscores the potential of specific interventions in enhancing antenatal screening rates in LMICs. However, there is a discernible research gap concerning hepatitis B. The findings emphasize the importance of capacity building and health systems strengthening in public health interventions., (© 2024 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To evaluate the serological diagnosis value of recombinant protein antigen Tp0608 for syphilis., Method: 406 patients with various stages of syphilis were enrolled. A recombinant protein antigen Tp0608 was established and ELISA was used to detect patients with various stages of syphilis. The results were compared with the conventional rapid plasma reagin test (RPR) and Treponema pallidum particle agglutination test (TPPA). The sensitivity of Tp0608 recombinant protein and RPR+TPPA screening was 96.6 % and 93.1 % respectively for patients with various stages of syphilis. For patients who may have cross reactivity, the specificity of Tp0608 recombinant protein screening is 98.9 %, and the AUC of the ROC curve is 0.99; The specificity of RPR+TPPA screening was 97.3 %, and the AUC of the ROC curve was 0.96. The sensitivity and specificity of Tp0608 recombinant protein in syphilis screening are higher than conventional RPR+TPPA methods, especially in congenital syphilis and primary syphilis., Conclusion: The Tp0608 recombinant protein is a promising diagnostic antigen for syphilis screening, but its intracellular location and protective response have not been determined, and further verification is needed., Competing Interests: Declaration of competing interest The authors declare no conflict interest exists in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is increasing interest in improving routine HIV screening in emergency departments and increasing HIV cotesting rates among patients tested for sexually transmitted infections (STIs), who are considered at elevated risk of acquiring HIV., Methods: This is a retrospective review of all ED encounters at a large, urban emergency departments with an existing HIV screening program for seven months before (November 1, 2018, to May 30, 2019) and after (June 1 to December 31, 2019) the implementation of a best practice advisory prompting universal HIV and syphilis screening., Results: The study included 14,767 unique encounters, with 3,982 pre-implementation encounters and 10,785 post-implementation. After implementation, HIV testing increased 242%, from 2,851 tests to 9,757, and syphilis testing increased 326%, from 2,191 tests to 9,330. The proportion of encounters for urogenital STI testing without HIV cotesting decreased by 10.3%, from 43.6% to 33.3%., Discussion: An automated electronic medical record (EMR) prompt can have a huge impact on both HIV and syphilis testing rates, as well as the rate of missed opportunities for cotesting among patients undergoing STI testing., Conclusions: Hospitals should support screening with automated alerts to help meet quality metrics, improve screening rates, and reduce missed opportunities for screening in vulnerable patients., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)