Single-test syphilis serology: A case of not seeing the forest for the trees.

INTRODUCTION: There have been few empirical studies for diagnostic test accuracy of syphilis using a sequence of rapid tests in populations with low prevalence of syphilis such as pregnant women. This analysis describes syphilis test positivity frequency among pregnant women at an antenatal clinic in Zambia using a reverse-sequence testing algorithm for antenatal syphilis screening. METHODS: Between August 2019 and May 2023, we recruited 1510 pregnant women from a peri-urban hospital in Lusaka, Zambia. HIV positive and HIV negative women were enrolled in a 1:1 ratio. Blood collected at recruitment from the pregnant mothers was tested on-site for syphilis using a rapid treponemal test. Samples that tested positive were further tested at a different laboratory, with rapid plasma reagin using archived plasma. RESULTS: Of the total 1,421 sera samples which were screened with a rapid treponemal test, 127 (8.9%) were positive and 1,294 (91.1%) were negative. Sufficient additional samples were available to perform RPR testing on 114 of the 127 (89.8%) RDT positive specimens. Thirty-one (27.2%) of these 114 were reactive by RPR and 83 (72.8%) were negative, resulting in a syphilis overtreatment rate of 3 fold (i.e, 84/114). Insufficient sample or test kit availability prevented any testing for the remaining 89 (5.9%) participants. CONCLUSION: Use of only treponemal tests in low prevalence populations, like pregnant women, subjects individuals with non-active syphilis to the costs and possible risks of overtreatment. The use of the dual treponemal and non-treponemal tests would minimize this risk at some additional cost.

Follmann Balanitis: An Unusual Case of Syphilis.

A 33-year-old man presented with suprapubic abdominal pain and small vesicular lesions on the foreskin of the penis. Based on the presentation, he was empirically treated for genital herpes, although the herpes simplex virus swab was negative. He returned to the emergency department 4 months after his initial presentation with worsening symptoms that were consistent with balanoposthitis and cystitis. He was tachycardic and febrile on presentation. He denied any sexual contact for the last 3 months, with previous negative screening tests for sexually transmitted infections. Syphilis was eventually diagnosed during this admission. The incidence rates of syphilis have increased in recent years, and the infection is often undiagnosed given atypical manifestations. Here we present an atypical manifestation of syphilis that was initially misdiagnosed as herpes simplex virus.

Interventions aimed at increasing syphilis screening among non-pregnant individuals in healthcare settings: a systematic review and meta-analysis.

Syphilis remains a pressing public health concern with potential severe morbidity if left untreated. To improve syphilis screening, targeted interventions are crucial, especially in at-risk populations. This systematic review synthesises studies that compare syphilis screening in the presence and absence of an intervention. A systematic search of four databases was conducted (Medline, Embase, Cinahl and Scopus). The primary outcomes evaluated included syphilis screening, re-screening and detection rates. Findings were synthesised narratively. Where multiple studies were clinically heterogenous, a pooled odds ratio was calculated. Twenty-four studies were included. A variety of interventions showed promise including clinician alerts, which increased syphilis screening rate (OR range, 1.25-1.45) and patient SMS reminders that mostly improved re-screening/re-attendance rates (OR range, 0.93-4.4). Coupling syphilis serology with routine HIV monitoring increased the proportion of HIV-positive individuals undergoing both tests. However, pooling three studies with this intervention using the outcome of syphilis detection rate yielded inconclusive results (pooled OR 1.722 [95% CI 0.721-2.723], I 2 =24.8%, P =0.264). The introduction of hospital-based packaged testing for screening high-risk individuals is unique given hospitals are not typical locations for public health initiatives. Nurse-led clinics and clinician incentives were successful strategies. Including syphilis screening with other existing programs has potential to increase screening rates (OR range, 1.06-2.08), but requires further investigation. Technology-driven interventions produced cost-effective, feasible and positive outcomes. Challenges were evident in achieving guideline-recommended screening frequencies for men who have sex with men, indicating the need for multifaceted approaches. Wider application of these interventions may improve syphilis screening and detection rates.

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.

Sexually Transmitted Infection Co-testing in a Large Urban Emergency Department.

Introduction: The incidence of sexually transmitted infections (STI) increased in the United States between 2017-2021. There is limited data describing STI co-testing practices and the prevalence of STI co-infections in emergency departments (ED). In this study, we aimed to describe the prevalence of co-testing and co-infection of HIV, hepatitis C virus (HCV), syphilis, gonorrhea, and chlamydia, in a large, academic ED. Methods: This was a single-center, retrospective cross-sectional study of ED patients tested for HIV, HCV, syphilis, gonorrhea or chlamydia between November 27, 2018-May 26, 2019. In 2018, the study institution implemented an ED-based infectious diseases screening program in which any patient being tested for gonorrhea/chlamydia was eligible for opt-out syphilis screening, and any patient 18-64 years who was having blood drawn for any clinical purpose was eligible for opt-out HIV and HCV screening. We analyzed data from all ED patients ≥13 years who had undergone STI testing. The outcomes of interest included prevalence of STI testing/co-testing and the prevalence of STI infection/co-infection. We describe data with simple descriptive statistics. Results: During the study period there were 30,767 ED encounters for patients ≥13 years (mean age: 43 ± 14 years, 52% female), and 7,866 (26%) were tested for at least one of HIV, HCV, syphilis, gonorrhea, or chlamydia. We observed the following testing frequencies (and prevalence of infection): HCV, 7,539 (5.0%); HIV, 7,359 (0.9%); gonorrhea, 574 (6.1%); chlamydia, 574 (9.8%); and syphilis, 420 (10.5%). Infectious etiologies with universal testing protocols (HIV and HCV) made up the majority of STI testing. In patients with syphilis, co-infection with chlamydia (21%, 9/44) and HIV (9%, 4/44) was high. In patients with gonorrhea, co-infection with chlamydia (23%, 8/35) and syphilis (9%, 3/35) was high, and in patients with chlamydia, co-infection with syphilis (16%, 9/56) and gonorrhea (14%, 8/56) was high. Patients with HCV had low co-infection proportions (<2%). Conclusion: Prevalence of STI co-testing was low among patients with clinical suspicion for STIs; however, co-infection prevalence was high in several co-infection pairings. Future efforts are needed to improve STI co-testing rates among high-risk individuals.

Gaps in the prevention of mother-to-child transmission of syphilis: a review of reported cases, South Africa, January 2020-June 2022.

INTRODUCTION: Congenital syphilis (CS) is preventable through timely antenatal care (ANC), syphilis screening and treatment among pregnant women. Robust CS surveillance can identify gaps in this prevention cascade. We reviewed CS cases reported to the South African notifiable medical conditions surveillance system (NMCSS) from January 2020 to June 2022. METHODS: CS cases are reported using a case notification form (CNF) containing limited infant demographic and clinical characteristics. During January 2020-June 2022, healthcare workers supplemented CNFs with a case investigation form (CIF) containing maternal and infant testing and treatment information. We describe CS cases with/without a matching CIF and gaps in the CS prevention cascade among those with clinical information. FINDINGS: During January 2020-June 2022, 938 CS cases were reported to the NMCSS with a median age of 1 day (interquartile range: 0-5). Nine percent were diagnosed based on clinical signs and symptoms only. During January 2020-June 2022, 667 CIFs were reported with 51% (343) successfully matched to a CNF. Only 57% of mothers of infants with a matching CIF had an ANC booking visit (entry into ANC). Overall, 87% of mothers were tested for syphilis increasing to 98% among mothers with an ANC booking visit. Median time between first syphilis test and delivery was 16 days overall increasing to 82 days among mothers with an ANC booking visit. DISCUSSION: Only 37% of CS cases had accompanying clinical information to support evaluation of the prevention cascade. Mothers with an ANC booking visit had increased syphilis screening and time before delivery to allow for adequate treatment.

Untreated maternal syphilis has devastating consequences for the foetus. Congenital syphilis (CS) is preventable through timely maternal screening and treatment with robust surveillance. We evaluated CS surveillance data to identify gaps in CS surveillance and in the prevention cascade in South Africa.

A systematic review of barriers and facilitators to antenatal screening for HIV, syphilis or hepatitis B in Asia: Perspectives of pregnant women, their relatives and health care providers.

BACKGROUND: Despite improvements, the prevalence of HIV, syphilis, and hepatitis B remains high in Asia. These sexually transmitted infections (STIs) can be transmitted from infected mothers to their children. Antenatal screening and treatment are effective interventions to prevent mother-to-child transmission (MTCT), but coverage of antenatal screening remains low. Understanding factors influencing antenatal screening is essential to increase its uptake and design effective interventions. This systematic literature review aims to investigate barriers and facilitators to antenatal screening for HIV, syphilis, and hepatitis B in Asia. METHODS: We conducted a systematic review by searching Ovid (MEDLINE, Embase, PsycINFO), Scopus, Global Index Medicus and Web of Science for published articles between January 2000 and June 2023, and screening abstracts and full articles. Eligible studies include peer-reviewed journal articles of quantitative, qualitative and mixed-method studies that explored factors influencing the use of antenatal screening for HIV, syphilis or hepatitis B in Asia. We extracted key information including study characteristics, sample, aim, identified barriers and facilitators to screening. We conducted a narrative synthesis to summarise the findings and presented barriers and facilitators following Andersen's conceptual model. RESULTS: The literature search revealed 23 articles suitable for inclusion, 19 used quantitative methods, 3 qualitative and one mixed method. We found only three studies on syphilis screening and one on hepatitis B. The analysis demonstrates that antenatal screening for HIV in Asia is influenced by many barriers and facilitators including (1) predisposing characteristics of pregnant women (age, education level, knowledge) (2) enabling factors (wealth, place of residence, husband support, health facilities characteristics, health workers support and training) (3) need factors of pregnant women (risk perception, perceived benefits of screening). CONCLUSION: Knowledge of identified barriers to antenatal screening may support implementation of appropriate interventions to prevent MTCT and help countries achieve Sustainable Development Goals' targets for HIV and STIs.

Communicable Disease Screening and Human Immunodeficiency Virus Prevention in the Emergency Department.

Emergency departments (ED) provide care to populations with high rates of communicable diseases, like HIV, hepatitis C virus, and syphilis. For many patients, the ED is their sole entry point into the healthcare system and they do not routinely access screening and prevention services elsewhere. As such, the ED can serve an important public health role through communicable disease identification, treatment, and prevention. In this article, we examine national recommendations, peer-reviewed literature, and expert consensus to provide cutting edge strategies for implementing communicable infectious disease screening and prevention programs into routine ED care.

Beyond Tumors: Gastric Syphilis Emulating a Gastric Neoplasia.

We present the case of a 35-year-old male with a first-degree family history of gastric cancer (his father was diagnosed at the age of 45), who was presumed to have gastric cancer himself when evaluating the features of his upper endoscopy performed after hematemesis. Surprisingly, no cancer cells were found in the biopsies. Thanks to a different diagnostic suspicion subsequent to performing a full clinical history, a more favorable diagnosis was reached: gastric syphilis.

Presentaciones de la sífilis anorrectal: la gran simuladora / Anorectal syphilis presentations: the great pretender

Antecedentes: La sífilis es una infección sexualmente transmisible sistémica crónica que afecta a docenas de millones de personas al año. A nivel anorrectal, su manifestación polimórfica obliga al diagnóstico diferencial con enfermedades anorrectales benignas y malignas. Objetivo: Describir las diferentes presentaciones de la sífilis anorrectal a propósito de 5 casos clínicos. Método: Estudio observacional, retrospectivo, descriptivo. Resultados: La mayoría de los pacientes fueron VIH positivos en edad sexual activa. Las manifestaciones registradas, al igual que las reportadas en la bibliografía fueron las fisuras, úlceras perianales y pseudotumores. Conclusiones: La sífilis es considerada "la gran simuladora". En la localización anorrectal se requiere una alta sospecha diagnóstica para diferenciarla de presentaciones similares de otras enfermedades anales benignas, la enfermedad inflamatoria intestinal y el cáncer anorrectal, con el fin de evitar el consiguiente riesgo de sobretratamiento. (AU)

Background: Syphilis is a chronic systemic sexually transmitted infection that affects tens of millions of people annually. At the anorectal level, its polymorphic manifestation requires differential diagnosis with benign and malignant anorectal diseases. Objective: To review the presentation of anorectal syphilis from 5 clinical cases. Methods: Observational, retrospective, descriptive study. Results: Most of the patients were HIV positive in sexually active age. The manifestations recorded and reported in the literature were fissures, perianal ulcers, and pseudotumors. Conclusions: Syphilis is considered "the great pretender". In anorectal syphilis, a high diagnostic suspicion is needed to differentiate it from similar presentations due to other anal conditions, inflammatory bowel disease, and anorectal cancer, to avoid the consequent risk of overtreatment. (AU)

A clinical utility evaluation of dual HIV/Syphilis point-of-care tests in non-clinical settings for screening for HIV and syphilis in men who have sex with men.

BACKGROUND: Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites. METHODS: This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study's conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method. RESULTS: The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers. CONCLUSIONS: The introduction of dual HIV and syphilis  POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM.

Temporal Trends in Syphilis Incidence among Men with HIV in Busan, Korea, 2005-2022: A Retrospective Cohort Study.

We aimed to assess the temporal trends of incident syphilis and its associated risk factors among men with HIV (Human Immunodeficiency Virus) in Korea during the COVID-19 pandemic. We conducted a retrospective cohort study of men with HIV attending an HIV clinic in Korea between 2005 and 2022. Of 767 men with HIV, 499 were included and contributed 3220 person-years (PY) of the observation period. Eighty-two patients were diagnosed with incident syphilis, with an overall incidence of 2.55/100 PY (95% confidence interval [CI] 20.56-31.53). The incidence of syphilis per 100 PY gradually decreased from 2.43 (0.79-7.42) in 2005-2007 to 1.85 (1.08-3.17) in 2014-2016; however, it increased to 3.0 (1.99-4.53) in 2017-2019, and further to 3.33 (2.26-4.89) in 2020-2022. A multivariate analysis identified young age (≤30 years versus >50, adjusted HR 6.27, 95% CI 2.38-16.56, p < 0.001), treponemal test positive at baseline (2.33, 1.48-3.67, p < 0.001), men who have sex with men (2.36, 1.34-4.16, p = 0.003), and history of incarceration (2.62, 1.21-5.67, p = 0.015) as risk factors for incident syphilis. Recently, syphilis incidence in men with HIV has increased in Korea, especially in young patients and at-risk groups, highlighting the need for enhanced regular screening and targeted behavioral interventions among these populations.

Secondary oral syphilis presenting as a tumor-like lesion on the lower lip.

This study presents a case of atypical manifestation of secondary syphilis. Diagnosis was initiated prompted by the patient's complaint of a lower lip lesion, present for three months, resembling a malignant neoplasm. The lesion, a 3 cm (diameter) ulcerated nodule, arising from conjunctive tissue, raised concern. However, further physical examination revealed additional clinical features, including cervical micropolyadenopathy and erythematous skin lesions, prompting a reevaluation of the diagnosis, most likely secondary syphilis. These findings led to a serological investigation, which, ultimately, confirmed the diagnosis of syphilis. The case underscores the importance of recognizing syphilis as a formidable imitator, posing challenges in establishing differential diagnoses of mucocutaneous diseases.

Ocular syphilis masquerading as refractory retinal diseases.

PURPOSE: To report two cases of syphilis masquerading as chronic refractory macular diseases. CASE DESCRIPTIONS: Two patients had been diagnosed with neovascular age-related macular degeneration (neovascular AMD) and diabetic macular edema (DME), respectively. The disease worsened despite repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) and also surgical treatment (in suspected case of DME). Systemic evaluations were positive for syphilis. Intravenous penicillin was started, and the macular diseases improved. The lesions were well controlled afterward. CONCLUSIONS: The current two cases demonstrated that ocular syphilis can masquerade as refractory chronic retinal diseases such as DME and neovascular AMD. Laboratory evaluations for syphilis may be needed, not only for uveitis but also for refractory retinal diseases. Indocyanine green angiography may be helpful to reveal occult syphilis.