Syphilis Research Articles

Parkinsonism as a manifestation of secondary syphilis

Parkinsonism as a manifestation of secondary syphilis

Gonorrhea and early syphilis treatment practices among community healthcare providers in Baltimore City, Maryland.

Substantial gaps in reporting gonorrhea treatment and prompt ES treatment were observed. Practice-level interventions to facilitate reporting gonorrhea treatment and provide prompt ES treatment are needed.

A Narrative Review of Congenital Syphilis in the United States: Innovative Perspectives on a Complex Public Health and Medical Disease.

Over the past two decades, congenital syphilis cases have risen 11-fold in the United States. While disparities across geography, race, and ethnicity exist, lack of timely screening or treatment is identified in 88% of cases nationally. Congenital syphilis is a public health and medical problem rooted in systematic and societal structural determinants of health and healthcare limitations. Early syphilis in pregnancy leads to congenital syphilis if untreated in 50 - 70% of cases, with risk for fetal demise, and among survivors, congenital anomalies, organ damage, and central nervous system disease. Prevention of congenital syphilis lies in early detection and treatment in pregnant persons. In this narrative review, we describe the evolving epidemiology of syphilis and congenital syphilis, highlighting unique aspects among women. We explore the role of novel screening and treatment strategies, public health policy, and medical considerations in terms of congenital syphilis prevention. Readers of this review will understand CS as a complex public health and medical disease that can be prevented through innovative and coordinated strategies in public health policy, expanded screening and research opportunities.

Secondary Syphilis in the Spotlight: Atypical Cutaneous Manifestation Overshadowing Kaposi Sarcoma in a Newly Diagnosed HIV Patient

Secondary Syphilis in the Spotlight: Atypical Cutaneous Manifestation Overshadowing Kaposi Sarcoma in a Newly Diagnosed HIV Patient

Enhancing insights in sexually transmitted infection mapping: Syphilis in Forsyth County, North Carolina, a case study.

In 2008-2011 Forsyth County, North Carolina experienced a four-fold increase in syphilis rising to over 35 cases per 100,000 mirroring the 2021 state syphilis rate. Our methodology extends current models with: 1) donut geomasking to enhance resolution while protecting patient privacy; 2) a moving window uniform grid to control the modifiable area unit problem, edge effect and remove kriging islands; and 3) mitigating the "small number problem" with Uniform Model Bayesian Maximum Entropy. Data is 2008-2011 early syphilis cases reported to the NC Department of Health and Human Services for Forsyth County. Results were assessed using latent rate theory cross validation. We show combining a moving window and a UMBME analysis with geomasked data effectively predicted the true or latent syphilis rate 5% to 26% more accurate than the traditional, geopolitical boundary method. It removed kriging islands, reduced background incidence rate to 0, relocated nine outbreak hotspots to more realistic locations, and elucidated hotspot connectivity producing more realistic geographical patterns for targeted insights. Using the Forsyth outbreak as a case study showed how the outbreak emerged from endemic areas spreading through sexual core transmitters and contextualizing the outbreak to current and past outbreaks. As the dynamics of sexually transmitted infections spread have changed to online partnership selection and demographically to include more women, partnership selection continues to remain highly localized. Furthermore, it is important to present methods to increase interpretability and accuracy of visual representations of data.

Concomitant primary and secondary syphilis: a case series from a reference center in Mexico

Primary syphilis is characterized by the presence of a chancre and secondary syphilis by the presence of syphilis. The presence of chancres within secondary syphilis have been reported, however, this form of presentation is rare. Patients with synchronous diagnosis of primary and secondary syphilis were included. They underwent a reverse sequence algorithm for syphilis diagnosis with a rapid syphilis test, if positive, a rapid plasma reagin (RPR) or venereal disease research laboratory (VDRL) tests were performed. A total of 15 patients were included. All were men. In primary syphilis, penile chancre predominated in 13 patients (86.6%), and one (6.7%) was in the tongue. In secondary syphilis syphilitic roseola was the most common type of presentation in 10 patients (66.6%), followed by the palmoplantar plaques in 6 patients (40%) and condyloma lata in 2 patients (13.3%). One patient presented alopecia in a “moth-eaten” pattern and this presentation coexisted with a condyloma lata and the palmoplantar plaques. Other patient presented with syphilitic roseola, palmoplantar plaques and condyloma lata. Clinical presentation as coexistent primary-secondary syphilis will become more frequent. First contact physicians and dermatologists would have to take more in consideration infrequent and atypical clinical forms of this disease.

Eosinophilic Meningitis in a Patient With Early HIV Infection, Latent Syphilis and HSV-2 Meningitis

Abstract Eosinophilic meningitis is an unusual condition, particularly in patients with HIV infection or syphilis. The detection of herpes simplex virus (HSV)-2 and HIV-1 in cerebrospinal fluid from a patient with acute eosinophilic meningitis has not been previously reported. Herein, we report a case of a 26-year-old cisgender man newly diagnosed with HIV-1 infection and latent syphilis, presenting with headache and low-grade fever. He was diagnosed with both acute eosinophilic meningitis and HSV-2 meningitis, and his condition improved after treatment with acyclovir and penicillin. The compelling case indicates that HSV-2 meningitis may manifest concurrently with acute eosinophilia meningitis in patients coinfected with HIV and Treponema pallidum. Metagenomics next-generation sequencing plays an important role in identifying and further confirming pathogens responsible for central nervous system infections.

Comment on Dutta Majumder et al.’s 2019 ‘Ocular Syphilis: An Update’

ABSTRACT The article ‘Ocular Syphilis: An Update (2019)’ provides a thorough review of the challenges in diagnosing ocular syphilis. However, our research on ‘Dermatological and Ocular Manifestations of Syphilis,’ identifies a significant gap in both literature and clinical practice: the lack of recognition of dermatological signs during ophthalmological assessments. Ocular syphilis often mimics other conditions and can remain undiagnosed for months or years. Detecting dermatological signs, such as the characteristic palmar rash of secondary syphilis and extragenital chancres, could prompt earlier investigation and serological testing, reducing unnecessary diagnostic workups and inappropriate management. Early recognition would facilitate timely administration of Penicillin G, helping prevent vision loss, which is often reversible with prompt treatment. We urge Ocular Immunology and Inflammation to highlight the importance of incorporating dermatological assessments in future ocular syphilis publications to improve diagnostic protocols and patient outcomes.

Granulomatous secondary syphilis - 2 case reports and review of the literature.

Granulomatous inflammation is usually described in association with tertiary syphilis up till recent years where there are emerging cases reporting its presence in secondary syphilis. Herein we present two patients who presented with erythematous infiltrated papules and nodules and were eventually diagnosed with granulomatous secondary syphilis, with clearance of their rashes after treatment. In this article, we highlight the important clues that point clinicians and histopathologists towards the diagnosis of syphilis compared to other similar differentials such as leprosy in reaction, cutaneous histiocytosis and lymphoma. Additionally, from literature review and own experiences, we wish to highlight that granulomatous syphilis is often palmoplantar sparing and its presence may not necessarily be a feature of immunocompromised states (e.g. human immunodeficiency virus) In this increasingly connected world, the recognition of an atypical presentation of an age-old disease in patients with different skin types needs to be underscored with close clinicopathological correlation.

Loop-Mediated Isothermal Amplification Assay Using Gold Nanoparticles for Detecting Treponema pallidum subspp. pallidum.

Venereal syphilis in humans is caused by Trepenoma pallidum subspp. pallidum. A study has shown that 30,302 individuals in Thailand had syphilis in 2020, with a male-to-female ratio of 1:0.8 and the highest incidence rate at ages between fifteen and twenty-four. This research aimed to develop a loop-mediated isothermal amplification assay using gold nanoparticles (LAMP-AuNPs). Analytical sensitivity, diagnostic specificity, accuracy, and predictive values for each technique are provided. The diagnosis sensitivities of polymerase chain reaction using agarose gel electrophoresis (PCR-AGE), loop-mediated isothermal amplification assay using agarose gel electrophoresis (LAMP-AGE), and LAMP-AuNPs were 116 ng/µL, 11.6 ng/µL, and 11.6 ng/µL, respectively. We evaluated the analytical specificity using PCR and a LAMP-based assay, and there was no cross-reactivity to Leptospira interrogans, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, human immunodeficiency virus (HIV), and healthy humans. After analyzing 400 serum samples of patients suspected of syphilis, the LAMP-AGE and LAMP-AuNPs assays displayed 100% diagnostic sensitivity scores, 91% diagnostic specificity scores, 95.5% accuracy rates, 100% positive predictive values (PPVs), and 91% negative predictive values (NPVs), the positive likelihood ratio (LR+) was 11.11, while the negative likelihood ratio (LR-) was 0. Conversely, for PCR assays displayed 100% diagnostic sensitivity scores, 94.5% diagnostic specificity scores, 97.25% accuracy rates, 100% PPVs, and 94.5% NPVs, LR+ was 18.18, and LR- was 0. The LAMP-AuNPs technique demonstrates rapidity, affordability, and convenience, rendering it well-suited for point-of-care applications in the diagnosis, prevention, and management of pathogenic infections.

Judicious Use of Benzathine Penicillin G in Response to a Medication Alert During a Critical Drug Shortage.

To evaluate judicious antibiotic prescribing of benzathine penicillin G (BPG) after implementation of an electronic health record-based medication shortage alert during a critical drug shortage. This was an institutional review board-approved retrospective cohort study of patients aged ≥3 months who received BPG between May 9, 2023, and February 28, 2024. The study included inpatient and outpatient visits after implementing a BPG medication shortage alert; patients with severe penicillin allergy, neurosyphilis, or congenital syphilis were excluded. Judicious BPG use was defined as use in patients diagnosed with primary, secondary, or latent syphilis or if they were prescribed a BPG alternative in response to the medication shortage alert; nonjudicious use included BPG for alternative diagnoses. Social determinants of health were assessed as exposure variables of interest. A separate cohort of syphilis patients receiving BPG or alternative therapy (i.e., doxycycline) was described. A total of 453 patients were included. Most patients were non-Hispanic Black (n = 273, 60%) men (n = 272, 60%) with a median (interquartile range) age of 32 (22-44) years. Of these, 318 (70%) received judicious BPG, whereas 135 (30%) received nonjudicious BPG. The most nonjudicious diagnosis was streptococcal pharyngitis (n = 128, 95%). Variables associated with judicious use included age >32 years (adjusted odds ratio [adjOR], 2.273; 95% CI, 1.488-3.472), male sex (adjOR, 1.835; 95% CI, 1.206-2.792), and black race (adjOR, 1.847; 95% CI, 1.212-2.815). Among a cohort of 128 syphilis patients who received BPG (n = 64, 50%) or doxycycline (n = 64, 50%), those who received doxycycline were more likely be uninsured (35 [54.7%] vs 43 [67.2%]; P = .15) and receive outpatient treatment (3 [4.7%] vs 12 [18.7%]; P = .13). Despite implementing an electronic health record drug shortage alert, 30% of BPG use was nonjudicious and mostly for pharyngitis.

A-170 Hypereosinophilic Syndrome and t(5;15): Case Report and Literature Review

Abstract Background Hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by persistent eosinophilia (absolute eosinophil count >1,500/mm3), classified into primary/clonal, reactive and idiopathic. After ruling out secondary causes of eosinophilia (parasitic infections, allergic conditions, vasculitis and collagenosis, drugs, eosinophilic lung disease, allergic gastroenteritis and metabolic conditions such as adrenal insufficiency), the main hypotheses become oncohematological diseases. Main entities to consider are myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, FDGFRB, FGFR1 or PCM1-JAK2 and chronic eosinophilic leukemia. Conventional and molecular cytogenetics are the basis for classification and diagnosis of various hematological malignancies. This report describes a rare case of HES with t(5;15) (q33;q22). Methods A 29-year-old male patient was admitted with leukocytosis with the following exams: hemoglobin 6.5g/dL, hematocrit 21.7%, platelets 71,000/mm3, leukocytes 56,190/mm3 (60% neutrophils with a left shift to pro-myelocyte; 6% monocytes and 24% eosinophils), DHL 277 U/L, B12 vitamin 932 pg/mL, folic acid 1.72ng/mL, ferritin 913ng/mL. Non-reactive results were detected for antinuclear antibody, rheumatoid Factor, HIV, hepatitis B and C, syphilis and chagas disease. Bone marrow was hypercellular for age with absolute granulocytic predominance (G:E ratio 64:1) and eosinophilia (38%) in all maturational stages without dysplasia. Bone marrow flow cytometry did not detect neither increases in blasts nor anomalous immunophenotype. Bone marrow biopsy demonstrated 99% cellularity with normal blasts. Cytogenetics with translocation between the long arms of chromosome 5 and 15 in 15 of 20 metaphases analyzed - 46,XY,t(5;15)(q33;q22). No other molecular tests were available for this patient. Results In the case described t(5;15)(q33;q22) was found, which may be related to the TP53BP1::PDGFRB gene rearrangement. This breakpoint generates a chimeric oncoprotein similar to other tyrosine kinase fusions responsive to Imatinib. 53BP1 is a cellular DNA damage response component that binds wild type (non-mutant) p53. Oncogenesis occurs since the coiled-coil domains of TP53BP1 can mediate the homodimerization of PDGFRB and the constitutive activation of its tyrosine kinase activity; on the other hand, the DNA damage response of TP53BP1 may be disrupted. Gene rearrangements involving PDGFRA and FDGFRB are associated with response to tyrosine kinase inhibitors. Elevated vitamin B12 is a common finding in myeloproliferations with eosinophilia due to the increased production of haptocorrins, which binds to vitamin B12 in serum and in other tissues. Conclusions To our knowledge, in the literature there is only one described case of Myeloproliferative Neoplasia with Eosinophilia related to t(5;15)(q33;q22).

Secondary Syphilis Can Simultaneously Mimic Cholestatic Liver Injury and Glomerular Nephropathy

ABSTRACT Syphilis, a disease affecting millions, still poses challenges for men who have sex with men in high-income countries and often presents in varying ways. It is exceedingly rare for syphilis to simultaneously cause an acute liver injury and nephropathy. This case describes the concomitant clinical presentation of these abnormalities and also describes a liver injury that mimicked cholestatic disease. Treatment of syphilis led to complete resolution of the liver and kidney injury. This case demonstrates a need to exclude syphilis in patients with high-risk behaviors who present with cholestatic liver injury in atypical fashions.

S4581 Syphilitic Hepatitis in an Immunocompetent Patient With Secondary Syphilis and Ocular Involvement

S4581 Syphilitic Hepatitis in an Immunocompetent Patient With Secondary Syphilis and Ocular Involvement

S4665 Secondary Syphilis Manifesting as Hepatitis in a Patient With Risk Factors for Metabolic Dysfunction-Associated Fatty Liver Disease

S4665 Secondary Syphilis Manifesting as Hepatitis in a Patient With Risk Factors for Metabolic Dysfunction-Associated Fatty Liver Disease

Caught by a Medieval Disease: A Monoarthritis Revealing Syphilis

Syphilis is a sexually transmitted bacterial infection that first appeared in Europe in the 15th century, responsible for deadly epidemics before the discovery of penicillin. It typically progresses through three phases: primary syphilis, characterized by a syphilitic chancre that may appear on the genital area, anus, or oral cavity and can go unnoticed; secondary syphilis, which corresponds to the hematogenous dissemination of the treponema, leading to skin eruptions occurring in two waves, also known as "florid" phases, with the second wave being the most characteristic, involving papular lesions on the palms and soles. During this phase, there may also be lymphadenopathy, early neurosyphilis, and osteoarticular manifestations such as periostitis and arthritis [1,2,3]. Finally, tertiary syphilis, a historical form, is characterized by cardiac, vascular, and/or neuropsychiatric involvement. We report the case of a patient with risky sexual behavior who presented with an oral ulceration possibly corresponding to an oral syphilitic chancre in the primary phase. The patient did not seek medical attention at that time and developed secondary syphilis with joint involvement two months later. This article aims to remind that syphilis should not be excluded when faced with the combination of oral ulceration and arthritis, alongside chronic inflammatory bowel diseases, Behçet's disease, and lupus. The infection has to be confirmed in the joint aspiration either by isolating the treponema or by finding the pathogen’s DNA or simply by TPHA and VDRL technique ; as for the syphilitic arthritis should be treated as a secondary siphilis.

Annular secondary syphilis with HIV coinfection that resembles other dermatoses

Annular secondary syphilis with HIV coinfection that resembles other dermatoses

Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: an international, molecular epidemiology study

The increase in syphilis rates worldwide necessitates development of a vaccine with global efficacy. Weaimed to explore Treponema pallidum subspecies pallidum (TPA) molecular epidemiology essential for vaccine research by analysing clinical data and specimens from early syphilis patients using whole-genome sequencing (WGS) and publicly available WGS data. In this multicentre, cross-sectional, molecular epidemiology study, we enrolled patients with primary, secondary, or early latent syphilis from clinics in China, Colombia, Malawi, and the USA between Nov 28, 2019, and May 27, 2022. Participants aged 18years or older with laboratory confirmation of syphilis by direct detection methods or serological testing, or both, were included. Patients were excluded from enrolment if they were unwilling or unable to give informed consent, did not understand the study purpose or nature of their participation, or received antibiotics active against syphilis in the past 30days. TPA detection and WGS were conducted on lesion swabs, skin biopsies, skin scrapings, whole blood, or rabbit-passaged isolates. We compared our WGS data to publicly available genomes and analysed TPA populations to identify mutations associated with lineage and geography. We screened 2802patients and enrolled 233participants, of whom 77 (33%) had primary syphilis, 154 (66%) had secondary syphilis, and two (1%) had early latent syphilis. The median age of participants was 28years (IQR22-35); 154 (66%) participants were cisgender men, 77 (33%) were cisgender women, and two (1%) were transgender women. Of the cisgender men, 66 (43%) identified as gay, bisexual, or other sexuality. Among all participants, 56(24%) had HIV co-infection. WGS data from 113participants showed a predominance of SS14-lineage strains with geographical clustering. Phylogenomic analyses confirmed that Nichols-lineage strains were more genetically diverse than SS14-lineage strains and clustered into more distinct subclades. Differences in single nucleotide variants (SNVs) were evident by TPA lineage and geography. Mapping of highly differentiated SNVs to three-dimensional protein models showed population-specific substitutions, some in outer membrane proteins (OMPs) of interest. Our study substantiates the global diversity of TPA strains. Additional analyses to explore TPA OMP variability within strains is vital for vaccine development and understanding syphilis pathogenesis on a population level. US National Institutes of Health National Institute for Allergy and Infectious Disease, the Bill & Melinda Gates Foundation, Connecticut Children's, and the Czech Republic National Institute of Virology and Bacteriology.

Ocular Syphilis – Clinical Features and Outcome in HIV Positive and HIV Negative Patients from a Tertiary Eye Center from India – A Comparative Study

ABSTRACT Purpose To study and compare the clinical characteristics and outcome of ocular syphilis between HIV positive and HIV negative patients. Methods Retrospective hospital-based case series from a tertiary eye care hospital in India. Patients with uveitis and positive syphilis serology were included. Demographics, clinical features, investigations, imaging and treatment modalities were noted. Results Hundred and five (105) eyes of 66 patients were analyzed. Males were predominantly affected (n = 57/66, 86.4%). Secondary syphilis was the most common stage of presentation (n = 48/66, 72.7%). Two groups were identified: HIV positive (HIVP) patients (n = 39/66, 59%) and HIV negative (HIVN) patients (n = 27/66, 41%). 12/39 (30.8%) patients were newly diagnosed with HIV at the time of ocular presentation. Panuveitis was the most common presenting feature in both groups (n = 66/105 eyes, 62.8%). Diffuse necrotizing retinitis was more common in HIV patients (HIVP - 15 Vs HIVN - 5 eyes). Ocular co-infections were more common in HIV patients, ocular tuberculosis, the commonest in both groups. Intravenous penicillin and titrated dose of systemic steroids were the mainstay of treatment. Improvement in mean logMAR was noted from 1.415 to 0.828 with p-value < 0.001. At final follow-up, 71.8% patients showed visual improvement. Complete resolution of ocular inflammation was noted in 95.5% patients. Conclusion Ocular syphilis poses a diagnostic challenge considering the varied presentations and clinical course both in immunocompromised and immunocompetent groups. Clinical presentations are not always classical. High index of suspicion with supportive laboratory investigations and with characteristic OCT features helps diagnosis. All uveitis patients, especially with those suspected with infectious etiology, need to be tested for syphilis serology to prevent vision loss in this resurgent disease.

Treponema pallidum Periplasmic and Membrane Proteins Are Recognized by Circulating and Skin CD4+ T Cells.

Histologic and serologic studies suggest the induction of local and systemic Treponema pallidum-specific CD4+ T-cell responses to T. pallidum infection. We hypothesized that T. pallidum-specific CD4+ T cells are detectable in blood and in the skin rash of secondary syphilis and persist in both compartments after treatment. Peripheral blood mononuclear cells collected from 67 participants were screened by interferon-γ (IFN-γ) ELISPOT response to T. pallidum sonicate. T. pallidum-reactive T-cell lines from blood and skin were probed for responses to 89 recombinant T. pallidum antigens. Peptide epitopes and HLA class II restriction were defined for selected antigens. We detected CD4+ T-cell responses to T. pallidum sonicate ex vivo. Using T. pallidum-reactive T-cell lines we observed recognition of 14 discrete proteins, 13 of which localize to bacterial membranes or the periplasmic space. After therapy, T. pallidum-specific T cells persisted for at least 6 months in skin and 10 years in blood. T. pallidum infection elicits an antigen-specific CD4+ T-cell response in blood and skin. T. pallidum-specific CD4+ T cells persist as memory in both compartments long after curative therapy. The T. pallidum antigenic targets we identified may be high-priority vaccine candidates.