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Background: The global resurgence of syphilis necessitates vaccine development., Methods: We collected ulcer exudates and blood from 17 participants with primary syphilis (PS) and skin biopsies and blood from 51 patients with secondary syphilis (SS) in Guangzhou, China, for Treponema pallidum subsp pallidum (TPA) quantitative polymerase chain reaction, whole genome sequencing (WGS), and isolation of TPA in rabbits., Results: TPA DNA was detected in 15 of 17 ulcer exudates and 3 of 17 blood PS specimens. TPA DNA was detected in 50 of 51 SS skin biopsies and 27 of 51 blood specimens. TPA was isolated from 47 rabbits with success rates of 71% (12/17) and 69% (35/51), respectively, from ulcer exudates and SS bloods. We obtained paired genomic sequences from 24 clinical samples and corresponding rabbit isolates. Six SS14- and 2 Nichols-clade genome pairs contained rare discordances. Forty-one of the 51 unique TPA genomes clustered within SS14 subgroups largely from East Asia, while 10 fell into Nichols C and E subgroups., Conclusions: Our TPA detection rate was high from PS ulcer exudates and SS skin biopsies and over 50% from SS blood, with TPA isolation in more than two-thirds of samples. Our results support the use of WGS from rabbit isolates to inform vaccine development., Competing Interests: Potential conflicts of interest. J. B. P. reports research support from Gilead Sciences, nonfinancial support from Abbott Laboratories, and consulting for Zymeron Corporation outside the scope of the current manuscript. J. D. R. has licensing agreements for recombinant TPA proteins as syphilis serodiagnostic reagents with Biokit SA, Chembio, and Span Diagnostics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The incidence of syphilis has clearly increased in Germany in recent years. This infectious disease has many forms of manifestation and can imitate surgical diseases., Material and Methods: Comprehensive footage of experiences in a proctological center demonstrates these manifestations and explains the correct management., Results: The likelihood of confusion of syphilis with anal fissures, anogenital warts, proctitis and rectal cancer is high., Conclusion: Surgeons can encounter syphilis, the "chameleon of medicine" and must know the differential diagnoses., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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.)

Syphilis is a sexually and vertically transmitted bacterial infection caused by the bacterium Treponema pallidum. Its prevalence is high in low-income and middle-income countries, and its incidence has increased in high-income countries in the last few decades among men who have sex with men. Syphilis is a major cause of adverse pregnancy outcomes in low-income and middle-income countries. Clinical features include a primary chancre at the point of inoculation, followed weeks later by the rash of secondary syphilis, a latent period, and in some cases, involvement of the eyes, CNS, and cardiovascular systems. It is diagnosed serologically. A single intramuscular dose of long-acting benzathine penicillin is recommended for people who have had syphilis for less than 1 year and longer courses for people with late latent syphilis. Control strategies include screening and treatment of all pregnant women, and targeted interventions for groups at high risk. Vaccine development, research on antibiotic prophylaxis, and digital messaging as prevention strategies are ongoing., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Syphilis is a sexually transmitted infectious disease caused by the spirochete bacterium Treponema pallidum . A characteristic lesion of primary syphilis is chancre. It can develop over genital or extra genital sites, depending on the site of contact with the infectious agent. Cases of oral syphilis have been on the rise in the previous two decades, probably because of the involvement of the oral cavity in sexual practices. We here report an unusual case of primary syphilis who presented with a painless indurated oral ulcer over the lateral borders of the tongue.

Ulcerations of the prepuce or foreskin of the penis are rare in the day-to-day life of a urologist. The most common differential diagnosis is invasive penile cancer, which is why other diagnoses are often overshadowed. We report a case of a syphilitic lesion which was initially misdiagnosed as penile cancer. Considering the rising incidence of syphilis worldwide, syphilis should be considered as a possible cause of any solitary penile ulcer., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Syphilis continues to be a significant public health concern worldwide. The disease is endemic in many low- and middle-income countries, and rates have risen sharply in high-income countries over the last decade. The continued prevalence of infectious and congenital syphilis worldwide highlights the need for the development of an effective syphilis vaccine to complement public health measures for syphilis control. The complex, multi-stage course of syphilis infection necessitates a holistic approach to the development of an effective vaccine, in which immunization prevents both the localized stage of infection (typified by the highly infectious chancre) and the disseminated stages of infection (typified by the secondary rash, neurosyphilis, and destructive tertiary lesions, as well as congenital syphilis). Inhibiting development of the infectious chancre would reduce transmission thus providing community- level protection, while preventing dissemination would provide individual-level protection by reducing serious sequelae and may also provide community level protection by reducing shedding during secondary syphilis. In the current study we build upon prior investigations which demonstrated that immunizations with individual, well characterized T. pallidum TprK, TprC, and Tp0751 peptides elicits partial protection against infection in the animal model. Specifically, we show here that immunization with a TprC/TprK/Tp0751 tri-antigen cocktail protects animals from progressive syphilis lesions and substantially inhibits dissemination of the infection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Caroline Cameron has patent issued to University of Victoria., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Syphilis is an infectious disease caused by the spirochete Treponema pallidum, transmitted mainly by direct contact with the lesion. Primary syphilis usually presents with a chancre at the site of infection, which is highly contagious and resolves without treatment. The aim of this article is to illustrate an unusual location of a syphilitic chancre, in order to consider this diagnosis within the approach to patients with oral ulcers., Clinical Case: a 30-year-old man who presented a dermatosis located in the left labial commissure, characterized by a painless ulcer of 1 cm in diameter of 20 days of evolution. The patient has a history of HIV/AIDS. A punch biopsy of the dermatosis was performed, with a histopathological report compatible with syphilitic chancre and a negative VDRL result. He was treated with penicillin G benzathine showing improvement., Conclusions: Primary syphilis is characterized by the development of the syphilitic chancre, which is the first manifestation of syphilis in up to 60% of cases. Extragenital presentation is rare, with only 12-14% of all cases, and of these between 40-70% occur in the mouth, being the lips the most frequent location. Oral manifestations can represent a diagnostic challenge due to its wide spectrum of clinical presentations., (© 2022 Revista Médica del Instituto Mexicano del Seguro Social.)

Genital ulcers (GUs) represent a diagnostic challenge and can be secondary to neoplastic and inflammatory processes of different causes. Among those of infectious etiology, there are sexually transmitted infections (STIs), a very frequent reason for seeking the health service. The most common agents are herpes simplex virus and Treponema pallidum and, more rarely, Haemophilus ducreyi, Klebsiella granulomatis and Chlamydia trachomatis. A careful dermatological examination offers important diagnostic elements; however, atypical manifestations are very common. Distinctive characteristics of ulcers to look out for include their margin, edge, bottom, and base. Regional lymph node chain alterations should be evaluated regarding their number, size, mobility, consistency, inflammation, and pain on palpation. Diagnostic tests have variable sensitivity and specificity, and molecular tests are currently considered the reference exams. The rapid immunochromatographic tests represented a significant advance, as they can be performed with blood obtained from the digital pulp, offer results in up to 30 minutes, and do not require a laboratory structure. The treatment of persons affected by GU/STIs must be immediate, as it aims to prevent complications, as well as reduce transmission. It is not always considered that people with GUs/STIs have varying degrees of depression, anxiety, and self-reproach, with an impact on relationships. Establishing a bond and trusting the professional is essential for adherence to treatment and preventive measures that must be discussed individually., (Copyright © 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Primary syphilis is characterised by the appearance of an ulcerated lesion (chancre) on the anogenital or oral mucosa from which Treponema pallidum DNA may be detectable by PCR. Serological tests for syphilis may be non-reactive in early infection, even after the appearance of a chancre. We reviewed the use of a multiplex-PCR (M-PCR) test to determine the added value of T. pallidum DNA detection in the management of individuals presenting with mucocutaneous ulceration at a sexual health service in central London., Methods: We performed a cross-sectional analysis of all individuals with detectable T. pallidum DNA from September 2019 to April 2020. Electronic patient records were reviewed and concomitant results for treponemal serology and/or rapid plasma reagin (RPR) extracted, along with demographic data, history of syphilis and indices of sexual behaviour including number of sexual partners contacted. Any subsequent treponemal serology and RPR results were also reviewed., Results: M-PCR swab specimens were performed in 450 individuals, of whom 63 (14%) had detectable T. pallidum DNA; 60 of 63 (95%) were gay or bisexual men and 11 of 63 (17%) were living with HIV. A history of treated syphilis was present in 17 of 63 (27%). Same-day treponemal serology/RPR testing was performed in 58 of 63 (92%) patients. Of the 58 who had same-day syphilis serology/RPR, 9 (16%) had their syphilis infection confirmed by treponemal DNA PCR alone. A total of 165 partners were traced as contacts of infection, of whom 25 (15%) were contacts of individuals diagnosed by M-PCR testing alone., Conclusion: In individuals with T. pallidum PCR-positive lesions, around one in six in our cohort were negative on standard diagnostic serological tests for syphilis. Treponemal DNA testing is an important addition to serological assays in individuals with mucocutaneous ulceration who are at risk of recent syphilis infection and facilitates early diagnosis and contact tracing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective To analyze the reasons of misdiagnosis of primary syphilitic chancre and strengthen the understanding of atypical features of this disease. Methods A case series of twenty-seven challenging primary syphilis patients who were not immediately recognized as chancre was included in our study. The clinical data including the patients' age, sex, skin lesions, HIV status, syphilis serologic test results, treatment, and follow-up results were collected. Hematoxylin-eosin and immunohistochemistry staining of skin biopsy sections were reviewed. Results Four female cases with extragenital chancres presenting as erythema or erosive skin lesions on the nipple were misdiagnosed as Paget's disease or eczema. The disorder of missed or misdiagnosed male cases manifested as syphilitic balanitis or multiple chancres on the penis root and adjacent pubis rather than coronal sulcus or frenum. Patients with nonreactive nontreponemal tests at initial presentation were also easily missed or misdiagnosed. Conclusion Primary syphilis presenting as multiple lesions rather than a single chancre, at atypical locations, or with a nonreactive nontreponemal test result, tends to be missed or misdiagnosed.

Abstract: Rapid emergence of syphilis and oral sexual behaviors has focused attention on oral syphilis, and published reports of cases with oral syphilis have increased in the recent decades. We performed a systematic literature review by searching articles from PubMed, EMBSE, and Google Scholar, looking for case reports or series that would potentially have the clinical characteristics and outcomes for each individual case with oral syphilis. A total of 145 cases with the infection, from 95 studies, were identified to include in our review. Two main clinical phenotypes (ulcerative lesions and mucous patches) appeared to be of particular relevance to oral manifestations. A solitary ulcer was mostly manifested as the lesion of primary syphilis (91.7%) preferentially located on the upper lip, tongue, palate, and buccal mucosa. The most affected anatomical site in the patients with single location involved was the tongue (37.5%), followed by the lips (29.5%), palates (19.3%), and buccal mucosa (6.8%). It is concluded that oral syphilis has its predominant clinical phenotypes although it can manifest in diverse manners., Competing Interests: Conflict of Interest: None declared., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Sexually Transmitted Diseases Association.)

Background: Syphilis is a sexually-transmitted infectious disease caused by Treponema pallidum. Cases of primary and secondary syphilis are on the rise in the United States, with a 14.4% increase in new cases noted from 2017 to 2018 and an escalation of 71% between the years 2014 and 2018. Fulfilling its nickname of "the great imitator," oral manifestations of syphilis may mimic a variety of infectious, neoplastic, or immune-mediated processes, both clinically and histopathologically. This large spectrum of appearances can create a diagnostic challenge to the clinician and/or pathologist, leading to delay in diagnosis or misdiagnosis., Methods: A database of oral syphilis cases was created from archives at the University of Kentucky, University of Pittsburgh, LIJMC, Columbia University MC, and University of Tennessee. The age, sex, race, location, duration, and clinical description were recorded. Cases without positive reaction upon immunohistochemistry or serologic tests were excluded., Results: We identified 19 new cases of oral syphilis (17 males, one female, and one case unknown sex) and described the clinical and histopathological features of this re-emerging and potentially fatal disease. All cases demonstrated dense lymphoplasmacytic inflammation, often with inflammatory exocytosis or ulceration at the surface, and perivascular inflammation., Conclusions: Early recognition of the histopathologic and clinical manifestations of oral syphilis is imperative for prompt diagnosis, improved patient outcomes, and disease prevention., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Syphilis is an increasingly common infectious disease caused by the bacterium Treponema pallidum . Atypical clinical presentations occur that may delay its diagnosis and treatment. Regional enlargement of lymph nodes is seen in both primary and secondary stages. Such lymph nodes very rarely become abscesses. Antibiotics should be administered in this situation; however, if this fails, the lymph nodes should be surgically excised.

Background: Whole-genome sequencing (WGS) of Treponema pallidum subspecies pallidum (TPA) has been constrained by the lack of in vitro cultivation methods for isolating spirochetes from patient samples., Methods: We built upon recently developed enrichment methods to sequence TPA directly from primary syphilis chancre swabs collected in Guangzhou, China., Results: By combining parallel, pooled whole-genome amplification with hybrid selection, we generated high-quality genomes from 4 of 8 chancre-swab samples and 2 of 2 rabbit-passaged isolates, all subjected to challenging storage conditions., Conclusions: This approach enabled the first WGS of Chinese samples without rabbit passage and provided insights into TPA genetic diversity in China., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Syphilis, a sexually transmitted disease, can be categorized as acquired syphilis and congenital syphilis, manifesting diverse lesions involving multiple sites. Oral manifestations at the primary stage of acquired syphilis are usually characterized by its short period and non-specific varied presentations. And oral ulcers as initial and the only presentation of syphilis oral lesions are infrequent and occur in less than 2% of patients. Because of its transient nature and variable manifestations which could mimic other oral ulcerative lesions, oral syphilis presenting as sole ulceration at early stage can be easily neglected and rather difficult to diagnose. Herein, we report a 35-year-old female patient manifested a sole atypical ulceration on her upper lip for approximately 1 month. We highlighted the importance of early and accurate diagnosis, focused on the characteristics of oral chancre, and gave an insight to the differential diagnoses, which would be enlightening and useful in clinical practice., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest regarding the publication of this paper., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

An atypical early primary syphilis case presentation with multiple umbilicated papular lesions on the penis and a nonreactive syphilis serology was misdiagnosed as molluscum contagiosum. Over a period of eight weeks, prior to dermatologic consultation, the papules enlarged, ulcerated, and healed. New plaque and patch formation on the penis and scrotum led to a differential diagnosis of inverse psoriasis vs. syphilis. Histological examination of a shave biopsy specimen revealed numerous Treponema pallidum organisms and repeat syphilis serological test results confirmed a syphilis diagnosis. Lesions responded to treatment with benzathine penicillin. One must keep a high index of suspicion for syphilis in light of its diverse presentation and increasing incidence.

The aim of this study was to describe 40 cases of acquired oral syphilis (AOS) and to discuss the distribution of demographic characteristics, clinical features, and differential diagnosis of the disease. A retrospective study was conducted covering a 17-year period at a single institution in southern Brazil. Moreover, a literature review was performed through a search of the PubMed database for articles on AOS published between 1955 and March 2018. Data were analyzed descriptively. The predominant group within the case series was male patients in their twenties. The vast majority of cases (92.5%) were in the secondary stage of the disease. The lips were the most commonly affected site, with greyish-white mucous patches and reddish ulcers. In the literature review, the largest number of reported cases came from North America. Male patients in the third and fourth decades of life were most affected. AOS occurred more commonly as mucous patches and ulcers on the tongue and palate. Similarities regarding the distribution by sex, age, and anatomical location were found in the present study when compared to cases reported elsewhere. Clinicians, oral pathologists, and maxillofacial surgeons should familiarize themselves with the variable spectrum of signs and symptoms of AOS in their clinical practice to improve diagnosis and management., (Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Syphilis and human immunodeficiency virus (HIV) infections are both transmitted sexually. Co-infection of HIV and syphilis alters the course of both diseases. Clinical presentation of syphilis in patients of HIV may be atypical. HIV-infected individuals are at risk of developing lues maligna, which is characterized by nodulo-ulcerative lesions associated with severe constitutional symptoms. Erythroderma secondary to generalized papulo-squamous lesions of secondary syphilis is also uncommon. Here we report two cases of atypical presentations of secondary syphilis in HIV-positive patients.

Rectal ulcerations are an uncommon presentation of a primary syphilis infection. Anorectal syphilis is difficult to diagnose because of its often asymptomatic or atypical clinical presentation. It is important to consider sexually transmitted diseases (STD) in all patients presenting with rectal symptoms. A history of anal sexual intercourse should be made, especially in men having sex with men (MSM). Moreover, the possibility of a primary syphilis infection of the rectum should be considered. Endoscopic findings might be diverse, whereas a typical chancre can present as an anorectal ulcer associated with regional lymphadenopathy. It is important to consider other causes of anorectal ulcers, like other STD, inflammatory bowel disease (IBD) or even malignant causes. The diagnosis of anorectal syphilis is based on the combination of the clinical presentation, serology tests, endoscopic findings and biopsies. The cornerstone of the treatment is based on an intramuscularly administration of a long-acting preparation of penicillin (benzathine penicillin G)., (© Acta Gastro-Enterologica Belgica.)

John Hunter's work included description of the nature of digestion, child development, role of the lymphatic system and proof that the maternal and foetal blood supplies are separate. His contribution to the understanding of venereal diseases is reviewed. Hunter's argument of the unitary nature of venereal diseases is examined and the progress he made in diagnosis and management is discussed., (© The Author(s) 2014.)

Between 2010 and 2014, we obtained swab specimens to detect Treponema pallidum, with PCR assays, from the oral cavities of 240 patients with 267 episodes of syphilis who reported engaging in unprotected sex practices. The detected treponemal DNA was subjected to genotyping. All of the syphilis cases occurred in men who have sex with men (MSM), and 242 (90.6%) occurred in human immunodeficiency virus-infected patients. The stages of syphilis included 38 cases (14.2%) of primary syphilis of the genital region, 76 (28.5%) of secondary syphilis, 21 (7.9%) of primary and secondary syphilis, 125 (46.8%) of early latent syphilis, and seven (2.6%) others. Concurrent oral ulcers were identified in 22 cases (8.2%). Treponemal DNA was identified from the swabs of 113 patients (42.2%), including 15 (68.2%) with oral ulcers. The most common genotype of T. pallidum was 14f/f. The presence of oral ulcers was associated with identification of T. pallidum in the swab specimens (15/22 (68.2%) vs. 98/245 (40.0%)) (p = 0.01). In multivariate analysis, secondary syphilis (adjusted OR 6.79; 95% CI 1.97-23.28) and rapid plasma reagin (RPR) titres of ≥1: 32 (adjusted OR 2.23; 95% CI 1.02-4.89) were independently associated with the presence of treponemal DNA in patients without oral ulcers. We conclude that detection of treponemal DNA in the oral cavity with PCR assays is not uncommon in MSM, most of whom reported having unprotected oral sex. Although the presence of oral ulcers is significantly associated with detection of treponemal DNA, treponemal DNA is more likely to be identified in patients without oral ulcers who present with secondary syphilis and RPR titres of ≥1: 32., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Syphilis is a complex, systemic disease caused by the spirochete Treponema pallidum. Syphilis is most commonly transmitted sexually or congenitally and can involve nearly every organ system. Its clinical progression involves several well-characterized stages: an incubation period, a primary stage, a secondary stage, a latent stage, and a late or tertiary stage. Syphilis during pregnancy is a leading cause of perinatal mortality in sub-Saharan Africa and can cause spontaneous abortion, stillbirth, prematurity, low birth weight, or congenital syphilis. Penicillin is highly effective against syphilis and remains the treatment of choice. This article reviews the epidemiology, clinical features, diagnostic approach, treatment, and prevention of syphilis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Rectal syphilis, known as a great masquerader, can be difficult to diagnose because of its variable symptoms. Gastroenterologists should be aware of the possibility of rectal syphilis when confronted with anorectal ulcers, and should gather a detailed history about sexual preferences and practices, including homosexuality. We report a case of primary rectal syphilis mimicking rectal cancer on radiologic imaging. In this report, we described the clinical, endoscopic, and radiologic features of this rare case.