Analysis of Treponema pallidum Strains From China Using Improved Methods for Whole-Genome Sequencing From Primary Syphilis Chancres.

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.

Syphilis: A Contemporary Clinicopathologic Assessment.

Syphilis is a sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum that has been of public health concern for centuries. In the United States, it is currently a reportable disease and one which is recently generating increasing case numbers especially in at risk populations of immune deficiency and men who have sex with men. The present series examines biopsies from 13 patients collected over a 12-year period from a general hospital network in north suburban Cook County, Illinois. There were 13 patients (11 male: 2 female) with varied presentations, including primary ulcerated anogenital chancres, mucosal lesions, peculiar rashes, and alopecia. The reason(s) for biopsy were not clear from the clinical record, as a clinical consideration of syphilis was recorded in only 3 cases. Histologic examination of the mucocutaneous lesions encompassed a spectrum of findings including ulceration, psoriasiform hyperplasia, intense mixed band-like inflammation at the dermal-epidermal junction with a prominent plasma cell component. The contemporary availability of an effective immunostain is a valuable diagnostic adjunct. The organisms generally parallel the intensity of the inflammatory infiltrate but the distribution may vary and rarely, organisms may be absent despite serologic confirmation. Previous corkscrew morphology of the organism described ultrastructurally is reflected in the immunostained representation. Although the diagnosis of syphilis remains a clinical one in most cases, some patients will have unusual presentations and biopsies will be done. The awareness of the pathologist will facilitate prompt and effective treatment.

[A chancre instead of cancer]. / Geen kanker, maar een sjanker.

BACKGROUND: Syphilis (lues) is a sexually transmitted infection caused by the spirochete Treponema pallidum. In adolescents, the diagnosis of primary syphilis can be made promptly by taking a sexual medical history and inspecting the glans penis. CASE DESCRIPTION: A 17-year-old male was referred to the paediatric oncology centre for additional diagnostics due to inguinal lymphadenopathy, with a strong suspicion of a malignant lymphoma. None of the physicians took a sexual medical history or investigated the glans penis, as a result of which essential information was lacking. The combination of inguinal lymphadenopathy and the ultrasound findings for the inguinal region made the physicians only consider a malignancy. However, it actually concerned a reactive lymphadenopathy associated with primary syphilis. CONCLUSION: This case demonstrates that a full medical history and thorough physical examination can prevent the need for costly and invasive diagnostics.

Dermatologically challenging syphilis presentation.

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.

Concurrent Primary Chancre and Ocular Syphilis in an Human Immunodeficiency Virus-Negative Man.

We believe this to be the first report of coexisting polymerase chain reaction (PCR)-confirmed primary genital and ocular syphilis in a patient with penicillin allergy treated with doxycycline. The case examines the use of nonpenicillin and corticosteroid treatment of ocular syphilis and highlights the risk of eye involvement early in the disease process.

An extraordinary case of syphilis presenting with a labial ulcer.

In the differential diagnosis of patients with ulcers on the lips characteristics like the duration of the ulcer, number, size, depth, shape, base, margins, and distribution are considered. Such ulcers arise from many diseases particularly, viral and bacterial infections, malignancies can also be responsible. Classic syphilitic chancres are painless erosions settled on hard papule; these are evident in the genital area in more than 90% of patients. This study describes a case of a 38-year-old female patient presenting with a painful ulcer covering 3 quarters of the upper lip showing settlement on erythematous, edematous, and indurated plaque covered with hemorrhagic crusts. The aim of this study was to consider differences between the classic syphilitic chancre typically found in the genital region from extragenital chancres and to raise awareness of the possibility of primary syphilis when patients present with painful ulcers on the lip.

Tonsillar chancre as unusual manifestation of primary syphilis.

Primary syphilis with oropharyngeal manifestations should be kept in mind, though. Lips and tongue ulcers are the most frequently reported lesions and tonsillar ulcers are much more rare. We report the case of a 24-year-old woman with a syphilitic ulcer localized in her left tonsil.

Oral syphilis: report of three cases and characterization of the inflammatory cells.

Syphilis is a sexually transmitted infectious disease caused by Treponema pallidum. This study reports 3 cases of syphilis and highlights the importance of identifying oral lesions for its final diagnosis. Case 1: a 48-year-old male patient presented with a bleeding ulcer in the lower lip. Overall clinical examination revealed patchy alopecia and skin target lesions. Case 2: a 61-year-old male patient presented with white spots on the lateral tongue and nodules on the dorsum of the tongue. Overall clinical examination showed erythematous target lesions on the abdomen, forearm, palms of the hand, and soles of the feet. Case 3: a 17-year-old male patient presented with an ulcerated lesion on the tongue and lymph node involvement. The following serologic tests were requested: Venereal Disease Research Laboratory, fluorescent treponemal antibody-absorption, anti-HIV-1 and anti-HIV-2, and anti-hepatitis C virus. An incisional biopsy revealed epithelial hyperplasia associated with intense and diffuse mononuclear inflammatory cell infiltration consisting mainly of plasma cells, in a perivascular and perineural distribution. The final diagnosis in the 3 patients was syphilis. Treatment consisted of 1 weekly dose of penicillin (2.4 million units, intramuscular) for 2 or 3 weeks. Immunohistochemical reactions for XIIIa, CD3, CD20, CD68, CD163, S100, CD1a, CD11c, CD83, CD138, and CD208 were performed. Clinicians should be familiarized with oral syphilis lesions in order to be able to diagnose this emerging infectious disease of variable clinical presentation.

Cell and tissue interactions of Treponema pallidum in primary and secondary syphilitic skin lesions: an ultrastructural study of serial sections.

There are limited reports on the ultrastructure of syphilis skin lesions. The aim of this study has been to perform an electron microscopic investigation of the morphology and the tissue distribution of treponemes in primary and secondary cutaneous lesions. Three cases of primary syphilitic chancre and one case of secondary syphilis were included. Prominent epidermal abnormalities in the primary chancre and a perivascular inflammatory infiltrate in the secondary lesion were found by light microscopy. Ultrastructurally, spirochetes were located mainly in the blood vessel walls and dermal tissue of the chancre lesions. In the secondary syphilis case, spirochetes were more abundant between epidermal keratinocytes. Most of them adjusted to the intercellular spaces. Occasionally, the electron microscopy images were highly suggestive of an intracellular location. Both the ultrastructural and immunohistochemical examination of the primary and secondary syphilis lesions showed a paradoxical distribution of the causative microorganisms compared to the light microscopic changes. In addition, the ultrastructural findings strongly suggest that Treponema pallidum subspecies pallidum invades tissues, not only through an intercellular, but also through a transcellular pathway.

Genital ulcer disease in India: etiologies and performance of current syndrome guidelines.

BACKGROUND: In India, genital ulcer disease (GUD) syndrome is clinically classified as herpetic or nonherpetic and managed accordingly; laboratory support is unavailable at most health facilities. We undertook a study to determine the etiology of GUDs in men presenting to sexually transmitted infection (STI) clinics and assess the performance of the national algorithm for syndromic management of herpetic and nonherpetic GUDs in India. METHOD: A cross-sectional study was conducted among men with complaints of genital ulcers attending 8 STI clinics in 4 states. Ulcer swabs were collected and tested by the multiplex polymerase chain reaction method to determine the etiology of GUD. RESULTS: Of the 194 men recruited, etiology was confirmed in 121 GUD cases (62%). Herpes simplex virus (48%) was the most common etiological agent identified, followed by Treponema pallidum (23%) and mixed infections (9%). One case of Haemophilus ducreyi was confirmed in this series. The overall sensitivity and specificity of the national syndromic management algorithm for GUD were 68% and 52%, respectively. Using the national algorithm, 52 (42%) cases clinically misclassified as either herpetic (18 cases) or nonherpetic (34 cases) GUD resulting in incorrect treatment. CONCLUSIONS: Our findings suggest a revision of existing national STI treatment guidelines in India to include treatment of syphilis infections of all GUD patients. Periodic studies are required to monitor changing spectrum of GUD etiologies in India.

Perivascular cuff and spread of Treponema pallidum.

BACKGROUND: The incidence of syphilis is on the rise in many cities worldwide. Both the clinical and histopathological changes do not always fulfil the typical diagnostic criteria. Immunohistochemistry is available to identify and localize Treponema pallidum. Two main patterns of T. pallidum distribution were described in the skin, namely heavy intraepidermal infiltration and scattered pattern inside the lichenoid cell infiltrate. OBJECTIVE: To search for a third pattern consistent with dissemination of the disease. METHODS: Immunohistochemistry using an antispirochete (T. pallidum and Borrelia) antibody was used in all cases of syphilis submitted to our laboratory. In addition, deposits of immunoglobulins and complement indicative of immune complexes were searched for. RESULTS: According to the cases, T. pallidum was disclosed in a combination of three patterns. The previously described epidermal and lichenoid patterns were confirmed, and a third pattern predominating in a perivascular location throughout the dermis was clearly identified in primary syphilis. The microorganisms were abundant in extracellular and intracellular locations, particularly inside endothelial cells. No deposits of immunoglobulins and complement were disclosed. CONCLUSION: The perivascular cuff of T. pallidum throughout the dermis might be representative of the dissemination phase of T. pallidum.

Multiple aphthoid syphilitic chancres of the oral cavity.

We describe the case of a 31-year-old man who was affected by three asymptomatic, aphthoid, syphilitic chancres of the oral cavity. These lesions were accompanied by right latero-cervical and chin lymphadenopathy. The infection was previously diagnosed as aphthous stomatitis. The search for Treponema pallidum by means of darkfield microscope examination was positive. The patient was successfully treated with oral erythromycin ethylsuccinate. To our knowledge, this is the first case of multiple aphthoid syphilitic chancres of the oral cavity reported in the literature. We suggest that all patients with a recent history of painless ulcers in the oral cavity, accompanied by regional lymphadenopathy in which the clinical diagnosis has not been confirmed, should undergo a darkfield microscope examination.

Primary syphilis.

Cases of syphilis have been increasing in the UK and it remains an important public health problem. Here, we provide an overview of syphilis, its presentation, diagnosis and management.

Sequence diversity of Treponema pallidum subsp. pallidum tprK in human syphilis lesions and rabbit-propagated isolates.

The tprK gene of Treponema pallidum subsp. pallidum, the causative agent of venereal syphilis, belongs to a 12-member gene family and encodes a protein with a predicted cleavable signal sequence and predicted transmembrane domains. Except for the Nichols type strain, all rabbit-propagated isolates of T. pallidum examined thus far are comprised of mixed populations of organisms with heterogeneous tprK sequences. We show that tprK sequences in treponemes obtained directly from syphilis patients are also heterogeneous. Clustering analysis demonstrates that primary chancre tprK sequences are more likely to cluster within a sample than among samples and that tighter clustering is seen within chancre samples than within rabbit-propagated isolates. Closer analysis of tprK sequences from a rabbit-propagated isolate reveals that individual variable regions have different levels of diversity, suggesting that variable regions may have different intrinsic rates of sequence change or may be under different levels of selection. Most variable regions show increased sequence diversity upon passage. We speculate that the diversification of tprK during infection allows organisms to evade the host immune response, contributing to reinfection and persistent infection.

Simple algorithms for the management of genital ulcers: evaluation in a primary health care centre in Kigali, Rwanda.

A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care centre in Kigali, Rwanda. Using clinical data and the results of a rapid plasma reagin (RPR) test, we simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers. These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis. The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease. The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis. In situations where no laboratory support is available, a simple syndromic approach is preferable to the clinical approach for the management of genital ulcer. If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection.

PIP: A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care center in Kigali, Rwanda. Using clinical data and the results of a rapid plasma reagin (RPR) test, the authors simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers. These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis. The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease. The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis. In situations where no laboratory support is available, a simply syndromic approach is preferable to the clinical approach for the management of genital ulcer. If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection. (author's)